FN Thomson Reuters Web of Science™ VR 1.0 PT J AU MacDonald, SM Patel, SA Hickey, S Specht, M Isakoff, SJ Gadd, M Smith, BL Yeap, BY Adams, J DeLaney, TF Kooy, H Lu, HM Taghian, AG AF MacDonald, Shannon M. Patel, Sagar A. Hickey, Shea Specht, Michelle Isakoff, Steven J. Gadd, Michele Smith, Barbara L. Yeap, Beow Y. Adams, Judith DeLaney, Thomas F. Kooy, Hanne Lu, Hsiao-Ming Taghian, Alphonse G. TI Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADIATION-THERAPY; RANDOMIZED-TRIAL; RADIOTHERAPY; HEART; MORTALITY; RISK; CHEMOTHERAPY; PNEUMONITIS AB Purpose: Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Methods and Materials: Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after thecompletion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Results: Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Conclusions: Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods. (C) 2013 Elsevier Inc. C1 [MacDonald, Shannon M.; Patel, Sagar A.; Hickey, Shea; Adams, Judith; DeLaney, Thomas F.; Kooy, Hanne; Lu, Hsiao-Ming; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Specht, Michelle; Gadd, Michele; Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA USA. [Isakoff, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Yawkey 117,54 Fruit St, Boston, MA 02114 USA. EM smacdonald@partners.org FU Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX Supported by the federal share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 20 TC 33 Z9 34 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2013 VL 86 IS 3 BP 484 EP 490 DI 10.1016/j.ijrobp.2013.01.038 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 152AE UT WOS:000319500700020 PM 23523326 ER PT J AU Hamstra, DA Conlon, ASC Daignault, S Dunn, RL Sandler, HM Hembroff, AL Zietman, AL Kaplan, I Ciezki, J Kuban, DA Wei, JT Sanda, MG Michalski, JM AF Hamstra, Daniel A. Conlon, Anna S. C. Daignault, Stephanie Dunn, Rodney L. Sandler, Howard M. Hembroff, A. Larry Zietman, Anthony L. Kaplan, Irving Ciezki, Jay Kuban, Deborah A. Wei, John T. Sanda, Martin G. Michalski, Jeff M. CA PROSTQA Consortium Study Grp TI Multi-institutional Prospective Evaluation of Bowel Quality of Life After Prostate External Beam Radiation Therapy Identifies Patient and Treatment Factors Associated With Patient-Reported Outcomes: The PROSTQA Experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID LATE RECTAL TOXICITY; RANDOMIZED-TRIAL; CONFORMAL RADIOTHERAPY; RADICAL PROSTATECTOMY; CANCER SURVIVORS; DOSE-RESPONSE; BRACHYTHERAPY; MEN AB Purpose: To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). Methods and Materials: Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. Results: Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum >= 25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P = .015) and predicted increased risks for moderate to big fecal incontinence (P = .0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 >= 25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P = .03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P = .018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P = .026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P = .03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P = .018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. Conclusion: After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 >= 25% as having significant impact on patient-reported outcomes. (C) 2013 Elsevier Inc. C1 [Hamstra, Daniel A.] Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 40185 USA. [Conlon, Anna S. C.; Daignault, Stephanie] Univ Michigan, Dept Biostat, Ctr Comprehens Canc, Ann Arbor, MI 40185 USA. [Dunn, Rodney L.; Wei, John T.] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI 40185 USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Hembroff, A. Larry] Michigan State Univ, Off Survey Res, E Lansing, MI 48824 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kaplan, Irving] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Ciezki, Jay] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Kuban, Deborah A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Sanda, Martin G.] Emory Univ, Med Ctr, Dept Urol, Atlanta, GA 30322 USA. [Michalski, Jeff M.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. RP Hamstra, DA (reprint author), Univ Michigan, Med Ctr, Dept Radiat Oncol, 1500 Med Ctr Dr, Ann Arbor, MI 40185 USA. EM dhamm@med.umich.edu RI Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012 FU National Institutes of Health [R01 CA 95662, CA083654, 1RC1CA146596]; Sanofi Aventis FX Funding was provided by National Institutes of Health grants R01 CA 95662, CA083654, and 1RC1CA146596.; M.G.S. reports grant funding from the National Institutes of Health and payment from Sanofi Aventis for speaking engagements. H.M.S. reports working as a consultant for Astellas, Bayer, and Millennium Pharmaceuticals. NR 23 TC 17 Z9 17 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2013 VL 86 IS 3 BP 546 EP 553 DI 10.1016/j.ijrobp.2013.01.036 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 152AE UT WOS:000319500700030 PM 23561651 ER PT J AU Brauns, S Gollub, RL Walton, E Hass, J Smolka, MN White, T Wassink, TH Calhoun, VD Ehrlich, S AF Brauns, Stefan Gollub, Randy L. Walton, Esther Hass, Johanna Smolka, Michael N. White, Tonya Wassink, Thomas H. Calhoun, Vince D. Ehrlich, Stefan TI Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Cortical thickness; Single nucleotide polymorphism; GAD1; COMT Val/Met polymorphism; Schizophrenia ID CATECHOL-O-METHYLTRANSFERASE; ANTERIOR CINGULATE CORTEX; HUMAN CEREBRAL-CORTEX; CHILDHOOD-ONSET SCHIZOPHRENIA; GLUTAMIC-ACID DECARBOXYLASE; 1ST EPISODE SCHIZOPHRENIA; TASK-INDUCED DEACTIVATION; SURFACE-BASED ANALYSIS; DEFAULT MODE NETWORK; GRAY-MATTER AB Patients with schizophrenia show widespread cortical thickness reductions throughout the brain. Likewise, reduced expression of the gamma-Aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD1) and a single nucleotide polymorphism (SNP) rs3749034 in the corresponding gene have been associated with schizophrenia. We tested whether this SNP is associated with reduced cortical thickness, an intermediate phenotype for schizophrenia. Because of the well known interactions between the GABAergic and dopaminergic systems, we examined whether associations between GAD1 rs3749034 and cortical thickness are modulated by the catechol-O-methyltransferase (COMT) Val158Met genotype. Structural MRI and genotype data was obtained from 94 healthy subjects enrolled in the Mind Clinical Imaging Consortium study to examine the relations between GAD1 genotype and cortical thickness. Our data show a robust reduction of cortical thickness in the left parahippocampal gyrus (PUG) in G allele hornozygotes of GAD1 rs3749034. When we stratified our analyses according to the COMT Val158Met genotype, cortical thickness reductions of G allele homozygotes were only found in the presence of the Val allele. Genetic risk variants of schizophrenia in the GABAergic system might interact with the dopaminergic system and impact brain structure and functioning. Our findings point to the importance of the GABAergic system in the pathogenesis of schizophrenia. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Brauns, Stefan; Walton, Esther; Hass, Johanna; Ehrlich, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Dresden, Germany. [Brauns, Stefan; Gollub, Randy L.; Walton, Esther; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Brauns, Stefan] Charite, Dept Psychiat, D-13353 Berlin, Germany. [Gollub, Randy L.; Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Smolka, Michael N.] Tech Univ Dresden, Dept Psychiat, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany. [White, Tonya] Erasmus MC Sophia, Dept Child Psychiat, Rotterdam, Netherlands. [Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, Fetscherstr 74, D-01307 Dresden, Germany. EM transden.lab@uniklinikum-dresden.de RI Calhoun, Vince/H-7146-2013; Smolka, Michael/B-4865-2011; OI Calhoun, Vince/0000-0001-9058-0747; Smolka, Michael/0000-0001-5398-5569; Ehrlich, Stefan/0000-0003-2132-4445; Walton, Esther/0000-0002-0935-2200; Gollub, Randy L./0000-0002-9434-4044 FU NIH/NCRR [P41RR14075]; Department of Energy [DE-FG02-99ER62764]; MIND Research Network [Morphometry BIRN 1U24, RR021382A, Function BIRN U24RR021992-01, NIH.NCRR MO1 RR025758-01]; Department of Energy for the Mental Illness and Neuroscience Discovery (MIND) Research Network [DE-FG02-99ER62764]; Deutsche Forschungsgemeinschaft; NARSAD; Biomedical Science Exchange Program; Deutscher Akademischer Austausch Dienst; Friedrich-Ebert-Stiftung FX This research was supported by grants from NIH/NCRR P41RR14075, Department of Energy DE-FG02-99ER62764, MIND Research Network, Morphometry BIRN 1U24, RR021382A, Function BIRN U24RR021992-01, NIH.NCRR MO1 RR025758-01, the Department of Energy for the Mental Illness and Neuroscience Discovery (MIND) Research Network [DE-FG02-99ER62764], the Deutsche Forschungsgemeinschaft and the NARSAD Young Investigator Award (Research Fellowship and Grant to S Ehrlich), the Biomedical Science Exchange Program (scholarship to S Brauns), the Deutscher Akademischer Austausch Dienst and the Friedrich-Ebert-Stiftung (scholarships to E Walton). These sources had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 101 TC 4 Z9 4 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUL PY 2013 VL 47 IS 7 BP 872 EP 879 DI 10.1016/j.jpsychires.2013.03.010 PG 8 WC Psychiatry SC Psychiatry GA 152RR UT WOS:000319549300004 PM 23566421 ER PT J AU Malone, JC Cohen, S Liu, SR Vaillant, GE Waldinger, RJ AF Malone, Johanna C. Cohen, Shiri Liu, Sabrina R. Vaillant, George E. Waldinger, Robert J. TI Adaptive midlife defense mechanisms and late-life health SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Personality; Defense mechanisms; Defense maturity; Coping; Social support; Physical health ID MALE PSYCHOLOGICAL HEALTH; SOCIAL SUPPORT; EGO MECHANISMS; NATURAL-HISTORY; PHYSICAL HEALTH; COPING STYLES; OLDER-ADULTS; PERSONALITY; PSYCHOPATHOLOGY; MORTALITY AB A growing body of research suggests that personality characteristics relate to physical health; however, this relationship has primarily been tested in cross-sectional studies that have not followed the participants into old age. The present study utilizes data from a 70-year longitudinal study to prospectively examine the relationship between the adaptive defense mechanisms in midlife and objectively assessed physical health in late life. In addition to examining the direct effect, we test whether social support mediates this relationship. The sample consisted of 90 men who were followed for over seven decades beginning in late adolescence. Health ratings from medical records were made at three time points (ages 70, 75, and 80). Defense mechanisms were coded from narratives by trained independent raters (Vaillant, Bond, & Vaillant, 1986). Independent raters assessed social supports between ages 50 and 70. More adaptive defenses in midlife were associated with better physical health at all three time points in late life. These relationships were partially mediated by social support. Findings are consistent with the theory that defense maturity is important for building social relationships, which in turn contribute to better late-life physical health. Psychological interventions aimed at improving these domains may be beneficial for physical health. (C) 2013 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Malone, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,701, Boston, MA 02114 USA. EM johanna.malone@gmail.com FU NIA NIH HHS [R01 AG034554] NR 41 TC 9 Z9 9 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JUL PY 2013 VL 55 IS 2 BP 85 EP 89 DI 10.1016/j.paid.2013.01.025 PG 5 WC Psychology, Social SC Psychology GA 146LF UT WOS:000319091900001 PM 24031102 ER PT J AU Vandenberg, LN Colborn, T Hayes, TB Heindel, JJ Jacobs, DR Lee, DH Myers, JP Shioda, T Soto, AM vom Saal, FS Welshons, WV Zoeller, RT AF Vandenberg, Laura N. Colborn, Theo Hayes, Tyrone B. Heindel, Jerrold J. Jacobs, David R., Jr. Lee, Duk-Hee Myers, John Peterson Shioda, Toshi Soto, Ana M. vom Saal, Frederick S. Welshons, Wade V. Zoeller, R. Thomas TI Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE Weight of evidence; Organizational; Adaptive effect; Hormesis; Human exposure; Epidemiology; Flare ID ORGANIZATIONAL-ACTIVATIONAL HYPOTHESIS; PRENATAL PHTHALATE EXPOSURE; NUCLEAR RECEPTOR SUPERFAMILY; NONMONOTONIC DOSE-RESPONSES; GOOD LABORATORY PRACTICES; BISPHENOL-A EXPOSURE; OF-EVIDENCE ANALYSIS; BREAST-CANCER CELLS; ANOGENITAL DISTANCE; RISK-ASSESSMENT AB For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialog on their impact on risk assessment. (c) 2013 Elsevier Inc. All rights reserved. C1 [Vandenberg, Laura N.] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Vandenberg, Laura N.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Colborn, Theo] Endocrine Disrupt Exchange, Paonia, CO USA. [Hayes, Tyrone B.] Univ Calif Berkeley, Museum Vertebrate Zool, Energy & Resources Grp, Grp Endocrinol,Lab Integrat Studies Amphibian Bio, Berkeley, CA 94720 USA. [Hayes, Tyrone B.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Heindel, Jerrold J.] NIEHS, Div Extramural Res & Training, NIH DHHS, Res Triangle Pk, NC 27709 USA. [Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN USA. [Lee, Duk-Hee] Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Taegu, South Korea. [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc Res, Mol Profiling Lab, Charlestown, MA USA. [Soto, Ana M.] Tufts Univ, Sch Med, Dept Anat & Cell Biol, Medford, MA 02155 USA. [vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Welshons, Wade V.] Univ Missouri, Dept Biomed Sci, Columbia, MO USA. [Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. RP Vandenberg, LN (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA. EM laura.vandenberg@tufts.edu FU NIH [GM 087107, ES 08314, ES 010026, ES 018764, HL 53560, UMC MO-VMFC0018]; Susan G. Komen for Cure grant [FAS0703860]; Mitchell Kapor Foundation; Cornell-Douglas Foundation; Wallace Global Fund; Kendeda Foundation FX The authors gratefully acknowledge the following funding sources: NIH grants GM 087107 (to LNV), ES 08314 (to AMS), ES 010026 (to RTZ), ES 018764 (to FSvS), HL 53560 (to DRJ), UMC MO-VMFC0018 (to WVW), a Susan G. Komen for Cure grant FAS0703860 (to TS), grants from the Mitchell Kapor Foundation, the Cornell-Douglas Foundation, and the Wallace Global Fund (to TBH) and a grant from the Kendeda Foundation (to JPM). The funders had no role in the preparation of this manuscript. NR 216 TC 54 Z9 58 U1 10 U2 108 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JUL PY 2013 VL 38 BP 1 EP 15 DI 10.1016/j.reprotox.2013.02.002 PG 15 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 152MG UT WOS:000319535200001 PM 23411111 ER PT J AU Antebi, B Cheng, XG Harris, JN Gower, LB Chen, XD Ling, J AF Antebi, Ben Cheng, Xingguo Harris, Jeffrey N. Gower, Laurie B. Chen, Xiao-Dong Ling, Jian TI Biomimetic Collagen-Hydroxyapatite Composite Fabricated via a Novel Perfusion-Flow Mineralization Technique SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID APATITE FORMATION; IN-VITRO; BONE; SCAFFOLDS; BIOMINERALIZATION; MATRIX; REGENERATION; MECHANISM; REPAIR; CELLS AB Prevalent three-dimensional scaffolds for bone tissue engineering are mineralized collagen-hydroxyapatite (Col/HA) composites. Conventional mineralization techniques are either to coat collagen scaffold surfaces with minerals or to simply mix collagen and mineral nanoparticles together. These conventional in vitro collagen mineralization methods are different from the in vivo bone formation process and often result in scaffolds that are not suitable for bone tissue engineering. In this study, a unique perfusion-flow (i.e., dynamic) in conjunction with a previously described polymer-induced liquid-precursor (PILP) method was used to fabricate a porous Col/HA composite. The dynamic flow emulated the physiological extracellular fluid flow containing the mineralization ions, while the PILP method facilitated the deposition of the HA crystals within the collagen fibrils (i.e., intrafibrillar mineralization). By utilizing a dynamic PILP technique to mimic the in vivo bone formation process, the resultant Col/HA composite has a similar structure and compositions like human trabecular bone. A comparison of the dynamic and static mineralization methods revealed that the novel dynamic technique facilitates more efficient and homogenous mineral deposition throughout the Col/HA composite. The dynamic intrafibrillar mineralization method generated stiff Col/HA composites with excellent surface property for cell attachment and growth. The human mesenchymal stem cells cultured on the Col/HA composites quickly remodeled the scaffolds and resulted in constructs with an extensive cell-derived extracellular matrix network. C1 [Antebi, Ben; Cheng, Xingguo; Harris, Jeffrey N.; Ling, Jian] SW Res Inst, Dept Microencapsulat & Nanomat, San Antonio, TX 78238 USA. [Antebi, Ben; Ling, Jian] Univ Texas Hlth Sci Ctr San Antonio, Univ Texas San Antonio, Biomed Engn Program, San Antonio, TX 78229 USA. [Gower, Laurie B.] Univ Florida, Dept Mat Sci & Engn, Gainesville, FL 32611 USA. [Chen, Xiao-Dong] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Chen, Xiao-Dong] South Texas Vet Hlth Care Syst, Audie L Murphy Div Hosp, San Antonio, TX USA. RP Ling, J (reprint author), SW Res Inst, Dept Microencapsulat & Nanomat, 6220 Culebra Rd, San Antonio, TX 78238 USA. EM jling@swri.org RI Gower, Laurie/A-5947-2008 OI Gower, Laurie/0000-0003-2927-5406 FU National Heart, Lung, and Blood Institute [1R21 HL102775-01] FX This work was supported by the National Heart, Lung, and Blood Institute: 1R21 HL102775-01. NR 38 TC 21 Z9 22 U1 8 U2 66 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD JUL PY 2013 VL 19 IS 7 BP 487 EP 496 DI 10.1089/ten.tec.2012.0452 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 150PY UT WOS:000319404500001 PM 23157544 ER PT J AU Unawane, AV Patel, K Bhullar, JS Subhas, G Mittal, VK Cheung, LY AF Unawane, Amruta V. Patel, Kashyap Bhullar, Jasneet S. Subhas, Gokulakkrishna Mittal, Vijay K. Cheung, Laurence Y. TI Success of Reminder Systems in Reducing Catheter-associated Urinary Tract Infections SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Scientific Meeting and Postgraduate Course Program of the Southeastern-Surgical-Congress CY FEB 09-12, 2013 CL Jacksonville, FL SP SE Surg Congress C1 [Unawane, Amruta V.; Patel, Kashyap; Bhullar, Jasneet S.; Subhas, Gokulakkrishna; Mittal, Vijay K.; Cheung, Laurence Y.] Providence Hosp & Med Ctr, Dept Gen Surg, Southfield, MI USA. RP Unawane, AV (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM amu0385@gmail.com NR 4 TC 1 Z9 1 U1 0 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD JUL PY 2013 VL 79 IS 7 BP 745 EP 746 PG 2 WC Surgery SC Surgery GA AI6ED UT WOS:000336962600023 PM 23816012 ER PT J AU Dranoff, G AF Dranoff, Glenn TI A Message from the Founding Editor-in-Chief SO CANCER IMMUNOLOGY RESEARCH LA English DT Editorial Material C1 [Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JUL PY 2013 VL 1 IS 1 BP 2 EP 4 DI 10.1158/2326-6066.CIR-13-0017 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM7FC UT WOS:000340029100001 PM 24777243 ER PT J AU Hacohen, N Fritsch, EF Carter, TA Lander, ES Wu, CJ AF Hacohen, Nir Fritsch, Edward F. Carter, Todd A. Lander, Eric S. Wu, Catherine J. TI Getting Personal with Neoantigen-Based Therapeutic Cancer Vaccines SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID TUMOR-SPECIFIC ANTIGENS; CYTOLYTIC T-LYMPHOCYTES; SOMATIC POINT MUTATION; LUNG-CARCINOMA; HUMAN-MELANOMA; COLORECTAL-CANCER; HIGH-FREQUENCY; CELL EPITOPES; VACCINATION; PEPTIDES AB Despite years of preclinical efforts and hundreds of clinical studies, therapeutic cancer vaccines with the routine ability to limit or eliminate tumor growth in humans have been elusive. With advances in genome sequencing, it is now possible to identify a new class of tumor-specific antigens derived from mutated proteins that are present only in the tumor. These "neoantigens" should provide highly specific targets for antitumor immunity. Although many challenges remain in producing and testing neoantigen-based vaccines customized for each patient, a neoantigen vaccine offers a promising new approach to induce highly focused antitumor T cells aimed at eradicating cancer cells. (C)2013 AACR. C1 [Hacohen, Nir; Fritsch, Edward F.; Carter, Todd A.; Lander, Eric S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Fritsch, Edward F.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Canc Vaccine Ctr, Boston, MA 02115 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Div Allergy Immunol & Rheumatol, Boston, MA 02114 USA. [Wu, Catherine J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Rm 420,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org FU Blavatnik Family Foundation; NIH [NHLBI:5 R01 HL103532-03, NCI:1R01CA155010-02] FX We acknowledge the generous support of the Blavatnik Family Foundation and the NIH (NHLBI:5 R01 HL103532-03; NCI:1R01CA155010-02) for our work on neoepitope-based vaccines. NR 38 TC 41 Z9 41 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JUL PY 2013 VL 1 IS 1 BP 11 EP 15 DI 10.1158/2326-6066.CIR-13-0022 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA AM7FC UT WOS:000340029100003 PM 24777245 ER PT J AU De Raedt, T Beert, E Pasmant, E Bradner, JE Wolkenstein, P Legius, E Cichowski, K AF De Raedt, Thomas Beert, Eline Pasmant, Eric Bradner, James E. Wolkenstein, Pierre Legius, Eric Cichowski, Karen TI SUZ12: A novel tumor suppressor and potential biomarker for efficacy of BRD4 inhibition SO CANCER RESEARCH LA English DT Meeting Abstract C1 [De Raedt, Thomas; Cichowski, Karen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beert, Eline; Legius, Eric] Katholieke Univ Leuven, Leuven, Belgium. [Pasmant, Eric] Univ Paris 05, Paris, France. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolkenstein, Pierre] Univ Paris Est Creteil, Creteil, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2013 VL 73 SU 13 MA PR15 DI 10.1158/1538-7445.CEC13-PR15 PG 1 WC Oncology SC Oncology GA V40RU UT WOS:000209496500109 ER PT J AU Clemons, JL Weinstein, M Guess, MK Alperin, M Moalli, P Gregory, WT Lukacz, ES Sung, VW Chen, BH Bradley, CS AF Clemons, Jeffrey L. Weinstein, Milena Guess, Marsha K. Alperin, Marianna Moalli, Pamela Gregory, William Thomas Lukacz, Emily S. Sung, Vivian W. Chen, Bertha H. Bradley, Catherine S. CA AUGS Res Committ TI Impact of the 2011 FDA Transvaginal Mesh Safety Update on AUGS Members' Use of Synthetic Mesh and Biologic Grafts in Pelvic Reconstructive Surgery SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY LA English DT Article DE mesh; pelvic organ prolapse; surgery; sling AB Objective: To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members. Methods: An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials' use before and after the statement were compared using Wilcoxon signed rank test. Results: Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures. Conclusions: Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease. C1 [Clemons, Jeffrey L.] MultiCare Hlth Syst, Tacoma, WA USA. [Weinstein, Milena] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guess, Marsha K.] Yale Univ, New Haven, CT USA. [Alperin, Marianna] Univ Calif San Diego, San Diego, CA 92103 USA. [Moalli, Pamela] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Gregory, William Thomas] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lukacz, Emily S.] UC San Diego Hlth Syst, San Diego, CA USA. [Sung, Vivian W.] Brown Univ, Women & Infants Hosp, Brown Med Sch, Providence, RI USA. [Chen, Bertha H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Bradley, Catherine S.] Iowa City VA Hlth Care Syst, Iowa City, IA USA. [Bradley, Catherine S.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Clemons, JL (reprint author), 1901 S Union Ave,Suite B-2006, Tacoma, WA 98405 USA. EM drclemons@yahoo.com NR 10 TC 20 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2151-8378 J9 FEMALE PELVIC MED RE JI Female Pelvic Med. Reconstr. Surg. PD JUL-AUG PY 2013 VL 19 IS 4 BP 191 EP 198 DI 10.1097/SPV.0b013e31829099c1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V35XR UT WOS:000209179000002 PM 23797515 ER PT J AU Greenhawt, M Weiss, C Conte, ML Doucet, M Engler, A Camargo, CA AF Greenhawt, Matthew Weiss, Christopher Conte, Marisa L. Doucet, Marlie Engler, Amy Camargo, Carlos A., Jr. TI Racial and Ethnic Disparity in Food Allergy in the United States: A Systematic Review SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Review DE Food allergy; Food sensitization; 95% Predictive Decision Points; Serum IgE; Race; Ethnicity; Children; Prevalence; Anaphylaxis; Disparity; Epinephrine; Black; African American AB BACKGROUND: The prevalence of food allergy is rising among US children. Little is known about racial/ethnic disparities in food allergy. OBJECTIVE: We performed a systematic literature review to understand racial/ethnic disparities in food allergy in the United States. METHODS: We searched PubMed/MEDLINE, Embase, and Scopus for original data about racial/ethnic disparities in the diagnosis, prevalence, treatment, or clinical course of food allergy or sensitization, with a particular focus on black (African American) race. Articles were analyzed by study methodology, racial/ethnic composition, food allergy definition, outcomes, summary statistic used, and covariate adjustment. RESULTS: Twenty of 645 identified articles met inclusion criteria. The studies used multiple differing criteria to define food allergy, including self-report, sensitization assessed by serum food-specific IgE to selected foods without corroborating history, discharge codes, clinic chart review, and event-reporting databases. None used oral food challenge. In 12 studies, black persons (primarily children) had significantly increased adjusted odds of food sensitization or significantly higher proportion or odds of food allergy by self-report, discharge codes, or clinic-based chart review than white children. Major differences in study methodology and reporting precluded calculation of a pooled estimate of effect. CONCLUSION: Sparse and methodologically limited data exist about racial/ethnic disparity in food allergy in the United States. Available data lack a common definition for food allergy and use indirect measures of allergy, not food challenge. Although data suggest an increased risk of food sensitization, self-reported allergy, or clinic-based diagnosis of food allergy among black children, no definitive racial/ethnic disparity could be found among currently available studies. (C) 2013 American Academy of Allergy, Asthma & Immunology C1 [Greenhawt, Matthew] Univ Michigan, Sch Med, Dept Internal Med, Div Allergy & Clin Immunol, Ann Arbor, MI USA. [Greenhawt, Matthew] Univ Michigan Hlth Syst, Ann Arbor, MI 48106 USA. [Weiss, Christopher] Global Food Protect Inst, Battle Creek, MI USA. [Conte, Marisa L.] Univ Michigan, Taubman Hlth Sci Lib, Ann Arbor, MI 48109 USA. [Doucet, Marlie] Ctr Dis Control & Prevent, Oak Ridge Inst Sci & Educ Fellow, Div Adolescent, Atlanta, GA USA. [Doucet, Marlie] Ctr Dis Control & Prevent, Sch Hlth, Atlanta, GA USA. [Engler, Amy] Stanford Univ, Dept Human Biol, Palo Alto, CA 94304 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Greenhawt, M (reprint author), Univ Michigan Hlth Syst, Div Allergy & Clin Immunol, 24 Frank Lloyd Wright Dr Lobby H-2100,Box 442, Ann Arbor, MI 48106 USA. EM mgreenha@med.umich.edu OI Greenhawt, Matthew/0000-0002-2365-9372; Conte, Marisa/0000-0001-7377-163X FU Centers for Disease Control and Prevention [214-2010-M-37396]; Food Allergy Research and Education; Michigan Institute for Clinical and Health Research; NIH [UL1RR024986] FX Supported by the Centers for Disease Control and Prevention contract 214-2010-M-37396 with the Food Allergy & Anaphylaxis Network (now the Food Allergy Research and Education) and the Michigan Institute for Clinical and Health Research, NIH UL1RR024986 (M.L.C. and M.G.). The findings and conclusions in this paper are those of the authors and do not necessarily represent the official positions of the Centers for Disease Control and Prevention (CDC) or Food Allergy Research and Education. NR 42 TC 10 Z9 10 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JUL-AUG PY 2013 VL 1 IS 4 BP 378 EP 386 DI 10.1016/j.jaip.2013.04.009 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA V38WW UT WOS:000209374500009 PM 24565543 ER PT J AU Rauh-Hain, JA Shoni, M Schorge, JO Goodman, A Horowitz, NS del Carmen, MG AF Rauh-Hain, J. Alejandro Shoni, Melina Schorge, John O. Goodman, Annekathryn Horowitz, Neil S. del Carmen, Marcela G. TI Prognostic Determinants in Patients with Uterine and Ovarian Carcinosarcoma SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE carcinosarcoma; ovarian cancer; uterine cancer AB OBJECTIVE: To analyze and compare the demographics, treatment, recurrence, and survival rates in patients with carcinosarcoma of the uterus and ovary. STUDY DESIGN: All patients with uterine and ovarian carcinosarcoma who underwent surgical staging at the 2 participating institutions between 1995 and 2007 were identified. The Kaplan Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: Analysis of 87 women with uterine carcino-" sarcoma and 71 with ovarian carcinosarcoma was performed. Of those, 47% of the patients with uterine carcinosarcoma, compared to 14% of the patients with ovarian carcinosarcoma, were diagnosed with localized disease (p <0.001). Age > 65 years old (p < 0.001), tumor extension (local versus regional versus distant, p <0.001), and platinum -based chemotherapy (p = 0.05) were all independent predictors of survival. In a multivariate Cox regression model, age > 65 years old (hazard ratio [HR] = 2.5, p <0.001), tumor extension (locoregional versus distant, HR= 3.9, p =0.006), and uterine versus ovarian carcinosarcoma (HR = 2.2, p = 0.009) were identified as independent predictors of OS. CONCLUSION: Uterine carcinosarcoma presents at an earlier stage than does ovarian carcinosarcoma. In the multivariate analysis uterine carcinosarcoma demonstrated shorter survival than did ovarian carcinosarcoma after adjustment for extent of disease spread, age, and platinum -based chemotherapy. C1 Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol,Med Sch, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 21 TC 4 Z9 5 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD JUL-AUG PY 2013 VL 58 IS 7-8 BP 297 EP 304 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V43RA UT WOS:000209697300004 PM 23947079 ER PT J AU Puntil, C York, J Limandri, B Greene, P Arauz, E Hobbs, D AF Puntil, Cheryl York, Janet Limandri, Barbara Greene, Pamela Arauz, Eric Hobbs, Deborah TI Competency-Based Training for PMH Nurse Generalists: Inpatient Intervention and Prevention of Suicide SO JOURNAL OF THE AMERICAN PSYCHIATRIC NURSES ASSOCIATION LA English DT Article DE suicide prevention; self-directed violence (SDV); psychiatric nursing; inpatient intervention; competencies; consumer perspective ID CONTROLLED-TRIAL; ATTEMPTERS; EDUCATION; PROGRAMS; VETERANS AB Suicide is the tenth leading cause of death in the United States. Approximately 90,000 psychiatric mental health (PMH) nurse generalists work in hospitals in the United States, mostly on inpatient psychiatric units where the most acutely suicidal patients are hospitalized. Although competencies have been developed for mental health clinicians in assessing and managing suicide risk, there are no standard competencies for PMH nurse generalists. Widely accepted nursing practices do not meet suicide-specific standards of care or evidence-based criteria. Although both the Commission on Collegiate Nursing Education Essentials for Baccalaureate Education and the Quality and Safety Education for Nurses competencies stress the necessity for comprehensive assessment, safe clinical practices, patient-centered care, evidence-based interventions, and interprofessional communication and collaboration, there are no specific requirements for suicide prevention training in educational and clinical programs. The American Psychiatric Nurses Association has an opportunity to provide leadership in developing, implementing, and evaluating competency-based training for nurses and partner with the national effort to increase the competencies in suicide prevention in the behavioral health workforce. C1 [Puntil, Cheryl] Univ Calif Los Angeles, Resnick Neuropsychiat Hosp, Los Angeles, CA 90095 USA. [York, Janet] Ralph H Johnson VAMC, Charleston, SC USA. [Limandri, Barbara] Linfield Coll, Mcminnville, OR USA. [Greene, Pamela] Menninger Clin, Houston, TX USA. [Arauz, Eric] Arauz Inspirat Enterprises LLC, East Brunswick, NJ USA. [Hobbs, Deborah] Amer Psychiat Nurses Assoc, Falls Church, VA USA. RP Puntil, C (reprint author), Univ Calif Los Angeles, Resnick Neuropsychiat Hosp, 195 Med Plaza, Los Angeles, CA 90095 USA. EM cpuntil@mednet.ucla.edu NR 42 TC 8 Z9 8 U1 2 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1078-3903 EI 1532-5725 J9 J AM PSYCHIAT NURSES JI J. Am. Psych. Nurses Assoc. PD JUL-AUG PY 2013 VL 19 IS 4 BP 205 EP 210 DI 10.1177/1078390313496275 PG 6 WC Nursing; Psychiatry SC Nursing; Psychiatry GA AJ5KK UT WOS:000337720900007 PM 23950543 ER PT J AU Muller, M Cassonnet, P Favre, M Jacob, Y Demeret, C AF Muller, Mandy Cassonnet, Patricia Favre, Michel Jacob, Yves Demeret, Caroline TI A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Immunology; Issue 77; Genetics; Microbiology; Biochemistry; Molecular Biology; Cellular Biology; Biomedical Engineering; Infection; Cancer Biology; Virology; Medicine; Host-Pathogen Interactions; Host-Pathogen Interactions; Protein-protein interaction; High-throughput screening; Luminescence; Yeast two-hybrid; HT-GPCA; Network; protein; yeast; cell; culture AB Significant efforts were gathered to generate large-scale comprehensive protein-protein interaction network maps. This is instrumental to understand the pathogen-host relationships and was essentially performed by genetic screenings in yeast two-hybrid systems. The recent improvement of protein-protein interaction detection by a Gaussia luciferase-based fragment complementation assay now offers the opportunity to develop integrative comparative interactomic approaches necessary to rigorously compare interaction profiles of proteins from different pathogen strain variants against a common set of cellular factors. This paper specifically focuses on the utility of combining two orthogonal methods to generate protein-protein interaction datasets: yeast two-hybrid (Y2H) and a new assay, high-throughput Gaussia princeps protein complementation assay (HT-GPCA) performed in mammalian cells. A large-scale identification of cellular partners of a pathogen protein is performed by mating-based yeast two-hybrid screenings of cDNA libraries using multiple pathogen strain variants. A subset of interacting partners selected on a high-confidence statistical scoring is further validated in mammalian cells for pair-wise interactions with the whole set of pathogen variants proteins using HT-GPCA. This combination of two complementary methods improves the robustness of the interaction dataset, and allows the performance of a stringent comparative interaction analysis. Such comparative interactomics constitute a reliable and powerful strategy to decipher any pathogen-host interplays. C1 [Muller, Mandy; Cassonnet, Patricia; Favre, Michel; Jacob, Yves; Demeret, Caroline] Inst Pasteur, Unite Genet Papillomavirus & Canc Humain GPCH, Paris, France. [Muller, Mandy] Univ Sorbonne Paris Cite, Paris, France. [Jacob, Yves] Harvard Univ, Sch Med, Dana Farber Canc Inst, CCSB,Dept Canc Biol, Cambridge, MA 02138 USA. RP Demeret, C (reprint author), Inst Pasteur, Unite Genet Papillomavirus & Canc Humain GPCH, Paris, France. EM caroline.demeret@pasteur.fr FU Institut Pasteur; Ligue nationale contre le Cancer [R05/75-129, RS07/75-75]; Association pour la Recherche sur le Cancer [ARC A09/1/5031, 4867]; Agence Nationale de la Recherche [ANR07 MIME 009 02, ANR09 MIEN 026 01]; M.E.N.R.T fellowship FX This work was supported in part by funding from the Institut Pasteur and by grants from the Ligue nationale contre le Cancer (grants R05/75-129 and RS07/75-75), the Association pour la Recherche sur le Cancer (grants ARC A09/1/5031 and 4867), and the Agence Nationale de la Recherche (ANR07 MIME 009 02 and ANR09 MIEN 026 01). M.M was a recipient of a M.E.N.R.T fellowship. NR 15 TC 2 Z9 2 U1 1 U2 3 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2013 IS 77 AR UNSP e50404 DI 10.3791/50404 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36RG UT WOS:000209227900017 PM 23893119 ER PT J AU Villamar, MF Volz, MS Bikson, M Datta, A DaSilva, AF Fregni, F AF Villamar, Mauricio F. Volz, Magdalena Sarah Bikson, Marom Datta, Abhishek DaSilva, Alexandre F. Fregni, Felipe TI Technique and Considerations in the Use of 4x1 Ring High-definition Transcranial Direct Current Stimulation (HD-tDCS) SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 77; Neurobiology; Neuroscience; Physiology; Anatomy; Biomedical Engineering; Biophysics; Neurophysiology; Nervous System Diseases; Diagnosis; Therapeutics; Anesthesia and Analgesia; Investigative Techniques; Equipment and Supplies; Mental; Disorders; Transcranial direct current stimulation; tDCS; High-definition transcranial direct current stimulation; HD-tDCS; Electrical brain stimulation; Transcranial electrical stimulation (tES); Noninvasive Brain Stimulation; Neuromodulation; non-invasive; brain; stimulation; clinical techniques AB High-definition transcranial direct current stimulation (HD-tDCS) has recently been developed as a noninvasive brain stimulation approach that increases the accuracy of current delivery to the brain by using arrays of smaller " high-definition" electrodes, instead of the larger padelectrodes of conventional tDCS. Targeting is achieved by energizing electrodes placed in predetermined configurations. One of these is the 4x1ring configuration. In this approach, a center ring electrode (anode or cathode) overlying the target cortical region is surrounded by four return electrodes, which help circumscribe the area of stimulation. Delivery of 4x1-ring HD-tDCS is capable of inducing significant neurophysiological and clinical effects in both healthy subjects and patients. Furthermore, its tolerability is supported by studies using intensities as high as 2.0 milliamperes for up to twenty minutes. Even though 4x1 HD-tDCS is simple to perform, correct electrode positioning is important in order to accurately stimulate target cortical regions and exert its neuromodulatory effects. The use of electrodes and hardware that have specifically been tested for HD-tDCS is critical for safety and tolerability. Given that most published studies on 4x1 HD-tDCS have targeted the primary motor cortex (M1), particularly for pain-related outcomes, the purpose of this article is to systematically describe its use for M1 stimulation, as well as the considerations to be taken for safe and effective stimulation. However, the methods outlined here can be adapted for other HD-tDCS configurations and cortical targets. C1 [Villamar, Mauricio F.; Volz, Magdalena Sarah; Datta, Abhishek; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Cambridge, MA 02138 USA. [Villamar, Mauricio F.; Volz, Magdalena Sarah; Datta, Abhishek; Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Villamar, Mauricio F.] Pontifical Catholic Univ Ecuador, Sch Med, Quito, Ecuador. [Volz, Magdalena Sarah] Charite Univ Med Berlin, Berlin, Germany. [Bikson, Marom; Datta, Abhishek] CUNY City Coll, New York, NY 10031 USA. [DaSilva, Alexandre F.] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Bikson, M (reprint author), CUNY City Coll, New York, NY 10031 USA. EM bikson@ccny.cuny.edu NR 28 TC 17 Z9 17 U1 1 U2 8 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2013 IS 77 AR UNSP e50309 DI 10.3791/50309 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36RG UT WOS:000209227900009 PM 23893039 ER PT J AU Dransfield, MT Lettis, S Barnhart, F Crim, C Calverley, PMA AF Dransfield, Mark T. Lettis, Sally Barnhart, Frank Crim, Courtney Calverley, Peter M. A. TI Fluticasone furoate and vilanterol for COPD Reply SO LANCET RESPIRATORY MEDICINE LA English DT Letter ID OBSTRUCTIVE PULMONARY-DISEASE; PROPIONATE/SALMETEROL 250/50; EXACERBATIONS; SALMETEROL C1 [Dransfield, Mark T.] Univ Alabama Birmingham, AB Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Barnhart, Frank; Crim, Courtney] GlaxoSmithKline, Res Triangle Pk, NC USA. [Lettis, Sally] GlaxoSmithKline, London, England. [Calverley, Peter M. A.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RP Dransfield, MT (reprint author), Univ Alabama Birmingham, AB Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. EM mdransfield99@msn.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD JUL PY 2013 VL 1 IS 5 BP E21 EP E22 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ3JS UT WOS:000342689300002 PM 24429207 ER PT J AU Besselink, M van Santvoort, H Freeman, M Gardner, T Mayerle, J Vege, SS Werner, J Banks, P Mckay, C Fernandez-Del Castillo, C French, J Gooszen, H Johnson, C Sarr, M Takada, T Windsor, J Saluja, A Liddle, R Papachristou, G Singh, V Runzi, M Wu, B Singh, V Bollen, T Morgan, D Mortele, K Mittal, A En-Qiang, M de Waele, J Petrov, M Dellinger, P Lerch, MM Anderson, R McClave, S Hartwig, W Bruno, M Oria, A Baron, T Fagenholz, P Horvath, K van Baal, M Nealon, W Andren-Sandberg, A Bakker, O Bassi, C Buchler, M Boermeester, M Bradley, E Chari, S Charnley, R Connor, S Dervenis, C Deviere, J Dudeja, V Fockens, P Forsmark, C Friess, H Isaji, S Isenmann, R Klar, E Levy, P Lillemoe, K Liu, X Lohr, CM Mayumi, T Mossner, J Neoptolemos, J Nordback, I Olah, A Padbury, R Parks, R Radenkovic, D Rau, B Rebours, V Seewald, S Seifert, H Shimosegawa, T Siriwardena, A Steinberg, W Sutton, R Tanaka, M Takeda, K Tse, F van Goor, H Warshaw, A Wang, C Whitcomb, D Zhao, Y Zyromski, N AF Besselink, Marc van Santvoort, Hjalmar Freeman, Martin Gardner, Timothy Mayerle, Julia Vege, Santhi Swaroop Werner, Jens Banks, Peter McKay, Colin Fernandez-del Castillo, Carlos French, Jeremy Gooszen, Hein Johnson, Colin Sarr, Mike Takada, Tadahiro Windsor, John Saluja, Ashok Liddle, Rodger Papachristou, Georgios Singh, Vijay Ruenzi, Michael Wu, Bechien Singh, Vikesh Bollen, Thomas Morgan, Desiree Mortele, Koenraad Mittal, Anubhav En-qiang, Mao de Waele, Jan Petrov, Maxim Dellinger, Patchen Lerch, Markus M. Anderson, Roland McClave, Stephen Hartwig, Werner Bruno, Marco Oria, Alejandro Baron, Todd Fagenholz, Peter Horvath, Karen van Baal, Mark Nealon, William Andren-Sandberg, Ake Bakker, Olaf Bassi, Claudio Buchler, Markus Boermeester, Marja Bradley, Ed Chari, Suresh Charnley, Richard Connor, Saxon Dervenis, Christos Deviere, Jacques Dudeja, Vikas Fockens, Paul Forsmark, Chris Friess, Helmut Isaji, Shuji Isenmann, Rainer Klar, Ernst Levy, Philippe Lillemoe, Keith Liu, Xubao Loehr, Chengdu Matthias Mayumi, Toshihiko Mossner, Joachim Neoptolemos, John Nordback, Isto Olah, Attila Padbury, Roy Parks, Rowan Radenkovic, Dejan Rau, Bettina Rebours, Vinciane Seewald, Stefan Seifert, Hans Shimosegawa, Tooru Siriwardena, Ajith Steinberg, William Sutton, Robert Tanaka, Masao Takeda, Kazunori Tse, Francis van Goor, Harry Warshaw, Andrew Wang, Chunyou Whitcomb, David Zhao, Yupei Zyromski, Nicholas CA Working Grp IAP APA Acute TI IAP/APA evidence-based guidelines for the management of acute pancreatitis SO PANCREATOLOGY LA English DT Article DE Acute pancreatitis; Pancreas; Guidelines; Diagnosis; Prediction; Prevention; Treatment; Intervention; Nutrition; Surgery; Radiology; Gastroenterology AB Background: There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting. Results: The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations. Conclusions: The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis. Copyright (C) 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. C1 UNSW Clin Sch, Int Assoc Pancreatol, Liverpool BC, NSW 1871, Australia. [Working Grp IAP APA Acute] Amer Pancreat Assoc, Minneapolis, MN 55414 USA. [Besselink, Marc] AMC Amsterdam, Amsterdam, Netherlands. [van Santvoort, Hjalmar] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Freeman, Martin] Univ Minnesota, Minneapolis, MN 55455 USA. [Gardner, Timothy] Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. [Mayerle, Julia] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Vege, Santhi Swaroop; Sarr, Mike] Mayo Clin, Rochester, MN USA. [Werner, Jens] Heidelberg Univ, Bergheimer Str 58, D-69115 Heidelberg, Germany. [Banks, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [McKay, Colin] Glasgow Royal Infirmary, Glasgow, Lanark, Scotland. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Boston, MA 02114 USA. [French, Jeremy] Freeman Rd Hosp, Newcastle Upon Tyne, Tyne & Wear, England. [Gooszen, Hein] Univ Med Ct St Radboud, Nijmegen, Netherlands. [Johnson, Colin] Southampton Gen Hosp, Southampton, Hants, England. [Takada, Tadahiro] Teikyo Univ, Sch Med, Tokyo, Japan. [Windsor, John] Univ Auckland, Auckland 1, New Zealand. RP Besselink, M (reprint author), AMC Amsterdam, Amsterdam, Netherlands. EM besselink@amc.nl; h.vansantvoort@umcutrecht.nl; werner@med.uni-heidelberg.de RI Sutton, Robert/I-3587-2016; Connor, Saxon/N-7641-2013; OI Sutton, Robert/0000-0001-6600-562X; Connor, Saxon/0000-0002-5788-2185; Lerch, Markus M./0000-0002-9643-8263 FU IAP/APA FX The IAP/APA provided organizational support for the development of these guidelines. No external funding was provided, and there was no financial support for anyone involved with the development of these guidelines. NR 96 TC 107 Z9 107 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD JUL-AUG PY 2013 VL 13 IS 4 SU 2 BP E1 EP E15 DI 10.1016/j.pan.2013.07.063 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V41QK UT WOS:000209560500001 ER PT J AU Culpepper, L Fried, R AF Culpepper, Larry Fried, Ronna TI Attention-Deficit/Hyperactivity Disorder in a Chronic Care Paradigm SO POSTGRADUATE MEDICINE LA English DT Article DE attention-deficit/hyperactivity disorder; life span disorder; chronic care models; primary care physician; integrated health care team ID DEFICIT-HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION IMPAIRMENTS; RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE; ADULT ADHD; MEDICATION ADHERENCE; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; LIFE-SPAN; MANAGEMENT AB The prevalence and disease burden of adult attention-deficit/hyperactivity disorder (ADHD) suggests that primary care physicians (PCPs) have an opportunity to improve the functioning and quality of life of a significant number of adult patients. The American Academy of Pediatrics provides evidence-based clinical practice guidelines that recognize ADHD as a chronic condition, and a large proportion of children with ADHD continue to meet diagnostic criteria as adults. Therefore, the management of ADHD should incorporate principles common to the management of other chronic conditions, including proactive planning for continuity of treatment across the life span and integrated, multidisciplinary health care teams for optimal disease management. This article describes a clinical approach whereby adult ADHD is treated within a chronic care paradigm that prominently features the involvement of the PCP. If PCPs envision ADHD as a chronic illness, similar to asthma or diabetes, they may be less likely to refer individuals to be managed by specialists, and more likely to see their role in coordinating and monitoring adult ADHD care, knowing when and how to bring other resources into play, and when and how to educate patients. C1 [Culpepper, Larry] Boston Univ, Dept Family Med, Boston, MA 02215 USA. [Fried, Ronna] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Culpepper, L (reprint author), Boston Univ, Dept Family Med, Boston, MA 02215 USA. OI Culpepper, Larry/0000-0002-7655-0477 NR 87 TC 3 Z9 3 U1 1 U2 5 PU JTE MULTIMEDIA PI WEST CONSHOHOCKEN PA 18 ELIZABETH ST, STE 110, WEST CONSHOHOCKEN, PA 19428 USA SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD JUL PY 2013 VL 125 IS 4 BP 78 EP 86 DI 10.3810/pgm.2013.07.2680 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AX2SQ UT WOS:000346795000008 PM 23933896 ER PT J AU Andresen, EM Peterson-Besse, JJ Krahn, GL Walsh, ES Horner-Johnson, W Iezzoni, LI AF Andresen, Elena M. Peterson-Besse, Jana J. Krahn, Gloria L. Walsh, Emily S. Horner-Johnson, Willi Iezzoni, Lisa I. TI Pap, Mammography, and Clinical Breast Examination Screening Among Women with Disabilities: A Systematic Review SO WOMENS HEALTH ISSUES LA English DT Review ID HEALTH-CARE ACCESS; PREVENTIVE MEDICAL-SERVICES; MOBILITY IMPAIRMENTS; INTERVIEW SURVEY; MENTAL-ILLNESS; RECEIPT; BARRIERS; BENEFICIARIES; DISPARITIES; PEOPLE AB Background: Research has found some disparities between U. S. women with and without disabilities in receiving clinical preventive services. Substantial differences may also exist within the population of women with disabilities. The current study examined published research on Pap smears, mammography, and clinical breast examinations across disability severity levels among women with disabilities. Methods: Informed by an expert panel, we followed guidelines for systematic literature reviews and searched MEDLINE, PsycINFO, and Cinahl databases. We also reviewed in-depth four disability- or preventive service-relevant journals. Two reviewers independently extracted data from all selected articles. Findings: Five of 74 reviewed publications of met all our inclusion criteria and all five reported data on Pap smears, mammography, and clinical breast examination. Articles classified disability severity groups by functional and/or activity levels. Associations between disability severity and Pap smear use were inconsistent across the publications. Mammography screening fell as disability level increased according to three of the five studies. Results demonstrated modestly lower screening, but also were inconsistent for clinical breast examinations across studies. Conclusion: Evidence is inconsistent concerning disparities in these important cancer screening services with increasing disability levels. Published studies used differing methods and definitions, adding to concerns about the evidence for screening disparities rising along with increasing disability. More focused research is required to determine whether significant disparities exist in cancer screening among women with differing disability levels. This information is essential for national and local public health and health care organizations to target interventions to improve care for women with disabilities. Copyright (C) 2013 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Andresen, Elena M.; Horner-Johnson, Willi] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Peterson-Besse, Jana J.] Univ Pacific, Dept Publ Hlth, Forest Grove, OR USA. [Krahn, Gloria L.] Ctr Dis Control & Prevent, Div Human Dev & Disabil, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Walsh, Emily S.] Kaiser Permanente, Kaiser Permanente Res Affiliates Evidence Based P, Portland, OR USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Andresen, EM (reprint author), Oregon Hlth & Sci Univ, Inst Dev & Disabil, Dept Publ Hlth & Prevent Med, 707 SE Gaines St, Portland, OR 97239 USA. EM andresee@ohsu.edu OI Horner-Johnson, Willi/0000-0003-3568-1400 FU Intramural CDC HHS [CC999999] NR 42 TC 18 Z9 18 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2013 VL 23 IS 4 BP E205 EP E214 DI 10.1016/j.whi.2013.04.002 PG 10 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1WW UT WOS:000341107200002 PM 23816150 ER PT J AU Toh, WS Foldager, CB Olsen, BR Spector, M AF Toh, Wei Seong Foldager, Casper Bindzus Olsen, Bjorn Reino Spector, Myron TI Basement membrane molecule expression attendant to chondrogenesis by nucleus pulposus cells and mesenchymal stem cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE laminin; type IV collagen; cartilage; nucleus pulposus; mesenchymal stem cells ID COLLAGEN-GAG SCAFFOLDS; INTERVERTEBRAL DISC; IN-VITRO; CARTILAGE FORMATION; DIFFERENTIATION; LAMININ; IMMUNOLOCALIZATION; RECEPTORS; PROTEINS; PERLECAN AB Bone marrow-derived mesenchymal stem cells (MSCs) represent an autologous cell source for nucleus pulposus (NP) tissue engineering and regeneration. Although studies have demonstrated the ability of MSCs to differentiate to NP-like chondrocytic cells, few have comparatively studied the matrix synthesis and composition of the cartilaginous tissue formed in vitro from both cell types, particularly with respect to the expression of basement membrane (BM) molecules. The objective of this study was to evaluate chondrogenesis and expression of BM molecules, laminin and type IV collagen, in monolayer and in pellet cultures of caprine NP cells and MSCs. Both cell types demonstrated comparable levels of chondrogenesis, indicated by the percentage of chondrocytic cells, and the amounts of glycosaminoglycan and type II collagen. Laminin and type IV collagen were expressed intracellularly by NP cells and MSCs cultured in monolayer. During chondrogenesis in pellet cultures, the deposition of BM molecules in NP and MSC pellets followed an orderly spatiotemporal shift in pattern from a diffuse territorial and interterritorial distribution to a defined pericellular localization, as seen in normal adult NP. These results inform the use of MSCs for NP regeneration and suggest the possible involvement of certain BM molecules in chondrogenesis and cartilage regeneration. (c) 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:11361143, 2013 C1 [Toh, Wei Seong; Foldager, Casper Bindzus; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Toh, Wei Seong; Foldager, Casper Bindzus; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Olsen, Bjorn Reino] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, 150 South Huntington Ave,MS 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Toh, Wei Seong/K-7720-2013 OI Toh, Wei Seong/0000-0001-9147-6423 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; A*STAR International Fellowship, Singapore; Danish Minister of Science, Technology and Innovation; Department of Veterans Affairs FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. W.S.T. is supported by A*STAR International Fellowship, Singapore. C.B.F. is supported by an Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation. M.S. is supported by a Research Career Scientist Award from the Department of Veterans Affairs. NR 23 TC 8 Z9 8 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUL PY 2013 VL 31 IS 7 BP 1136 EP 1143 DI 10.1002/jor.22330 PG 8 WC Orthopedics SC Orthopedics GA 149VW UT WOS:000319350500021 PM 23508654 ER PT J AU Elshihawy, H Hammad, M AF Elshihawy, Hosam Hammad, Mohamed TI Molecular modeling studies and synthesis of novel quinoxaline derivatives with potential anti-cancer activity as inhibitors of methionine synthase SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article DE Cobalamin; MCF-7 cells; Methionine; Methionine synthase; PC-3; Quinoxaline derivatives and tumor ID CELLS; DEPENDENCE AB Methionine synthase (MetS) catalyses the transfer of a methyl group from the methyltetrahydrofolate (MTHF) to homocysteine to produce methionine and tetrahydrofolate. MetS is over-expressed in the cytosol of certain breast and prostate tumor cells. In this article, we designed, synthesized, and evaluated the biological activity of a series of substituted quinoxaline derivatives that mimic the MTHF in the structure. The main aim was to develop inhibitors that could inhibit the enzyme reaction by blocking the binding of MTHF. These inhibitors were docked into the MTHF binding domain in such the same way as MTHF in its binding domain. Compound 4-({(6-nitro-quinoxalin-2-yl)methylamino}methyl)benzoic acid showed the lowest free energy of the binding (-152.62 kJ/mol) and showed the lowest IC50 values of 45 +/- A 9 and 53 +/- A 9 mu M against two types of cancer cell lines PC-3 and MCF-7, respectively. C1 [Elshihawy, Hosam] Suez Canal Univ, Sch Pharm, Div Organ Chem, Ismailia 41522, Egypt. [Hammad, Mohamed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA USA. RP Elshihawy, H (reprint author), Suez Canal Univ, Sch Pharm, Div Organ Chem, Ismailia 41522, Egypt. EM h.elshihawy@uea.ac.uk NR 12 TC 1 Z9 1 U1 2 U2 19 PU SPRINGER BIRKHAUSER PI NEW YORK PA 233 SPRING STREET, 6TH FLOOR, NEW YORK, NY 10013 USA SN 1054-2523 EI 1554-8120 J9 MED CHEM RES JI Med. Chem. Res. PD JUL PY 2013 VL 22 IS 7 BP 3405 EP 3415 DI 10.1007/s00044-012-0307-4 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 149ZK UT WOS:000319359800036 ER PT J AU Tang, MH AF Tang, Michael H. TI The lance armstrong story: Should we find another hero? SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 [Tang, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tang, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. RP Tang, MH (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM mhtang@partners.org NR 1 TC 0 Z9 0 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2013 VL 60 IS 7 BP 1071 EP 1072 DI 10.1002/pbc.24513 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 149ZZ UT WOS:000319361300011 PM 23483728 ER PT J AU Skapek, SX Anderson, JR Hill, DA Henry, D Spunt, SL Meyer, W Kao, S Hoffer, FA Grier, HE Hawkins, DS Raney, RB AF Skapek, Stephen X. Anderson, James R. Hill, D. Ashley Henry, David Spunt, Sheri L. Meyer, William Kao, Simon Hoffer, Fredric A. Grier, Holcombe E. Hawkins, Douglas S. Raney, R. Beverly TI Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: Results of a Children's Oncology Group (COG) Phase II Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chemotherapy; desmoid-type fibromatosis; sulindac; tamoxifen ID FAMILIAL ADENOMATOUS POLYPOSIS; NONCYTOTOXIC DRUG-THERAPY; AGGRESSIVE FIBROMATOSIS; MUTATIONS; METHOTREXATE; VINBLASTINE; GENE AB Background Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Procedures Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Results Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 1018 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.230.48) and 96%, respectively. All three deaths were due to progressive DT. Conclusions Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Pediatr Blood Cancer 2013; 60: 11081112. (c) 2012 Wiley Periodicals, Inc. C1 [Skapek, Stephen X.] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA. [Skapek, Stephen X.] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA. [Anderson, James R.] Univ Nebraska, Coll Publ Hlth, Med Ctr, Dept Biostat, Omaha, NE USA. [Hill, D. Ashley] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Hill, D. Ashley] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Hill, D. Ashley] George Washington Univ, Dept Integrat Syst Biol, Washington, DC USA. [Henry, David] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Spunt, Sheri L.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Spunt, Sheri L.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Meyer, William] Univ Oklahoma, Hlth Sci Ctr, Jimmy Everest Sect Pediat Hematol Oncol, Oklahoma City, OK USA. [Kao, Simon] Univ Iowa Hosp & Clin, Dept Radiol, Iowa City, IA 52242 USA. [Hoffer, Fredric A.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hoffer, Fredric A.] Qual Assurance Review Ctr, Providence, RI USA. [Grier, Holcombe E.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Grier, Holcombe E.] Childrens Hosp, Boston, MA 02115 USA. [Hawkins, Douglas S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Raney, R. Beverly] UT MD Anderson Canc Ctr, Childrens Canc Hosp, Houston, TX USA. [Raney, R. Beverly] UT MD Anderson Canc Ctr, Div Pediat, Houston, TX USA. RP Skapek, SX (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Hematol Oncol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM stephen.skapek@UTSouthwestern.edu FU National Cancer Institute, Bethesda, Maryland [CA-24507, CA-29511, CA-72989, CA-98543] FX Grant sponsor: National Cancer Institute, Bethesda, Maryland; Grant numbers: CA-24507, CA-29511, CA-72989, CA-98543. NR 31 TC 20 Z9 22 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2013 VL 60 IS 7 BP 1108 EP 1112 DI 10.1002/pbc.24457 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 149ZZ UT WOS:000319361300016 PM 23281268 ER PT J AU Reeve, BB Withycombe, JS Baker, JN Hooke, MC Lyons, JC Mowbray, C Wang, JC Freyer, DR Joffe, S Sung, L Tomlinson, D Gold, SH Hinds, PS AF Reeve, Bryce B. Withycombe, Janice S. Baker, Justin N. Hooke, Mary C. Lyons, Jessica C. Mowbray, Catriona Wang, Jichuan Freyer, David R. Joffe, Steven Sung, Lillian Tomlinson, Deborah Gold, Stuart H. Hinds, Pamela S. TI The first step to integrating the child's voice in adverse event reporting in oncology trials: A content validation study among pediatric oncology clinicians SO PEDIATRIC BLOOD & CANCER LA English DT Article DE adverse events; cancer; clinical trials; patient-reported outcomes; pediatric; validity ID QUALITY-OF-LIFE; CANCER; ADOLESCENTS; CHEMOTHERAPY; SYMPTOMS; HEALTH; QUESTIONNAIRE; FATIGUE; PATIENT; VALIDITY AB Purpose Children with cancer experience significant toxicities while undergoing treatment. Documentation of adverse events (AEs) in clinical trials is mandated by federal agencies. Although many AEs are subjective, the current standard is clinician reporting. Our long-term goal is to create and validate a self-report measure of subjective AEs for children aged 7 years and older that will inform AE reporting for the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). This content validation study aimed to identify which of the AEs in the current CTCAE should be included in a pediatric self-report measure. Methods We sought expert panel review and consensus among 187 pediatric clinicians from seven Children's Oncology Group institutions to determine which of the 790 AEs are amenable to child self-report. Two survey iterations were used to identify suitable AEs, and clinician agreement estimated by the content-validity ratio (CVR) was assessed. Results Response rates for surveys 1 and 2 were 72% and 67%, respectively. After the surveys, 64 CTCAE terms met the criteria of being subjective, relevant for use in pediatric cancer trials, and amenable to self-report by a child. The most frequent reasons for removal of CTCAE terms were that they relied on laboratory or clinical measures or were not applicable to children. Conclusion The 64 CTCAE terms will be translated into child-friendly terms as the basis of the child-report toxicity measure. Ultimately, systematic collection of these data will improve care by enhancing the accuracy and completeness of treatment toxicity reports for childhood cancer. Pediatr Blood Cancer 2013; 60: 12311236. (c) 2013 Wiley Periodicals, Inc. C1 [Reeve, Bryce B.; Lyons, Jessica C.; Gold, Stuart H.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Withycombe, Janice S.] Palmetto Hlth Childrens Hosp, Columbia, SC USA. [Baker, Justin N.] St Jude Childrens Res Hosp, Memphis, NC USA. [Hooke, Mary C.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Mowbray, Catriona; Wang, Jichuan; Hinds, Pamela S.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wang, Jichuan; Hinds, Pamela S.] George Washington Univ, Sch Med, Washington, DC USA. [Freyer, David R.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Freyer, David R.] Univ So Calif, Los Angeles, CA USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Boston Childrens Hosp, Boston, MA USA. [Sung, Lillian; Tomlinson, Deborah] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Reeve, BB (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, 1101-D McGavran Greenberg Bldg,135 Dauer Dr,CB 74, Chapel Hill, NC 27599 USA. EM bbreeve@email.UNC.edu OI Joffe, Steven/0000-0002-0667-7384 FU Alex's Lemonade Stand Foundation; American Lebanese Syrian Associated Charities FX Grant sponsor: Alex's Lemonade Stand Foundation; Grant sponsor: American Lebanese Syrian Associated Charities. NR 37 TC 8 Z9 8 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2013 VL 60 IS 7 BP 1231 EP 1236 DI 10.1002/pbc.24463 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 149ZZ UT WOS:000319361300037 PM 23335328 ER PT J AU Sakai, N Tager, AM AF Sakai, Norihiko Tager, Andrew M. TI Fibrosis of two: Epithelial cell-fibroblast interactions in pulmonary fibrosis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Pulmonary fibrosis; Epithelial cells; Apoptosis; Fibroblasts; Myofibroblasts; Extracellular matrix ID TISSUE GROWTH-FACTOR; INTERSTITIAL LUNG-DISEASE; PROSTAGLANDIN E-2 RESISTANCE; ENDOPLASMIC-RETICULUM STRESS; BLEOMYCIN-INDUCED APOPTOSIS; TGF-BETA ACTIVATION; SONIC HEDGEHOG SHH; MYOFIBROBLAST DIFFERENTIATION; TRANSCRIPTIONAL ACTIVATION; MESENCHYMAL INTERACTIONS AB Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the "pas de deux" (steps of two), or perhaps more appropriate to IPF pathogenesis, the "folie a deux" (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their "fibrosis of two", including transforming growth factor-beta, connective tissue growth factor, sonic hedgehog, prostaglandin E-2, angiotensin II and reactive oxygen species. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. (C) 2013 Elsevier B.V. All rights reserved. C1 [Sakai, Norihiko; Tager, Andrew M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Sakai, Norihiko; Tager, Andrew M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Tager, Andrew M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU NIH [R01-HL095732, R01-HL108975]; Scleroderma Research Foundation; Coalition for Pulmonary Fibrosis; Pulmonary Fibrosis Foundation; Nirenberg Center for Advanced Lung Disease; Japan Society for the Promotion of Science (JSPS) FX The authors gratefully acknowledge support from NIH R01-HL095732 and R01-HL108975, and Scleroderma Research Foundation, Coalition for Pulmonary Fibrosis, Pulmonary Fibrosis Foundation and Nirenberg Center for Advanced Lung Disease Grants to A.M.T., and from the Japan Society for the Promotion of Science (JSPS) Excellent Young Researcher Overseas Visit Program to N.S. The authors have no conflicting financial interests. NR 175 TC 41 Z9 46 U1 1 U2 50 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JUL PY 2013 VL 1832 IS 7 SI SI BP 911 EP 921 DI 10.1016/j.bbadis,2013.03.001 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 143SC UT WOS:000318887500008 PM 23499992 ER PT J AU Thomas, JJ Hartmann, AS Killgore, WDS AF Thomas, Jennifer J. Hartmann, Andrea S. Killgore, William D. S. TI Non-fat-phobic eating disorders: Why we need to investigate implicit associations and neural correlates SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article C1 [Thomas, Jennifer J.; Hartmann, Andrea S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Thomas, Jennifer J.; Hartmann, Andrea S.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Thomas, Jennifer J.; Hartmann, Andrea S.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. [Killgore, William D. S.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02178 USA. RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, WAC 816D,15 Parkman St, Boston, MA 02114 USA. EM jjthomas@partners.org OI Killgore, William/0000-0002-5328-0208 FU Hilda and Preston Davis Foundation; Klarman Family Foundation; Swiss National Science Foundation [PBSKP1_134330/1, PBSKP1_140040] FX Supported by Hilda and Preston Davis Foundation, Klarman Family Foundation, and Swiss National Science Foundation post-doctoral fellowship (PBSKP1_134330/1, PBSKP1_140040). NR 6 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2013 VL 46 IS 5 SI SI BP 416 EP 419 DI 10.1002/eat.22098 PG 4 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 142EJ UT WOS:000318779000008 PM 23658082 ER PT J AU Katzman, DK Misra, M AF Katzman, Debra K. Misra, Madhusmita TI Bone health in adolescent females with anorexia nervosa: What is a clinician to do? SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE anorexia nervosa; adolescence; bone mineral density; estrogen; insulin-like growth factor-1 ID MINERAL DENSITY; YOUNG-WOMEN; VITAMIN-D; GROWTH-HORMONE; DOUBLE-BLIND; GIRLS; CHILDREN; OSTEOPOROSIS; INCREASES; FRACTURE AB The objective of this case report is to present a pharmacologic strategy for treatment of adolescents with anorexia nervosa (AN) and low bone mineral density (BMD). We present a 17.5-year-old girl with a 3-year history of AN and longstanding inability to optimize nutrition and gain weight, and a decrease over time in her already low BMD. A year after treatment with the 17- estradiol patch (100 mcg twice weekly) with cyclic oral progesterone (2.5 mg medroxyprogesterone acetate daily for days 110 of every month), her spine and hip BMD Z-scores improved, and a further decrease was prevented. This novel treatment is a consideration for girls with AN at greatest risk for low BMD. Adolescents with AN are at risk for low BMD, and the most effective treatment is weight and menses restoration, which can be difficult to attain and to sustain. Recent studies have shown promising results with pharmacological therapy for low BMD in AN. This article discusses current concepts related to bone loss in AN, and new pharmacologic considerations for adolescents at greatest risk for low BMD. (c) 2013 by Wiley Periodicals, Inc. C1 [Katzman, Debra K.] Hosp Sick Children, Dept Pediat, Div Adolescent Med, Toronto, ON M5G 1X8, Canada. [Katzman, Debra K.] Univ Toronto, Toronto, ON, Canada. [Misra, Madhusmita] Massachusetts Gen Hosp, Div Pediat Endocrinol, Dept Pediat, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Katzman, DK (reprint author), Hosp Sick Children, Dept Pediat, Div Adolescent Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM debra.katzman@sickkids.ca FU NICHD NIH HHS [R01 HD060827] NR 27 TC 3 Z9 3 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2013 VL 46 IS 5 SI SI BP 456 EP 460 DI 10.1002/eat.22102 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 142EJ UT WOS:000318779000017 PM 23658091 ER PT J AU Becker, AE AF Becker, Anne E. TI Introduction SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Editorial Material C1 [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Becker, Anne E.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu NR 0 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2013 VL 46 IS 5 SI SI BP 507 EP 507 DI 10.1002/eat.22125 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 142EJ UT WOS:000318779000027 PM 23658101 ER PT J AU Pretz, JL Wo, JY Mamon, HJ Kachnic, LA Hong, TS AF Pretz, Jennifer L. Wo, Jennifer Y. Mamon, Harvey J. Kachnic, Lisa A. Hong, Theodore S. TI Chemoradiation Therapy Localized Esophageal, Gastric, and Pancreatic Cancer SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Gastrointestinal; Cancer; Chemoradiation; Surgery; Targeted therapy ID PHASE-III TRIAL; RANDOMIZED CONTROLLED-TRIAL; HER2-POSITIVE BREAST-CANCER; COOPERATIVE-ONCOLOGY-GROUP; COMBINED-MODALITY THERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; PREOPERATIVE CHEMORADIATION; STEREOTACTIC RADIOSURGERY; SURGERY AB Chemoradiation plays an important role in management of locally advanced gastrointestinal tumors. This article reviews data regarding chemoradiation for tumors of the upper gastrointestinal tract. For esophageal and gastroesophageal junction cancers, chemoradiation is standard of care in the preoperative setting. In gastric cancer, two standards have emerged: definitively treating with perioperative chemotherapy alone and using chemoradiation postoperatively. For pancreatic cancer, the benefit of radiation is less well-defined. The future of treatment sites lies in trials evaluating new chemotherapy regimens, alternative systemic therapies, and different radiation fractionation schema. Because care of these patients is complex, multimodality team evaluation before treatment is encouraged. C1 [Pretz, Jennifer L.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Wo, Jennifer Y.; Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Mamon, Harvey J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Kachnic, Lisa A.] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM tshong1@partners.org NR 66 TC 5 Z9 5 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2013 VL 22 IS 3 BP 511 EP + DI 10.1016/j.soc.2013.02.005 PG 16 WC Oncology; Surgery SC Oncology; Surgery GA 146IQ UT WOS:000319085200009 PM 23622077 ER PT J AU Thomas, CP Garnick, DW Horgan, CM Miller, K Harris, AHS Rosen, MM AF Thomas, Cindy Parks Garnick, Deborah W. Horgan, Constance M. Miller, Kay Harris, Alex H. S. Rosen, Melissa M. TI Establishing the feasibility of measuring performance in use of addiction pharmacotherapy SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Performance measurement; Pharmacotherapy; Addiction medication; Veterans health; Medicaid ID ALCOHOL-DEPENDENT PATIENTS; SUBSTANCE-ABUSE TREATMENT; RANDOMIZED CONTROLLED TRIAL/; USE DISORDERS; HEALTH-CARE; MEDICATION COMPLIANCE; COST-EFFECTIVENESS; OPIOID DEPENDENCE; MEASURING QUALITY; MENTAL-HEALTH AB This paper presents the rationale and feasibility of standardized performance measures for use of pharmacotherapy in the treatment of substance use disorders (SUD), an evidence-based practice and critical component of treatment that is often underused. These measures have been developed and specified by the Washington Circle, to measure treatment of alcohol and opioid dependence with FDA-approved prescription medications for use in office-based general health and addiction specialty care. Measures were pilot tested in private health plans, the Veterans Health Administration (VHA), and Medicaid. Testing revealed that use of standardized measures using administrative data for overall use and initiation of SUD pharmacotherapy is feasible and practical. Prevalence of diagnoses and use of pharmacotherapy vary widely across health systems. Pharmacotherapy is generally used in a limited portion of those for whom it might be indicated. An important methodological point is that results are sensitive to specifications, so that standardization is critical to measuring performance across systems. (c) 2013 Elsevier Inc. All rights reserved. C1 [Thomas, Cindy Parks; Garnick, Deborah W.; Horgan, Constance M.; Rosen, Melissa M.] Brandeis Univ, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. [Harris, Alex H. S.] US Dept Vet Affairs, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Miller, Kay] Truven Hlth Analyt, Santa Barbara, CA 93111 USA. RP Thomas, CP (reprint author), Brandeis Univ, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. EM cthomas@brandeis.edu RI Thomas, Cindy/L-3204-2015; Garnick, Deborah/I-9009-2012 OI Thomas, Cindy/0000-0001-5855-1196; FU NIDA NIH HHS [R01 DA029316] NR 72 TC 9 Z9 9 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL PY 2013 VL 45 IS 1 BP 11 EP 18 DI 10.1016/j.jsat.2013.01.004 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 141VU UT WOS:000318755400002 PM 23490233 ER PT J AU Hagedorn, HJ Noorbaloochi, S Simon, AB Bangerter, A Stitzer, ML Stetler, CB Kivlahan, D AF Hagedorn, Hildi J. Noorbaloochi, Siamak Simon, Alisha Baines Bangerter, Ann Stitzer, Maxine L. Stetler, Cheryl B. Kivlahan, Daniel TI Rewarding early abstinence in Veterans Health Administration addiction clinics SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Alcohol dependence; Stimulant dependence; Contingency management; Substance use disorders treatment; Effectiveness ID SUBSTANCE USE DISORDERS; COST CONTINGENCY MANAGEMENT; COCAINE ABSTINENCE; REINFORCEMENT THERAPY; RANDOMIZED-TRIAL; MAINTAINED PATIENTS; METHADONE PATIENTS; FOLLOW-UP; INCENTIVES; DEPENDENCE AB This study investigates the addition of a contingency management (CM) intervention to Veterans Health Administration substance use disorders treatment on during- and post-treatment outcomes for Veterans diagnosed with alcohol dependence only (n = 191) or stimulant dependence (n = 139). Participants were randomly assigned to 8 weeks of usual care or usual care plus CM. Follow-up assessments occurred at 2, 6 and 12 months. In the alcohol dependent subgroup, CM participants submitted significantly more negative samples (13 versus 11 samples, Cohen's d = 0.54), were retained significantly longer (7 versus 6 weeks, d = 0.47), achieved significantly longer median durations of abstinence (16 versus 9 consecutive visits; median difference = 7, 95% CI = 4-8), and submitted significantly more negative samples at follow-ups (unstandardized effect size = 0.669, se = 0.2483) compared to usual care participants. Intervention effects were nonsignificant for the stimulant dependent subgroup. The study provides support for the effectiveness of CM interventions for alcohol dependent patients. Published by Elsevier Inc. C1 [Hagedorn, Hildi J.] Minneapolis VA Healthcare Syst, Vet Hlth Adm Subst Use Disorder Qual Enhancement, Minneapolis, MN 55417 USA. [Hagedorn, Hildi J.; Noorbaloochi, Siamak; Simon, Alisha Baines; Bangerter, Ann] Minneapolis VA Healthcare Syst, Vet Hlth Adm Hlth Serv Res & Dev Ctr Excellence, Minneapolis, MN 55417 USA. [Hagedorn, Hildi J.; Noorbaloochi, Siamak] Univ Minnesota, Minneapolis, MN 55455 USA. [Stitzer, Maxine L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. [Stetler, Cheryl B.] Boston Univ, Sch Hlth & Independent Consultant, Dept Hlth Serv, Amherst, MA 01002 USA. [Kivlahan, Daniel] VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Kivlahan, Daniel] Univ Washington, Sch Med, Seattle, WA 98185 USA. RP Hagedorn, HJ (reprint author), Minneapolis VA Healthcare Syst, 1 Vet Dr, Minneapolis, MN 55417 USA. EM hildi.hagedorn@va.gov NR 30 TC 5 Z9 5 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL PY 2013 VL 45 IS 1 BP 109 EP 117 DI 10.1016/j.jsat.2013.01.006 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 141VU UT WOS:000318755400014 PM 23453480 ER PT J AU Rakvongthai, Y Oraintara, S AF Rakvongthai, Yothin Oraintara, Soontorn TI Estimating the relative phase parameters of complex wavelet coefficients in noise SO SIGNAL PROCESSING LA English DT Article DE Complex Gaussian scale mixtures; Complex wavelet phase; Relative phase; Parameter estimation in noise ID TRANSFORM; SIGNALS AB This paper proposes a method to estimate the parameters of the relative phase probability density function (RP pdf) of the complex coefficients when an image is corrupted by additive white Gaussian noise. With the complex Gaussian scale mixture (CGSM) assumption of the clean coefficients, we first introduce the relative phase mixture (RPM) pdf by deriving the pdf of the relative phase of the noisy coefficients. Along with the derived pdf, a parameter estimation method based on the maximum likelihood approach is proposed by exploiting the relationships between the pdfs parameters and the complex covariance matrix of the corresponding complex coefficient vector. Simulation studies using simulated data are performed to show the effectiveness of the estimation method. Moreover, we use the proposed estimation method in the application of texture retrieval in a noisy environment. The results show that the proposed method can estimate the parameters of the clean vector well in the case of simulated data and that the proposed estimation method improves the retrieval accuracy rate. (C) 2013 Elsevier B.V. All rights reserved. C1 [Rakvongthai, Yothin; Oraintara, Soontorn] Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. RP Rakvongthai, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol, 55 Fruit St, Boston, MA 02114 USA. EM yothin.rakvongthai@mavs.uta.edu; oraintar@uta.edu NR 19 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD JUL PY 2013 VL 93 IS 7 BP 1738 EP 1747 DI 10.1016/j.sigpro.2013.01.012 PG 10 WC Engineering, Electrical & Electronic SC Engineering GA 135ZT UT WOS:000318329900004 ER PT J AU Shaw, ME Hamalainen, MS Gutschalk, A AF Shaw, Marnie E. Hamalainen, Matti S. Gutschalk, Alexander TI How anatomical asymmetry of human auditory cortex can lead to a rightward bias in auditory evoked fields SO NEUROIMAGE LA English DT Article DE Asymmetry; Signal; Cortical curvature; Signal cancelation; Nonuniformity; Dipole amplitude ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN-BRAIN; PLANUM TEMPORALE; SPEECH REGION; ORGANIZATION; RESPONSES; FMRI; MEG AB Auditory evoked fields and potentials, such as the N-1 or the 40-Hz steady state response, are often stronger in the right compared to the left auditory cortex. Here we investigated whether a greater degree of cortical folding in left auditory cortex could result in increased MEG signal cancelation and a subsequent bias in MEG auditory signals toward the right hemisphere. Signal cancelation, due to non-uniformity of the orientations of underlying neural currents, affects MEG and EEG signals generated by any neuronal activity of reasonable spatial extent. We simulated MEG signals in patches of auditory cortex in seventeen subjects, and measured the relationships between underlying activity distribution, cortical non-uniformity, signal cancelation and resulting (fitted) dipole strength and position. Our results suggest that the cancelation of MEG signals from auditory cortex is asymmetric, due to underlying anatomy, and this asymmetry may result in a rightward bias in measurable dipole amplitudes. The effect was significant across all auditory areas tested, with the exception of planum temporale. Importantly, we also show how the rightward bias could be partially or completely offset by increased cortical area, and therefore increased cortical activity, on the left side. We suggest that auditory researchers are aware of the impact of cancelation and its resulting rightward bias in signal strength from auditory cortex. These findings are important for studies seeking functional hemispheric specialization in the auditory cortex with MEG as well as for integration of MEG with other imaging modalities. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shaw, Marnie E.; Gutschalk, Alexander] Heidelberg Univ, Dept Neurol, D-69120 Heidelberg, Germany. [Hamalainen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Hamalainen, Matti S.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Gutschalk, A (reprint author), Heidelberg Univ, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM Alexander.Gutschalk@med.uni-heidelberg.de RI Hamalainen, Matti/C-8507-2013 FU Bundesministerium fur Bildung und Forschung (BMBF) [01EV0712] FX This study was supported by Bundesministerium fur Bildung und Forschung (BMBF, grant 01EV0712 to A.G.). NR 43 TC 20 Z9 22 U1 2 U2 37 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 JUL 1 PY 2013 VL 74 BP 22 EP 29 DI 10.1016/j.neuroimage.2013.02.002 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 124CL UT WOS:000317441300003 PM 23415949 ER PT J AU Das, F Ghosh-Choudhury, N Bera, A Kasinath, BS Choudhury, GG AF Das, Falguni Ghosh-Choudhury, Nandini Bera, Amit Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI TGF-induced PI 3 kinase-dependent Mnk-1 activation is necessary for Ser-209 phosphorylation of eIF4E and mesangial cell hypertrophy SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INITIATION-FACTOR 4E; PROTEIN-KINASE; MESSENGER-RNA; TRANSLATION INITIATION; AKT KINASE; BETA; EXPRESSION; DISEASE; GROWTH; TUMORIGENESIS AB Transforming growth factor (TGF)-induced canonical signal transduction is involved in glomerular mesangial cell hypertrophy; however, the role played by the noncanonical TGF signaling remains largely unexplored. TGF time-dependently stimulated eIF4E phosphorylation at Ser-209 concomitant with enhanced phosphorylation of Erk1/2 (extracellular signal regulated kinase1/2) and MEK (mitogen-activated and extracellular signal-regulated kinase kinase) in mesangial cells. Inhibition of Erk1/2 by MEK inhibitor or by expression of dominant negative Erk2 blocked eIF4E phosphorylation, resulting in attenuation of TGF-induced protein synthesis and mesangial cell hypertrophy. Expression of constitutively active (CA) MEK was sufficient to induce protein synthesis and hypertrophy similar to those induced by TGF. Pharmacological or dominant negative inhibition of phosphatidylinositol (PI) 3 kinase decreased MEK/Erk1/2 phosphorylation leading to suppression of eIF4E phosphorylation. Inducible phosphorylation of eIF4E at Ser-209 is mediated by Mnk-1 (mitogen-activated protein kinase signal-integrating kinase-1). Both PI 3 kinase and Erk1/2 promoted phosphorylation of Mnk-1 in response to TGF. Dominant negative Mnk-1 significantly inhibited TGF-stimulated protein synthesis and hypertrophy. Interestingly, inhibition of mTORC1 activity, which blocks dissociation of eIF4E-4EBP-1 complex, decreased TGF-stimulated phosphorylation of eIF4E without any effect on Mnk-1 phosphorylation. Furthermore, mutant eIF4E S209D, which mimics phosphorylated eIF4E, promoted protein synthesis and hypertrophy similar to TGF. These results were confirmed using phosphorylation deficient mutant of eIF4E. Together our results highlight a significant role of dissociation of 4EBP-1-eIF4E complex for Mnk-1-mediated phosphorylation of eIF4E. Moreover, we conclude that TGF-induced noncanonical signaling circuit involving PI 3 kinase-dependent Mnk-1-mediated phosphorylation of eIF4E at Ser-209 is required to facilitate mesangial cell hypertrophy. J. Cell. Physiol. 228: 16171626, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Das, Falguni; Bera, Amit; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIH [RO1 DK50190, RO1 AR52425, RO1 DK077295, RC2A 036613]; VA Merit Review grants; VA Senior Research Career Scientist Award; VA Research Service FX Contract grant sponsor: NIH;; Contract grant numbers: RO1 DK50190, RO1 AR52425, RO1 DK077295, RC2A 036613.; Contract grant sponsor: VA Merit Review grants.; Contract grant sponsor: VA Senior Research Career Scientist Award.; Contract grant sponsor: VA Research Service. NR 29 TC 9 Z9 9 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2013 VL 228 IS 7 BP 1617 EP 1626 DI 10.1002/jcp.24327 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 113PX UT WOS:000316681100029 PM 23359369 ER PT J AU Seif, AE Naranjo, A Baker, DL Bunin, NJ Kletzel, M Kretschmar, CS Maris, JM McGrady, PW von Allmen, D Cohn, SL London, WB Park, JR Diller, LR Grupp, SA AF Seif, A. E. Naranjo, A. Baker, D. L. Bunin, N. J. Kletzel, M. Kretschmar, C. S. Maris, J. M. McGrady, P. W. von Allmen, D. Cohn, S. L. London, W. B. Park, J. R. Diller, L. R. Grupp, S. A. TI A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1 SO BONE MARROW TRANSPLANTATION LA English DT Article DE pediatric; neuroblastoma; tandem transplant; hematopoietic SCT ID PERIPHERAL-BLOOD; LYMPHOPROLIFERATIVE DISEASE; INTENSIVE CHEMOTHERAPY; SOLID TUMORS; TRANSPLANTATION; THERAPY; MEGATHERAPY; DEPLETION; SURVIVAL; PATIENT AB Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 +/- 9.6% and 59.2 +/- 9.2% (N = 41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma. C1 [Seif, A. E.; Bunin, N. J.; Maris, J. M.; Grupp, S. A.] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Seif, A. E.; Bunin, N. J.; Maris, J. M.; Grupp, S. A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Naranjo, A.; McGrady, P. W.] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA. [Naranjo, A.; McGrady, P. W.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA. [Naranjo, A.; McGrady, P. W.] Childrens Oncol Grp Stat & Data Ctr, Arcadia, CA USA. [Baker, D. L.] Princess Margaret Hosp Children, Dept Haematol & Oncol, Perth, WA, Australia. [Kletzel, M.] Childrens Mem Hosp, Dept Pediat, Div Hematol Oncol & Stem Cell Transplant, Chicago, IL 60614 USA. [Kletzel, M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [von Allmen, D.] Cincinnati Childrens Hosp, Med Ctr, Div Gen & Thorac Surg, Dept Surg, Cincinnati, OH USA. [Cohn, S. L.] Comer Childrens Hosp, Dept Pediat, Div Hematol Oncol, Chicago, IL USA. [London, W. B.; Diller, L. R.] Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA. [Park, J. R.] Seattle Childrens Hosp, Dept Pediat, Div Oncol, Seattle, WA USA. [Park, J. R.] Univ Washington, Sch Med, Seattle, WA USA. [Grupp, S. A.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. RP Grupp, SA (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, 3501 Civ Ctr Blvd,CTRB 3006, Philadelphia, PA 19104 USA. EM grupp@email.chop.edu RI Seif, Alix/B-9918-2013; OI Seif, Alix/0000-0002-1799-2582; Cohn, Susan/0000-0001-5749-7650 FU WW Smith Charitable Trust; Foerderer-Murray, Weinberg; Sanford Funds of the Children's Hospital of Philadelphia (S.A. Grupp); Robert A. Good/ASBMT New Investigator Award; NIH [U10 CA98413, U10 CA98543] FX Supported in part by the WW Smith Charitable Trust, and the Foerderer-Murray, Weinberg and Sanford Funds of the Children's Hospital of Philadelphia (S.A. Grupp); the Robert A. Good/ASBMT New Investigator Award (A.E. Seif); NIH grants U10 CA98413 (COG SDC grant) and U10 CA98543 (COG Chair's grant). We would also like to thank Danniel Gaidula, MFA, for assistance in preparing Figure 1. NR 33 TC 9 Z9 10 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2013 VL 48 IS 7 BP 947 EP 952 DI 10.1038/bmt.2012.276 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 176KF UT WOS:000321302300011 PM 23334272 ER PT J AU Garfall, A Kim, HT Sun, L Ho, VT Armand, P Koreth, J Alyea, EP Soiffer, RJ Antin, JH Ritz, J Cutler, C AF Garfall, A. Kim, H. T. Sun, L. Ho, V. T. Armand, P. Koreth, J. Alyea, E. P. Soiffer, R. J. Antin, J. H. Ritz, J. Cutler, C. TI KIR ligand incompatibility is not associated with relapse reduction after double umbilical cord blood transplantation SO BONE MARROW TRANSPLANTATION LA English DT Letter ID STEM-CELL TRANSPLANTATION; LEUKEMIA; ALLOREACTIVITY; RECEPTORS; OUTCOMES C1 [Garfall, A.; Ho, V. T.; Armand, P.; Koreth, J.; Alyea, E. P.; Soiffer, R. J.; Antin, J. H.; Ritz, J.; Cutler, C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kim, H. T.; Sun, L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ho, V. T.; Armand, P.; Koreth, J.; Alyea, E. P.; Soiffer, R. J.; Antin, J. H.; Ritz, J.; Cutler, C.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02115 USA. RP Garfall, A (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu NR 15 TC 7 Z9 7 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2013 VL 48 IS 7 BP 1000 EP 1002 DI 10.1038/bmt.2012.272 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 176KF UT WOS:000321302300023 PM 23318536 ER PT J AU Thomas, ML Brown, GG Thompson, WK Voyvodic, J Greve, DN Turner, JA Mathalon, DH Ford, J Wible, CG Potkin, SG AF Thomas, Michael L. Brown, Gregory G. Thompson, Wesley K. Voyvodic, James Greve, Douglas N. Turner, Jessica A. Mathalon, Daniel H. Ford, Judith Wible, Cynthia G. Potkin, Steven G. CA FBIRN TI An application of item response theory to fMRI data: Prospects and pitfalls SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Functional MRI; Item response theory; Bayesian analysis; Task design ID WORKING-MEMORY; SCHIZOPHRENIA; INFORMATION; MODEL AB When using functional brain imaging to study neuropsychiatric patients an important challenge is determining whether the imaging task assesses individual differences with equal precision in healthy control and impaired patient groups. Classical test theory (CTT) requires separate reliability studies of patients and controls to determine equivalent measurement precision with additional studies to determine measurement precision for different levels of disease severity. Unlike CTT, item response theory (IRT) provides estimates of measurement error for different levels of ability, without the need for separate studies, and can determine if different tests are equivalently difficult when investigating differential deficits between groups. To determine the potential value of IRT in functional brain imaging, IRT was applied to behavioral data obtained during a multi-center functional MRI (fMRI) study of working memory (WM). Average item difficulty was approximately one standard deviation below the ability scale mean, supporting the task's sensitivity to individual differences within the ability range of patients with WM impairment, but not within the range of most controls. The correlation of IRT estimated ability with fMRI activation during the task recognition period supported the linkage of the latent IRT scale to brain activation data. IRT can meaningfully contribute to the design of fMRI tasks. Published by Elsevier Ireland Ltd. C1 [Thomas, Michael L.; Brown, Gregory G.; Thompson, Wesley K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. [Brown, Gregory G.] VA San Diego Healthcare Syst, VISN 22, Mental Illness Res Educ & Clin Ctr, San Diego, CA 92161 USA. [Voyvodic, James] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02114 USA. [Turner, Jessica A.] Mind Res Network, Albuquerque, NM 87106 USA. [Mathalon, Daniel H.; Ford, Judith] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Mathalon, Daniel H.; Ford, Judith] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02301 USA. [Wible, Cynthia G.] Brockton VAMC, Cambridge, MA 02301 USA. [Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92697 USA. RP Brown, GG (reprint author), VA San Diego Healthcare Syst, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM gbrown@ucsd.edu RI Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Potkin, Steven/0000-0003-1028-1013; Mathalon, Daniel/0000-0001-6090-4974 FU National Center for Research Resources (National Institutes of Health) [1 U24 RR021992]; VA Grant FX This research was supported by a grant from the National Center for Research Resources to the Function Biomedical Informatics Research Network (National Institutes of Health grant 1 U24 RR021992) and by a VA Grant to Desert Pacific Mental Illness, Research, Education, and Clinical Center. The authors have no conflict of interest to declare. NR 44 TC 1 Z9 1 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUN 30 PY 2013 VL 212 IS 3 BP 167 EP 174 DI 10.1016/j.pscychresns.2013.01.009 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 169DD UT WOS:000320756500001 PM 23642468 ER PT J AU Uno, H Tian, L Cai, TX Kohane, IS Wei, LJ AF Uno, Hajime Tian, Lu Cai, Tianxi Kohane, Isaac S. Wei, L. J. TI A unified inference procedure for a class of measures to assess improvement in risk prediction systems with survival data SO STATISTICS IN MEDICINE LA English DT Article DE area under the receiver operating characteristic curve; C-statistic; Cox's regression; integrated discrimination improvement; net reclassification improvement; risk prediction ID GENE-EXPRESSION SIGNATURE; C-REACTIVE PROTEIN; BREAST-CANCER; INTEGRATED DISCRIMINATION; CARDIOVASCULAR RISK; ROC CURVE; MODELS; RECLASSIFICATION; MARKER; AREA AB Risk prediction procedures can be quite useful for the patient's treatment selection, prevention strategy, or disease management in evidence-based medicine. Often, potentially important new predictors are available in addition to the conventional markers. The question is how to quantify the improvement from the new markers for prediction of the patient's risk in order to aid cost-benefit decisions. The standard method, using the area under the receiver operating characteristic curve, to measure the added value may not be sensitive enough to capture incremental improvements from the new markers. Recently, some novel alternatives to area under the receiver operating characteristic curve, such as integrated discrimination improvement and net reclassification improvement, were proposed. In this paper, we consider a class of measures for evaluating the incremental values of new markers, which includes the preceding two as special cases. We present a unified procedure for making inferences about measures in the class with censored event time data. The large sample properties of our procedures are theoretically justified. We illustrate the new proposal with data from a cancer study to evaluate a new gene score for prediction of the patient's survival. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Uno, Hajime; Cai, Tianxi; Wei, L. J.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Tian, Lu] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Kohane, Isaac S.] Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Kohane, Isaac S.] MIT, Cambridge, MA 02139 USA. RP Uno, H (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. EM huno@jimmy.harvard.edu FU NCI NIH HHS [P30 CA124435, RC4 CA155940]; NIAID NIH HHS [R01 AI024643]; NIGMS NIH HHS [R01 GM079330]; NLM NIH HHS [U54 LM008748] NR 33 TC 65 Z9 65 U1 0 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 2013 VL 32 IS 14 BP 2430 EP 2442 DI 10.1002/sim.5647 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 157FA UT WOS:000319880100008 PM 23037800 ER PT J AU Paschalis, EI Chodosh, J Sperling, RA Salvador-Culla, B Dohlman, C AF Paschalis, Eleftherios I. Chodosh, James Sperling, Ralph A. Salvador-Culla, Borja Dohlman, Claes TI A Novel Implantable Glaucoma Valve Using Ferrofluid SO PLOS ONE LA English DT Article ID AQUEOUS-HUMOR; SURGERY; SHUNTS AB Purpose: To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve. Setting: Massachusetts Eye & Ear Infirmary, Boston, USA. Methods: A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed (TM) glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits. Results: In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 mu l/min at 12 mmHg; 4.3 mu l/min at 16 mmHg; 7.6 mu l/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits. Conclusions: The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway. C1 [Paschalis, Eleftherios I.; Chodosh, James; Salvador-Culla, Borja; Dohlman, Claes] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Sperling, Ralph A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Paschalis, EI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM Eleftherios_paschalis@meei.harvard.edu RI Sperling, Ralph /I-7050-2013; OI Sperling, Ralph /0000-0002-8027-0697; Paschalis, Eleftherios/0000-0002-4544-4452 FU Boston Keratoprosthesis Fund; Massachusetts Eye and Ear Infirmary, Boston, USA FX This work was funded by the Boston Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary, Boston, USA. The authors would like to acknowledge the contribution of Dr. Kuldip Raj and Ms. Vanessa Rene from Ferrotec (USA) Corporation for providing the custom fluorophilic ferrofluid material. NR 21 TC 6 Z9 6 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 28 PY 2013 VL 8 IS 6 AR e67404 DI 10.1371/journal.pone.0067404 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 174IH UT WOS:000321148400075 PM 23840691 ER PT J AU Wilson, PC Lee, MH Appleton, KM El-Shewy, HM Morinelli, TA Peterson, YK Luttrell, LM Jaffa, AA AF Wilson, Parker C. Lee, Mi-Hye Appleton, Kathryn M. El-Shewy, Hesham M. Morinelli, Thomas A. Peterson, Yuri K. Luttrell, Louis M. Jaffa, Ayad A. TI The Arrestin-selective Angiotensin AT(1) Receptor Agonist [Sar(1),Ile(4),Ile(8)]-AngII Negatively Regulates Bradykinin B-2 Receptor Signaling via AT(1)-B-2 Receptor Heterodimers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KALLIKREIN-KININ SYSTEM; OXIDE-GENERATING VASODILATORS; VASCULAR SMOOTH-MUSCLE; G-PROTEIN; BETA-ARRESTIN; NITRIC-OXIDE; IN-VIVO; DIABETIC-NEPHROPATHY; HEART-FAILURE; BIASED LIGAND AB The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT(1) receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B-1 and B-2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT(1)-B-2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT(1) agonist, [Sar(1),Ile(4),Ile(8)]-AngII, but not the neutral AT(1) antagonist, losartan, inhibits endogenous B-2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar(1), Ile(4), Ile(8)]-AngII require the AT(1) receptor and result from arrestin-dependent co-internalization of AT(1)-B-2 heterodimers. BRET50 measurements indicate that AT(1) and B-2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar(1),Ile(4),Ile(8)]-AngII blunts B-2 receptor activation of G(q/11)-dependent intracellular calcium influx and G(i/o)-dependent inhibition of adenylyl cyclase. In contrast, [Sar(1),Ile(4),Ile(8)]-AngII has no effect on B-2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar(1),Ile(4),Ile(8)]-AngII promotes internalization of AT(1)-B-2 heterodimers. Thus, [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B-2 receptor signaling by binding to the orthosteric ligand binding site of the AT(1) receptor and promoting co-sequestration of AT(1)-B-2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT(1) receptor ligands may translate into different pharmacologic actions. C1 [Wilson, Parker C.; Lee, Mi-Hye; El-Shewy, Hesham M.; Morinelli, Thomas A.; Luttrell, Louis M.; Jaffa, Ayad A.] Med Univ S Carolina, Coll Med, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Coll Med, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [Jaffa, Ayad A.] Amer Univ Beirut, Dept Biochem, Beirut 11072020, Lebanon. [Jaffa, Ayad A.] Amer Univ Beirut, Dept Mol Genet, Beirut 11072020, Lebanon. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816CSB,MSC624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU National Institutes of Health [R01 HL087986, HL077192, R01 DK55524, F30 DK083208]; National Center for Research Resources [S10 RR027777]; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL087986 and HL077192 (to A. A. J.), R01 DK55524 (to L. M. L.), and F30 DK083208 (to P. C. W.) and National Center for Research Resources Grant S10 RR027777 (to T. A. M. and L. M. L.). This work was also supported by the Research Service of the Ralph H. Johnson Veterans Affairs Medical Center. NR 56 TC 15 Z9 15 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 2013 VL 288 IS 26 BP 18872 EP 18884 DI 10.1074/jbc.M113.472381 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176WB UT WOS:000321335800025 PM 23661707 ER PT J AU Prasad, R Katiyar, SK AF Prasad, Ram Katiyar, Santosh K. TI Grape seed proanthocyanidins inhibit migration potential of pancreatic cancer cells by promoting mesenchymal-to-epithelial transition and targeting NF-kappa B SO CANCER LETTERS LA English DT Article DE NF-kappa B; Epithelial-to-mesenchymal transition; Pancreatic cancer cells; Cancer cell migration; Grape seed proanthocyanidins ID REPRESSES E-CADHERIN; BREAST-CANCER; TUMOR PROGRESSION; EXPRESSION; TRANSCRIPTION; INFLAMMATION; SNAIL; SLUG; METASTASIS; ALPHA AB Here we explore the effect of grape seed proanthocyanidins (GSPs) on pancreatic cancer cell migration and the molecular mechanisms underlying these effects. Treatment of human pancreatic cancer cell lines Miapaca-2, PANC-1 and AsPC-1 with GSPs resulted in inhibition of cell migration (19-82%, P < 0.01-0.001), which was associated with decreased phosphorylation of ERK1/2 and inactivation of NF-kappa B. Treatment of cells with UO126, an inhibitor of MEK, and caffeic acid phenethyl ester, an inhibitor of NE-kappa B, also inhibited the migration of cells (40-80%, P < 0.01-0.001). Inhibition of cell migration by GSPs was associated with reversal of the epithelial-to-mesenchymal transition. This was associated with upregulation of E-cadherin and desmoglein-2 and down-regulation of fibronectin, N-cadherin and vimentin. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Sch Publ Hlth, Nutr Obes Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award FX This work was supported partially by the funds from the Veterans Administration Merit Review Award (SKK). Grateful thanks to Dr. Fiona Hunter for editorial assistance. The content of this article does not necessarily reflect the views or policies of the funding sources, and also the funders had no role in study design, data analysis and preparation of the manuscript. NR 35 TC 7 Z9 11 U1 1 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 28 PY 2013 VL 334 IS 1 SI SI BP 118 EP 126 DI 10.1016/j.canlet.2012.08.003 PG 9 WC Oncology SC Oncology GA 164MF UT WOS:000320413500018 PM 22902508 ER PT J AU Jones, JC Freeman, GJ AF Jones, Jennifer C. Freeman, Gordon J. TI Costimulatory Genes: Hotspots of Conflict between Host Defense and Autoimmunity SO IMMUNITY LA English DT Editorial Material C1 [Jones, Jennifer C.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Gordon_Freeman@dfci.harvard.edu RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 FU NIAID NIH HHS [R01 AI089955, P01 AI056299, P01 AI080192, U19 AI082630] NR 10 TC 2 Z9 2 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JUN 27 PY 2013 VL 38 IS 6 BP 1083 EP 1085 DI 10.1016/j.immuni.2013.06.008 PG 4 WC Immunology SC Immunology GA AA2TR UT WOS:000330947500002 PM 23809156 ER PT J AU Heesters, BA Chatterjee, P Kim, YA Gonzalez, SF Kuligowski, MP Kirchhausen, T Carroll, MC AF Heesters, Balthasar A. Chatterjee, Priyadarshini Kim, Young-A. Gonzalez, Santiago F. Kuligowski, Michael P. Kirchhausen, Tomas Carroll, Michael C. TI Endocytosis and Recycling of Immune Complexes by Follicular Dendritic Cells Enhances B Cell Antigen Binding and Activation SO IMMUNITY LA English DT Article ID ALPHA-DEFICIENT MICE; GERMINAL-CENTERS; AFFINITY MATURATION; LYMPHOTOXIN BETA; HUMORAL IMMUNITY; CYTOCHALASIN-D; STROMAL CELLS; IGG RESPONSES; FOLLICLES; RECEPTOR AB Stromal-derived follicular dendritic cells (FDCs) are a major reservoir for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate. A long-standing question is how FDCs retain antigen in its native form for extended periods and how they display it to specific B cells. Here we found that FDCs acquired complement-coated immune complexes (ICs) from noncognate B cells via complement receptors 1 and 2 (CD35 and CD21, respectively) and rapidly internalized them by an actin-dependent pathway. ICs were retained intact within a nondegradative cycling compartment and were displayed periodically on the cell surface where they were accessible to antigen-specific B cells. This would explain how antigens are protected from damage and retained over long periods of time, while remaining accessible for B cells. C1 [Heesters, Balthasar A.; Chatterjee, Priyadarshini; Kim, Young-A.; Gonzalez, Santiago F.; Kuligowski, Michael P.; Kirchhausen, Tomas; Carroll, Michael C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Heesters, Balthasar A.] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. EM michael.carroll@childrens.harvard.edu FU National Institutes of Health [RO1 AI039246-16, R37 AI054636, PO1 AI078897-04]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases [GM-075252, U54 AI057159]; Glaxo-Smith Kline [GSK-P-11-02]; Marie Curie International Outgoing Fellowship for Career Development [220044] FX The authors thank all members of the M.C.C. lab and P. Reeves of the T.K. lab for suggestions and help with experiments. We acknowledge the valuable technical assistance with live cell and confocal imaging from E. Marino and H. Leung, respectively, and help by M. Coughlin for preparation of EM sections. Supported by the National Institutes of Health (RO1 AI039246-16, R37 AI054636, and PO1 AI078897-04 to M.C.C.), New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (GM-075252 and U54 AI057159 to T.K.), Glaxo-Smith Kline (GSK-P-11-02 to M.C.C. and GSK postdoctoral fellowship to P.C.), and Marie Curie International Outgoing Fellowship for Career Development (220044 to S.F.G.). NR 39 TC 65 Z9 65 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JUN 27 PY 2013 VL 38 IS 6 BP 1164 EP 1175 DI 10.1016/j.immuni.2013.02.023 PG 12 WC Immunology SC Immunology GA AA2TR UT WOS:000330947500012 PM 23770227 ER PT J AU Le Page, AK Jager, MM Kotton, CN Simoons-Smit, A Rawlinson, WD AF Le Page, Amelia K. Jager, Mischa M. Kotton, Camille N. Simoons-Smit, Alberdina Rawlinson, William D. TI International Survey of Cytomegalovirus Management in Solid Organ Transplantation After the Publication of Consensus Guidelines SO TRANSPLANTATION LA English DT Article DE Cytomegalovirus; Transplantation; Survey; Prophylaxis; Guidelines ID LUNG TRANSPLANTATION; DISEASE; RECIPIENTS; VALGANCICLOVIR; PROPHYLAXIS; EFFICACY; KIDNEY AB Background. The Transplantation Society published guidelines on cytomegalovirus (CMV) management after solid organ transplantation in 2010, which provide recommendations on prevention, treatment, diagnostics, and resistance. We aimed to survey international clinicians on their posttransplantation CMV management practices with reference to these guidelines to see if they altered the management of clinicians caring for transplant patients. Methods. The members of The Transplantation Society were emailed an electronic survey 12 months after the guideline publication. Results. A total of 155 clinicians responded, representing 126 centers in 41 countries. Overall, there was a high uptake of usage of the guidelines. High rates of initial CMV prevention were used (93%), with 46% using only universal prophylaxis, 21% only preemptive therapy, and 33% a hybrid combination dependent on recipient risk for CMV. Socioeconomic and geographic influence was evident, with 26% of respondents from developing countries using no CMV prevention, and more preemptive therapy used in Asia. Valganciclovir was the most common antiviral used, with dosing often below recommendations (33% in infection). Molecular monitoring was used by 84% of clinicians. Management of antiviral-associated neutropenia commonly included antiviral dose reduction or withdrawal (51%). Conclusions. We conclude that there is significant geographic variation in CMV management after solid organ transplantation. Although the majority of clinicians adhere to consensus guidelines, opportunity exists to encourage better guideline uptake. C1 [Le Page, Amelia K.; Rawlinson, William D.] Prince Wales Hosp, POWH & UNSW Res Labs, Randwick, NSW 2031, Australia. [Le Page, Amelia K.; Rawlinson, William D.] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia. [Jager, Mischa M.; Rawlinson, William D.] Prince Wales Hosp, Div Virol, SEALS Microbiol, Randwick, NSW 2031, Australia. [Jager, Mischa M.; Simoons-Smit, Alberdina] Vrije Univ Amsterdam, Med Ctr, Dept Med Microbiol & Infect Control, Amsterdam, Netherlands. [Kotton, Camille N.; Rawlinson, William D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Rawlinson, WD (reprint author), Prince Wales Hosp, Div Virol, SEALS Microbiol, Barker St, Randwick, NSW 2031, Australia. EM w.rawlinson@unsw.edu.au OI Rawlinson, William/0000-0003-0988-7827 NR 16 TC 23 Z9 23 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2013 VL 95 IS 12 BP 1455 EP 1460 DI 10.1097/TP.0b013e31828ee12e PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299EF UT WOS:000330377600010 PM 23640298 ER PT J AU Leen, AM Bollard, CM Mendizabal, AM Shpall, EJ Szabolcs, P Antin, JH Kapoor, N Pai, SY Rowley, SD Kebriaei, P Dey, BR Grilley, BJ Gee, AP Brenner, MK Rooney, CM Heslop, HE AF Leen, Ann M. Bollard, Catherine M. Mendizabal, Adam M. Shpall, Elizabeth J. Szabolcs, Paul Antin, Joseph H. Kapoor, Neena Pai, Sung-Yun Rowley, Scott D. Kebriaei, Partow Dey, Bimalangshu R. Grilley, Bambi J. Gee, Adrian P. Brenner, Malcolm K. Rooney, Cliona M. Heslop, Helen E. TI Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID LYMPHOPROLIFERATIVE DISEASE; CLINICAL-TRIALS; CYTOMEGALOVIRUS; RECIPIENTS; IMMUNOTHERAPY; THERAPY; ADENOVIRUS; MORTALITY; LYMPHOMAS; CRITERIA AB Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2%-96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-elated adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035. C1 [Leen, Ann M.; Bollard, Catherine M.; Grilley, Bambi J.; Gee, Adrian P.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.] Methodist Hosp, Ctr Cell & Gene Therapy, Baylor Coll Med, Texas Childrens Hosp, Houston, TX 77030 USA. [Mendizabal, Adam M.; Kebriaei, Partow] EMMES Corp, Rockville, MD USA. [Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Szabolcs, Paul] Duke Univ, Med Ctr, Durham, NC USA. [Antin, Joseph H.; Pai, Sung-Yun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kapoor, Neena] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Boston, MA USA. [Rowley, Scott D.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Dey, Bimalangshu R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gee, Adrian P.; Rooney, Cliona M.] Baylor Coll Med, Prod Assistance Cell Therapy Ctr, Houston, TX 77030 USA. RP Heslop, HE (reprint author), Ctr Cell & Gene Therapy, 1102 Bates St,Suite 1640, Houston, TX 77030 USA. EM hheslop@bcm.edu FU National Institutes of Health-NHLBI [U54HL08100]; Specialized Centers for Cellular Therapy; [P30CA125123] FX The clinical trial was supported by National Institutes of Health-NHLBI grant U54HL08100, Specialized Centers for Cellular Therapy, and the manufacture of VSTs by NHLBI Production Assistance for Cellular Therapy. The authors also appreciate the support of shared resources by cancer center support grant P30CA125123. NR 28 TC 130 Z9 137 U1 5 U2 16 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 JUN 27 PY 2013 VL 121 IS 26 BP 5113 EP 5123 DI 10.1182/blood-2013-02-486324 PG 11 WC Hematology SC Hematology GA 184OJ UT WOS:000321900700005 PM 23610374 ER PT J AU Qu, J Jakobs, TC AF Qu, Juan Jakobs, Tatjana C. TI The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve SO PLOS ONE LA English DT Article ID ELEVATED INTRAOCULAR-PRESSURE; AXONAL-TRANSPORT; RAT GLAUCOMA; MOUSE RETINA; ASTROCYTES; HEAD; INJURY; MODEL; BRAIN; NEURONS AB Reactive gliosis is a complex process that involves changes in gene expression and morphological remodeling. The mouse optic nerve, where astrocytes, microglia and oligodendrocytes interact with retinal ganglion cell axons and each other, is a particularly suitable model for studying the molecular mechanisms of reactive gliosis. We triggered gliosis at the mouse optic nerve head by retro orbital nerve crush. We followed the expression profiles of 14,000 genes from 1 day to 3 months, as the optic nerve formed a glial scar. The transcriptome showed profound changes. These were greatest shortly after injury; the numbers of differentially regulated genes then dropped, returning nearly to resting levels by 3 months. Different genes were modulated with very different time courses, and functionally distinct groups of genes responded in partially overlapping waves. These correspond roughly to two quick waves of inflammation and cell proliferation, a slow wave of tissue remodeling and debris removal, and a final stationary phase that primarily reflects permanent structural changes in the axons. Responses from astrocytes, microglia and oligodendrocytes were distinctively different, both molecularly and morphologically. Comparisons to other models of brain injury and to glaucoma indicated that the glial responses depended on both the tissue and the injury. Attempts to modulate glial function after axonal injuries should consider different mechanistic targets at different times following the insult. C1 [Qu, Juan; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. RP Jakobs, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. EM tatjana_jakobs@meei.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU National Institutes of Health (NIH) [EY019703, EY14104]; Research to Prevent Blindness; Massachusetts Lions Eye Research Fund FX This project was funded by National Institutes of Health (NIH) grant EY019703, core grant EY14104, and grants from Research to Prevent Blindness and the Massachusetts Lions Eye Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 30 Z9 30 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 27 PY 2013 VL 8 IS 6 AR e67094 DI 10.1371/journal.pone.0067094 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 174IX UT WOS:000321150000024 PM 23826199 ER PT J AU Smith, AK White, DB Arnold, RM AF Smith, Alexander K. White, Douglas B. Arnold, Robert M. TI Uncertainty - The Other Side of Prognosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [White, Douglas B.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. FU NIA NIH HHS [K23 AG040772] NR 5 TC 33 Z9 34 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 27 PY 2013 VL 368 IS 26 BP 2448 EP 2450 DI 10.1056/NEJMp1303295 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 171KQ UT WOS:000320926900004 PM 23802514 ER PT J AU Puig, A Dighe, AS AF Puig, Alberto Dighe, Anand S. TI Case 20-2013: A 29-Year-Old Man with Anemia and Jaundice SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DEFICIENCY C1 [Puig, Alberto] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Puig, Alberto] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dighe, Anand S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Puig, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 27 PY 2013 VL 368 IS 26 BP 2502 EP 2509 DI 10.1056/NEJMcpc1302333 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 171KQ UT WOS:000320926900012 PM 23802518 ER PT J AU Mannstadt, M Harris, M Bravenboer, B Chitturi, S Dreijerink, KMA Lambright, DG Lim, ET Daly, MJ Gabriel, S Juppner, H AF Mannstadt, Michael Harris, Mark Bravenboer, Bert Chitturi, Sridhar Dreijerink, Koen M. A. Lambright, David G. Lim, Elaine T. Daly, Mark J. Gabriel, Stacey Jueppner, Harald TI Germline Mutations Affecting G alpha(11) in Hypoparathyroidism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Mannstadt, Michael; Daly, Mark J.; Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Mark] Univ Queensland, Mater Childrens Hosp, Brisbane, Qld 4101, Australia. [Bravenboer, Bert] Catharina Hosp, Eindhoven, Netherlands. [Chitturi, Sridhar] Royal Darwin Hosp, Tiwi, NT, Australia. [Dreijerink, Koen M. A.] Univ Med Ctr, Utrecht, Netherlands. [Lambright, David G.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lim, Elaine T.; Gabriel, Stacey] Broad Inst, Cambridge, MA USA. RP Mannstadt, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hjueppner@partners.org OI Dreijerink, Koen/0000-0002-3140-3502 FU NHGRI NIH HHS [X01 HG006062-01]; NHLBI NIH HHS [RC2 HL103010, HL103010, UC2 HL103010, HL102923-26, RC2 HL102923, UC2 HL102923]; NIDDK NIH HHS [P01 DK011794, P01DK11794, K08DK081669-01, R01DK46718-20, R01 DK046718, K08 DK081669] NR 5 TC 31 Z9 31 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 JUN 27 PY 2013 VL 368 IS 26 BP 2532 EP 2534 DI 10.1056/NEJMc1300278 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 171KQ UT WOS:000320926900033 PM 23802536 ER PT J AU Park, E Kim, H Kim, JM Primack, B Vidal-Cardenas, S Xu, Y Price, BD Mills, AA D'Andrea, AD AF Park, Eunmi Kim, Hyungjin Kim, Jung Min Primack, Benjamin Vidal-Cardenas, Sofia Xu, Ye Price, Brendan D. Mills, Alea A. D'Andrea, Alan D. TI FANCD2 Activates Transcription of TAp63 and Suppresses Tumorigenesis SO MOLECULAR CELL LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FANCONI-ANEMIA PATHWAY; HOLLIDAY JUNCTION RESOLVASE; ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE; KNOCKOUT MICE; P63; SLX4; REPAIR; PROTEIN AB Fanconi anemia (FA) is a rare genetic disorder characterized by an increased susceptibility to squamous cell cancers. Fifteen FA genes are known, and the encoded proteins cooperate in a common DNA repair pathway. A critical step is the monoubiquitination of the FANCD2 protein, and cells from most FA patients are deficient in this step. How monoubiquitinated FANCD2 suppresses squamous cell cancers is unknown. Here we show that Fancd2-deficient mice are prone to Ras-oncogene-driven skin carcinogenesis, while Usp1-deficient mice, expressing elevated cellular levels of Fancd2-Ub, are resistant to skin tumors. Moreover, Fancd2-Ub activates the transcription of the tumor suppressor TAp63, thereby promoting cellular senescence and blocking skin tumorigenesis. For FA patients, the reduction of FANCD2-Ub and TAp63 protein levels may account for their susceptibility to squamous cell neoplasia. Taken together, Usp1 inhibition may be a useful strategy for upregulating TAp63 and preventing or treating squamous cell cancers in the general non-FA population. C1 [Park, Eunmi; Kim, Hyungjin; Kim, Jung Min; Primack, Benjamin; Vidal-Cardenas, Sofia; Xu, Ye; Price, Brendan D.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Mills, Alea A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu FU Susan G. Komen Foundation [KG101186]; ASCO-Gianni Bonadonna Fellowship; NIH [R01DK43889, R01HL52725, P01HL048546] FX We thank Youngeun Choi for help in real-time PCR analysis and Jason T. Tsichlis for technical assistance. We thank Markus Grompe, K.J. Patel, Alec Kimmelman, David Pellman, Dipanjan Chowdhury, Geoffrey Shapiro, Kalindi Parmar, David Kozono, Younghoon Kee, Min Huang, and other members of the D'Andrea Laboratory for helpful discussions. E.P. is supported by postdoctoral fellowships from the Susan G. Komen Foundation (KG101186) and the ASCO-Gianni Bonadonna Fellowship. This study was also supported by NIH grants R01DK43889, R01HL52725, and P01HL048546 to A.D.D. E.P and A.D.D conceived and designed the study. E.P. performed all experiments and analyzed the data. J.M.K. was involved in the establishment of mouse models and animal experiments. H.K. contributed to the xenograft study, and B.P. provided technical assistance during animal experiments. Y.X. and B.P. contributed to the elucidation of the transcriptional activity of the FANCD2-Ub protein. E.P., J.M.K., H.K., A.M., and A.D.D. participated in discussions and interpretations of the experiments. E.P., J.M.K., and A.D.D. wrote the manuscript. NR 45 TC 27 Z9 27 U1 0 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 JUN 27 PY 2013 VL 50 IS 6 BP 908 EP 918 DI 10.1016/j.molcel.2013.05.017 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 176QT UT WOS:000321319900013 PM 23806336 ER PT J AU Amatruda, JF Ross, JA Christensen, B Fustino, NJ Chen, KS Hooten, AJ Nelson, H Kuriger, JK Rakheja, D Frazier, AL Poynter, JN AF Amatruda, James F. Ross, Julie A. Christensen, Brock Fustino, Nicholas J. Chen, Kenneth S. Hooten, Anthony J. Nelson, Heather Kuriger, Jacquelyn K. Rakheja, Dinesh Frazier, A. Lindsay Poynter, Jenny N. TI DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors SO BMC CANCER LA English DT Article DE Germ Cell Tumor; Teratoma; DNA Methylation; Imprinting ID YOLK-SAC TUMOR; IMPRINTING ANALYSIS; OVARIAN TERATOMAS; TESTICULAR CANCER; GENES; H19; HYPERMETHYLATION; PROMOTER; DIFFERENTIATION; RESISTANCE AB Background: Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. Methods: We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Results: Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Conclusion: Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy. C1 [Amatruda, James F.; Fustino, Nicholas J.; Chen, Kenneth S.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Rakheja, Dinesh] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Amatruda, James F.; Fustino, Nicholas J.; Chen, Kenneth S.] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75390 USA. [Ross, Julie A.; Poynter, Jenny N.] Div Pediat Epidemiol & Clin Res, Dept Pediat, Minneapolis, MN 55455 USA. [Ross, Julie A.; Hooten, Anthony J.; Nelson, Heather; Kuriger, Jacquelyn K.; Poynter, Jenny N.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Nelson, Heather; Kuriger, Jacquelyn K.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Christensen, Brock] Dartmouth Med Sch, Sect Biostat & Epidemiol, Dept Community & Family Med, Hanover, NH 03755 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Amatruda, JF (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. EM james.amatruda@utsouthwestern.edu FU National Institutes of Health [R01 CA135731, R03 CA141481, K05 CA157439]; Minnesota Medical Foundation; Cancer Prevention and Research Institute of Texas [RP110394]; Amon G. Carter Foundation, Fort Worth, TX; Children's Cancer Research Fund, Minneapolis, MN FX The authors would like to acknowledge the Biomedical Genomics Center at the University of Minnesota for performing the DNA methylation analysis. Supported by grants from the National Institutes of Health (R01 CA135731 to J.F.A., R03 CA141481 to J.N.P., K05 CA157439 toJ.A.R.); the Minnesota Medical Foundation; the Cancer Prevention and Research Institute ofTexas (RP110394 to J.F.A.); the Amon G. Carter Foundation, Fort Worth, TX;andtheChildren's Cancer Research Fund, Minneapolis, MN. NR 40 TC 16 Z9 16 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 27 PY 2013 VL 13 AR 313 DI 10.1186/1471-2407-13-313 PG 13 WC Oncology SC Oncology GA 176MH UT WOS:000321308300001 PM 23806198 ER PT J AU Gerszten, PC Sahgal, A Sheehan, JP Kersh, R Chen, S Flickinger, JC Quader, M Fahim, D Grills, I Shin, JH Winey, B Oh, K Sweeney, RA Guckenberger, M AF Gerszten, Peter C. Sahgal, Arjun Sheehan, Jason P. Kersh, Ronald Chen, Stephanie Flickinger, John C. Quader, Mubina Fahim, Daniel Grills, Inga Shin, John H. Winey, Brian Oh, Kevin Sweeney, Reinhart A. Guckenberger, Matthias TI A multi-national report on methods for institutional credentialing for spine radiosurgery SO RADIATION ONCOLOGY LA English DT Article DE Spine Radiosurgery; Stereotactic Body Radiotherapy; Credentialing; Spine Tumors ID INTENSITY-MODULATED RADIOTHERAPY; STEREOTACTIC BODY RADIOTHERAPY; ACR PRACTICE GUIDELINES; RADIATION-THERAPY; QUALITY-ASSURANCE; CLINICAL-TRIALS; CONFORMAL RADIOTHERAPY; ADVANCED TECHNOLOGY; CYBERKNIFE RADIOSURGERY; PARASPINAL TUMORS AB Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program. C1 [Gerszten, Peter C.; Chen, Stephanie; Flickinger, John C.; Quader, Mubina] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Sahgal, Arjun] Univ Toronto, Toronto, ON, Canada. [Sheehan, Jason P.] Univ Virginia, Charlottesville, VA USA. [Kersh, Ronald] Riverside Med Ctr, Newport News, VA USA. [Fahim, Daniel; Grills, Inga] Oakland Univ, William Beaumont Sch Med, Royal Oak, MI USA. [Shin, John H.; Winey, Brian; Oh, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sweeney, Reinhart A.; Guckenberger, Matthias] Univ Hosp Wurzburg, Wurzburg, Germany. [Gerszten, Peter C.] Presbyterian Univ Hosp, Dept Neurol Surg, Pittsburgh, PA 15213 USA. RP Gerszten, PC (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. EM gersztenpc@upmc.edu OI Flickinger, John/0000-0001-6900-1384; Guckenberger, Matthias/0000-0002-7146-9071 FU Elekta Stereotactic research grant FX This research was partially supported through an Elekta Stereotactic research grant with all institutions being members of the Elekta Spine Radiosurgery Research Consortium. This work and these data, however, are the intellectual property of the individual group members and their sponsoring institutions. NR 45 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PD JUN 27 PY 2013 VL 8 AR 158 DI 10.1186/1748-717X-8-158 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 176VK UT WOS:000321333900003 PM 23806078 ER PT J AU Nayak, BK Feliers, D Sudarshan, S Friedrichs, WE Day, RT New, DD Fitzgerald, JP Eid, A DeNapoli, T Parekh, DJ Gorin, Y Block, K AF Nayak, B. K. Feliers, D. Sudarshan, S. Friedrichs, W. E. Day, R. T. New, D. D. Fitzgerald, J. P. Eid, A. DeNapoli, T. Parekh, D. J. Gorin, Y. Block, K. TI Stabilization of HIF-2 alpha through redox regulation of mTORC2 activation and initiation of mRNA translation SO ONCOGENE LA English DT Article DE mTOR; Nox oxidase; Rictor; p22(phox); HIF-2 alpha; renal cancer ID TUMOR-SUPPRESSOR PROTEIN; CANCER; PHOSPHORYLATION; EXPRESSION; CARCINOMA; COMPLEX; EIF4E; AKT; TRANSFORMATION; CONTRIBUTES AB Hypoxia inducible factor-2 alpha (HIF-2 alpha) has a critical role in renal tumorigenesis. HIF-2 alpha is stabilized in von Hippel-Lindau (VHL)-deficient renal cell carcinoma through mechanisms that require ongoing mRNA translation. Mammalian target of rapamycin (mTOR) functions in two distinct complexes: Raptor-associated mTORC1 and Rictor-associated mTORC2. Rictor-associated mTORC2 complex has been linked to maintaining HIF-2 alpha protein in the absence of VHL; however, the mechanisms remain to be elucidated. Although Raptor-associated mTORC1 is a known key upstream regulator of mRNA translation, initiation and elongation, the role of mTORC2 in regulating mRNA translation is not clear. Complex assembly of the mRNA cap protein, eukaryotic translation initiation factor 4 (eIF4)E, with activators (eIF4 gamma (eIF4G)) and inhibitors (eIF4E-binding protein 1 (4E-BP1)) are rate-limiting determinants of mRNA translation. Our laboratory has previously demonstrated that reactive oxygen species, mediated by p22(phox)-based Nox oxidases, are enhanced in VHL-deficient cells and have a role in the activation of Akt on S473, a site phosphorylated by the mTORC2 complex. In this study, we examined the role of Rictor-dependent regulation of HIF-2 alpha through eIF4E-dependent mRNA translation and examined the effects of p22(phox)-based Nox oxidases on TORC2 regulation. We demonstrate for the first time that mTORC2 complex stability and activation is redox sensitive, and further defined a novel role for p22(phox)-based Nox oxidases in eIF4E-dependent mRNA translation through mTORC2. Furthermore, we provide the first evidence that silencing of p22(phox) reduces HIF-2 alpha-dependent gene targeting in vitro and tumor formation in vivo. The clinical relevance of these studies is demonstrated. C1 [Nayak, B. K.; Feliers, D.; Friedrichs, W. E.; Day, R. T.; New, D. D.; Eid, A.; Gorin, Y.; Block, K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Sudarshan, S.; Fitzgerald, J. P.; Parekh, D. J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [DeNapoli, T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Block, K.] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. RP Block, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu FU Veterans Administration; NIH [R01 NCI CA131272, K08 CA138774]; Voelcker Fund Young Investigator Award; Cancer Center Support Grant, National Cancer Institute [5 P30 CA054174-18] FX We acknowledge Dr Goutam Gosh-Choudhury for the HRE responsive element, Cynthia Galindo for technical contributions and Dr Hanna E. Abboud for helpful discussions and critical reading of the manuscript. This study was supported by the Veterans Administration Career Development Award and NIH R01 NCI CA131272 (KB), and NIH K08 CA138774 and Voelcker Fund Young Investigator Award (SS). This study was also supported in part by the Cancer Center Support Grant, National Cancer Institute, 5 P30 CA054174-18 (DJP). NR 28 TC 18 Z9 19 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 27 PY 2013 VL 32 IS 26 BP 3147 EP 3155 DI 10.1038/onc.2012.333 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 172LL UT WOS:000321004600005 PM 22869144 ER PT J AU Yang, Q Liao, L Deng, X Chen, R Gray, NS Yates, JR Lee, JD AF Yang, Q. Liao, L. Deng, X. Chen, R. Gray, N. S. Yates, J. R., III Lee, J. D. TI BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction SO ONCOGENE LA English DT Article DE BMK1; PML; p53 ID HUMAN-PAPILLOMAVIRUS TYPE-16; MAMMALIAN MAP KINASE; PREMATURE SENESCENCE; SIGNAL-TRANSDUCTION; CUTANEOUS MELANOMA; CELL-PROLIFERATION; GENE-EXPRESSION; E6 ONCOPROTEIN; ONCOGENIC RAS; GROWTH-FACTOR AB Promyelocytic leukemia protein (PML) modulates the p53 tumor suppressor through its interaction with p53 and MDM2. We found that activated big MAP kinase 1 (BMK1) preferentially associates with PML isoform IV and disrupts PML-MDM2 interaction. Doxorubicin, a common chemotherapeutic agent, is known to promote PML-mediated p53 activation in part by promoting PML-dependent MDM2 nucleolar sequestration. We discovered that BMK1 deactivation coupled with doxorubicin synergistically enhanced MDM2 nucleolar sequestration and, consequently, promoted PML-mediated p53 upregulation leading to tumor cell apoptosis in vitro and tumor regression in vivo. Collectively, these results not only suggest that BMK1 activity has a role in suppressing p53 by blocking the interaction between PML and MDM2, but also implicate that pharmacological BMK1 inhibitor should significantly enhance the anticancer capacity of doxorubicin-based chemotherapy. C1 [Yang, Q.; Chen, R.; Lee, J. D.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Liao, L.; Yates, J. R., III] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Deng, X.; Gray, N. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, JD (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA. EM jdlee@scripps.edu FU National Institutes of Health [CA079871, CA114059]; University of California [19XT-0084] FX We thank Dr Giovanni Blandino, Dr Myung Kim and Dr Pier Paolo Pandolfi for generously providing the PML null and control cell lines. This work was supported by the National Institutes of Health [CA079871 and CA114059 to JDL] and by the funds from the Tobacco-Related Disease, Research Program of the University of California [19XT-0084 to JDL]. NR 37 TC 14 Z9 17 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 27 PY 2013 VL 32 IS 26 BP 3156 EP 3164 DI 10.1038/onc.2012.332 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 172LL UT WOS:000321004600006 PM 22869143 ER PT J AU Haeno, H Maruvka, YE Iwasa, Y Michor, F AF Haeno, Hiroshi Maruvka, Yosef E. Iwasa, Yoh Michor, Franziska TI Stochastic Tunneling of Two Mutations in a Population of Cancer Cells SO PLOS ONE LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; COLORECTAL-CANCER; EVOLUTIONARY DYNAMICS; MUTATOR PHENOTYPE; STEM-CELLS; INSTABILITY; INITIATION; RETINOBLASTOMA; THERAPY; MODEL AB Cancer initiation, progression, and the emergence of drug resistance are driven by specific genetic and/or epigenetic alterations such as point mutations, structural alterations, DNA methylation and histone modification changes. These alterations may confer advantageous, deleterious or neutral effects to mutated cells. Previous studies showed that cells harboring two particular alterations may arise in a fixed-size population even in the absence of an intermediate state in which cells harboring only the first alteration take over the population; this phenomenon is called stochastic tunneling. Here, we investigated a stochastic Moran model in which two alterations emerge in a cell population of fixed size. We developed a novel approach to comprehensively describe the evolutionary dynamics of stochastic tunneling of two mutations. We considered the scenarios of large mutation rates and various fitness values and validated the accuracy of the mathematical predictions with exact stochastic computer simulations. Our theory is applicable to situations in which two alterations are accumulated in a fixed-size population of binary dividing cells. C1 [Haeno, Hiroshi; Iwasa, Yoh] Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 812, Japan. [Maruvka, Yosef E.; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Maruvka, Yosef E.; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Iwasa, Y (reprint author), Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 812, Japan. EM yohiwasa@kyudai.jp; michor@jimmy.harvard.edu RI Iwasa, Yoh/G-5368-2010 OI Iwasa, Yoh/0000-0003-0691-1852 FU NCI FX This work was supported by NCI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 2 Z9 2 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2013 VL 8 IS 6 AR e65724 DI 10.1371/journal.pone.0065724 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178DN UT WOS:000321424400011 PM 23840359 ER PT J AU Trudeau, MB Catalano, PJ Jindrich, DL Dennerlein, JT AF Trudeau, Matthieu B. Catalano, Paul J. Jindrich, Devin L. Dennerlein, Jack T. TI Tablet Keyboard Configuration Affects Performance, Discomfort and Task Difficulty for Thumb Typing in a Two-Handed Grip SO PLOS ONE LA English DT Article ID MOBILE PHONE USE; TRAPEZIOMETACARPAL JOINT; FEASIBILITY; MOTION; VARIES AB When holding a tablet computer with two hands, the touch keyboard configuration imposes postural constraints on the user because of the need to simultaneously hold the device and type with the thumbs. Designers have provided users with several possible keyboard configurations (device orientation, keyboard layout and location). However, potential differences in performance, usability and postures among these configurations have not been explored. We hypothesize that (1) the narrower standard keyboard layout in the portrait orientation leads to lower self-reported discomfort and less reach than the landscape orientation; (2) a split keyboard layout results in better overall outcomes compared to the standard layout; and (3) the conventional bottom keyboard location leads to the best outcomes overall compared to other locations. A repeated measures laboratory experiment of 12 tablet owners measured typing speed, discomfort, task difficulty, and thumb/wrist joint postures using an active marker system during typing tasks for different combinations of device orientation (portrait and landscape), keyboard layout (standard and split), and keyboard location (bottom, middle, top). The narrower standard keyboard with the device in the portrait orientation was associated with less discomfort (least squares mean (and S.E.) 2.9 +/- 0.6) than the landscape orientation (4.5 +/- 0.7). Additionally, the split keyboard decreased the amount of reaching required by the thumb in the landscape orientation as defined by a reduced range of motion and less MCP extension, which may have led to reduced discomfort (2.7 +/- 0.6) compared to the standard layout (4.5 +/- 0.7). However, typing speed was greater for the standard layout (127 +/- 5 char./min.) compared to the split layout (113 +/- 4 char./min.) regardless of device orientation and keyboard location. Usage guidelines and designers can incorporate these findings to optimize keyboard design parameters and form factors that promote user performance and usability for thumb interaction. C1 [Trudeau, Matthieu B.; Catalano, Paul J.; Dennerlein, Jack T.] Harvard Sch Publ Hlth, Boston, MA USA. [Catalano, Paul J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jindrich, Devin L.] Calif State Univ San Marcos, San Marcos, TX USA. [Dennerlein, Jack T.] Harvard Univ, Sch Med, Boston, MA USA. [Dennerlein, Jack T.] Northeastern Univ, Boston, MA 02115 USA. RP Dennerlein, JT (reprint author), Harvard Sch Publ Hlth, Boston, MA USA. EM j.dennerlein@neu.edu OI Dennerlein, Jack/0000-0001-7703-643X FU NIOSH [R01 OH008373]; Harvard-NIOSH Education and Research Center [2 T42 OH008416-07]; National Science Foundation [0964220] FX This study was funded in part by NIOSH R01 OH008373, a pilot project grant awarded by the Harvard-NIOSH Education and Research Center under Grant No. 2 T42 OH008416-07, and the National Science Foundation grant 0964220. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 5 Z9 5 U1 2 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2013 VL 8 IS 6 AR e67525 DI 10.1371/journal.pone.0067525 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178DN UT WOS:000321424400109 PM 23840730 ER PT J AU Tso, FY Abrahamyan, L Hu, SL Ruprecht, RM Wood, C AF Tso, For Yue Abrahamyan, Levon Hu, Shiu-Lok Ruprecht, Ruth M. Wood, Charles TI Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZATION SENSITIVITY; MULLER RATCHET; FITNESS; GP120; ENV; R5; CCR5; CD4 AB A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human. C1 [Tso, For Yue; Abrahamyan, Levon; Wood, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. [Tso, For Yue; Abrahamyan, Levon; Wood, Charles] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. [Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Hu, Shiu-Lok] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. RP Wood, C (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. EM cwood1@unl.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU Public Health Service [CA75903, TW001429]; National Institute of Medical Sciences, Center for Biomedical Research Excellence [P30 GM103509, R01 AI076170, P01 AI48240]; American Recovery and Reinvestment Act [3P01 AI048240-08S1] FX This work was supported by Public Health Service grants, CA75903, TW001429 and the National Institute of Medical Sciences, Center for Biomedical Research Excellence grant P30 GM103509 to C. W; R01 AI076170 to S. L. H; P01 AI48240 to R. M. R., S. L. H and C. W.; American Recovery and Reinvestment Act funding 3P01 AI048240-08S1 to R. M. R., C. W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 0 Z9 0 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2013 VL 8 IS 6 AR e66973 DI 10.1371/journal.pone.0066973 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178DN UT WOS:000321424400060 PM 23840566 ER PT J AU Liu, H Rose, ME Miller, TM Li, WJ Shinde, SN Pickrell, AM Poloyac, SM Graham, SH Hickey, RW AF Liu, Hao Rose, Marie E. Miller, Tricia M. Li, Wenjin Shinde, Sunita N. Pickrell, Alicia M. Poloyac, Samuel M. Graham, Steven H. Hickey, Robert W. TI COX2-derived primary and cyclopentenone prostaglandins are increased after asphyxial cardiac arrest SO BRAIN RESEARCH LA English DT Article DE Prostaglandin; Cyclopentenone; Hypoxic-ischemia; Cardiac arrest; Cyclooxygenase ID CEREBRAL-ISCHEMIA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); BRAIN-INJURY; PPAR-GAMMA; CYCLOOXYGENASE-2; INHIBITION; ELECTROPHILE; MECHANISMS; RAT AB Background: Cyclopentenone prostaglandins have been identified as potential neurotoxic agents in the setting of hypoxia-ischemia. Cyclooxygenase-2 (COX-2), the upstream enzyme responsible for prostaglandin production is upregulated following hypoxic-ischemic brain injury. However, the temporal production and concentration of cyclopentenone prostaglandins has not been described following global brain ischemia. Methods Global brain ischemia was induced in rats by asphyxial cardiac arrest (ACA) followed by resuscitation. Rats were sacrificed between 24 h and 7 days following resuscitation and their brains removed. Western blot, immunohistochemistry, and mass spectroscopy were performed. A cohort of rats was pretreated with the COX-2 inhibitor SC58125. Results COX-2 is induced in hippocampus at 24 h following ACA. Multiple prostaglandins, including cyclopentenone prostaglandin species, are increased in hippocampus as 24 h following ACA. Prostaglandin and cyclopentenone prostaglandin concentrations are returned to baseline at 3 and 7 days post-ischemia. The COX-2 inhibitor SC58125 completely abrogates the post-ischemic increase in prostaglandins and cyclopentenone prostaglandins. Conclusions Prostaglandins, including cyclopentenone prostaglandins, are increased in ischemic brain, peak at 24 h and can be attenuated by the COX-2 inhibitor SC58125. These data establish the presence of potentially neurotoxic cyclopentenone prostaglandins in post-ischemic brains, thus identifying a target and therapeutic window for neuroprotective therapies. (C) 2013 Elsevier B.V. All rights reserved. C1 [Liu, Hao; Rose, Marie E.; Li, Wenjin; Graham, Steven H.] VA Pittsburgh Healthcare, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA USA. [Liu, Hao; Rose, Marie E.; Li, Wenjin; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Miller, Tricia M.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Shinde, Sunita N.; Pickrell, Alicia M.; Hickey, Robert W.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA. RP Hickey, RW (reprint author), Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA. EM Robert.hickey@chp.edu FU National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [5UL1 RR024153-05]; NIH Roadmap for Medical Research; [R21HD058846]; [R01NS37459] FX We would like to thank Li Wang, MS for her help with statistical support. Supported by R21HD058846 (RWH), R01NS37459 (SHG). Statistical support was provided by the Clinical Translational Science Institute of the University of Pittsburgh: Grant number 5UL1 RR024153-05 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 27 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 26 PY 2013 VL 1519 BP 71 EP 77 DI 10.1016/j.brainres.2013.04.029 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 178US UT WOS:000321473500008 PM 23624225 ER PT J AU Shah, NJ Hyder, MN Moskowitz, JS Quadir, MA Morton, SW Seeherman, HJ Padera, RF Spector, M Hammond, PT AF Shah, Nisarg J. Hyder, Md. Nasim Moskowitz, Joshua S. Quadir, Mohiuddin A. Morton, Stephen W. Seeherman, Howard J. Padera, Robert F. Spector, Myron Hammond, Paula T. TI Surface-Mediated Bone Tissue Morphogenesis from Tunable Nanolayered Implant Coatings SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POLYELECTROLYTE MULTILAYER FILMS; LAYER-BY-LAYER; BIOMEDICAL APPLICATIONS; TITANIUM IMPLANTS; ELASTIC-MODULUS; REVISION; BMP-2; REGENERATION; PERFORMANCE; PROTEINS AB The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for more than half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein-2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(beta-amino ester), was essential for tissue regeneration, and in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. In vivo, the bone-implant interfacial tensile strength was significantly higher than standard bioactive bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure. C1 [Shah, Nisarg J.; Hyder, Md. Nasim; Moskowitz, Joshua S.; Quadir, Mohiuddin A.; Morton, Stephen W.; Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Morton, Stephen W.; Hammond, Paula T.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Seeherman, Howard J.] Restituo LLC, Cambridge, MA 02138 USA. [Padera, Robert F.; Spector, Myron] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Spector, Myron] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hammond, Paula T.] MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. RP Hammond, PT (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hammond@mit.edu FU NIH [R01 AG029601]; Institute for Soldier Nanotechnologies; U.S. Army Research Office [W911NF-07-D-0004]; Koch Institute at MIT; National Cancer Institute [P30 CA014051]; Natural Sciences and Engineering Research Council of Canada; NSF FX Funding: This work was supported by the NIH (R01 AG029601), in part by the Institute for Soldier Nanotechnologies (supported by the U.S. Army Research Office under contract W911NF-07-D-0004), and the Koch Institute (supported by the National Cancer Institute under grant P30 CA014051) at MIT. M.N.H. and S. W. M. acknowledge fellowships from the Natural Sciences and Engineering Research Council of Canada and the NSF, respectively. P. T. H. acknowledges the David H. Koch (1962) Chair Professorship in Engineering. NR 38 TC 19 Z9 19 U1 6 U2 65 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 JUN 26 PY 2013 VL 5 IS 191 AR 191ra83 DI 10.1126/scitranslmed.3005576 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 171KX UT WOS:000320928000004 PM 23803705 ER PT J AU Nishihara, R Lochhead, P Kuchiba, A Jung, S Yamauchi, M Liao, XY Imamura, Y Qian, ZR Morikawa, T Wang, ML Spiegelman, D Cho, E Giovannucci, E Fuchs, CS Chan, AT Ogino, S AF Nishihara, Reiko Lochhead, Paul Kuchiba, Aya Jung, Seungyoun Yamauchi, Mai Liao, Xiaoyun Imamura, Yu Qian, Zhi Rong Morikawa, Teppei Wang, Molin Spiegelman, Donna Cho, Eunyoung Giovannucci, Edward Fuchs, Charles S. Chan, Andrew T. Ogino, Shuji TI Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; COLON-CANCER; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; PIK3CA MUTATION; FAMILY-HISTORY; KRAS MUTATION; LIFE-STYLE; SURVIVAL AB Importance Aspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2), suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type neoplastic cells. Objective To examine whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation. Design and Setting We collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 1, 2006, for cancer incidence and until January 1, 2012, for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for colorectal carcinoma incidence according to BRAF mutation status. Main Outcomes and Measures Incidence of colorectal cancer cases according to tumor BRAF mutation status. Results Among 127 865 individuals, with 3 165 985 person-years of follow-up, we identified 1226 incident rectal and colon cancers with available molecular data. Compared with nonuse, regular aspirin use was associated with lower BRAF-wild-type cancer risk (multivariable HR, 0.73; 95% CI, 0.64 to 0.83; age-adjusted incidence rate difference [RD], -9.7; 95% CI, -12.6 to -6.7 per 100 000 person-years). This association was observed irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation. In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer (multivariable HR, 1.03; 95% CI, 0.76 to 1.38; age-adjusted, incidence RD, 0.7; 95% CI, -0.3 to 1.7 per 100 000 person-years: P for heterogeneity = .037, between BRAF-wild-type vs BRAF-mutated cancer risks). Compared with no aspirin use, aspirin use of more than 14 tablets per week was associated with a lower risk of BRAF-wild-type cancer (multivariable HR, 0.43; 95% CI, 0.25 to 0.75; age-adjusted incidence RD, -19.8; 95% CI, -26.3 to -13.3 per 100 000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (P for heterogeneity = .005). Conclusions and Relevance Regular aspirin use was associated with lower risk of BRAF-wild-type colorectal cancer but not with BRAF-mutated cancer risk. These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin. Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings. C1 [Nishihara, Reiko; Lochhead, Paul; Kuchiba, Aya; Yamauchi, Mai; Liao, Xiaoyun; Imamura, Yu; Qian, Zhi Rong; Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jung, Seungyoun; Wang, Molin; Spiegelman, Donna; Cho, Eunyoung; Giovannucci, Edward; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Nishihara, Reiko; Kuchiba, Aya; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wang, Molin; Spiegelman, Donna; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, Molin; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lochhead, Paul] Univ Aberdeen, Gastrointestinal Res Grp, Inst Med Sci, Aberdeen, Scotland. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org; shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA137178, K24 DK098311, R01 CA151993]; Bennett Family Fund for Targeted Therapies Research; National Colorectal Cancer Research Alliance; Harvard University FX This work was supported by grants P01 CA87969 to Dr Hankinson; P01 CA55075 and UM1 CA167552 to Dr Willett; P50 CA127003 to Dr Fuchs.; R01 CA137178 and K24 DK098311 to Dr Chan; and R01 CA151993 to Dr Ogino from the National Institutes of Health (NIH); the Bennett Family Fund for Targeted Therapies Research; and the National Colorectal Cancer Research Alliance. Dr Lochhead is a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Frank Knox Memorial Fellowship. Dr Chan is a Damon Runyon Clinical Investigator. NR 43 TC 65 Z9 66 U1 5 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 26 PY 2013 VL 309 IS 24 BP 2563 EP 2571 DI 10.1001/jama.2013.6599 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 170KD UT WOS:000320848100026 PM 23800934 ER PT J AU Joynt, KE Gawande, AA Orav, EJ Jha, AK AF Joynt, Karen E. Gawande, Atul A. Orav, E. John Jha, Ashish K. TI Contribution of Preventable Acute Care Spending to Total Spending for High-Cost Medicare Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; SENSITIVE CONDITIONS; HEALTH-CARE; HOSPITALIZATIONS; BENEFICIARIES; PROGRAMS AB Importance A small proportion of patients account for the majority of US health care spending, and understanding patterns of spending among this cohort is critical to reducing health care costs. The degree to which preventable acute care services account for spending among these patients is largely unknown. Objective To quantify preventable acute care services among high-cost Medicare patients. Design, Setting, and Participants We summed standardized costs for each inpatient and outpatient service contained in standard 5% Medicare files from 2009 and 2010 across the year for each patient in our sample, and defined those in the top decile of spending in 2010 as high-cost patients and those in the top decile in both 2009 and 2010 as persistently high-cost patients. We used standard algorithms to identify potentially preventable emergency department (ED) visits and acute care inpatient hospitalizations. A total of 1 114 469 Medicare fee-for-service beneficiaries aged 65 years or older were included. Main Outcomes and Measures Proportion of acute care hospital and ED costs deemed preventable among high-cost patients. Results The 10% of Medicare patients in the high-cost group were older, more often male, more often black, and had more comorbid illnesses than non-high-cost patients. In 2010, 32.9% (95% CI, 32.9%-32.9%) of total ED costs were incurred by high-cost patients. Based on validated algorithms, 41.0% (95% CI, 40.9%-41.0%) of these costs among high-cost patients were potentially preventable compared with 42.6% (95% CI, 42.6%-42.6%) among non-high-cost patients. High-cost patients accounted for 79.0% (95% CI, 79.0%-79.0%) of inpatient costs, 9.6% (95% CI, 9.6%-9.6%) of which were due to preventable hospitalizations; 16.8% (95% CI, 16.8%-16.8%) of costs within the non-high-cost group were due to preventable hospitalizations. Comparable proportions of ED spending (43.3%; 95% CI, 43.3%-43.3%) and inpatient spending (13.5%; 95% CI, 13.5%-13.5%) were preventable among persistently high-cost patients. Regions with high primary care physician supply had higher preventable spending for high-cost patients. Conclusions and Relevance Among a sample of patients in the top decile of Medicare spending in 2010, only a small percentage of costs appeared to be related to preventable ED visits and hospitalizations. The ability to lower costs for these patients through better outpatient care may be limited. C1 [Joynt, Karen E.; Gawande, Atul A.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Joynt, Karen E.; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org OI Gawande, Atul/0000-0002-1824-9176 FU Rx Foundation; West Wireless Foundation FX This study was funded by the Rx Foundation and the West Wireless Foundation. NR 21 TC 46 Z9 46 U1 1 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 26 PY 2013 VL 309 IS 24 BP 2572 EP 2578 DI 10.1001/jama.2013.7103 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 170KD UT WOS:000320848100027 PM 23797716 ER PT J AU Carroll, AE Frakt, AB AF Carroll, Aaron E. Frakt, Austin B. TI New Evidence Supports, Challenges, and Informs the Ambitions of Health Reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARE C1 [Carroll, Aaron E.] Indiana Univ Sch Med, Ctr Hlth Policy & Professionalism Res, Childrens Hlth Serv Res, Indianapolis, IN 46202 USA. [Frakt, Austin B.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Frakt, Austin B.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. [Frakt, Austin B.] Univ Penn, Leonard Davis Inst, Philadelphia, PA 19104 USA. RP Carroll, AE (reprint author), Indiana Univ Sch Med, Childrens Hlth Serv Res, 410 W 10th St,HITS Bldg,Ste 1020, Indianapolis, IN 46202 USA. EM aaecarro@iupui.edu NR 7 TC 1 Z9 1 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 26 PY 2013 VL 309 IS 24 BP 2600 EP 2601 DI 10.1001/jama.2013.7685 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 170KD UT WOS:000320848100032 PM 23797767 ER PT J AU Lee, TR Choi, M Kopacz, AM Yun, SH Liu, WK Decuzzi, P AF Lee, Tae-Rin Choi, Myunghwan Kopacz, Adrian M. Yun, Seok-Hyun Liu, Wing Kam Decuzzi, Paolo TI On the near-wall accumulation of injectable particles in the microcirculation: smaller is not better SO SCIENTIFIC REPORTS LA English DT Article ID FINITE-ELEMENT-METHOD; BLOOD-CELL AGGREGATION; MACROMOLECULAR THERAPEUTICS; TUMORITROPIC ACCUMULATION; SHEAR FLOWS; CANCER; DESIGN; TUMORS; SHAPE; SIZE AB Although most nanofabrication techniques can control nano/micro particle (NMP) size over a wide range, the majority of NMPs for biomedical applications exhibits a diameter of similar to 100 nm. Here, the vascular distribution of spherical particles, from 10 to 1,000 nm in diameter, is studied using intravital microscopy and computational modeling. Small NMPs (<= 100 nm) are observed to move with Red Blood Cells (RBCs), presenting an uniform radial distribution and limited near-wall accumulation. Larger NMPs tend to preferentially accumulate next to the vessel walls, in a size-dependent manner (similar to 70% for 1,000 nm NMPs). RBC-NMP geometrical interference only is responsible for this behavior. In a capillary flow, the effective radial dispersion coefficient of 1,000 nm particles is similar to 3-fold larger than Brownian diffusion. This suggests that sub-micron particles could deposit within diseased vascular districts more efficiently than conventional nanoparticles. C1 [Lee, Tae-Rin; Decuzzi, Paolo] Methodist Hosp, Res Inst, Dept Translat Imaging, Houston, TX 77030 USA. [Lee, Tae-Rin; Decuzzi, Paolo] Methodist Hosp, Res Inst, Dept Nanomed, Houston, TX 77030 USA. [Lee, Tae-Rin; Kopacz, Adrian M.; Liu, Wing Kam] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA. [Choi, Myunghwan; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Choi, Myunghwan; Yun, Seok-Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, Wing Kam] Sungkyunkwan Univ, Sch Mech Engn, Suwon, Kyonggi Do, South Korea. [Liu, Wing Kam] King Abdulaziz Univ, Distinguished Scientists Program Comm, Jeddah 21413, Saudi Arabia. [Decuzzi, Paolo] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. RP Liu, WK (reprint author), Northwestern Univ, Dept Mech Engn, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM liu@northwestern.edu; pdecuzzi@tmhs.org RI Liu, Wing/B-7599-2009; Decuzzi, Paolo/F-1899-2016; OI Decuzzi, Paolo/0000-0001-6050-4188; Choi, Myunghwan/0000-0002-4235-7003 FU Cancer Prevention Research Institute of Texas [CPRIT RP110262]; U.S. National Institutes of Health [U54CA143837, U54CA151668]; Office of Science of the U.S. Department of Energy [DE-AC02-06CH11357]; World Class University Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [R33-10079]; [CMMI-0856492]; [CMMI-0856333] FX PD acknowledges partial support from the Cancer Prevention Research Institute of Texas through (grant CPRIT RP110262); the U.S. National Institutes of Health (grants U54CA143837 and U54CA151668). WKL acknowledges the support of CMMI-0856492 and CMMI-0856333 and this research used resources of the QUEST cluster at Northwestern University and the Argonne Leadership Computing Facility at Argonne National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-06CH11357. WKL also acknowledges the support of the World Class University Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (R33-10079). SHY acknowledges support from the U.S. National Institutes of Health (grant U54CA143837). NR 41 TC 29 Z9 29 U1 2 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUN 26 PY 2013 VL 3 AR 2079 DI 10.1038/srep02079 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171IQ UT WOS:000320919800001 PM 23801070 ER PT J AU Natasha, G Tan, A Farhatnia, Y Rajadas, J Hamblin, MR Khaw, PT Seifalian, AM AF Natasha, G. Tan, Aaron Farhatnia, Yasmin Rajadas, Jayakumar Hamblin, Michael R. Khaw, Peng T. Seifalian, Alexander M. TI Channelrhodopsins: visual regeneration and neural activation by a light switch SO NEW BIOTECHNOLOGY LA English DT Review ID RETINAL-PIGMENT EPITHELIUM; EMBRYONIC STEM-CELLS; IN-VIVO; GENE-TRANSFER; PHOTORECEPTOR DEGENERATION; RETINITIS-PIGMENTOSA; TRANSGENIC MICE; OPTICAL CONTROL; RCS RATS; MILLISECOND-TIMESCALE AB The advent of optogenetics provides a new direction for the field of neuroscience and biotechnology, serving both as a refined investigative tool and as potential cure for many medical conditions via genetic manipulation. Although still in its infancy, recent advances in optogenetics has made it possible to remotely manipulate in vivo cellular functions using light. Coined Nature Methods' 'Method of the Year' in 2010, the optogenetic toolbox has the potential to control cell, tissue and even animal behaviour. This optogenetic toolbox consists of light-sensitive proteins that are able to modulate membrane potential in response to light. Channelrhodopsins (ChR) are light-gated microbial ion channels, which were first described in green algae. ChR2 (a subset of ChR) is a seven transmembrane a helix protein, which evokes membrane depolarization and mediates an action potential upon photostimulation with blue (470 nm) light. By contrast to other seven-transmembrane proteins that require second messengers to open ion channels, ChR2 form ion channels themselves, allowing ultrafast depolarization (within 50 milliseconds of illumination). It has been shown that integration of ChR2 into various tissues of mice can activate neural circuits, control heart muscle contractions, and even restore breathing after spinal cord injury. More compellingly, a plethora of evidence has indicated that artificial expression of ChR2 in retinal ganglion cells can reinstate visual perception in mice with retinal degeneration. C1 [Natasha, G.; Tan, Aaron; Farhatnia, Yasmin; Seifalian, Alexander M.] UCL, UCL Div Surg & Intervent Sci, Ctr Nanotechnol & Regenerat Med, London, England. [Natasha, G.; Tan, Aaron] UCL, UCL Med Sch, London, England. [Rajadas, Jayakumar] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Biomat & Adv Drug Delivery Lab, Stanford, CA 94305 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Khaw, Peng T.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England. [Khaw, Peng T.] UCL, UCL Inst Ophthalmol, London, England. [Khaw, Peng T.] UCL, UCL Partners AHSC, London, England. [Seifalian, Alexander M.] Royal Free London NHS Fdn Trust, London, England. RP Seifalian, AM (reprint author), UCL, UCL Div Surg & Intervent Sci, Ctr Nanotechnol & Regenerat Med, London, England. EM a.seifalian@ucl.ac.uk RI Seifalian, Alexander/I-6028-2013; OI Seifalian, Alexander/0000-0002-1180-3322; G, Natasha/0000-0002-9262-4595; Hamblin, Michael/0000-0001-6431-4605 NR 90 TC 1 Z9 2 U1 4 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1871-6784 EI 1876-4347 J9 NEW BIOTECHNOL JI New Biotech. PD JUN 25 PY 2013 VL 30 IS 5 BP 461 EP 474 DI 10.1016/j.nbt.2013.04.007 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 181US UT WOS:000321695200006 ER PT J AU Truong, QA Hayden, D Woodard, PK Kirby, R Chou, ET Nagurney, JT Wiviott, SD Fleg, JL Schoenfeld, DA Udelson, JE Hoffmann, U AF Truong, Quynh A. Hayden, Douglas Woodard, Pamela K. Kirby, Ruth Chou, Eric T. Nagurney, John T. Wiviott, Stephen D. Fleg, Jerome L. Schoenfeld, David A. Udelson, James E. Hoffmann, Udo TI Sex Differences in the Effectiveness of Early Coronary Computed Tomographic Angiography Compared With Standard Emergency Department Evaluation for Acute Chest Pain The Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II Trial SO CIRCULATION LA English DT Article DE acute coronary syndrome; chest pain; emergency service, hospital; sex; tomography; x-ray computed ID AMERICAN-HEART-ASSOCIATION; CT ANGIOGRAPHY; ARTERY-DISEASE; CARDIOVASCULAR-RADIOLOGY; DIAGNOSTIC PERFORMANCE; CLINICAL-CARDIOLOGY; DOSE REDUCTION; RADIATION; RISK; INTERVENTION AB Background We evaluate sex-based differences in the effectiveness of early cardiac computed tomographic angiography (CCTA) and standard emergency department (ED) evaluation in patients with acute chest pain. Methods and Results In the Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II multicenter, controlled trial, we randomized 1000 patients (47% women) 40 to 74 years of age with symptoms suggestive of acute coronary syndrome to an early CCTA or standard ED evaluation. In this prespecified analysis, women in the CCTA arm had a greater reduction in length of stay, lower hospital admission rates, and lesser increased cumulative radiation dose than men in a comparison of ED strategies (P for interaction 0.02). Although women had lower acute coronary syndrome rates than men (3% versus 12%; P<0.0001), sex differences in length of stay persisted after adjustment for baseline differences, including acute coronary syndrome rate (P for interaction <0.03). Length of stay was similar between sexes with normal CCTA findings (P=0.11). There was no missed acute coronary syndrome for either sex. No difference was observed in major adverse cardiac events between sexes and ED strategies (P for interaction =0.39). Women had more normal CCTA examinations than men (58% versus 37%; P<0.0001), less obstructive coronary disease by CCTA (5% versus 17%; P=0.0001), but similar normalcy rates for functional testing (P=0.65). Men in the CCTA arm had the highest rate of invasive coronary angiography (18%), whereas women had comparable low 5% rates regardless of ED strategy. Conclusions This trial provides data supporting an early CCTA strategy as an attractive option in women presenting to the ED with symptoms suggestive of acute coronary syndrome. The findings may be explained by lower CAD prevalence and severity in women than men. C1 [Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Div Cardiol, Boston, MA 02114 USA. [Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Dept, Boston, MA 02114 USA. [Hayden, Douglas; Schoenfeld, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Kirby, Ruth; Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Chou, Eric T.] Kaiser Permanente Fontana Med Ctr, Fontana, CA USA. [Wiviott, Stephen D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. RP Truong, QA (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, 165 Cambridge St,Ste 400, Boston, MA 02114 USA. EM qtruong@partners.org FU National Institutes of Health/National Heart, Lung, and Blood Institute [U01HL092040, U01HL092022, K23HL098370, L30HL093896]; Qi Imaging; St. Jude Medical; American College of Radiology Imaging Network; Duke Clinical Research Institute FX The study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (U01HL092040 and U01HL092022). Dr Truong was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (K23HL098370 and L30HL093896).; Dr Truong receives grant support from Qi Imaging, St. Jude Medical, American College of Radiology Imaging Network, and Duke Clinical Research Institute. The other authors report no conflicts. NR 22 TC 9 Z9 9 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 25 PY 2013 VL 127 IS 25 BP 2494 EP 2502 DI 10.1161/CIRCULATIONAHA.113.001736 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171HU UT WOS:000320916900013 PM 23685743 ER PT J AU Bangalore, S Bhatt, DL AF Bangalore, Sripal Bhatt, Deepak L. TI Coronary Intravascular Ultrasound SO CIRCULATION LA English DT Article ID FRACTIONAL FLOW RESERVE; ARTERY-DISEASE; INTRACORONARY ULTRASOUND; MYOCARDIAL-INFARCTION; ANGIOGRAPHIC DETERMINATION; INTEROBSERVER VARIABILITY; STENOSIS; ATHEROSCLEROSIS; SAFETY; ANGIOPLASTY C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@post.harvard.edu OI Bangalore, Sripal/0000-0001-9485-0652 FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX Dr Bhatt discloses the following relationships - Advisory Board: Elsevier Practice Update Cardiology, Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); Other: Senior Associate Editor, Journal of Invasive Cardiology; Data Monitoring Committees: Duke Clinical Research Institute, Population Health Research Institute; Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Dr Bangalore reports no conflicts. NR 34 TC 3 Z9 3 U1 1 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 JUN 25 PY 2013 VL 127 IS 25 BP E868 EP E874 DI 10.1161/CIRCULATIONAHA.113.003534 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171HU UT WOS:000320916900002 PM 23797744 ER PT J AU Woodell, A Coughlin, B Kunchithapautham, K Casey, S Williamson, T Ferrell, WD Atkinson, C Jones, BW Rohrer, B AF Woodell, Alex Coughlin, Beth Kunchithapautham, Kannan Casey, Sarah Williamson, Tucker Ferrell, W. Drew Atkinson, Carl Jones, Bryan W. Rohrer, Baerbel TI Alternative Complement Pathway Deficiency Ameliorates Chronic Smoke-Induced Functional and Morphological Ocular Injury SO PLOS ONE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM; CAUSES OXIDATIVE DAMAGE; MACULAR DEGENERATION; CIGARETTE-SMOKE; BRUCHS MEMBRANE; FACTOR-B; CHOROIDAL NEOVASCULARIZATION; MITOCHONDRIAL DYSFUNCTION AB Background: Age-related macular degeneration (AMD), a complex disease involving genetic variants and environmental insults, is among the leading causes of blindness in Western populations. Genetic and histologic evidence implicate the complement system in AMD pathogenesis; and smoking is the major environmental risk factor associated with increased disease risk. Although previous studies have demonstrated that cigarette smoke exposure (CE) causes retinal pigment epithelium (RPE) defects in mice, and smoking leads to complement activation in patients, it is unknown whether complement activation is causative in the development of CE pathology; and if so, which complement pathway is required. Methods: Mice were exposed to cigarette smoke or clean, filtered air for 6 months. The effects of CE were analyzed in wildtype (WT) mice or mice without a functional complement alternative pathway (AP; CFB-/-) using molecular, histological, electrophysiological, and behavioral outcomes. Results: CE in WT mice exhibited a significant reduction in function of both rods and cones as determined by electroretinography and contrast sensitivity measurements, concomitant with a thinning of the nuclear layers as measured by SD-OCT imaging and histology. Gene expression analyses suggested that alterations in both photoreceptors and RPE/choroid might contribute to the observed loss of function, and visualization of complement C3d deposition implies the RPE/Bruch's membrane (BrM) complex as the target of AP activity. RPE/BrM alterations include an increase in mitochondrial size concomitant with an apical shift in mitochondrial distribution within the RPE and a thickening of BrM. CFB-/- mice were protected from developing these CE-mediated alterations. Conclusions: Taken together, these findings provide clear evidence that ocular pathology generated in CE mice is dependent on complement activation and requires the AP. Identifying animal models with RPE/BrM damage and verifying which aspects of pathology are dependent upon complement activation is essential for developing novel complement-based treatment approaches for the treatment of AMD. C1 [Woodell, Alex; Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA. [Coughlin, Beth; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Casey, Sarah; Williamson, Tucker; Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Ferrell, W. Drew; Jones, Bryan W.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA. EM rohrer@musc.edu OI Jones, Bryan/0000-0001-5527-6643 FU Department for Veterans Affairs [RX000444]; Research to Prevent Blindness (RPB), New York, NY; Foundation Fighting Blindness, Columbia, MD; NIH NHLBI [RO1 091944]; NIH [C06RR015455] FX This work was supported in part by a Department for Veterans Affairs merit award RX000444 (BR), unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY and Foundation Fighting Blindness, Columbia, MD, and NIH NHLBI RO1 091944 (CA). Animal studies were conducted in a facility constructed with support from the NIH (C06RR015455). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 93 TC 9 Z9 9 U1 0 U2 0 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 JUN 25 PY 2013 VL 8 IS 6 AR e67894 DI 10.1371/journal.pone.0067894 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175IB UT WOS:000321223000122 PM 23825688 ER PT J AU Kaymakcalan, MD Je, Y Sonpavde, G Galsky, M Nguyen, PL Heng, DYC Richards, CJ Choueiri, TK AF Kaymakcalan, M. D. Je, Y. Sonpavde, G. Galsky, M. Nguyen, P. L. Heng, D. Y. C. Richards, C. J. Choueiri, T. K. TI Risk of infections in renal cell carcinoma (RCC) and non-RCC patients treated with mammalian target of rapamycin inhibitors SO BRITISH JOURNAL OF CANCER LA English DT Article DE renal cell carcinoma; mTOR inhibitors; temsirolimus; everolimus; infections; meta-analysis ID CANCER-TREATMENT-GROUP; PHASE-III TRIAL; NEUROENDOCRINE TUMORS; INTERFERON-ALPHA; CLINICAL-TRIALS; EVEROLIMUS; TEMSIROLIMUS; PLACEBO; THERAPY; METAANALYSIS AB Background: Mammalian target of rapamycin (mTOR) inhibitors are used in a variety of malignancies. Infections have been reported with these drugs. We performed an up-to-date meta-analysis to further characterise the risk of infections in cancer patients treated with these agents. Methods: Pubmed and oncology conferences' proceedings were searched for studies from January 1966 to June 2012. Studies were limited to phase II and III randomised controlled trials (RCTs) of everolimus or temsirolimus reporting on cancer patients with adequate safety profiles. Summary incidences, relative risks (RRs), and 95% confidence intervals (CIs) were calculated. Results: A total of 3180 patients were included. The incidence of all-grade and high-grade infections due to mTOR inhibitors was 33.1% (95% CI, 24.5-43.0%) and 5.6% (95% CI, 3.8-8.3%), respectively. Compared with controls, the RR of all-grade and high-grade infections due to mTOR inhibitors was 2.00 (95% CI, 1.76-2.28, P<0.001) and 2.60 (95% CI, 1.54-4.41, P<0.001), respectively. Subgroup analysis found no difference in incidences or risks between everolimus and temsirolimus or between different tumour types (renal cell carcinoma (RCC) vs non-RCC). Infections included respiratory tract (61.7%), genitourinary (29.4%), skin/soft tissue (4.2%), and others (4.9%). Conclusion: Treatment with mTOR inhibitors is associated with a significant increase in risk of infections. Close monitoring for any signs of infections is warranted. C1 [Kaymakcalan, M. D.; Nguyen, P. L.] Dana Farber Canc Inst, Dept Pharm, Boston, MA 02215 USA. [Je, Y.] Kyung Hee Univ, Dept Food & Nutr, Seoul 130701, South Korea. [Sonpavde, G.] UAB, Ctr Comprehens Canc, Dept Med Oncol, Birmingham, AL 35205 USA. [Galsky, M.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Heng, D. Y. C.] Tom Baker Canc Clin, Dept Med Oncol, Calgary, AB T2N 4N2, Canada. [Heng, D. Y. C.] Univ Alberta, Calgary, AB T2N 4N2, Canada. [Richards, C. J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Richards, C. J.; Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Choueiri, T. K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Toni_Choueiri@dfci.harvard.edu FU Trust Family Research Fund for Kidney Cancer FX This study was supported by Trust Family Research Fund for Kidney Cancer. NR 40 TC 13 Z9 13 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 25 PY 2013 VL 108 IS 12 BP 2478 EP 2484 DI 10.1038/bjc.2013.278 PG 7 WC Oncology SC Oncology GA 172LD UT WOS:000321003700010 PM 23736025 ER PT J AU Salanitro, AH Kripalani, S Resnic, J Mueller, SK Wetterneck, TB Haynes, KT Stein, J Kaboli, PJ Labonville, S Etchells, E Cobaugh, DJ Hanson, D Greenwald, JL Williams, MV Schnipper, JL AF Salanitro, Amanda H. Kripalani, Sunil Resnic, JoAnne Mueller, Stephanie K. Wetterneck, Tosha B. Haynes, Katherine Taylor Stein, Jason Kaboli, Peter J. Labonville, Stephanie Etchells, Edward Cobaugh, Daniel J. Hanson, David Greenwald, Jeffrey L. Williams, Mark V. Schnipper, Jeffrey L. TI Rationale and design of the Multicenter Medication Reconciliation Quality Improvement Study (MARQUIS) SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Medication reconciliation; Hospitalization; Quality improvement; Care transitions ID PATIENT SAFETY RESEARCH; ADVERSE DRUG EVENTS; HEALTH-CARE; EPISTEMOLOGY; FRAMEWORK; DISCREPANCIES; ADMISSION; ERRORS; TRIAL; INTERVENTIONS AB Background: Unresolved medication discrepancies during hospitalization can contribute to adverse drug events, resulting in patient harm. Discrepancies can be reduced by performing medication reconciliation; however, effective implementation of medication reconciliation has proven to be challenging. The goals of the Multi-Center Medication Reconciliation Quality Improvement Study (MARQUIS) are to operationalize best practices for inpatient medication reconciliation, test their effect on potentially harmful unintentional medication discrepancies, and understand barriers and facilitators of successful implementation. Methods: Six U. S. hospitals are participating in this quality improvement mentored implementation study. Each hospital has collected baseline data on the primary outcome: the number of potentially harmful unintentional medication discrepancies per patient, as determined by a trained on-site pharmacist taking a "gold standard" medication history. With the guidance of their mentors, each site has also begun to implement one or more of 11 best practices to improve medication reconciliation. To understand the effect of the implemented interventions on hospital staff and culture, we are performing mixed methods program evaluation including surveys, interviews, and focus groups of front line staff and hospital leaders. Discussion: At baseline the number of unintentional medication discrepancies in admission and discharge orders per patient varies by site from 2.35 to 4.67 (mean=3.35). Most discrepancies are due to history errors (mean 2.12 per patient) as opposed to reconciliation errors (mean 1.23 per patient). Potentially harmful medication discrepancies averages 0.45 per patient and varies by site from 0.13 to 0.82 per patient. We discuss several barriers to implementation encountered thus far. In the end, we anticipate that MARQUIS tools and lessons learned have the potential to decrease medication discrepancies and improve patient outcomes. C1 [Salanitro, Amanda H.] VA Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. [Salanitro, Amanda H.; Kripalani, Sunil] Vanderbilt Univ, Dept Med, Sect Hosp Med, Div Gen Internal Med & Publ Hlth, Nashville, TN USA. [Resnic, JoAnne] Soc Hosp Med, Ctr Hosp Innovat & Improvement, Philadelphia, PA USA. [Mueller, Stephanie K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Mueller, Stephanie K.; Greenwald, Jeffrey L.; Schnipper, Jeffrey L.] Harvard Univ, Sch Med, Boston, MA USA. [Wetterneck, Tosha B.] UW Madison, Ctr Qual & Prod Improvement, Madison, WI USA. [Wetterneck, Tosha B.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Haynes, Katherine Taylor] Vanderbilt Univ, Peabody Coll, Nashville, TN 37203 USA. [Stein, Jason] Emory Univ, Dept Med, Qual Program, Atlanta, GA 30322 USA. [Kaboli, Peter J.] Univ Iowa, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City VA Healthcare Syst, Carver Coll Med, Iowa City, IA USA. [Labonville, Stephanie] Brigham & Womens Hosp, Dept Pharm Serv, Boston, MA 02115 USA. [Etchells, Edward] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Cobaugh, Daniel J.] Amer Soc Hlth Syst Pharmacists Res & Educ Fdn, Bethesda, MD USA. [Hanson, David] Amer Assoc Crit Care Nurses, Aliso Viejo, CA USA. [Greenwald, Jeffrey L.] Massachusetts Gen Hosp, Inpatient Clinician Educ Serv, Boston, MA 02114 USA. [Williams, Mark V.] Northwestern Univ, Div Hosp Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, BWH Hospitalist Serv, Boston, MA 02115 USA. RP Salanitro, AH (reprint author), VA Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. EM Amanda.Salanitro@Vanderbilt.Edu FU Agency for Healthcare Research and Quality (AHRQ) [R18HS019598-01] FX Grant support: Agency for Healthcare Research and Quality (AHRQ) R18HS019598-01 to the Society of Hospital Medicine (SHM) with Dr. Schnipper as principle investigator. NR 34 TC 9 Z9 9 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JUN 25 PY 2013 VL 13 AR 230 DI 10.1186/1472-6963-13-230 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 174JQ UT WOS:000321151900001 PM 23800355 ER PT J AU Wessler, JD Grip, LT Mendell, J Giugliano, RP AF Wessler, Jeffrey D. Grip, Laura T. Mendell, Jeanne Giugliano, Robert P. TI The P-Glycoprotein Transport System and Cardiovascular Drugs SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE adverse drug event(s); drug-drug interaction; P-glycoprotein; pharmacology ID FACTOR XA INHIBITOR; MULTIDRUG-RESISTANCE; IN-VITRO; ORAL ANTICOAGULANTS; ATRIAL-FIBRILLATION; CLINICAL-RELEVANCE; CARDIAC GLYCOSIDE; HEALTHY-SUBJECTS; DIGOXIN; CLOPIDOGREL AB Permeability glycoprotein (P-gp) mediates the export of drugs from cells located in the small intestine, blood-brain barrier, hepatocytes, and kidney proximal tubule, serving a protective function for the body against foreign substances. Intestinal absorption, biliary excretion, and urinary excretion of P-gp substrates can therefore be altered by either the inhibition or induction of P-gp. A wide spectrum of drugs, such as anticancer agents and steroids, are known P-gp substrates and/or inhibitors, and many cardiovascular drugs have recently been observed to have clinically relevant interactions as well. We review the interactions among commonly prescribed cardiovascular drugs that are P-gp substrates and observe interactions involving P-gp that may be relevant to clinical practice. Cardiovascular drugs with narrow therapeutic indexes (e.g., antiarrhythmic agents, anticoagulant agents) have demonstrated large increases in concentrations when coadministered with potent P-gp inhibitors, thus increasing the risk for drug toxicity. Therefore, dose adjustment or use of alternative agents should be considered when strong P-gp-mediated drug-drug interactions are present. Finally, interactions between novel drugs and known P-gp inhibitors are now being systematically evaluated during drug development, and recommended guidelines for the administration of P-gp substrate drugs will be expanded. (C) 2013 by the American College of Cardiology Foundation C1 [Wessler, Jeffrey D.] Harvard Univ, Sch Med, Boston, MA USA. [Grip, Laura T.; Giugliano, Robert P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,TIMI Study Grp, Boston, MA USA. [Mendell, Jeanne] Daiichi Sankyo Pharma Dev, Edison, NJ USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Daiichi Sankyo FX The ENGAGE AF-TIMI 48 trial is funded by Daiichi Sankyo. Dr. Mendell is an employee of and has stock options with Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 52 TC 57 Z9 59 U1 2 U2 28 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 JUN 25 PY 2013 VL 61 IS 25 BP 2495 EP 2502 DI 10.1016/j.jacc.2013.02.058 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167AO UT WOS:000320602700001 PM 23563132 ER PT J AU Jung, M AF Jung, Minsoo TI Sexual Behavior and Condom Use among Gay Men, Female Sex Workers, and Their Customers: Evidence from South Korea SO PLOS ONE LA English DT Article ID RISK BEHAVIOR; DETERMINANTS; VIETNAM; WOMEN AB Background: Despite the significance for sexually transmitted diseases (STD) control in East Asia, few studies have examined the relationship between high-risk sexual behavior and condom use. We investigated how three sexually vulnerable groups for STDs show differences in condom use behaviors (CUBs) depending on their STD infection. Methods: The source of data came from the National Survey for STD Prevalence Rate and Sexual Behavior of the High-Risk Sexual Community. The effects of behavioral determinants on CUBs were estimated by using path analysis models. An 11-item questionnaire assessing subjects' health risk behaviors, sexual beliefs, sexual risk behaviors, and condom use. Results: Condom use was higher for men who have sex with men (MSM; n = 108) when they were bisexuals and had high self-efficacy, for Johns (Johns; n = 118) when they had experience of STD infection, and for female sex workers (FSWs; n = 1,083) when they had high self-efficacy, did not engage in drunken sex, and were anxious about infection. Regardless of whether they were infected with STDs, FSWs always used condom when they had high sexual beliefs. On the contrary, Johns exhibited a negative relationship between sexual risk behavior and condom use when they had experience of STD infection. The variable commonly significant to all three groups was the number of sex partners; but it exhibited a positive relationship with MSMs and Johns, and a negative one with FSWs. Conclusions: CUBs were related to sexual beliefs as well as sexual risk behavior. At the same time, the experience of STD infection mediated the relationship between the two. Therefore, we need to draw social attention to promote safer sex among STD-vulnerable groups. C1 [Jung, Minsoo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. RP Jung, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM minsoo_jung@dfci.harvard.edu OI Jung, Minsoo/0000-0003-3317-6507 FU National Research Foundation of Korea; Korean Government [NRF-2007-E00049-00] FX This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2007-E00049-00). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 5 Z9 5 U1 0 U2 5 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 JUN 24 PY 2013 VL 8 IS 6 AR e66867 DI 10.1371/journal.pone.0066867 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182JP UT WOS:000321738400072 PM 23950786 ER PT J AU Simon, SR Keohane, CA Amato, M Coffey, M Cadet, B Zimlichman, E Bates, DW AF Simon, Steven R. Keohane, Carol A. Amato, Mary Coffey, Michael Cadet, Bismarck Zimlichman, Eyal Bates, David W. TI Lessons learned from implementation of computerized provider order entry in 5 community hospitals: a qualitative study SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Quality of care; Clinical decision support; Meaningful use; Transformation ID HEALTH INFORMATION-TECHNOLOGY; ADOPTION; SYSTEMS; IMPACT; CARE; CONSEQUENCES; INNOVATIONS AB Background: Computerized Provider Order Entry (CPOE) can improve patient safety, quality and efficiency, but hospitals face a host of barriers to adopting CPOE, ranging from resistance among physicians to the cost of the systems. In response to the incentives for meaningful use of health information technology and other market forces, hospitals in the United States are increasingly moving toward the adoption of CPOE. The purpose of this study was to characterize the experiences of hospitals that have successfully implemented CPOE. Methods: We used a qualitative approach to observe clinical activities and capture the experiences of physicians, nurses, pharmacists and administrators at five community hospitals in Massachusetts (USA) that adopted CPOE in the past few years. We conducted formal, structured observations of care processes in diverse inpatient settings within each of the hospitals and completed in-depth, semi-structured interviews with clinicians and staff by telephone. After transcribing the audiorecorded interviews, we analyzed the content of the transcripts iteratively, guided by principles of the Immersion and Crystallization analytic approach. Our objective was to identify attitudes, behaviors and experiences that would constitute useful lessons for other hospitals embarking on CPOE implementation. Results: Analysis of observations and interviews resulted in findings about the CPOE implementation process in five domains: governance, preparation, support, perceptions and consequences. Successful institutions implemented clear organizational decision-making mechanisms that involved clinicians (governance). They anticipated the need for education and training of a wide range of users (preparation). These hospitals deployed ample human resources for live, in-person training and support during implementation. Successful implementation hinged on the ability of clinical leaders to address and manage perceptions and the fear of change. Implementation proceeded smoothly when institutions identified and anticipated the consequences of the change. Conclusions: The lessons learned in the five domains identified in this study may be useful for other community hospitals embarking on CPOE adoption. C1 [Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Simon, Steven R.; Keohane, Carol A.; Amato, Mary; Zimlichman, Eyal; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amato, Mary] Massachusetts Coll Pharm & Hlth Sci Boston, Boston, MA USA. [Coffey, Michael] North Shore Phys Grp, Saugus, MA USA. [Cadet, Bismarck] Winchester Hosp, Winchester, MA USA. RP Simon, SR (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM Steven.simon2@va.gov FU Rx Foundation; Commonwealth Fund FX The Rx Foundation and Commonwealth Fund supported the study. They commented on its design, but were not involved in data collection, data management, analysis, interpretation, or writing of the manuscript. The authors thank Mr. Max Stewart for editorial assistance. NR 29 TC 13 Z9 13 U1 4 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUN 24 PY 2013 VL 13 AR 67 DI 10.1186/1472-6947-13-67 PG 10 WC Medical Informatics SC Medical Informatics GA 172JD UT WOS:000320998100001 PM 23800211 ER PT J AU Toteberg-Harms, M Hanson, JVM Funk, J AF Toeteberg-Harms, Marc Hanson, James V. M. Funk, Jens TI Cataract Surgery combined with excimer laser trabeculotomy to lower intraocular pressure: effectiveness dependent on preoperative IOP SO BMC OPHTHALMOLOGY LA English DT Article DE Cataract; Cataract surgery; Extracapsular cataract extraction; Phacoemulsification; Glaucoma; Glaucoma surgery; Excimer laser trabeculotomy; Excimer laser trabeculostomy; Trabecular meshwork; Primary open angle glaucoma; Ocular hypertension ID CHAMBER LENS IMPLANTATION; NORMAL-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; TERM-FOLLOW-UP; VISUAL-ACUITY; AB-INTERNO; 308 NM; PHACOEMULSIFICATION; TRABECULECTOMY; PROGRESSION AB Background: Cataract surgery combined with excimer laser trabeculotomy (phaco-ELT) can reduce intraocular pressure (IOP). The aim of this study was to evaluate the effect of phaco-ELT on IOP in patients as a function of preoperative IOP. Methods: Patients with open-angle glacuoma or ocular hypertension who received phaco-ELT between 01/2008 and 10/2009 were included. Patients were assigned based on preoperative IOP either to the study group (<= 21 mmHg) or control group (>21 mmHg) in this IRB-approved, prospective, consecutive case series. Visual Acuity, IOP, and number of anti-glaucoma drugs (AGD) were recorded at baseline and 12 months after phaco-ELT. Any postoperative complications were also recorded. Results: 64 eyes of 64 patients (76.5 +/- 9.4 years) were included. Baseline IOP was 19.8 +/- 5.3 mmHg (AGD 2.4 +/- 1.1) for all eyes, 16.5 +/- 2.9 mmHg (AGD 2.5 +/- 1.0) for the study group, and 25.8 +/- 2.9 mmHg (AGD 2.2 +/- 1.4) for the control group. Across the two groups, IOP was reduced by 4.5 +/- 5.9 mmHg (-23.0%, p < 0.001) and AGD by 0.9 +/- 1.5 (-38.9%, p < 0.001). For the study group IOP was reduced by 1.9 +/- 4.4 mmHg (-11. 5 %, p = 0.012) and AGD by 1.1 +/- 1.4 (-42.9%, p < 0.001), and for the control group by 9.5 +/- 5.4 mmHg (-36.6%, p < 0.001) and AGD by 0.7 +/- 1.6 (-29.5%, p = 0.085). There were no serious postoperative complications such as endophthalmitis, significant hyphema, or a severe fibrinous reaction of the anterior chamber. Conclusions: IOP remained significantly reduced from baseline 12 months after phaco-ELT regardless of preoperative IOP levels, with no major complications. The IOP reduction remained constant over the entire follow-up. Hence, phaco-ELT can be considered in glaucoma and ocular hypertensive patients whenever cataract surgery is performed, in order to further reduce IOP or to reduce the requirement for IOP-reducing medications. C1 [Toeteberg-Harms, Marc] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Toeteberg-Harms, Marc; Hanson, James V. M.; Funk, Jens] Univ Zurich Hosp, Dept Ophthalmol, CH-8091 Zurich, Switzerland. RP Toteberg-Harms, M (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM MarcToeteberg@aol.com RI Toteberg-Harms, Marc/J-4954-2013 OI Toteberg-Harms, Marc/0000-0002-2134-1336 NR 41 TC 2 Z9 3 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD JUN 24 PY 2013 VL 13 AR UNSP 24 DI 10.1186/1471-2415-13-24 PG 9 WC Ophthalmology SC Ophthalmology GA 175DC UT WOS:000321209000001 PM 23799932 ER PT J AU Stickrath, C Noble, M Prochazka, A Anderson, M Griffiths, M Manheim, J Sillau, S Aagaard, E AF Stickrath, Chad Noble, Melissa Prochazka, Allan Anderson, Mel Griffiths, Megan Manheim, Jonathan Sillau, Stefan Aagaard, Eva TI Attending Rounds in the Current Era What Is and Is Not Happening SO JAMA INTERNAL MEDICINE LA English DT Article ID DUTY-HOUR REGULATIONS; INTERNAL-MEDICINE; EDUCATION; BEDSIDE; FACULTY; MODEL AB Importance: General medicine rounds by attending physicians provide the foundation for patient care and education in teaching hospitals. However, the detailed activities of these rounds in the current era are not well characterized. Objective: To describe the characteristics of attending rounds for internal medicine inpatients in a large teaching hospital system. Design: A cross-sectional observational study of attending rounds in internal medicine. Rounds were observed directly by research assistants. Setting: Four teaching hospitals associated with a large public medical school. Participants: Fifty-six attending physicians and 279 trainees treating 807 general medicine inpatients. Main Outcomes and Measures: Duration and location of rounds, composition of teams, and frequency of 19 potential activities during rounds. Results: We observed 90 days of rounds. A typical rounding day consisted of 1 attending with 3 trainees visiting a median of 9 (range, 2-18 [SD, 2.9]) patients for a median of 2.0 hours (range, 25-241 [SD, 2.7] minutes). On rounds, teams most frequently discussed the patient care plan (96.7% of patients), reviewed diagnostic studies (90.7%), communicated with patients (73.4%), and discussed the medication list (68.8%). Teams infrequently discussed invasive lines or tubes (9.3%) or nursing notes (6.2%) and rarely communicated with nurses (12.0%) or taught physical examination skills (14.6%), evidence-based medicine topics (7.2%), or learner-identified topics (3.2%). Many commonly performed activities occurred infrequently at the bedside. Conclusions and Relevance: Most activities on attending rounds do not take place at the bedside. The teams discuss patient care plans and test results most of the time but fail to include many items that may be of significant value, including specific aspects of patient care, interprofessional communication, and learner-centered education. Future studies are needed to further assess the implications of these observations. C1 [Stickrath, Chad; Prochazka, Allan; Anderson, Mel; Manheim, Jonathan; Sillau, Stefan; Aagaard, Eva] Univ Colorado, Sch Med, Dept Med, Denver, CO 80220 USA. [Stickrath, Chad; Prochazka, Allan; Anderson, Mel] Denver Vet Affairs Med Ctr, Med Serv, Denver, CO USA. [Noble, Melissa; Griffiths, Megan] Univ Colorado, Sch Med, Denver, CO 80220 USA. RP Stickrath, C (reprint author), Univ Colorado, Sch Med, Med Serv, Denver VA Med Ctr, 1055 Clermont St,Box 111, Denver, CO 80220 USA. EM Chad.stickrath@va.gov FU University of Colorado Academy of Medical Educators Rymer Family Endowment Grant FX This study was supported by the University of Colorado Academy of Medical Educators Rymer Family Endowment Grant. NR 20 TC 22 Z9 22 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 24 PY 2013 VL 173 IS 12 BP 1084 EP 1089 DI 10.1001/jamainternmed.2013.6041 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 170OE UT WOS:000320861700012 PM 23649040 ER PT J AU Schwartz, JAT Pearson, SD AF Schwartz, Jennifer A. T. Pearson, Steven D. TI Cost Consideration in the Clinical Guidance Documents of Physician Specialty Societies in the United States SO JAMA INTERNAL MEDICINE LA English DT Article ID PRACTICE GUIDELINES; AMERICAN-COLLEGE; TASK-FORCE; HEART-ASSOCIATION; MEDICINE; ALLOCATION; CARDIOLOGY; ISSUES; CARE AB Importance: Despite increasing concerns regarding the cost of health care, the consideration of costs in the development of clinical guidance documents by physician specialty societies has received little analysis. Objective: To evaluate the approach to consideration of cost in publicly available clinical guidance documents and methodological statements produced between 2008 and 2012 by the 30 largest US physician specialty societies. Design: Qualitative document review. Main Outcomes and Measures: Whether costs are considered in clinical guidance development, mechanism of cost consideration, and the way that cost issues were used in support of specific clinical practice recommendations. Results: Methodological statements for clinical guidance documents indicated that 17 of 30 physician societies (57%) explicitly integrated costs, 4 (13%) implicitly considered costs, 3 (10%) intentionally excluded costs, and 6 (20%) made no mention. Of the 17 societies that explicitly integrated costs, 9 (53%) consistently used a formal system in which the strength of recommendation was influenced in part by costs, whereas 8 (47%) were inconsistent in their approach or failed to mention the exact mechanism for considering costs. Among the 138 specific recommendations in these guidance documents that included cost as part of the rationale, the most common form of recommendation (50 [36%]) encouraged the use of a specific medical service because of equal effectiveness and lower cost. Conclusions and Relevance: Slightly more than half of the largest US physician societies explicitly consider costs in developing their clinical guidance documents; among these, approximately half use an explicit mechanism for integrating costs into the strength of recommendations. Many societies remain vague in their approach. Physician specialty societies should demonstrate greater transparency and rigor in their approach to cost consideration in documents meant to influence care decisions. C1 [Schwartz, Jennifer A. T.; Pearson, Steven D.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Inst Technol Assessment, Boston, MA 02114 USA. RP Pearson, SD (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov NR 39 TC 19 Z9 19 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 24 PY 2013 VL 173 IS 12 BP 1091 EP 1097 DI 10.1001/jamainternmed.2013.817 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 170OE UT WOS:000320861700014 PM 23649494 ER PT J AU Balboni, TA Balboni, M Enzinger, AC Gallivan, K Paulk, E Wright, A Steinhauser, K VanderWeele, TJ Prigerson, HG AF Balboni, Tracy A. Balboni, Michael Enzinger, Andrea C. Gallivan, Kathleen Paulk, Elizabeth Wright, Alexi Steinhauser, Karen VanderWeele, Tyler J. Prigerson, Holly G. TI Provision of Spiritual Support to Patients With Advanced Cancer by Religious Communities and Associations With Medical Care at the End of Life SO JAMA INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; TREATMENT PREFERENCES; ETHNIC-DIFFERENCES; NEAR-DEATH; PALLIATIVE CARE; PHYSICIANS; ACKNOWLEDGMENT; QUESTIONNAIRE; BENEFICIARIES; VALIDITY AB Importance: Previous studies report associations between medical utilization at the end-of-life (EoL) and religious coping and spiritual support from the medical team. However, the influence of clergy and religious communities on EoL outcomes is unclear. Objective: To determine whether spiritual support from religious communities influences terminally ill patients' medical care and quality of life (QoL) near death. Design, Setting, and Participants: A US-based, multisite cohort study of 343 patients with advanced cancer enrolled from September 2002 through August 2008 and followed up (median duration, 116 days) until death. Baseline interviews assessed support of patients' spiritual needs by religious communities. End-of-life medical care in the final week included the following: hospice, aggressive EoL measures (care in an intensive care unit [ICU], resuscitation, or ventilation), and ICU death. Main Outcomes and Measures: End-of-life QoL was assessed by caregiver ratings of patient QoL in the last week of life. Multivariable regression analyses were performed on EoL care outcomes in relation to religious community spiritual support, controlling for confounding variables, and were repeated among high religious coping and racial/ethnic minority patients. Results: Patients reporting high spiritual support from religious communities (43%) were less likely to receive hospice (adjusted odds ratio [AOR], 0.37; 95% CI, 0.20-0.70 [P=.002]), more likely to receive aggressive EoL measures (AOR, 2.62; 95% CI, 1.14-6.06 [P=.02]), and more likely to die in an ICU (AOR, 5.22; 95% CI, 1.71-15.60 [P=.004]). Risks of receiving aggressive EoL interventions and ICU deaths were greater among high religious coping (AOR, 11.02; 95% CI, 2.83-42.89 [P<.001]; and AOR, 22.02; 95% CI, 3.24-149.58 [P=.002]; respectively) and racial/ethnic minority patients (AOR, 8.03; 95% CI, 2.04-31.55 [P=.003]; and AOR, 11.21; 95% CI, 2.29-54.88 [P=.003]; respectively). Among patients well-supported by religious communities, receiving spiritual support from the medical team was associated with higher rates of hospice use (AOR, 2.37; 95% CI, 1.03-5.44 [P=.04]), fewer aggressive interventions (AOR, 0.23; 95% CI, 0.06-0.79 [P=.02]) and fewer ICU deaths (AOR, 0.19; 95% CI, 0.05-0.80 [P=.02]); and EoL discussions were associated with fewer aggressive interventions (AOR, 0.12; 95% CI, 0.02-0.63 [P=.01]). Conclusions and Relevance: Terminally ill patients who are well supported by religious communities access hospice care less and aggressive medical interventions more near death. Spiritual care and EoL discussions by the medical team may reduce aggressive treatment, highlighting spiritual care as a key component of EoL medical care guidelines. C1 [Balboni, Tracy A.; Balboni, Michael; Enzinger, Andrea C.; Wright, Alexi; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Balboni, Tracy A.; Balboni, Michael; Enzinger, Andrea C.; Wright, Alexi; Prigerson, Holly G.] Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Balboni, Tracy A.; Balboni, Michael; Enzinger, Andrea C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Wright, Alexi] Dana Farber Canc Inst, Div Womens Cancers, Boston, MA 02115 USA. [Enzinger, Andrea C.; Wright, Alexi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Balboni, Tracy A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Balboni, Michael; Prigerson, Holly G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wright, Alexi] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Enzinger, Andrea C.] Harvard Univ, Sch Med, Boston, MA USA. [Balboni, Michael] Harvard Univ, Sch Divin, Cambridge, MA 02138 USA. [Gallivan, Kathleen] Brigham & Womens Hosp, Dept Chaplaincy, Boston, MA 02115 USA. [Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Paulk, Elizabeth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Steinhauser, Karen] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Balboni, TA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM tbalboni@lroc.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370, CA 156732]; Fetzer Foundation; American Society of Clinical Oncology Young Investigator Award; Career Development Award; Healthcare Chaplaincy/John Templeton Foundation Award; University of Chicago Program in Religion and Medicine Faculty Scholars Award; John Templeton Foundation grant FX This research was supported by grant MH63892 from the National Institute of Mental Health and grants CA 106370 and CA 156732 from the National Cancer Institute (Dr Prigerson); by the Fetzer Foundation (Drs Prigerson and Paulk); by an American Society of Clinical Oncology Young Investigator Award and Career Development Award and a Healthcare Chaplaincy/John Templeton Foundation Award (Dr T. A. Balboni); by a University of Chicago Program in Religion and Medicine Faculty Scholars Award (Dr M. Balboni); and by a John Templeton Foundation grant (Dr VanderWeele). NR 36 TC 46 Z9 46 U1 3 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 24 PY 2013 VL 173 IS 12 BP 1109 EP 1117 DI 10.1001/jamainternmed.2013.903 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 170OE UT WOS:000320861700018 PM 23649656 ER PT J AU Lee, BY Sonnenberg, A AF Lee, Brent Y. Sonnenberg, Amnon TI Time Trends of Mortality From Colorectal Cancer in the United States: A Birth-Cohort Analysis SO JAMA INTERNAL MEDICINE LA English DT Letter ID HELICOBACTER-PYLORI INFECTION; PEPTIC-ULCER; RISK; METAANALYSIS C1 [Lee, Brent Y.; Sonnenberg, Amnon] Portland VA Med Ctr, Div Gastroenterol & Hepatol, Portland, OR USA. [Lee, Brent Y.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Div Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 6 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 24 PY 2013 VL 173 IS 12 BP 1148 EP 1150 DI 10.1001/jamainternmed.2013.656 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 170OE UT WOS:000320861700029 PM 23700085 ER PT J AU Ishida, JH McCulloch, CE Dudley, RA Grimes, BA Johansen, KL AF Ishida, Julie H. McCulloch, Charles E. Dudley, R. Adams Grimes, Barbara A. Johansen, Kirsten L. TI Dialysis Facility Profit Status and Compliance With a Black Box Warning SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Ishida, Julie H.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Dudley, R. Adams] Univ Calif San Francisco, Dept Med, Div Pulm Dis & Crit Care Med, San Francisco, CA 94143 USA. [McCulloch, Charles E.; Dudley, R. Adams; Grimes, Barbara A.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Dudley, R. Adams] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Dept Med, Div Nephrol, San Francisco, CA USA. RP Ishida, JH (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, 521 Parnassus Ave,Clin Sci C443,Box 0532, San Francisco, CA 94143 USA. EM julie.ishida@ucsf.edu FU NIDDK NIH HHS [K24DK085153, N01-DK-7-0005, T32 DK007219, K24 DK085153] NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 24 PY 2013 VL 173 IS 12 BP 1152 EP 1153 DI 10.1001/jamainternmed.2013.979 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 170OE UT WOS:000320861700031 PM 23699967 ER PT J AU Zhu, JQ Zhu, JH Springer, TA AF Zhu, Jieqing Zhu, Jianghai Springer, Timothy A. TI Complete integrin headpiece opening in eight steps SO JOURNAL OF CELL BIOLOGY LA English DT Article ID X-RAY-SCATTERING; I-LIKE DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HYBRID DOMAIN; EXTRACELLULAR SEGMENT; OUTSIDE-IN; TGF-BETA; A-DOMAIN; ACTIVATION AB Carefully soaking crystals with Arg-Gly-Asp (RGD) peptides, we captured eight distinct RGD-bound conformations of the alpha(IIb)beta(3) integrin headpiece. Starting from the closed beta I domain conformation, we saw six intermediate beta I conformations and finally the fully open beta I with the hybrid domain swung out in the crystal lattice. The beta 1-alpha 1 backbone that hydrogen bonds to the Asp side chain of RGD was the first element to move followed by adjacent to metal ion-dependent adhesion site Ca2+, alpha 1 helix, alpha 1' helix, beta 6-alpha 7 loop, alpha 7 helix, and hybrid domain. We define in atomic detail how conformational change was transmitted over long distances in integrins, 40 angstrom from the ligand binding site to the opposite end of the beta I domain and 80 angstrom to the far end of the hybrid domain. During these movements, RGD slid in its binding groove toward alpha(IIb), and its Arg side chain became ordered. RGD concentration requirements in soaking suggested a >200-fold higher affinity after opening. The thermodynamic cycle shows how higher affinity pays the energetic cost of opening. C1 [Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Program Cellular & Mol Med,Childrens Hosp Boston, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Program Cellular & Mol Med,Childrens Hosp Boston, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu RI Zhu, Jianghai/B-7339-2014 FU National Institutes of Health [HL-103526]; American Heart Association; American Society of Hematology FX This work was supported by National Institutes of Health grant HL-103526. Jieqing Zhu is a recipient of a Scientist Development Grant from the American Heart Association and an ASH Scholar Award for junior faculty from the American Society of Hematology. NR 55 TC 47 Z9 47 U1 1 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 JUN 24 PY 2013 VL 201 IS 7 BP 1053 EP 1068 DI 10.1083/jcb.201212037 PG 16 WC Cell Biology SC Cell Biology GA 169IK UT WOS:000320773500009 PM 23798730 ER PT J AU Guha, M Castellanos-Rizaldos, E Makrigiorgos, GM AF Guha, Minakshi Castellanos-Rizaldos, Elena Makrigiorgos, G. Mike TI DISSECT Method Using PNA-LNA Clamp Improves Detection of EGFR T790m Mutation SO PLOS ONE LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; REAL-TIME PCR; COLD-PCR; ACQUIRED-RESISTANCE; GENE-MUTATIONS; GEFITINIB; ERLOTINIB; IDENTIFICATION; ENRICHMENT AB Non-small cell lung cancer (NSCLC) patients treated with small molecule EGFR inhibitors, such as gefitinib, frequently develop drug resistance due to the presence of secondary mutations like the T790M mutation on EGFR exon 20. These mutations may originate from small subclonal populations in the primary tumor that become dominant later on during treatment. In order to detect these low-level DNA variations in the primary tumor or to monitor their progress in plasma, it is important to apply reliable and sensitive mutation detection methods. Here, we combine two recently developed methodologies, Differential Strand Separation at Critical Temperature (DISSECT), with peptide nucleic acid-locked nucleic acid (PNA-LNA) polymerase chain reaction (PCR) for the detection of T790M EGFR mutation. DISSECT pre-enriches low-abundance T790M EGFR mutations from target DNA prior to implementing PNA-LNA PCR, a method that can detect 1 mutant allele in a background of 100-1000 wild type alleles. The combination of DISSECT and PNA-LNA PCR enables the detection of 1 mutant allele in a background of 10,000 wild type alleles. The combined DISSECT-PNA-LNA PCR methodology is amenable to adaptation for the sensitive detection of additional emerging resistance mutations in cancer. C1 [Guha, Minakshi; Castellanos-Rizaldos, Elena; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Phys & Biophys,Dept Radiat Oncol,Sch Med, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU Innovative Molecular Analysis Technologies Program of National Cancer Institute [CA-111994] FX This work was supported in part by grant CA-111994 of the Innovative Molecular Analysis Technologies Program of National Cancer Institute. The contents of this manuscript do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. NR 22 TC 9 Z9 10 U1 3 U2 15 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 JUN 21 PY 2013 VL 8 IS 6 AR e67782 DI 10.1371/journal.pone.0067782 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 170JP UT WOS:000320846500155 PM 23805327 ER PT J AU Hass, J Walton, E Kirsten, H Liu, JY Priebe, L Wolf, C Karbalai, N Gollub, R White, T Roessner, V Muller, KU Paus, T Smolka, MN Schumann, G Scholz, M Cichon, S Calhoun, V Ehrlich, S AF Hass, Johanna Walton, Esther Kirsten, Holger Liu, Jingyu Priebe, Lutz Wolf, Christiane Karbalai, Nazanin Gollub, Randy White, Tonya Roessner, Veit Mueller, Kathrin U. Paus, Tomas Smolka, Michael N. Schumann, Gunter Scholz, Markus Cichon, Sven Calhoun, Vince Ehrlich, Stefan CA IMAGEN Consortium TI A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; DATA QUALITY-CONTROL; HIPPOCAMPAL ATROPHY; PSYCHOTIC DISORDERS; ALZHEIMERS-DISEASE; QUANTITATIVE TRAIT; BIPOLAR DISORDER; STRUCTURAL MRI; VERBAL MEMORY; GENE AB Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75x10(-6) and 8.3x10(-7). Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of causal variants and their functional effects may unveil yet unknown players in the neurodevelopment and the pathogenesis of neuropsychiatric disorders. C1 [Hass, Johanna; Walton, Esther; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Kirsten, Holger; Scholz, Markus] Univ Leipzig, IMISE, D-04109 Leipzig, Germany. [Kirsten, Holger; Scholz, Markus] Univ Leipzig, LIFE Leipzig Interdisciplinary Res Cluster Genet, D-04109 Leipzig, Germany. [Liu, Jingyu; Calhoun, Vince] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Liu, Jingyu; Calhoun, Vince] MIND Res Network, Albuquerque, NM USA. [Priebe, Lutz] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Priebe, Lutz; Cichon, Sven] Univ Bonn, Inst Human Genet, Bonn, Germany. [Wolf, Christiane; Karbalai, Nazanin; Cichon, Sven] Max Planck Inst Psychiat, RG Stat Genet, D-80804 Munich, Germany. [Gollub, Randy] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gollub, Randy; Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [White, Tonya; Ehrlich, Stefan] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [White, Tonya; Ehrlich, Stefan] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. [Mueller, Kathrin U.; Smolka, Michael N.] Tech Univ Dresden, Dept Psychiat, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. [Paus, Tomas] Univ Nottingham, Brain & Body Ctr, Nottingsham, England. [Paus, Tomas] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Schumann, Gunter] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. EM transden.lab@uniklinikum-dresden.de RI Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Smolka, Michael/B-4865-2011; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Smolka, Michael/0000-0001-5398-5569; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044; Walton, Esther/0000-0002-0935-2200; Liu, Jingyu/0000-0002-1724-7523 FU National Institutes of Health [NIH/NCRR P41RR14075]; Department of Energy [DE-FG02-99ER62764]; MIND Research Network; Morphometry Biomedical Informatics Research Network (BIRN) [1U24, RR021382A]; Function BIRN [U24RR021992-01, NIH.NCRR MO1 RR025758-01]; NARSAD; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF), within the context of the National Genome Research Network plus (NGFNplus) [PtJ-Bio 0313909]; German Federal Ministry of Education and Research (BMBF), within the Integrated Genome Research Network (IG) MooDS [01GS08144]; Leipzig Interdisciplinary Research Cluster of Genetic Factors, Clinical Phenotypes and Environment (LIFE Center, Universitat Leipzig); European Union; European Regional Development Fund (ERDF); Free State of Saxony within the framework of the excellence initiative; European Commission Framework Programme 6 (FP-6) Integrated Project IMAGEN [PL037286]; European Commission Framework Programme 7 (FP-7) Project Alzheimer's Disease, Alcoholism, Memory, Schizophrenia (ADAMS); FP-7 Innovative Medicine Initiative Project European Autism Interventions (AIMS); UK Department of Health National Institute of Health Research (NIHR)-Biomedical Research Centre Mental Health program; MRC programme grant Developmental Pathways into Adolescent Substance Abuse [93558]; Eli Lilly; Janssen-Cilag; Medice; Novartis FX This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), MIND Research Network, Morphometry Biomedical Informatics Research Network (BIRN) (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01), NARSAD Young Investigator Grant (SE), and the Deutsche Forschungsgemeinschaft (Research Fellowship to SE). Further funding came from the German Federal Ministry of Education and Research (BMBF, grant PtJ-Bio 0313909 to HK), within the context of the National Genome Research Network plus (NGFNplus), and the Integrated Genome Research Network (IG) MooDS (grant 01GS08144 to SC). HK and MS are supported by the Leipzig Interdisciplinary Research Cluster of Genetic Factors, Clinical Phenotypes and Environment (LIFE Center, Universitat Leipzig). LIFE is funded by the European Union, the European Regional Development Fund (ERDF) and the Free State of Saxony within the framework of the excellence initiative. IMAGEN is funded by the European Commission Framework Programme 6 (FP-6) Integrated Project IMAGEN (PL037286), the European Commission Framework Programme 7 (FP-7) Project Alzheimer's Disease, Alcoholism, Memory, Schizophrenia (ADAMS), the FP-7 Innovative Medicine Initiative Project European Autism Interventions (AIMS), the UK Department of Health National Institute of Health Research (NIHR)-Biomedical Research Centre Mental Health program and the MRC programme grant Developmental Pathways into Adolescent Substance Abuse (93558). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Veit Roessner has received lecture fees from Eli Lilly, Janssen-Cilag, Medice, and Novartis and was a member of advisory boards of Eli Lilly, Novartis. All other authors declare no biomedical financial interests or other potential conflict of interests. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. NR 83 TC 6 Z9 6 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 21 PY 2013 VL 8 IS 6 AR e64872 DI 10.1371/journal.pone.0064872 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 170JP UT WOS:000320846500007 PM 23805179 ER PT J AU Lewinsohn, DM Swarbrick, GM Cansler, ME Null, MD Rajaraman, V Frieder, MM Sherman, DR McWeeney, S Lewinsohn, DA AF Lewinsohn, David M. Swarbrick, Gwendolyn M. Cansler, Meghan E. Null, Megan D. Rajaraman, Veena Frieder, Marisa M. Sherman, David R. McWeeney, Shannon Lewinsohn, Deborah A. TI Human Mycobacterium tuberculosis CD8 T Cell Antigens/Epitopes Identified by a Proteomic Peptide Library SO PLOS ONE LA English DT Article ID PROTECTIVE IMMUNITY; DENDRITIC CELLS; INFECTED-CELLS; HIV-INFECTION; HLA-B; LYMPHOCYTES; VACCINES; ANTIGEN; MICE; VACCINATION AB Identification of CD8(+) T cell antigens/epitopes expressed by human pathogens with large genomes is especially challenging, yet necessary for vaccine development. Immunity to tuberculosis, a leading cause of mortality worldwide, requires CD8(+) T cell immunity, yet the repertoire of CD8 antigens/epitopes remains undefined. We used integrated computational and proteomic approaches to screen 10% of the Mycobacterium tuberculosis (Mtb) proteome for CD8 Mtb antigens. We designed a weighting schema based upon a Multiple Attribute Decision Making: framework to select 10% of the Mtb proteome with a high probability of containing CD8(+) T cell epitopes. We created a synthetic peptide library consisting of 15-mers overlapping by 11 aa. Using the interferon-gamma ELISPOT assay and Mtb-infected dendritic cells as antigen presenting cells, we screened Mtb-specific CD8(+) T cell clones restricted by classical MHC class I molecules (MHC class Ia molecules), that were isolated from Mtb-infected humans, against this library. Three novel CD8 antigens were unambiguously identified: the EsxJ family (Rv1038c, Rv1197, Rv3620c, Rv2347c, Rv1792), PE9 (Rv1088), and PE_PGRS42 (Rv2487c). The epitopes are B5701-restricted EsxJ(24-34), B3905-restricted PE9(53-67), and B3514-restricted PE_PGRS42(48-56), respectively. The utility of peptide libraries in identifying unknown epitopes recognized by classically restricted CD8(+) T cells was confirmed, which can be applied to other intracellular pathogens with large size genomes. In addition, we identified three novel Mtb epitopes/antigens that may be evaluated for inclusion in vaccines and/or diagnostics for tuberculosis. C1 [Lewinsohn, David M.; Frieder, Marisa M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Lewinsohn, David M.; Rajaraman, Veena; Frieder, Marisa M.] Portland VA Med Ctr, Portland, OR USA. [Swarbrick, Gwendolyn M.; Cansler, Meghan E.; Null, Megan D.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Rajaraman, Veena; McWeeney, Shannon] Oregon Hlth & Sci Univ, Oregon Canc Inst, Portland, OR 97201 USA. [Sherman, David R.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Lewinsohn, DM (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. EM lewinsde@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI McWeeney, Shannon/0000-0001-8333-6607; Lewinsohn, David/0000-0001-9906-9494 FU VA Merit Review Grant; Portland VA Medical Center, US National Institutes of Health [HHSN266200400081C (NO1-A1-400081), R01AI48090] FX This work was supported by a VA Merit Review Grant and the Portland VA Medical Center, US National Institutes of Health HHSN266200400081C (NO1-A1-400081), and R01AI48090. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 13 Z9 14 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 21 PY 2013 VL 8 IS 6 AR e67016 DI 10.1371/journal.pone.0067016 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 170JP UT WOS:000320846500117 PM 23805289 ER PT J AU Liu, XH Wu, Y Yao, S Levine, AC Kirschenbaum, A Collier, L Bauman, WA Cardozo, CP AF Liu, Xin-Hua Wu, Yong Yao, Shen Levine, Alice C. Kirschenbaum, Alexander Collier, Lauren Bauman, William A. Cardozo, Christopher P. TI Androgens Up-regulate Transcription of the Notch Inhibitor Numb in C2C12 Myoblasts via Wnt/beta-Catenin Signaling to T Cell Factor Elements in the Numb Promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN; MYOGENIC DIFFERENTIATION; SKELETAL-MUSCLE; POSTNATAL MYOGENESIS; WNT; ACTIVATION; RECEPTOR; FATE; TESTOSTERONE; PATHWAY AB Androgen signaling via the androgen receptor is a key pathway that contributes to development, cell fate decisions, and differentiation, including that of myogenic progenitors. Androgens and synthetic steroids have well established anabolic actions on skeletal muscle. Wnt and Notch signaling pathways are also essential to myogenic cell fate decisions during development and tissue repair. However, the interactions among these pathways are largely unknown. Androgenic regulation of Wnt signaling has been reported. Nandrolone, an anabolic steroid, has been shown to inhibit Notch signaling and up-regulate Numb, a Notch inhibitor. To elucidate the mechanisms of interaction between nandrolone and Wnt/Notch signaling, we investigated the effects of nandrolone on Numb expression and Wnt signaling and determined the roles of Wnt signaling in nandrolone-induced Numb expression in C2C12 myoblasts. Nandrolone increased Numb mRNA and protein levels and T cell factor (Tcf) transcriptional activity via inhibition of glycogen synthase kinase 3 beta. Up-regulation of Numb expression by nandrolone was blocked by the Wnt inhibitors, sFRP1 and DKK1, whereas Wnt3a increased Numbm RNA and protein expression. In addition, we observed that the proximal promoter of the Numb gene had functional Tcf binding elements to which beta-catenin was recruited in a manner enhanced by both nandrolone and Wnt3a. Moreover, site-directed mutagenesis indicated that the Tcf binding sites in the Numb promoter are required for the nandrolone-induced Numb transcriptional activation in this cell line. These results reveal a novel molecular mechanism underlying up-regulation of Numb transcription with a critical role for increased canonical Wnt signaling. In addition, the data identify Numb as a novel target gene of the Wnt signaling pathway by which Wnts would be able to inhibit Notch signaling. C1 [Liu, Xin-Hua; Wu, Yong; Collier, Lauren; Bauman, William A.; Cardozo, Christopher P.] James J Peter Vet Affairs Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Yao, Shen; Levine, Alice C.; Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Kirschenbaum, Alexander] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peter Vet Affairs Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, F7756R, F6997R] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service Grants B4162C, F7756R, and F6997R. NR 47 TC 7 Z9 7 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 2013 VL 288 IS 25 BP 17990 EP 17998 DI 10.1074/jbc.M113.478487 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 168QZ UT WOS:000320721900006 PM 23649620 ER PT J AU Buck, TM Plavchak, L Roy, A Donnelly, BF Kashlan, OB Kleyman, TR Subramanya, AR Brodsky, JL AF Buck, Teresa M. Plavchak, Lindsay Roy, Ankita Donnelly, Bridget F. Kashlan, Ossama B. Kleyman, Thomas R. Subramanya, Arohan R. Brodsky, Jeffrey L. TI The Lhs1/GRP170 Chaperones Facilitate the Endoplasmic Reticulum-associated Degradation of the Epithelial Sodium Channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ER-ASSOCIATED DEGRADATION; TRANSMEMBRANE CONDUCTANCE REGULATOR; NUCLEOTIDE-EXCHANGE FACTOR; HEAT-SHOCK PROTEINS; NA+ CHANNEL; MOLECULAR CHAPERONES; MISFOLDED GLYCOPROTEINS; HSP70 CHAPERONES; QUALITY-CONTROL; MECHANISTICALLY DISTINCT AB The epithelial sodium channel, ENaC, plays a critical role in maintaining salt and water homeostasis, and not surprisingly defects in ENaC function are associated with disease. Like many other membrane-spanning proteins, this trimeric protein complex folds and assembles inefficiently in the endoplasmic reticulum (ER), which results in a substantial percentage of the channel being targeted for ER-associated degradation (ERAD). Because the spectrum of factors that facilitates the degradation of ENaC is incomplete, we developed yeast expression systems for each ENaC subunit. We discovered that a conserved Hsp70-like chaperone, Lhs1, is required for maximal turnover of the ENaC alpha subunit. By expressing Lhs1 ATP binding mutants, we also found that the nucleotide exchange properties of this chaperone are dispensable for ENaC degradation. Consistent with the precipitation of an Lhs1-alpha ENaC complex, Lhs1 holdase activity was instead most likely required to support the ERAD of alpha ENaC. Moreover, a complex containing the mammalian Lhs1 homolog GRP170 and alpha ENaC co-precipitated, and GRP170 also facilitated ENaC degradation in human, HEK293 cells, and in a Xenopus oocyte expression system. In both yeast and higher cell types, the effect of Lhs1 on the ERAD of alpha ENaC was selective for the unglycosylated form of the protein. These data establish the first evidence that Lhs1/Grp170 chaperones can act as mediators of ERAD substrate selection. C1 [Buck, Teresa M.; Plavchak, Lindsay; Brodsky, Jeffrey L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Roy, Ankita; Donnelly, Bridget F.; Kashlan, Ossama B.; Kleyman, Thomas R.; Subramanya, Arohan R.] Univ Pittsburgh, Renal Electrolyte Div, Dept Med, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. RP Brodsky, JL (reprint author), Univ Pittsburgh, Dept Biol Sci, A320 Langley Hall,4249 5th Ave, Pittsburgh, PA 15260 USA. EM jbrodsky@pitt.edu FU National Institutes of Health [K01DK090195, DK65161, GM75061, DK79307]; United States Department of Veterans Affairs; University of Pittsburgh George O'Brien Kidney Research Center; American Heart Association [10BGIA3890010] FX This work was supported, in whole or in part, by National Institutes of Health Grants K01DK090195 (to T. M. B.), DK65161 (to T. K.), GM75061 (to J. L. B.), and DK79307 (to the University of Pittsburgh George O'Brien Kidney Research Center).; Supported by a Mid-level Career Development Award from the United States Department of Veterans Affairs, pilot funds from the University of Pittsburgh George O'Brien Kidney Research Center, and by James A. Shaver Fund of the American Heart Association Grant 10BGIA3890010. NR 116 TC 17 Z9 17 U1 0 U2 7 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 JUN 21 PY 2013 VL 288 IS 25 BP 18366 EP 18380 DI 10.1074/jbc.M113.469882 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 168QZ UT WOS:000320721900040 PM 23645669 ER PT J AU Wei, SC Tsao, PN Weng, MT Cao, ZF Wong, JM AF Wei, Shu-Chen Tsao, Po-Nien Weng, Meng-Tzu Cao, Zhifang Wong, Jau-Min TI Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE Colorectal cancer; Flt-1; PlGF; Invasion; Migration; MMP9 ID FACTOR RECEPTOR-1; PROGNOSTIC-SIGNIFICANCE; MICROVESSEL DENSITY; ENDOTHELIAL-CELLS; ANGIOGENESIS; EXPRESSION; VEGF; METASTASIS; SURVIVAL; MACROPHAGES AB Background: Placenta growth factor (PlGF), a dimeric glycoprotein with 53% homology to VEGF, binds to VEGF receptor-1 (Flt-1), but not to VEGF receptor-2 (Flk-1), and may function by modulating VEGF activity. We previously have showed that PlGF displays prognostic value in colorectal cancer (CRC) but the mechanism remains elucidated. Results: Overexpression of PlGF increased the invasive/migration ability and decreased apoptosis in CRC cells showing Flt-1 expression. Increased migration was associated with increasing MMP9 via p38 MAPK activation. Tumors grew faster, larger; with higher vascularity from PlGF over-expression cells in xenograft assay. In two independent human CRC tissue cohorts, PlGF, MMP9, and Flt-1 expressions were higher in the advanced than the localized disease group. PlGF expression correlated with MMP9, and Flt-1 expression. CRC patients with high PlGF and high Flt-1 expression in tissue had poor prognosis. Conclusion: PlGF/Flt-1 signaling plays an important role in CRC progression, blocking PlGF/Flt-1 signaling maybe an alternative therapy for CRC. C1 [Wei, Shu-Chen; Wong, Jau-Min] Natl Taiwan Univ Hosp & Coll Med, Dept Internal Med, Taipei 100, Taiwan. [Tsao, Po-Nien] Natl Taiwan Univ Hosp & Coll Med, Dept Pediat, Taipei 100, Taiwan. [Weng, Meng-Tzu] Far Eastern Mem Hosp, Dept Internal Med, Taipei 100, Taiwan. [Cao, Zhifang] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Wong, JM (reprint author), Natl Taiwan Univ Hosp & Coll Med, Dept Internal Med, Taipei 100, Taiwan. EM jmwong@ntu.edu.tw OI TSAO, PO-NIEN/0000-0002-6114-1769 FU National Science Council of Taiwan [100-2314-B-002-071-]; Liver Disease Prevention & Treatment Research Foundation FX We thank the second Core Laboratory of the Department of Medical Research of the National Taiwan University Hospital for technical assistance, Dr. Hwai-I Yang for his kind help in statistical analysis, Prof. Wen-Fang Cheng and Min-Hung Hsu for technical support in tumor xenograft experiment. We thank the critical review and comments from Dr. Ji Luo (Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA). The in vitro work was supported partially by the National Science Council of Taiwan (100-2314-B-002-071-), and others by the Liver Disease Prevention & Treatment Research Foundation. NR 39 TC 11 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUN 21 PY 2013 VL 20 AR 39 DI 10.1186/1423-0127-20-39 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 179GD UT WOS:000321506900001 PM 23799978 ER PT J AU Brown, MC Lee, DJ Benson, TE AF Brown, M. Christian Lee, Daniel J. Benson, Thane E. TI Ultrastructure of spines and associated terminals on brainstem neurons controlling auditory input SO BRAIN RESEARCH LA English DT Article DE Olivocochlear; Stapedius; Tensor tympani; Middle ear muscle; Vesicle morphometry; Electron microscopy ID MEDIAL OLIVOCOCHLEAR NEURONS; TENSOR TYMPANI MOTONEURONS; POSTEROVENTRAL COCHLEAR NUCLEUS; MIDDLE-EAR MUSCLES; DENDRITIC SPINES; GUINEA-PIG; HORSERADISH-PEROXIDASE; REFLEX PATHWAYS; INFERIOR COLLICULUS; SYNAPTIC PLASTICITY AB Spines are unique cellular appendages that isolate synaptic input to neurons and play a role in synaptic plasticity. Using the electron microscope, we studied spines and their associated synaptic terminals on three groups of brainstem neurons: tensor tympani motoneurons, stapedius motoneurons, and medial olivocochlear neurons, all of which exert reflexive control of processes in the auditory periphery. These spines are generally simple in shape; they are infrequent and found on the somata as well as the dendrites. Spines do not differ in volume among the three groups of neurons. In all cases, the spines are associated with a synaptic terminal that engulfs the spine rather than abuts its head. The positions of the synapses are variable, and some are found at a distance from the spine, suggesting that the isolation of synaptic input is of diminished importance for these spines. Each group of neurons receives three common types of synaptic terminals. The type of terminal associated with spines of the motoneurons contains pleomorphic vesicles, whereas the type associated with spines of olivocochlear neurons contains large round vesicles. Thus, spine-associated terminals in the motoneurons appear to be associated with inhibitory processes but in olivocochlear neurons they are associated with excitatory processes. (c) 2013 Elsevier B.V. All rights reserved. C1 [Brown, M. Christian; Lee, Daniel J.; Benson, Thane E.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Chris_Brown@meei.harvard.edu; Daniel_Lee@meei.harvard.edu; Thane_Benson@meei.harvard.edu FU National Institutes of Health-NIDCD [DC01089, DC06285] FX National Institutes of Health-NIDCD, grant numbers DC01089 (to M.C.B.) and DC06285 (to D.J.L.). NR 67 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 21 PY 2013 VL 1516 BP 1 EP 10 DI 10.1016/j.brainres.2013.04.020 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 173OV UT WOS:000321089700001 ER PT J AU Bachler, BC Humbert, M Lakhashe, SK Rasmussen, RA Ruprecht, RM AF Bachler, Barbara C. Humbert, Michael Lakhashe, Samir K. Rasmussen, Robert A. Ruprecht, Ruth M. TI Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia SO RETROVIROLOGY LA English DT Article DE Macaque model; Recombinant protein vaccine; Heterologous R5 SHIV clade C challenge; Complete protection; Subtractive peptide phage display; V3 crown; Boosting of vaccine-induced Ab titers after multiple challenges; Neo-antigen reactivity ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORIGINAL ANTIGENIC SIN; T-CELL RESPONSES; HIV-1 VACCINE; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSE; RHESUS MACAQUES; PEPTIDE LIBRARIES; CHIMERIC VIRUS; PHAGE DISPLAY AB Background: We addressed the question whether live-virus challenges could alter vaccine-induced antibody (Ab) responses in vaccinated rhesus macaques (RMs) that completely resisted repeated exposures to R5-tropic simian-human immunodeficiency viruses encoding heterologous HIV clade C envelopes (SHIV-Cs). Results: We examined the Ab responses in aviremic RMs that had been immunized with a multi-component protein vaccine (multimeric HIV-1 gp160, HIV-1 Tat and SIV Gag-Pol particles) and compared anti-Env plasma Ab titers before and after repeated live-virus exposures. Although no viremia was ever detected in these animals, they showed significant increases in anti-gp140 Ab titers after they had encountered live SHIVs. When we investigated the dynamics of anti-Env Ab titers during the immunization and challenge phases further, we detected the expected, vaccine-induced increases of Ab responses about two weeks after the last protein immunization. Remarkably, these titers kept rising during the repeated virus challenges, although no viremia resulted. In contrast, in vaccinated RMs that were not exposed to virus, anti-gp140 Ab titers declined after the peak seen two weeks after the last immunization. These data suggest boosting of pre-existing, vaccine-induced Ab responses as a consequence of repeated live-virus exposures. Next, we screened polyclonal plasma samples from two of the completely protected vaccinees by peptide phage display and designed a strategy that selects for recombinant phages recognized only by Abs present after - but not before - any SHIV challenge. With this "subtractive biopanning" approach, we isolated V3 mimotopes that were only recognized after the animals had been exposed to live virus. By detailed epitope mapping of such anti-V3 Ab responses, we showed that the challenges not only boosted pre-existing binding and neutralizing Ab titers, but also induced Abs targeting neo-antigens presented by the heterologous challenge virus. Conclusions: Anti-Env Ab responses induced by recombinant protein vaccination were altered by the multiple, live SHIV challenges in vaccinees that had no detectable viral loads. These data may have implications for the interpretation of "vaccine only" responses in clinical vaccine trials. C1 [Bachler, Barbara C.; Humbert, Michael; Lakhashe, Samir K.; Rasmussen, Robert A.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Bachler, Barbara C.] Univ Vet Med, VetCore Facil Res, A-1210 Vienna, Austria. [Humbert, Michael; Lakhashe, Samir K.; Rasmussen, Robert A.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM ruth_ruprecht@dfci.harvard.edu RI Lakhashe, Samir/F-1150-2014 FU National Institutes of Health [P01 AI048240, R37 AI034266]; NCRR [P51 DRR00016500] FX This work was supported by National Institutes of Health grants P01 AI048240 and R37 AI034266 to R. M. R., and NCRR P51 DRR00016500 to Yerkes. NR 55 TC 1 Z9 1 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUN 21 PY 2013 VL 10 AR 63 DI 10.1186/1742-4690-10-63 PG 13 WC Virology SC Virology GA 172PZ UT WOS:000321017900001 PM 23800339 ER PT J AU Puli, SR Kalva, N Bechtold, ML Pamulaparthy, SR Cashman, MD Estes, NC Pearl, RH Volmar, FH Dillon, S Shekleton, MF Forcione, D AF Puli, Srinivas R. Kalva, Nikhil Bechtold, Matthew L. Pamulaparthy, Smitha R. Cashman, Micheal D. Estes, Norman C. Pearl, Richard H. Volmar, Fritz-Henry Dillon, Sonu Shekleton, Michael F. Forcione, David TI Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Endoscopic ultrasound; Ultrasound; Endosonography; Pancreatic mass; Neuroendocrine tumors; Sensitivity; Specificity; Positive predictive value; Negative predictive value ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; FINE-NEEDLE-ASPIRATION; ENDOCRINE TUMORS; PREOPERATIVE LOCALIZATION; CONTROLLED-TRIALS; ULTRASONOGRAPHY; INSULINOMAS; METAANALYSIS; EUS; GASTRINOMAS AB AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs. METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95% CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95% CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95% CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95% CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95% CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for chi(2) heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs. (C) 2013 Baishideng. All rights reserved. C1 [Puli, Srinivas R.; Pamulaparthy, Smitha R.; Cashman, Micheal D.; Volmar, Fritz-Henry; Dillon, Sonu; Shekleton, Michael F.] Univ Illinois, Div Gastroenterol & Hepatol, OSF St Francis Med Ctr, Peoria, IL 61637 USA. [Kalva, Nikhil] Univ Illinois, Dept Internal Med, OSF St Francis Med Ctr, Peoria, IL 61637 USA. [Bechtold, Matthew L.] Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO 65212 USA. [Estes, Norman C.; Pearl, Richard H.] Univ Illinois, Dept Surg, OSF St Francis Med Ctr, Peoria, IL 61637 USA. [Forcione, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Intervent Endoscopy Serv,Gastrointestinal Unit, Boston, MA 02114 USA. RP Puli, SR (reprint author), Univ Illinois, Div Gastroenterol & Hepatol, OSF St Francis Med Ctr, Peoria Campus,100 NE Randolph Ave, Peoria, IL 61637 USA. EM srinivaspuli@yahoo.com NR 37 TC 19 Z9 23 U1 2 U2 6 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUN 21 PY 2013 VL 19 IS 23 BP 3678 EP 3684 DI 10.3748/wjg.v19.i23.3678 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 167ZV UT WOS:000320675100020 PM 23801872 ER PT J AU Dowdell, S Grassberger, C Sharp, GC Paganetti, H AF Dowdell, S. Grassberger, C. Sharp, G. C. Paganetti, H. TI Interplay effects in proton scanning for lung: a 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PARTICLE BEAMS; STATISTICAL-ANALYSIS; DOSIMETRIC IMPACT; MOVING TARGETS; MOTION; THERAPY; RADIOTHERAPY; SIMULATION; IRRADIATION; DESIGN AB Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of five lung cancer patients of varying tumor size (50.4-167.1 cc) and motion amplitude (2.9-30.1 mm). Treatments were planned assuming delivery in 35 x 2.5 Gy(RBE) fractions. The spot size, time to change the beam energy (tau(es)), time required for magnet settling (tau(ss)), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the five patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior-inferior motion amplitude alone. Larger spot sizes (sigma similar to 9-16 mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0 +/- 4.4% (1 standard deviation) in a single fraction compared to 86.1 +/- 13.1% for smaller spots (sigma similar to 2-4 mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively. The interplay effect is highly patient specific, depending on the motion amplitude, tumor location and the delivery parameters. Large degradations of the dose distribution in a single fraction were observed, but improved significantly using conventional fractionation. C1 [Dowdell, S.; Grassberger, C.; Sharp, G. C.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dowdell, S.; Grassberger, C.; Sharp, G. C.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grassberger, C.] Paul Scherrer Inst, Ctr Proton Radiotherapy, CH-5232 Villigen, Switzerland. RP Dowdell, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM sdowdell@partners.org FU NCI [CA111590] FX This work was funded by NCI grant CA111590. The authors would like to thank Partners Research Computing, particularly Jon Jackson, for maintenance of the computing cluster. NR 41 TC 26 Z9 26 U1 1 U2 17 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2013 VL 58 IS 12 BP 4137 EP 4156 DI 10.1088/0031-9155/58/12/4137 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 158JP UT WOS:000319966100013 PM 23689035 ER PT J AU Rottmann, J Keall, P Berbeco, R AF Rottmann, J. Keall, P. Berbeco, R. TI Markerless EPID image guided dynamic multi-leaf collimator tracking for lung tumors SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BODY RADIATION-THERAPY; RESPIRATORY MOTION; INTRAFRACTION MOTION; MLC TRACKING; PHASE-II; RADIOTHERAPY; CANCER; FEASIBILITY; MANAGEMENT; PREDICTION AB Compensation of target motion during the delivery of radiotherapy has the potential to improve treatment accuracy, dose conformity and sparing of healthy tissue. We implement an online image guided therapy system based on soft tissue localization (STiL) of the target from electronic portal images and treatment aperture adaptation with a dynamic multi-leaf collimator (DMLC). The treatment aperture is moved synchronously and in real time with the tumor during the entire breathing cycle. The system is implemented and tested on a Varian TX clinical linear accelerator featuring an AS-1000 electronic portal imaging device (EPID) acquiring images at a frame rate of 12.86 Hz throughout the treatment. A position update cycle for the treatment aperture consists of four steps: in the first step at time t = t(0) a frame is grabbed, in the second step the frame is processed with the STiL algorithm to get the tumor position at t = t(0), in a third step the tumor position at t = t(i) + delta t is predicted to overcome system latencies and in the fourth step, the DMLC control software calculates the required leaf motions and applies them at time t = t(i) + delta t. The prediction model is trained before the start of the treatment with data representing the tumor motion. We analyze the system latency with a dynamic chest phantom (4D motion phantom, Washington University). We estimate the average planar position deviation between target and treatment aperture in a clinical setting by driving the phantom with several lung tumor trajectories (recorded from fiducial tracking during radiotherapy delivery to the lung). DMLC tracking for lung stereotactic body radiation therapy without fiducial markers was successfully demonstrated. The inherent system latency is found to be delta t = (230 +/- 11) ms for a MV portal image acquisition frame rate of 12.86 Hz. The root mean square deviation between tumor and aperture position is smaller than 1 mm. We demonstrate the feasibility of real-time markerless DMLC tracking with a standard LINAC-mounted (EPID). C1 [Rottmann, J.; Berbeco, R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rottmann, J.; Berbeco, R.] Harvard Univ, Sch Med, Boston, MA USA. [Keall, P.] Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. RP Rottmann, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM jrottmann@lroc.harvard.edu FU National Cancer Institute [R21CA156068, R01CA93626]; NHMRC Australia Fellowship FX This work was supported by awards R21CA156068 and R01CA93626 from the National Cancer Institute and NHMRC Australia Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Also, we would like to thank Varian Medical Systems, Inc. for providing us with the frame grabber soft- and hardware. NR 30 TC 11 Z9 11 U1 0 U2 12 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2013 VL 58 IS 12 BP 4195 EP 4204 DI 10.1088/0031-9155/58/12/4195 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 158JP UT WOS:000319966100016 PM 23715431 ER PT J AU D'Souza, G Gross, ND Pai, SI Haddad, RI Gillison, ML Posner, MR AF D'Souza, Gypsyamber Gross, Neil D. Pai, Sara I. Haddad, Robert I. Gillison, Maura L. Posner, Marshall R. TI Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2013 VL 31 IS 18 SU S MA CRA6031 PG 1 WC Oncology SC Oncology GA AG6YC UT WOS:000335564000009 ER PT J AU Hodi, FS Lee, SJ McDermott, DF Rao, UNM Butterfield, LH Tarhini, AA Leming, PD Puzanov, I Kirkwood, JM AF Hodi, F. Stephen Lee, Sandra J. McDermott, David F. Rao, Uma N. M. Butterfield, Lisa H. Tarhini, Ahmad A. Leming, Philip D. Puzanov, Igor Kirkwood, John M. CA Eastern Cooperative Oncology Grp TI Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus Ipi alone in metastatic melanoma: E1608. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Pittsburgh Phys, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Cincinnati Hematol Oncol Inc, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2013 VL 31 IS 18 SU S MA CRA9007 PG 1 WC Oncology SC Oncology GA AG6YC UT WOS:000335564000014 ER PT J AU Kang, YK Ryu, MH Ryoo, BY Kim, HJ Lee, JJ Yoo, C Nam, BH Ramaiya, N Jagannathan, JP Demetri, GD AF Kang, Yoon-Koo Ryu, Min-Hee Ryoo, Baek-Yeol Kim, Hyun Jin Lee, Jong Jin Yoo, Changhoon Nam, Byung-Ho Ramaiya, Nikhil Jagannathan, Jyothi Priya Demetri, George D. TI Randomized phase III trial of imatinib (IM) rechallenge versus placebo (PL) in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): RIGHT study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea. Natl Canc Ctr, Goyang, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2013 VL 31 IS 18 SU S MA LBA10502 PG 1 WC Oncology SC Oncology GA AG6YC UT WOS:000335564000016 ER PT J AU Stupp, R Hegi, ME Gorlia, T Erridge, S Grujicic, D Steinbach, JP Wick, W Tarnawski, R Nam, DH Weyerbrock, A Hau, P Taphoorn, MJB Nabors, LB Reardon, DA Van den Bent, MJ Perry, JR Hong, YK Hicking, C Picard, M Weller, M AF Stupp, Roger Hegi, Monika E. Gorlia, Thierry Erridge, Sara Grujicic, Danica Steinbach, Joachim Peter Wick, Wolfgang Tarnawski, Rafal Nam, Do-Hyun Weyerbrock, Astrid Hau, Peter Taphoorn, Martin J. B. Nabors, Louis B. Reardon, David A. Van den Bent, Martin J. Perry, James R. Hong, Yong Kil Hicking, Christine Picard, Martin Weller, Michael CA EORTC Canadian Brain Tumor Consortium CENTRIC Study Team TI Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma and methylated O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter: Key results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 CHU Vaudois, CH-1011 Lausanne, Switzerland. Eortc Data Ctr, Brussels, Belgium. Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. Clin Ctr Serbia, Inst Neurosurg, Belgrade, Serbia. Klinikum JW Goethe Univ Frankfurt, Dr Senkenberg Inst Neuroonkol, Frankfurt, Germany. Univ Klinikum Heidelberg, Heidelberg, Germany. Maria Sklodowska Curie Mem Canc Ctr, Gliwice, Poland. Inst Oncol, Gliwice Branch, Radiotherapy & Chemotherapy Clin, Gliwice, Poland. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Univ Klinikum Freiburg, Freiburg, Germany. Univ Klinikum Regensburg, Regensburg, Germany. Med Ctr Haaglanden, The Hague, Netherlands. Univ Alabama Birmingham, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus MC, Rotterdam, Netherlands. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. Merck KGaA, Darmstadt, Germany. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RI Tarnawski, Rafal/N-7526-2016 NR 0 TC 0 Z9 0 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2013 VL 31 IS 18 SU S MA LBA2009 PG 1 WC Oncology SC Oncology GA AG6YC UT WOS:000335564000019 ER PT J AU Sznol, M Kluger, HM Hodi, FS McDermott, DF Carvajal, RD Lawrence, DP Topalian, SL Atkins, MB Powderly, JD Sharfman, WH Puzanov, I Smith, DC Wigginton, JM Kollia, G Gupta, AK Sosman, JA AF Sznol, Mario Kluger, Harriet M. Hodi, F. Stephen McDermott, David F. Carvajal, Richard D. Lawrence, Donald P. Topalian, Suzanne Louise Atkins, Michael B. Powderly, John D. Sharfman, William Howard Puzanov, Igor Smith, David C. Wigginton, Jon M. Kollia, Georgia Gupta, Ashok Kumar Sosman, Jeffrey Alan TI Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Yale Canc Ctr, New Haven, CT USA. Yale Univ, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Carolina BioOncol Inst, Huntersville, NC USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2013 VL 31 IS 18 SU S MA CRA9006 PG 1 WC Oncology SC Oncology GA AG6YC UT WOS:000335564000013 ER PT J AU Chen, XL Lei, YH Liu, CF Yang, QF Zuo, PY Liu, CY Chen, CZ Liu, YW AF Chen, Xing-Lin Lei, Ying-Hong Liu, Cun-Fei Yang, Qun-Fang Zuo, Pei-Yuan Liu, Cheng-Yun Chen, Chang-Zhong Liu, Yu-Wei TI Angiogenesis Inhibitor Bevacizumab Increases the Risk of Ischemic Heart Disease Associated with Chemotherapy: A Meta-Analysis SO PLOS ONE LA English DT Article ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; PHASE-III; CARDIOVASCULAR COMPLICATIONS; 1ST-LINE CHEMOTHERAPY; SYSTEMATIC REVIEWS; RANDOMIZED-TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND AB Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%-1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37-4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09-4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03-22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11-4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed. C1 [Chen, Xing-Lin; Lei, Ying-Hong; Zuo, Pei-Yuan; Liu, Cheng-Yun; Liu, Yu-Wei] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Key Lab Geriatr,Hlth Minist,Dept Geriatr, Wuhan 430074, Peoples R China. [Liu, Cun-Fei] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Geriatr, Shanghai 200030, Peoples R China. [Yang, Qun-Fang] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Hyperbar Oxygen Ctr, Wuhan 430074, Peoples R China. [Chen, Chang-Zhong] Dana Farber Canc Inst, Microarray Core Facil, Boston, MA 02115 USA. RP Liu, CY (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Key Lab Geriatr,Hlth Minist,Dept Geriatr, Wuhan 430074, Peoples R China. EM lcyun@medmail.com.cn FU Health Department of Hubei Province [JX4C47] FX This study was supported by a grant from Health Department of Hubei Province (No. JX4C47). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 14 Z9 15 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 20 PY 2013 VL 8 IS 6 AR e66721 DI 10.1371/journal.pone.0066721 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190LY UT WOS:000322342800099 PM 23818962 ER PT J AU Parker, NH Donninger, H Birrer, MJ Leaner, VD AF Parker, Nina Holderness Donninger, Howard Birrer, Michael J. Leaner, Virna D. TI p21-Activated Kinase 3 (PAK3) Is an AP-1 Regulated Gene Contributing to Actin Organisation and Migration of Transformed Fibroblasts SO PLOS ONE LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; C-JUN ACTIVATION; CELL-MIGRATION; PROTEIN-KINASE; MENTAL-RETARDATION; FOCAL COMPLEXES; STRESS FIBERS; RAT-1A CELLS; EXPRESSION; CANCER AB Activating Protein 1 (AP-1) plays a vital role in cell proliferation, differentiation and apoptosis. While de-regulation of AP-1 has been linked to many cancers, little is known regarding its downstream transcriptional targets that associate with cellular transformation. Previous studies identified PAK3, a serine/threonine kinase, as a potential AP-1 target gene. PAK3 has been implicated in a variety of pathological disorders and over-expression of other PAK-family members has been linked to cancer. In this study, we investigate AP-1 regulation of PAK3 expression and the role of PAK3 in cJun/AP-1-associated cellular transformation. Our results showed elevated PAK3 expression at both the mRNA and protein level in cJun-over-expressing Rat1a fibroblasts, as well as in transformed human fibroblasts. Elevated PAK3 expression in cJun/AP-1 over-expressing cells associated with a significant increase in PAK3 promoter activation. This increased promoter activity was lost when a single putative Jun binding site, which can bind AP-1 directly both in vitro and in vivo, was mutated. Further, inhibition of PAK3 using siRNA showed a regression in the cell morphology, migratory potential and actin organisation associated with AP-1 transformed cells. Our study is a first to describe a role for AP-1 in regulating PAK3 expression and suggest that PAK3 is an AP-1 target required for actin organization and migration observed in transformed cells. C1 [Parker, Nina Holderness; Leaner, Virna D.] Univ Cape Town, Div Med Biochem, Fac Hlth Sci, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Donninger, Howard] Univ Louisville, Dept Med, James Graham Brown Canc Ctr, Mol Targets Program, Louisville, KY 40292 USA. [Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Gynecol Canc Res Program,Med Sch, Boston, MA 02115 USA. RP Leaner, VD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Gynecol Canc Res Program,Med Sch, Boston, MA 02115 USA. EM Virna.Leaner@uct.ac.za FU University of Cape Town/Carnegie Corporation of New York Development Grants; Medical Research Council (SA) FX This work is supported by grants from the University of Cape Town/Carnegie Corporation of New York Development Grants, the Medical Research Council (SA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 6 Z9 6 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 JUN 20 PY 2013 VL 8 IS 6 AR e66892 DI 10.1371/journal.pone.0066892 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190LY UT WOS:000322342800107 ER PT J AU Neuberg, D Arceci, RJ AF Neuberg, Donna Arceci, Robert J. TI When "rare" is no excuse for progress SO BLOOD LA English DT Editorial Material ID LANGERHANS CELL HISTIOCYTOSIS; LONG-TERM SURVIVORS; MUTATIONS C1 [Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Arceci, Robert J.] Phoenix Childrens Hosp, Ron Matricaria Inst Mol Med, Phoenix, AZ USA. RP Neuberg, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 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 JUN 20 PY 2013 VL 121 IS 25 BP 4970 EP 4972 DI 10.1182/blood-2013-05-498675 PG 5 WC Hematology SC Hematology GA 184NR UT WOS:000321898500003 PM 23788022 ER PT J AU Olenchock, BA Vander Heiden, MG AF Olenchock, Benjamin A. Vander Heiden, Matthew G. TI Pyruvate as a Pivot Point for Oncogene-Induced Senescence SO CELL LA English DT Editorial Material ID CANCER C1 [Olenchock, Benjamin A.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Olenchock, Benjamin A.; Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Olenchock, Benjamin A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu FU NCI NIH HHS [R01 CA168653]; NHLBI NIH HHS [K08 HL119355, T32 HL007604] NR 9 TC 3 Z9 3 U1 0 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 20 PY 2013 VL 153 IS 7 BP 1429 EP 1430 DI 10.1016/j.cell.2013.06.001 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168RA UT WOS:000320722000011 PM 23791173 ER PT J AU Sun, S Del Rosario, BC Szanto, A Ogawa, Y Jeon, Y Lee, JT AF Sun, Sha Del Rosario, Brian C. Szanto, Attila Ogawa, Yuya Jeon, Yesu Lee, Jeannie T. TI Jpx RNA Activates Xist by Evicting CTCF SO CELL LA English DT Article ID X-CHROMOSOME INACTIVATION; EMBRYONIC STEM-CELLS; DOSAGE COMPENSATION; SEX DETERMINATION; MOUSE; TSIX; GENE; TRANSCRIPTION; SWITCH; BINDING AB In mammals, dosage compensation between XX and XY individuals occurs through X chromosome inactivation (XCI). The noncoding Xist RNA is expressed and initiates XCI only when more than one X chromosome is present. Current models invoke a dependency on the X-to-autosome ratio (X:A), but molecular factors remain poorly defined. Here, we demonstrate that molecular titration between an X-encoded RNA and an autosomally encoded protein dictates Xist induction. In pre-XCI cells, CTCF protein represses Xist transcription. At the onset of XCI, Jpx RNA is upregulated, binds CTCF, and extricates CTCF from one Xist allele. We demonstrate that CTCF is an RNA-binding protein and is titrated away from the Xist promoter by Jpx RNA. Thus, Jpx activates Xist by evicting CTCF. The functional antagonism via molecular titration reveals a role for long noncoding RNA in epigenetic regulation. C1 [Sun, Sha; Del Rosario, Brian C.; Szanto, Attila; Ogawa, Yuya; Jeon, Yesu; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. [Sun, Sha; Del Rosario, Brian C.; Szanto, Attila; Ogawa, Yuya; Jeon, Yesu; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sun, Sha; Del Rosario, Brian C.; Szanto, Attila; Ogawa, Yuya; Jeon, Yesu; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU National Institutes of Health [RO1-GM58839] FX We are grateful to R. Jaenisch for the gift of F1-2.1 ES cells and G. Daley for Ainv15. We thank S. Pinter for sharing unpublished data, J. Ahn for sharing ChIP primers, B. Payer and D. Lessing for critically reading the manuscript, and all lab members for engaging discussions. This work is supported by a grant from the National Institutes of Health (RO1-GM58839 to J.T.L.). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 53 TC 98 Z9 99 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 20 PY 2013 VL 153 IS 7 BP 1537 EP 1551 DI 10.1016/j.cell.2013.05.028 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168RA UT WOS:000320722000021 PM 23791181 ER PT J AU Shaw, AT Kim, DW Nakagawa, K Seto, T Crino, L Ahn, MJ De Pas, T Besse, B Solomon, BJ Blackhall, F Wu, YL Thomas, M O'Byrne, KJ Moro-Sibilot, D Camidge, DR Mok, T Hirsh, V Riely, GJ Iyer, S Tassell, V Polli, A Wilner, KD Janne, PA AF Shaw, Alice T. Kim, Dong-Wan Nakagawa, Kazuhiko Seto, Takashi Crino, Lucio Ahn, Myung-Ju De Pas, Tommaso Besse, Benjamin Solomon, Benjamin J. Blackhall, Fiona Wu, Yi-Long Thomas, Michael O'Byrne, Kenneth J. Moro-Sibilot, Denis Camidge, D. Ross Mok, Tony Hirsh, Vera Riely, Gregory J. Iyer, Shrividya Tassell, Vanessa Polli, Anna Wilner, Keith D. Jaenne, Pasi A. TI Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EML4-ALK FUSION GENE; CLINICAL-TRIALS; OPEN-LABEL; PHASE-III; LYMPHOMA; ONCOLOGY; EGFR; REARRANGEMENT; GEFITINIB; DOCETAXEL AB Background In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. Methods We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. Results The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P = 0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. Conclusions Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. C1 [Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Nakagawa, Kazuhiko] Kinki Univ, Fac Med, Osakasayama City, Osaka, Japan. [Seto, Takashi] Kyushu Natl Canc Ctr, Fukuoka, Japan. [Crino, Lucio] Azienda Osped Perugia, Perugia, Italy. [De Pas, Tommaso] European Inst Oncol, Milan, Italy. [Polli, Anna] Pfizer Italia, Milan, Italy. [Besse, Benjamin] Inst Gustave Roussy, Villejuif, France. [Moro-Sibilot, Denis] CHU Grenoble, Thorac Oncol Unit, F-38043 Grenoble, France. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Blackhall, Fiona] Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England. [Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Thomas, Michael] Univ Klinikum Heidelberg, Thoraxklinik, Heidelberg, Germany. [Thomas, Michael] Translat Lung Res Ctr Heidelberg, Heidelberg, Germany. [O'Byrne, Kenneth J.] St James Hosp, Dublin, Ireland. [Camidge, D. Ross] Univ Colorado, Aurora, CO USA. [Mok, Tony] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Hirsh, Vera] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Iyer, Shrividya] Pfizer Oncol, New York, NY USA. [Tassell, Vanessa; Wilner, Keith D.] Pfizer Oncol, La Jolla, CA USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7B,32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org RI MORO-SIBILOT, denis/N-6493-2013; Blackhall, Fiona/N-2186-2015; OI Blackhall, Fiona/0000-0001-8716-3395; MORO-SIBILOT, Denis/0000-0001-6776-8610; Wu, Yi-Long/0000-0002-3611-0258 FU Pfizer FX Funded by Pfizer; ClinicalTrials.gov number, NCT00932893. NR 30 TC 1089 Z9 1149 U1 20 U2 136 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 JUN 20 PY 2013 VL 368 IS 25 BP 2385 EP 2394 DI 10.1056/NEJMoa1214886 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 167AE UT WOS:000320601700008 PM 23724913 ER PT J AU Awad, MM Katayama, R McTigue, M Liu, W Deng, YL Brooun, A Friboulet, L Huang, DH Falk, MD Timofeevski, S Wilner, KD Lockerman, EL Khan, TM Mahmood, S Gainor, JF Digumarthy, SR Stone, JR Mino-Kenudson, M Christensen, JG Iafrate, AJ Engelman, JA Shaw, AT AF Awad, Mark M. Katayama, Ryohei McTigue, Michele Liu, Wei Deng, Ya-Li Brooun, Alexei Friboulet, Luc Huang, Donghui Falk, Matthew D. Timofeevski, Sergei Wilner, Keith D. Lockerman, Elizabeth L. Khan, Tahsin M. Mahmood, Sidra Gainor, Justin F. Digumarthy, Subba R. Stone, James R. Mino-Kenudson, Mari Christensen, James G. Iafrate, A. John Engelman, Jeffrey A. Shaw, Alice T. TI Acquired Resistance to Crizotinib from a Mutation in CD74-ROS1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELL LUNG-CANCER; GEFITINIB; EML4-ALK; SAFETY; GENE; INHIBITOR; EFFICACY; THERAPY; KINASE AB Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. C1 [Awad, Mark M.; Katayama, Ryohei; Friboulet, Luc; Lockerman, Elizabeth L.; Khan, Tahsin M.; Mahmood, Sidra; Gainor, Justin F.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Digumarthy, Subba R.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiol, Boston, MA 02114 USA. [Stone, James R.; Mino-Kenudson, Mari; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [McTigue, Michele; Liu, Wei; Deng, Ya-Li; Brooun, Alexei; Huang, Donghui; Falk, Matthew D.; Timofeevski, Sergei; Wilner, Keith D.; Christensen, James G.] Pfizer Worldwide Res & Dev, La Jolla, CA USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM jengelman@partners.org; ashaw1@partners.org RI friboulet, luc/N-7276-2015 OI friboulet, luc/0000-0002-1129-4978 FU Pfizer; National Cancer Institute [5R01CA164273-02, R01CA137008, Lung SPORE P50CA090578, a1R21CA161590-01]; V Foundation Translational Research Grant; Be a Piece of the Solution; Evan Spirito Memorial Foundation FX Supported by Pfizer, by grants from the National Cancer Institute (5R01CA164273-02, to Drs. Shaw and Engelman; R01CA137008 and Lung SPORE P50CA090578, to Dr. Engelman; and a1R21CA161590-01, to Dr. Iafrate), by a V Foundation Translational Research Grant (to Drs. Shaw and Engelman), by Be a Piece of the Solution, and by the Evan Spirito Memorial Foundation. NR 25 TC 96 Z9 97 U1 4 U2 20 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 JUN 20 PY 2013 VL 368 IS 25 BP 2395 EP 2401 DI 10.1056/NEJMoa1215530 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 167AE UT WOS:000320601700009 PM 23724914 ER PT J AU Alexander, EK Chan-Smutko, G Saksena, MA Popa, I AF Alexander, Erik K. Chan-Smutko, Gayun Saksena, Mansi A. Popa, Ion TI Case 19-2013: A 35-Year-Old Woman with Recurrent Goiter and Ductal Carcinoma of the Breast SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THYROID-NODULES; RADIATION; CANCER C1 [Alexander, Erik K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chan-Smutko, Gayun] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Saksena, Mansi A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Popa, Ion] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Alexander, Erik K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Saksena, Mansi A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Popa, Ion] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alexander, EK (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 16 TC 1 Z9 1 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 2013 VL 368 IS 25 BP 2416 EP 2424 DI 10.1056/NEJMcpc1209273 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 167AE UT WOS:000320601700013 PM 23782181 ER PT J AU Wilfond, BS Magnus, D Antommaria, AH Appelbaum, P Aschner, J Barrington, KJ Beauchamp, T Boss, RD Burke, W Caplan, AL Capron, AM Cho, M Clayton, EW Cole, FS Darlow, BA Diekema, D Faden, RR Feudtner, C Fins, JJ Fost, NC Frader, J Hester, DM Janvier, A Joffe, S Kahn, J Kass, NE Kodish, E Lantos, JD McCullough, L McKinney, R Meadow, W O'Rourke, PP Powderly, KE Pursley, DM Ross, LF Sayeed, S Sharp, RR Sugarman, J Tarnow-Mordi, WO Taylor, H Tomlinson, T Truog, RD Unguru, YT Weise, KL Woodrum, D Youngner, S AF Wilfond, Benjamin S. Magnus, David Antommaria, Armand H. Appelbaum, Paul Aschner, Judy Barrington, Keith J. Beauchamp, Tom Boss, Renee D. Burke, Wylie Caplan, Arthur L. Capron, Alexander M. Cho, Mildred Clayton, Ellen Wright Cole, F. Sessions Darlow, Brian A. Diekema, Douglas Faden, Ruth R. Feudtner, Chris Fins, Joseph J. Fost, Norman C. Frader, Joel Hester, D. Micah Janvier, Annie Joffe, Steven Kahn, Jeffrey Kass, Nancy E. Kodish, Eric Lantos, John D. McCullough, Laurence McKinney, Ross, Jr. Meadow, William O'Rourke, P. Pearl Powderly, Kathleen E. Pursley, DeWayne M. Ross, Lainie Friedman Sayeed, Sadath Sharp, Richard R. Sugarman, Jeremy Tarnow-Mordi, William O. Taylor, Holly Tomlinson, Tom Truog, Robert D. Unguru, Yoram T. Weise, Kathryn L. Woodrum, David Youngner, Stuart TI The OHRP and SUPPORT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Wilfond, Benjamin S.; Diekema, Douglas] Univ Washington, Sch Med, Dept Pediat, Div Bioeth, Seattle, WA 98195 USA. [Wilfond, Benjamin S.; Diekema, Douglas; Woodrum, David] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Magnus, David; Cho, Mildred] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Magnus, David] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Magnus, David; Cho, Mildred] Stanford Univ, Stanford Ctr Biomed Eth, Stanford, CA 94305 USA. [Antommaria, Armand H.] Cincinnati Childrens Hosp Med Ctr, Eth Ctr, Cincinnati, OH 45229 USA. [Antommaria, Armand H.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Appelbaum, Paul] Columbia Univ, Dept Psychiat, New York, NY USA. [Aschner, Judy] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Aschner, Judy] Childrens Hosp Montefiore, Bronx, NY USA. [Barrington, Keith J.; Janvier, Annie] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Barrington, Keith J.; Janvier, Annie] St Justine Univ Hlth Ctr, Montreal, PQ, Canada. [Beauchamp, Tom] Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. [Boss, Renee D.] Johns Hopkins Sch Med, Dept Pediat, Div Neonatol, Baltimore, MD USA. [Boss, Renee D.; Faden, Ruth R.; Kahn, Jeffrey; Kass, Nancy E.; Taylor, Holly; Unguru, Yoram T.] Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA. [Burke, Wylie] Univ Washington, Sch Med, Dept Bioeth & Humanities, Seattle, WA USA. [Caplan, Arthur L.] NYU, Div Med Eth, Langone Med Ctr, New York, NY USA. [Capron, Alexander M.] Univ So Calif, Keck Sch Med, Gould Sch Law, Los Angeles, CA 90033 USA. [Capron, Alexander M.] Univ So Calif, Pacific Ctr Hlth Policy & Eth, Los Angeles, CA USA. [Clayton, Ellen Wright] Vanderbilt Univ, Sch Med, Ctr Biomed Eth & Soc, Nashville, TN 37212 USA. [Clayton, Ellen Wright] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Clayton, Ellen Wright] Vanderbilt Law Sch, Nashville, TN USA. [Cole, F. Sessions] Washington Univ, Sch Med, St Louis Childrens Hosp, Div Newborn Med, St Louis, MO USA. [Cole, F. Sessions] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Darlow, Brian A.] Univ Otago, Dept Pediat, Christchurch, New Zealand. [Feudtner, Chris] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Feudtner, Chris] Childrens Hosp Philadelphia, Dept Med Eth, Philadelphia, PA 19104 USA. [Fins, Joseph J.] Cornell Univ, Weill Med Coll, Dept Med, Div Med Eth, New York, NY 10021 USA. [Fins, Joseph J.] NewYork Presbyterian Hosp, Weill Cornell Med Ctr, Div Med Eth, New York, NY USA. [Fost, Norman C.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA. [Fost, Norman C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Hist & Bioeth, Madison, WI USA. [Frader, Joel] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. [Frader, Joel] Northwestern Univ, Dept Med Humanities & Bioeth, Chicago, IL 60611 USA. [Hester, D. Micah] Univ Arkansas Med Sci, Div Med Humanities, Little Rock, AR 72205 USA. [Hester, D. Micah] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Joffe, Steven] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Joffe, Steven] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kahn, Jeffrey; Kass, Nancy E.; Taylor, Holly] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Kodish, Eric] Cleveland Clin, Lerner Coll Med, Dept Bioeth, Cleveland, OH 44106 USA. [Kodish, Eric] Cleveland Clin, Lerner Coll Med, Dept Pediat, Cleveland, OH 44106 USA. [Lantos, John D.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. [Lantos, John D.] Childrens Mercy Hosp Bioeth Ctr, Kansas City, MO USA. [McCullough, Laurence] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [McKinney, Ross, Jr.] Duke Univ, Sch Med, Dept Pediat, Durham, NC USA. [McKinney, Ross, Jr.] Duke Univ, Sch Med, Trent Ctr Bioeth Humanities & Hist Med, Durham, NC USA. [Meadow, William] Univ Chicago, Dept Pediat, Div Neonatol, Chicago, IL 60637 USA. [O'Rourke, P. Pearl] Partners HealthCare, Human Res Affairs, Boston, MA USA. [Powderly, Kathleen E.] Suny Downstate Med Ctr, John Conley Div Med Eth & Humanities, Brooklyn, NY 11203 USA. [Pursley, DeWayne M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pursley, DeWayne M.] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. [Ross, Lainie Friedman] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Ross, Lainie Friedman] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ross, Lainie Friedman] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Ross, Lainie Friedman] Univ Chicago, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. [Sayeed, Sadath] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Sayeed, Sadath] Boston Childrens Hosp, Boston, MA USA. [Sharp, Richard R.; Weise, Kathryn L.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44106 USA. [Sharp, Richard R.] Cleveland Clin, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44106 USA. [Sugarman, Jeremy] Johns Hopkins Berman Inst Bioeth, Dept Med, Div Gen Internal Med, Baltimore, MD USA. [Tarnow-Mordi, William O.] Univ Sydney, Dept Pediat, Sydney, NSW 2006, Australia. [Tarnow-Mordi, William O.] Westmead Hosp, Sydney, NSW, Australia. [Tomlinson, Tom] Michigan State Univ, Coll Human Med, Ctr Eth & Humanities Life Sci, E Lansing, MI 48824 USA. [Truog, Robert D.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Div Med Eth, Boston, MA USA. [Truog, Robert D.] Boston Childrens Hosp, Div Crit Care Med, Boston, MA USA. [Unguru, Yoram T.] Herman & Walter Samuelson Childrens Hosp Sinai, Div Pediat Hematol Oncol, Baltimore, MD USA. [Woodrum, David] Univ Washington, Sch Med, Dept Pediat, Div Neonatol, Seattle, WA 98195 USA. [Youngner, Stuart] Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH USA. RP Wilfond, BS (reprint author), Univ Washington, Sch Med, Dept Pediat, Div Bioeth, Seattle, WA 98195 USA. OI Barrington, Keith/0000-0001-9669-5094; Clayton, Ellen/0000-0002-0308-4110; Joffe, Steven/0000-0002-0667-7384 NR 0 TC 28 Z9 28 U1 1 U2 9 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 JUN 20 PY 2013 VL 368 IS 25 BP E36 EP + DI 10.1056/NEJMc1307008 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 167AE UT WOS:000320601700038 PM 23738513 ER PT J AU Ng, AK Garber, JE Diller, LR Birdwell, RL Feng, Y Neuberg, DS Silver, B Fisher, DC Marcus, KJ Mauch, PM AF Ng, Andrea K. Garber, Judy E. Diller, Lisa R. Birdwell, Robyn L. Feng, Yang Neuberg, Donna S. Silver, Barbara Fisher, David C. Marcus, Karen J. Mauch, Peter M. TI Prospective Study of the Efficacy of Breast Magnetic Resonance Imaging and Mammographic Screening in Survivors of Hodgkin Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; HIGH FAMILIAL RISK; CANCER-RISK; 2ND MALIGNANCY; BRCA2 MUTATION; YOUNG-WOMEN; FOLLOW-UP; DISEASE; SURVEILLANCE; RADIATION AB Purpose Current guidelines recommend breast magnetic resonance imaging (MRI) as an adjunct to mammography for breast cancer screening in female cancer survivors treated with chest irradiation at a young age, beginning 8 to 10 years after treatment. Prospective data evaluating its efficacy in female cancer survivors are lacking. This study sought to compare the sensitivity and specificity of breast MRI with those of mammography in women who received chest irradiation for Hodgkin lymphoma (HL). Patients and Methods We enrolled 148 women treated with chest irradiation for HL at age <= 35 years who were > 8 years beyond treatment. Yearly breast MRI and mammogram were performed over a 3-year period. Sensitivity and specificity of the two screening modalities were compared. Results With the screening, 63 biopsies were performed in 45 women; 18 (29%) showed a malignancy. All but one of the screen-detected malignancies were preinvasive or subcentimeter node-negative breast cancers. After excluding first-screen MRI and mammogram, mammogram sensitivity was 68% as compared with 67% for MRI (P = 1.0). Sensitivity increased to 94% using both screening modalities. The specificities of mammogram alone, MRI alone, and both were 93%, 94%, and 90%, respectively. Conclusion In contrast to women with genetic or familial risk, in HL survivors breast MRI was not more sensitive than mammogram for breast cancer detection. However, the two screening modalities complement each other in the detection of early cases of disease. Early diagnosis is particularly important in these patients, given the breast cancer treatment challenges in patients who have received prior cancer therapy. (C) 2013 by American Society of Clinical Oncology C1 [Ng, Andrea K.; Birdwell, Robyn L.; Silver, Barbara; Marcus, Karen J.; Mauch, Peter M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ng, Andrea K.; Garber, Judy E.; Diller, Lisa R.; Feng, Yang; Neuberg, Donna S.; Silver, Barbara; Fisher, David C.; Marcus, Karen J.; Mauch, Peter M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, AK (reprint author), 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu FU Lance Armstrong Foundation; Susan G. Komen Foundation [BCTR0600221] FX Supported by an Issues of Cancer Survivorship Research Grant from the Lance Armstrong Foundation and Grant No. BCTR0600221 from the Susan G. Komen Foundation. NR 38 TC 30 Z9 30 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 JUN 20 PY 2013 VL 31 IS 18 BP 2282 EP U91 DI 10.1200/JCO.2012.46.5732 PG 8 WC Oncology SC Oncology GA 164XV UT WOS:000320446700013 PM 23610104 ER PT J AU Terpos, E Morgan, G Dimopoulos, MA Drake, MT Lentzsch, S Raje, N Sezer, O Garcia-Sanz, R Shimizu, K Turesson, I Reiman, T Jurczyszyn, A Merlini, G Spencer, A Leleu, X Cavo, M Munshi, N Rajkumar, SV Durie, BGM Roodman, GD AF Terpos, Evangelos Morgan, Gareth Dimopoulos, Meletios A. Drake, Matthew T. Lentzsch, Suzanne Raje, Noopur Sezer, Orhan Garcia-Sanz, Ramon Shimizu, Kazuyuki Turesson, Ingemar Reiman, Tony Jurczyszyn, Artur Merlini, Giampaolo Spencer, Andrew Leleu, Xavier Cavo, Michele Munshi, Nikhil Rajkumar, S. Vincent Durie, Brian G. M. Roodman, G. David TI International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma-Related Bone Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SPINAL-CORD COMPRESSION; RANDOMIZED CONTROLLED-TRIAL; CLINIC CONSENSUS STATEMENT; SKELETAL-RELATED EVENTS; VITAMIN-D DEFICIENCY; ZOLEDRONIC ACID; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; DOUBLE-BLIND; VERTEBRAL AUGMENTATION AB Purpose The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease. Methodology An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Recommendations Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability. (C) 2013 by American Society of Clinical Oncology C1 [Terpos, Evangelos; Dimopoulos, Meletios A.] Univ Athens, Sch Med, Athens 11528, Greece. [Morgan, Gareth] Royal Marsden Hosp, London SW3 6JJ, England. [Drake, Matthew T.; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Lentzsch, Suzanne] Columbia Univ, New York, NY USA. [Raje, Noopur; Munshi, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sezer, Orhan] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Garcia-Sanz, Ramon] Univ Salamanca, E-37008 Salamanca, Spain. [Shimizu, Kazuyuki] Nagoya City Midori Gen Hosp, Nagoya, Aichi, Japan. [Turesson, Ingemar] Malmo Univ, Malmo, Sweden. [Reiman, Tony] Univ New Brunswick, St John, NB E2L 4L5, Canada. [Jurczyszyn, Artur] Univ Hosp, Krakow, Poland. [Merlini, Giampaolo] Univ Pavia, I-27100 Pavia, Italy. [Cavo, Michele] Univ Bologna, Sch Med, Bologna, Italy. [Spencer, Andrew] Monash Univ, Melbourne, Vic 3004, Australia. [Leleu, Xavier] Ctr Hosp Reg Univ, Hop Claude Huriez, Lille, France. [Durie, Brian G. M.] Samuel Oschin Canc Ctr, Los Angeles, CA USA. [Roodman, G. David] Indiana Univ, Sch Med, Indianapolis, IN USA. RP Terpos, E (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, 80 Vas Sofias Ave, Athens 11528, Greece. EM eterpos@med.uoa.gr RI Garcia-Sanz, Ramon/B-7986-2017; OI Garcia-Sanz, Ramon/0000-0003-4120-2787; CAVO, MICHELE/0000-0003-4514-3227; Merlini, Giampaolo/0000-0001-7680-3254 FU NIAMS NIH HHS [R01 AR059679] NR 90 TC 75 Z9 78 U1 2 U2 14 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 JUN 20 PY 2013 VL 31 IS 18 BP 2347 EP U179 DI 10.1200/JCO.2012.47.7901 PG 13 WC Oncology SC Oncology GA 164XV UT WOS:000320446700020 PM 23690408 ER PT J AU Tobwala, S Zhang, XS Zheng, YY Wang, HJ Banks, WA Ercal, N AF Tobwala, Shakila Zhang, Xinsheng Zheng, Youyou Wang, Hsiu-Jen Banks, William A. Ercal, Nuran TI Disruption of the integrity and function of brain microvascular endothelial cells in culture by exposure to diesel engine exhaust particles SO TOXICOLOGY LETTERS LA English DT Article DE Diesel engine exhaust; Diesel exhaust particles; Oxidative stress; Reactive oxygen species; Glutathione ID PARTICULATE AIR-POLLUTION; TERT-BUTYL HYDROPEROXIDE; OXIDATIVE STRESS; IN-VITRO; GLUTATHIONE METABOLISM; DOPAMINERGIC-NEURONS; ULTRAFINE PARTICLES; LIPID-PEROXIDATION; BARRIER; DAMAGE AB Diesel exhaust particles (DEPs), a by-product of diesel engine exhaust (DEE), are known to produce pro-oxidative and pro-inflammatory effects, thereby leading to oxidative stress-induced damage. Given the key role of DEPs in inducing oxidative stress, we investigated the role of DEPs in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (HBMVEC). To study this, HBMVEC cells were exposed to media containing three different concentrations of DEPs or plain media for 24 h. Those exposed to DEPs showed significantly higher oxidative stress than the untreated group, as indicated by the glutathione (GSH) and malondialdehyde (MDA) levels, and the glutathione peroxidase and glutathione reductase activities. DEPs also induced oxidative stress-related disruption of the HBMVEC cells monolayer, as measured by trans-epithelial electrical resistance. Taken together, these data suggest that DEPs induce cell death and disrupt the function and integrity of HBMVEC cells, indicating a potential role of DEPs in neurotoxicities. (c) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Tobwala, Shakila; Zhang, Xinsheng; Zheng, Youyou; Wang, Hsiu-Jen; Ercal, Nuran] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO 65409 USA. [Banks, William A.] Univ Washington, Sch Med, GRECC, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Ercal, N (reprint author), Missouri Univ Sci & Technol, Dept Chem, 400 West 11th St,142 Schrenk Hall, Rolla, MO 65409 USA. EM nercal@mst.edu FU NIDA, NIH [1 R15DA023409-01A2] FX Dr. Ercal was supported by 1 R15DA023409-01A2 from the NIDA, NIH and the contents of this paper are solely the responsibility of the authors and do not necessarily represent official views of the NIDA or NIH. The authors appreciate the editorial efforts of Barbara Harris. NR 58 TC 9 Z9 9 U1 1 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUN 20 PY 2013 VL 220 IS 1 BP 1 EP 7 DI 10.1016/j.toxlet.2013.03.023 PG 7 WC Toxicology SC Toxicology GA 151GS UT WOS:000319449300001 PM 23542817 ER PT J AU Yehia, BR Kangovi, S Frank, I AF Yehia, Baligh R. Kangovi, Shreya Frank, Ian TI Patients in transition: avoiding detours on the road to HIV treatment success SO AIDS LA English DT Article DE behavioral model; care transitions; health outcomes; HIV; quality of care ID HEALTH-CARE TRANSITION; ANTIRETROVIRAL THERAPY; YOUTH; PERSPECTIVES; PREVENTION; RELEASE; SYSTEM; ADULTS; PRISON C1 [Yehia, Baligh R.; Kangovi, Shreya; Frank, Ian] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Yehia, BR (reprint author), Univ Penn, Perelman Sch Med, 1309 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM byehia@upenn.edu FU Penn Center for AIDS Research [P30 AI 045008]; National Institutes of Health [K23-MH097647-01A1] FX This work was support, in part, by the Penn Center for AIDS Research, P30 AI 045008. B.R.Y. was supported by the National Institutes of Health (K23-MH097647-01A1). NR 20 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 19 PY 2013 VL 27 IS 10 BP 1529 EP 1533 DI 10.1097/QAD.0b013e328360104e PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 250HG UT WOS:000326840700001 PM 23435297 ER PT J AU Manchia, M Adli, M Akula, N Ardau, R Aubry, JM Backlund, L Banzato, CEM Baune, BT Bellivier, F Bengesser, S Biernacka, JM Brichant-Petitjean, C Bui, E Calkin, CV Cheng, ATA Chillotti, C Cichon, S Clark, S Czerski, PM Dantas, C Del Zompo, M DePaulo, JR Detera-Wadleigh, SD Etain, B Falkai, P Frisen, L Frye, MA Fullerton, J Gard, S Garnham, J Goes, FS Grof, P Gruber, O Hashimoto, R Hauser, J Heilbronner, U Hoban, R Hou, LP Jamain, S Kahn, JP Kassem, L Kato, T Kelsoe, JR Kittel-Schneider, S Kliwicki, S Kuo, PH Kusumi, I Laje, G Lavebratt, C Leboyer, M Leckband, SG Jaramillo, CAL Maj, M Malafosse, A Martinsson, L Masui, T Mitchell, PB Mondimore, F Monteleone, P Nallet, A Neuner, M Novak, T O'Donovan, C Osby, U Ozaki, N Perlis, RH Pfennig, A Potash, JB Reich-Erkelenz, D Reif, A Reininghaus, E Richardson, S Rouleau, GA Rybakowski, JK Schalling, M Schofield, PR Schubert, OK Schweizer, B Seemuller, F Grigoroiu-Serbanescu, M Severino, G Seymour, LR Slaney, C Smoller, JW Squassina, A Stamm, T Steele, J Stopkova, P Tighe, SK Tortorella, A Turecki, G Wray, NR Wright, A Zandi, PP Zilles, D Bauer, M Rietschel, M McMahon, FJ Schulze, TG Alda, M AF Manchia, Mirko Adli, Mazda Akula, Nirmala Ardau, Raffaella Aubry, Jean-Michel Backlund, Lena Banzato, Claudio E. M. Baune, Bernhard T. Bellivier, Frank Bengesser, Susanne Biernacka, Joanna M. Brichant-Petitjean, Clara Bui, Elise Calkin, Cynthia V. Cheng, Andrew Tai Ann Chillotti, Caterina Cichon, Sven Clark, Scott Czerski, Piotr M. Dantas, Clarissa Del Zompo, Maria DePaulo, J. Raymond Detera-Wadleigh, Sevilla D. Etain, Bruno Falkai, Peter Frisen, Louise Frye, Mark A. Fullerton, Jan Gard, Sebastien Garnham, Julie Goes, Fernando S. Grof, Paul Gruber, Oliver Hashimoto, Ryota Hauser, Joanna Heilbronner, Urs Hoban, Rebecca Hou, Liping Jamain, Stephane Kahn, Jean-Pierre Kassem, Layla Kato, Tadafumi Kelsoe, John R. Kittel-Schneider, Sarah Kliwicki, Sebastian Kuo, Po-Hsiu Kusumi, Ichiro Laje, Gonzalo Lavebratt, Catharina Leboyer, Marion Leckband, Susan G. Lopez Jaramillo, Carlos A. Maj, Mario Malafosse, Alain Martinsson, Lina Masui, Takuya Mitchell, Philip B. Mondimore, Frank Monteleone, Palmiero Nallet, Audrey Neuner, Maria Novak, Tomas O'Donovan, Claire Osby, Urban Ozaki, Norio Perlis, Roy H. Pfennig, Andrea Potash, James B. Reich-Erkelenz, Daniela Reif, Andreas Reininghaus, Eva Richardson, Sara Rouleau, Guy A. Rybakowski, Janusz K. Schalling, Martin Schofield, Peter R. Schubert, Oliver K. Schweizer, Barbara Seemueller, Florian Grigoroiu-Serbanescu, Maria Severino, Giovanni Seymour, Lisa R. Slaney, Claire Smoller, Jordan W. Squassina, Alessio Stamm, Thomas Steele, Jo Stopkova, Pavla Tighe, Sarah K. Tortorella, Alfonso Turecki, Gustavo Wray, Naomi R. Wright, Adam Zandi, Peter P. Zilles, David Bauer, Michael Rietschel, Marcella McMahon, Francis J. Schulze, Thomas G. Alda, Martin TI Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report SO PLOS ONE LA English DT Article ID MAPPING SUSCEPTIBILITY GENES; PROPHYLACTIC LITHIUM; OBSERVER AGREEMENT; MOOD DISORDERS; ONSET; ASSOCIATION; RELIABILITY; MORTALITY; ILLNESS; AGE AB Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (kappa)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (kappa = 0.66 and kappa = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. C1 [Manchia, Mirko; Calkin, Cynthia V.; Garnham, Julie; O'Donovan, Claire; Slaney, Claire; Alda, Martin] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Adli, Mazda; Stamm, Thomas] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. [Akula, Nirmala; Bui, Elise; Detera-Wadleigh, Sevilla D.; Hou, Liping; Kassem, Layla; Laje, Gonzalo; Richardson, Sara; Steele, Jo; McMahon, Francis J.; Schulze, Thomas G.] NIMH, Human Genet Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. [Ardau, Raffaella; Chillotti, Caterina; Del Zompo, Maria] Univ Hosp Cagliari, Clin Pharmacol Unit, Cagliari, Italy. [Aubry, Jean-Michel; Malafosse, Alain; Nallet, Audrey] Hop Univ Geneve, Dept Mental Hlth & Psychiat, Geneva, Switzerland. [Backlund, Lena; Frisen, Louise; Martinsson, Lina] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Banzato, Claudio E. M.; Dantas, Clarissa] Univ Estadual Campinas, Dept Psychiat, Campinas, Brazil. [Baune, Bernhard T.; Clark, Scott; Schubert, Oliver K.] Univ Adelaide, Dept Psychiat, Adelaide, SA, Australia. [Bellivier, Frank; Brichant-Petitjean, Clara] Grp Hosp Lariboisiere F Widal, AP HP, Paris, France. [Bengesser, Susanne; Reininghaus, Eva] Med Univ Graz, Dept Psychiat, Graz, Austria. [Biernacka, Joanna M.; Frye, Mark A.; Seymour, Lisa R.] Mayo Clin, Dept Psychiat, Rochester, MN USA. [Cheng, Andrew Tai Ann] Acad Sinica, Inst Biomed Sci, Div Epidemiol & Genet, Taipei, Taiwan. [Cichon, Sven] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, Sven] Univ Bonn, Inst Human Genet, Bonn, Germany. [Czerski, Piotr M.] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland. [Del Zompo, Maria; Severino, Giovanni; Squassina, Alessio] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy. [DePaulo, J. Raymond; Goes, Fernando S.; Mondimore, Frank; Potash, James B.; Schweizer, Barbara; Tighe, Sarah K.; Schulze, Thomas G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Fac Med, Equipe 15, Inst Mondor Rech Biomed, INSERM,Unite 955, Creteil, France. [Falkai, Peter; Seemueller, Florian] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. [Fullerton, Jan; Schofield, Peter R.] Neurosci Res Australia Genet Mental Illness & Bra, Sydney, NSW, Australia. [Gard, Sebastien] Hop Charles Perrens, Psychiat Serv, Bordeaux, France. [Grof, Paul] Mood Disorders Ctr Ottawa, Ottawa, ON, Canada. [Grof, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Gruber, Oliver; Heilbronner, Urs; Reich-Erkelenz, Daniela; Zilles, David; Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany. [Hashimoto, Ryota] Osaka Univ, Grad Sch Med, Osaka, Japan. [Hauser, Joanna] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland. [Hoban, Rebecca; Kelsoe, John R.; Leckband, Susan G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Hoban, Rebecca; Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA. [Kahn, Jean-Pierre] Ctr Hosp Univ Nancy, Serv Psychiat & Psychol Clin, Nancy, France. [Kato, Tadafumi; Kusumi, Ichiro] RIKEN, Brain Sci Inst, Lab Mol Dynam Mental Disorders, Saitama, Japan. [Kittel-Schneider, Sarah; Neuner, Maria; Reif, Andreas] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany. [Kliwicki, Sebastian; Rybakowski, Janusz K.] Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland. [Kuo, Po-Hsiu] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan. [Kusumi, Ichiro; Masui, Takuya] Hokkaido Univ, Grad Sch Med, Dept Psychiat, Sapporo, Hokkaido, Japan. [Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Leckband, Susan G.] Vet Affairs San Diego Healthcare Syst, Dept Pharm, San Diego, CA USA. [Leckband, Susan G.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Lopez Jaramillo, Carlos A.] Univ Antioquia, Dept Psychiat, Medellin, Colombia. [Maj, Mario; Monteleone, Palmiero; Tortorella, Alfonso] Univ Naples Federico II, Dept Psychiat, Naples, Italy. [Mitchell, Philip B.; Wright, Adam] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Mitchell, Philip B.; Wright, Adam] Black Dog Inst, Sydney, NSW, Australia. [Novak, Tomas; Stopkova, Pavla] Univ Prague, Prague Psychiat Ctr, Prague, Czech Republic. [Ozaki, Norio] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. [Ozaki, Norio] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan. [Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. [Pfennig, Andrea; Bauer, Michael] Tech Univ Dresden, Dept Psychiat & Psychotherapy, Dresden, Germany. [Potash, James B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Rouleau, Guy A.] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Excellence Neurosci, Montreal, PQ, Canada. [Rouleau, Guy A.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Grigoroiu-Serbanescu, Maria] Alexandru Obregia Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania. [Turecki, Gustavo] Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada. [Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Rietschel, Marcella; Schulze, Thomas G.] Heidelberg Univ, Univ Med Ctr Mannheim, Cent Inst Mental Hlth Mannheim, Dept Genet Epidemiol Psychiat, Mannheim, Germany. RP Schulze, TG (reprint author), NIMH, Human Genet Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. EM thomas.schulze@med.uni-goettingen.de; malda@dal.ca RI Banzato, Claudio/B-2517-2008; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Ozaki, Norio/M-8908-2014; Hou, Liping/G-1648-2011; BELLIVIER, FRANK/H-5197-2012; Novak, Tomas/B-8008-2017; Kato, Tadafumi/J-3583-2014; Serbanescu, Maria/D-4306-2011; Hashimoto, Ryota/P-8572-2014; Wray, Naomi/C-8639-2015 OI Kuo, Po-Hsiu/0000-0003-0365-3587; Jamain, Stephane/0000-0002-4321-4100; McMahon, Francis/0000-0002-9469-305X; Backlund, Lena/0000-0001-9399-5024; Banzato, Claudio/0000-0002-8556-3982; Manchia, Mirko/0000-0003-4175-6413; Lavebratt, Catharina/0000-0003-4987-2718; Reininghaus, Eva/0000-0001-5964-4087; Kittel-Schneider, Sarah/0000-0003-3057-6150; Mitchell, Philip/0000-0002-7954-5235; Lopez, Carlos/0000-0002-1875-1369; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Ozaki, Norio/0000-0002-7360-4898; Hou, Liping/0000-0003-3972-245X; Novak, Tomas/0000-0001-9156-9654; Kato, Tadafumi/0000-0001-7856-3952; Serbanescu, Maria/0000-0002-1304-6687; Hashimoto, Ryota/0000-0002-5941-4238; Wray, Naomi/0000-0001-7421-3357 FU Canadian Institutes of Health Research [64410]; Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Bucharest, Romania [89/2012]; Swiss National Foundation [32003B_125469/1]; National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH), Department of Health and Human Services, United States Government; Deutsche Forschungsgemeinschaft [RI 908/7-1] FX The work on assessment of lithium response has been supported by a grant from Canadian Institutes of Health Research #64410 to MA. MG-S was supported by Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Bucharest, Romania (grant no. 89/2012). JMA and AN were supported by a grant from the Swiss National Foundation (#32003B_125469/1 to JM Aubry). ConLiGen is in part supported by funds from the Intramural Research Program of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH), Department of Health and Human Services, United States Government. It is further supported by a grant from the Deutsche Forschungsgemeinschaft to MR, MB, and TGS (RI 908/7-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 25 Z9 26 U1 7 U2 32 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 JUN 19 PY 2013 VL 8 IS 6 AR e65636 DI 10.1371/journal.pone.0065636 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190ST UT WOS:000322361200028 PM 23840348 ER PT J AU Konadhode, RR Pelluru, D Blanco-Centurion, C Zayachkivsky, A Liu, M Uhde, T Glen, WB van den Pol, AN Mulholland, PJ Shiromani, PJ AF Konadhode, Roda Rani Pelluru, Dheeraj Blanco-Centurion, Carlos Zayachkivsky, Andrew Liu, Meng Uhde, Thomas Glen, W. Bailey, Jr. van den Pol, Anthony N. Mulholland, Patrick J. Shiromani, Priyattam J. TI Optogenetic Stimulation of MCH Neurons Increases Sleep SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MELANIN-CONCENTRATING HORMONE; LOCUS-COERULEUS; OREXIN NEURONS; RAT; MICE; HYPOTHALAMUS; HYPOCRETIN; NUCLEUS; BRAIN; GENE AB Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia. C1 [Shiromani, Priyattam J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Liu, Meng; Uhde, Thomas; Mulholland, Patrick J.; Shiromani, Priyattam J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Glen, W. Bailey, Jr.; Mulholland, Patrick J.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Zayachkivsky, Andrew; van den Pol, Anthony N.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. RP Shiromani, PJ (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Psychiat, 114 Doughty St,MSC404 STB 404, Charleston, SC 29425 USA. EM shiroman@musc.edu FU NIH [AA017922, MH055772, NS052287, NS079940, NS48476]; Medical Research Service of the Department of Veterans Affairs FX This work was supported by NIH grants AA017922, MH055772, NS052287, NS079940, and NS48476 and the Medical Research Service of the Department of Veterans Affairs. We thank Dr. Mahesh Thakkar for helpful comments during the writing of this manuscript, and Sundaravadivel Balasubramanian for assistance with the confocal microscope. NR 23 TC 71 Z9 73 U1 0 U2 16 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 JUN 19 PY 2013 VL 33 IS 25 BP 10257 EP 10263 DI 10.1523/JNEUROSCI.1225-13.2013 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 166YF UT WOS:000320596400008 PM 23785141 ER PT J AU Burra, N Hervais-Adelman, A Kerzel, D Tamietto, M de Gelder, B Pegna, AJ AF Burra, Nicolas Hervais-Adelman, Alexis Kerzel, Dirk Tamietto, Marco de Gelder, Beatrice Pegna, Alan J. TI Amygdala Activation for Eye Contact Despite Complete Cortical Blindness SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PERCEIVED GAZE DIRECTION; EMOTIONAL FACES; BRAIN; PERCEPTION; CORTEX; FEAR; RECOGNITION; RESPONSES; SIGNALS; SYSTEM AB Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the amygdala response to eye contact does not require an intact primary visual cortex. C1 [Pegna, Alan J.] Univ Hosp Geneva, Dept Clin Neurosci & Dermatol, Neurol Clin, Lab Expt,Neuropsychol Unit, CH-1211 Geneva 4, Switzerland. [Burra, Nicolas; Kerzel, Dirk; Pegna, Alan J.] Univ Geneva, Fac Psychol & Educ Sci, CH-1211 Geneva, Switzerland. [Burra, Nicolas; Hervais-Adelman, Alexis; Kerzel, Dirk; Pegna, Alan J.] Univ Geneva, Neurosci Ctr, CH-1211 Geneva, Switzerland. [Hervais-Adelman, Alexis] Univ Geneva, Sch Med, Brain & Language Lab, CH-1211 Geneva, Switzerland. [Tamietto, Marco; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 AB Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tamietto, Marco] Univ Turin, Dept Psychol, I-10126 Turin, Italy. RP Pegna, AJ (reprint author), Univ Hosp Geneva, Lab Expt Neuropsychol, Neuropsychol Unit, Neurol Clin, 4 Gabrielle Perret Gentil, CH-1211 Geneva 4, Switzerland. EM alan.pegna@hcuge.ch RI Pegna, Alan/D-1297-2017; OI Pegna, Alan/0000-0001-9920-9290; Hervais-Adelman, Alexis/0000-0002-5232-626X; Tamietto, Marco/0000-0002-8815-8499 FU Swiss National Science Foundation [320030144187, PDFMP1_129459] FX This work was supported by the Swiss National Science Foundation for Scientific Research Grants 320030144187 and PDFMP1_129459. NR 37 TC 34 Z9 35 U1 3 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 19 PY 2013 VL 33 IS 25 BP 10483 EP 10489 DI 10.1523/JNEUROSCI.3994-12.2013 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 166YF UT WOS:000320596400027 PM 23785160 ER PT J AU Beissner, F Meissner, K Bar, KJ Napadow, V AF Beissner, Florian Meissner, Karin Baer, Karl-Juergen Napadow, Vitaly TI The Autonomic Brain: An Activation Likelihood Estimation Meta-Analysis for Central Processing of Autonomic Function SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HEART-RATE-VARIABILITY; RESTING-STATE CONNECTIVITY; PREFRONTAL CORTEX; SKIN-CONDUCTANCE; NERVOUS-SYSTEM; CINGULATE CORTEX; INDIVIDUAL-DIFFERENCES; NEURAL ACTIVITY; FEAR RESPONSES; HUMAN AMYGDALA AB The autonomic nervous system (ANS) is of paramount importance for daily life. Its regulatory action on respiratory, cardiovascular, digestive, endocrine, and many other systems is controlled by a number of structures in the CNS. While the majority of these nuclei and cortices have been identified in animal models, neuroimaging studies have recently begun to shed light on central autonomic processing in humans. In this study, we used activation likelihood estimation to conduct a meta-analysis of human neuroimaging experiments evaluating central autonomic processing to localize (1) cortical and subcortical areas involved in autonomic processing, (2) potential subsystems for the sympathetic and parasympathetic divisions of the ANS, and (3) potential subsystems for specific ANS responses to different stimuli/tasks. Across all tasks, we identified a set of consistently activated brain regions, comprising left amygdala, right anterior and left posterior insula and midcingulate cortices that form the core of the central autonomic network. While sympathetic-associated regions predominate in executive-and salience-processing networks, parasympathetic regions predominate in the default mode network. Hence, central processing of autonomic function does not simply involve a monolithic network of brain regions, instead showing elements of task and division specificity. C1 [Beissner, Florian; Baer, Karl-Juergen] Jena Univ Hosp, Dept Psychiat & Psychotherapy, D-07743 Jena, Germany. [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80336 Munich, Germany. [Beissner, Florian; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Beissner, F (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, 149 13th St,Room 2316, Charlestown, MA 02129 USA. EM florian@nmr.mgh.harvard.edu FU German Research Foundation [BE4677/1-1]; National Center for Complementary and Alternative Medicine [R01-AT004714, R01-AT005280, P01-AT006663]; NIDDK [R21-DK097499] FX This work was supported by German Research Foundation Grant BE4677/1-1 (F.B.) and National Center for Complementary and Alternative Medicine Grants R01-AT004714, R01-AT005280, and P01-AT006663 and NIDDK Grant R21-DK097499 (V.N.). NR 98 TC 96 Z9 96 U1 11 U2 44 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 JUN 19 PY 2013 VL 33 IS 25 BP 10503 EP + DI 10.1523/JNEUROSCI.1103-13.2013 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 166YF UT WOS:000320596400029 PM 23785162 ER PT J AU Kullgren, JT Duey, KA Werner, RM AF Kullgren, Jeffrey T. Duey, Katia A. Werner, Rachel M. TI A Census of State Health Care Price Transparency Websites SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kullgren, Jeffrey T.] Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Duey, Katia A.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kullgren, JT (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI 48105 USA. EM jkullgre@med.umich.edu NR 6 TC 10 Z9 10 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 19 PY 2013 VL 309 IS 23 BP 2437 EP 2438 DI 10.1001/jama.2013.6557 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 165SW UT WOS:000320505100019 PM 23780454 ER PT J AU Saver, JL Fonarow, GC Smith, EE Reeves, MJ Grau-Sepulveda, MV Pan, WQ Olson, DM Hernandez, AF Peterson, ED Schwamm, LH AF Saver, Jeffrey L. Fonarow, Gregg C. Smith, Eric E. Reeves, Mathew J. Grau-Sepulveda, Maria V. Pan, Wenqin Olson, DaiWai M. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. TI Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GUIDELINES-STROKE; THROMBOLYSIS; CARE; ASSOCIATION; SYSTEMS; IMPROVEMENT; EXPERIENCE; MANAGEMENT; ALTEPLASE; THERAPY AB Importance Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain. Objective To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA. Design, Setting, and Patients Data were analyzed from 58 353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012. Main Outcomes and Measures Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination. Results Among the 58 353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45 029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [ OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19 491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22 541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001). Conclusions and Relevance In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke. C1 [Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Grau-Sepulveda, Maria V.; Pan, Wenqin; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Saver, JL (reprint author), Univ Calif Los Angeles, Comprehens Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM jsaver@mednet.ucla.edu RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016 OI Smith, Eric/0000-0003-3956-1668; Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Boehringer-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; AHA Pharmaceutical Roundtable FX The GWTG-Stroke Program is provided by the AHA/American Stroke Association. The GWTG-Stroke Program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. The GWTG-Stroke Program has been funded in the past through support from Boehringer-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the AHA Pharmaceutical Roundtable. NR 31 TC 196 Z9 201 U1 3 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 19 PY 2013 VL 309 IS 23 BP 2480 EP 2488 DI 10.1001/jama.2013.6959 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 165SW UT WOS:000320505100029 PM 23780461 ER PT J AU Thompson, GR Kontoyiannis, DP Patterson, TF AF Thompson, George R., III Kontoyiannis, Dimitrios P. Patterson, Thomas F. TI Real-world Experience in the Midst of an Exserohilum Meningitis Outbreak SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID FUNGAL-INFECTIONS C1 [Thompson, George R., III] Univ Calif Davis, Div Infect Dis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Thompson, George R., III] Univ Calif Davis, Dept Internal Med, Div Infect Dis, Davis, CA 95616 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Control, Houston, TX 77030 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Employee Hlth, Houston, TX 77030 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Infect Dis, San Antonio, TX 78229 USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Room 5-035R,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM patterson@uthscsa.edu NR 8 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 19 PY 2013 VL 309 IS 23 BP 2493 EP 2495 DI 10.1001/jama.2013.6294 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 165SW UT WOS:000320505100032 PM 23780464 ER PT J AU Seo, JH Li, QY Fatima, A Eklund, A Szallasi, Z Polyak, K Richardson, AL Freedman, ML AF Seo, Ji-Heui Li, Qiyuan Fatima, Aquila Eklund, Aron Szallasi, Zoltan Polyak, Kornelia Richardson, Andrea L. Freedman, Matthew L. TI Deconvoluting complex tissues for expression quantitative trait locus-based analyses SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE expression quantitative trait locus; heterogeneous tissue; breast cancer risk single nucleotide polymorphisms ID BREAST-CANCER RISK; GENE-EXPRESSION; FGFR2 EXPRESSION; NONCODING RNA; DISEASE; DNA; AKR1C1 AB Breast cancer genome-wide association studies have pinpointed dozens of variants associated with breast cancer pathogenesis. The majority of risk variants, however, are located outside of known protein-coding regions. Therefore, identifying which genes the risk variants are acting through presents an important challenge. Variants that are associated with mRNA transcript levels are referred to as expression quantitative trait loci (eQTLs). Many studies have demonstrated that eQTL-based strategies provide a direct way to connect a trait-associated locus with its candidate target gene. Performing eQTL-based analyses in human samples is complicated because of the heterogeneous nature of human tissue. We addressed this issue by devising a method to computationally infer the fraction of cell types in normal human breast tissues. We then applied this method to 13 known breast cancer risk loci, which we hypothesized were eQTLs. For each risk locus, we took all known transcripts within a 2 Mb interval and performed an eQTL analysis in 100 reduction mammoplasty cases. A total of 18 significant associations were discovered (eight in the epithelial compartment and 10 in the stromal compartment). This study highlights the ability to perform large-scale eQTL studies in heterogeneous tissues. C1 [Seo, Ji-Heui; Li, Qiyuan; Polyak, Kornelia; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02215 USA. [Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Li, Qiyuan; Freedman, Matthew L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Li, Qiyuan; Eklund, Aron; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Szallasi, Zoltan] Harard MIT Div Hlth Sci & Technol CHIP HST, Childrens Hosp Informat Program, Boston, MA USA. [Szallasi, Zoltan; Polyak, Kornelia; Richardson, Andrea L.; Freedman, Matthew L.] Harvard Univ, Sch Med, Boston, MA USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02215 USA. EM freedman@broadinstitute.org OI Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001 NR 28 TC 4 Z9 4 U1 1 U2 9 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD JUN 19 PY 2013 VL 368 IS 1620 AR 20120363 DI 10.1098/rstb.2012.0363 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 139WD UT WOS:000318614800007 PM 23650637 ER PT J AU Kerenyi, MA Shao, Z Hsu, YJ Guo, GJ Luc, S O'Brien, K Fujiwara, Y Peng, C Nguyen, M Orkin, SH AF Kerenyi, Marc A. Shao, Zhen Hsu, Yu-Jung Guo, Guoji Luc, Sidinh O'Brien, Kassandra Fujiwara, Yuko Peng, Cong Nguyen, Minh Orkin, Stuart H. TI Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation SO ELIFE LA English DT Article ID BONE-MARROW-CELLS; GENE-EXPRESSION; DNA METHYLATION; HUMAN GENOME; DIFFERENTIATION; ENHANCERS; CHROMATIN; LEUKEMIA; TRANSCRIPTION; PLURIPOTENT AB Here, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis, combining global occupancy of Lsd1, genome-wide analysis of its substrates H3K4 monomethylation and dimethylation, and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 acts at transcription start sites, as well as enhancer regions. Loss of Lsd1 was associated with increased H3K4me1 and H3K4me2 methylation on HSPC genes and gene derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells as well as mature blood cell lineages. Collectively, our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation. C1 [Kerenyi, Marc A.; Shao, Zhen; Hsu, Yu-Jung; Guo, Guoji; Luc, Sidinh; O'Brien, Kassandra; Fujiwara, Yuko; Peng, Cong; Nguyen, Minh; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Kerenyi, Marc A.; Shao, Zhen; Hsu, Yu-Jung; Guo, Guoji; Luc, Sidinh; O'Brien, Kassandra; Fujiwara, Yuko; Peng, Cong; Nguyen, Minh; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. EM orkin@bloodgroup.tch.harvard.edu FU NIH National Heart, Lung and Blood Institute [R01HL075735]; Howard Hughes Medical Institute; Austrian Science Fund (FWF) [J 2948-B19] FX NIH National Heart, Lung and Blood Institute R01HL075735 Marc A Kerenyi; Howard Hughes Medical Institute Stuart H Orkin; Austrian Science Fund (FWF) J 2948-B19 Marc A Kerenyi NR 63 TC 63 Z9 63 U1 0 U2 9 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 18 PY 2013 VL 2 AR e00633 DI 10.7554/eLife.00633 PG 23 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274PR UT WOS:000328619000003 PM 23795291 ER PT J AU Hudson, NE Ding, F Bucay, I O'Brien, ET Gorkun, OV Superfine, R Lord, ST Dokholyan, NV Falvo, MR AF Hudson, Nathan E. Ding, Feng Bucay, Igal O'Brien, E. Timothy, III Gorkun, Oleg V. Superfine, Richard Lord, Susan T. Dokholyan, Nikolay V. Falvo, Michael R. TI Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics SO BIOPHYSICAL JOURNAL LA English DT Article ID BETA-SHEET TRANSITION; ALPHA-C REGION; DYNAMICS SIMULATIONS; COILED-COILS; CLOT; PROTEINS; EXTENSIBILITY; NETWORKS; MODULUS; FORCE AB Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured alpha C regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. C1 [Hudson, Nathan E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [Hudson, Nathan E.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hudson, Nathan E.; Bucay, Igal; O'Brien, E. Timothy, III; Superfine, Richard; Falvo, Michael R.] Univ N Carolina, Dept Phys & Astron, Ctr Computat & Syst Biol, Program Cellular & Mol Biophys, Chapel Hill, NC 27515 USA. [Gorkun, Oleg V.; Lord, Susan T.] Univ N Carolina, Dept Pathol & Lab Med, Program Cellular & Mol Biophys, Ctr Computat & Syst Biol, Chapel Hill, NC USA. [Dokholyan, Nikolay V.] Univ N Carolina, Dept Biochem & Biophys, Program Cellular & Mol Biophys, Ctr Computat & Syst Biol, Chapel Hill, NC USA. [Ding, Feng] Clemson Univ, Dept Phys & Astron, Clemson, SC 29634 USA. RP Falvo, MR (reprint author), Univ N Carolina, Dept Phys & Astron, Ctr Computat & Syst Biol, Program Cellular & Mol Biophys, Chapel Hill, NC 27515 USA. EM falvo@physics.unc.edu RI Ding, Feng/G-6029-2011; OI Ding, Feng/0000-0003-1850-6336; GORKUN, OLEG/0000-0002-3068-3389; Dokholyan, Nikolay/0000-0002-8225-4025; Hudson, Nathan/0000-0003-0573-7661 FU National Institutes of Health [GM080742, HL31048, P41-EB002025]; National Science Foundation [CMMI-1030640, DMR-0705977] FX This work was supported by National Institutes of Health grants GM080742, HL31048, and P41-EB002025, and National Science Foundation grants CMMI-1030640 and DMR-0705977. NR 63 TC 6 Z9 6 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN 18 PY 2013 VL 104 IS 12 BP 2671 EP 2680 DI 10.1016/j.bpj.2013.04.052 PG 10 WC Biophysics SC Biophysics GA 169DI UT WOS:000320757100012 PM 23790375 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Francois Jacob memorial SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT News Item ID EXPRESSION; PROTEINS C1 Dana Farber Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Inst, Dept Adult Oncol, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu NR 12 TC 1 Z9 2 U1 2 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 JUN 18 PY 2013 VL 110 IS 25 BP 10053 EP 10054 DI 10.1073/pnas.1309173110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 179DU UT WOS:000321500200016 ER PT J AU Tolstorukov, MY Sansam, CG Lu, P Koellhoffer, EC Helming, KC Alver, BH Tillman, EJ Evans, JA Wilson, BG Park, PJ Roberts, CWM AF Tolstorukov, Michael Y. Sansam, Courtney G. Lu, Ping Koellhoffer, Edward C. Helming, Katherine C. Alver, Burak H. Tillman, Erik J. Evans, Julia A. Wilson, Boris G. Park, Peter J. Roberts, Charles W. M. TI Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RHABDOID TUMORS; GENE-REGULATION; HUMAN GENOME; CANCER; TRANSCRIPTION; SNF5; MUTATIONS; LANDSCAPE; MICE; INI1 AB Precise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established, are dynamically maintained, and subsequently contribute to transcriptional control are poorly understood. The switch/sucrose non-fermentable chromatin remodeling complex, also known as the Brg1 associated factors complex, is a master developmental regulator and tumor suppressor capable of mobilizing nucleosomes in biochemical assays. However, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genomewide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation. C1 [Tolstorukov, Michael Y.; Alver, Burak H.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Tolstorukov, Michael Y.; Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Sansam, Courtney G.; Lu, Ping; Koellhoffer, Edward C.; Helming, Katherine C.; Tillman, Erik J.; Evans, Julia A.; Wilson, Boris G.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sansam, Courtney G.; Lu, Ping; Koellhoffer, Edward C.; Helming, Katherine C.; Tillman, Erik J.; Evans, Julia A.; Wilson, Boris G.; Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sansam, Courtney G.; Lu, Ping; Koellhoffer, Edward C.; Helming, Katherine C.; Tillman, Erik J.; Evans, Julia A.; Wilson, Boris G.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. EM peter_park@harvard.edu; charles_roberts@dfci.harvard.edu OI Koellhoffer, Edward/0000-0002-7260-9507; Tillman, Erik/0000-0003-3599-0297; Alver, Burak/0000-0002-5019-7652 FU Ruth L. Kirschstein National Research Service Award Fellowship from the National Cancer Institute [5F32 CA123776]; Ruth L. Kirschstein National Research Service Award Fellowship [U01HG004258, R01GM082798, R01CA113794]; Innovative Research Grant from Stand Up 2 Cancer; U01 NCI Mouse Models of Cancer Consortium Award; Sloan Research Fellowship; Garrett B. Smith Foundation; Miles for Mary; foundation Cure AT/RT Now FX We thank Xi Wang for critical review of the manuscript and Lee Whale for the artwork in Figs. 1A and 5. This work was supported in part by a Ruth L. Kirschstein National Research Service Award Fellowship 5F32 CA123776 from the National Cancer Institute (to C. G. S.), U01HG004258 (to M.Y.T.), R01GM082798 (to P.J.P.), R01CA113794 (to C. W. M. R.); an Innovative Research Grant from Stand Up 2 Cancer (to C. W. M. R.); and a U01 NCI Mouse Models of Cancer Consortium Award (to C. W. M. R.). The Sloan Research Fellowship (P.J.P.), Garrett B. Smith Foundation, Miles for Mary, and the foundation Cure AT/RT Now (C. W. M. R.) provided additional support. NR 52 TC 62 Z9 62 U1 0 U2 24 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 JUN 18 PY 2013 VL 110 IS 25 BP 10165 EP 10170 DI 10.1073/pnas.1302209110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 179DU UT WOS:000321500200039 PM 23723349 ER PT J AU Li, XH Burnight, ER Cooney, AL Malani, N Brady, T Sander, JD Staber, J Wheelan, SJ Joung, JK McCray, PB Bushman, FD Sinn, PL Craig, NL AF Li, Xianghong Burnight, Erin R. Cooney, Ashley L. Malani, Nirav Brady, Troy Sander, Jeffry D. Staber, Janice Wheelan, Sarah J. Joung, J. Keith McCray, Paul B., Jr. Bushman, Frederic D. Sinn, Patrick L. Craig, Nancy L. TI piggyBac transposase tools for genome engineering SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GULOP; ROSA26; protein-DNA interaction; induced pluripotent stem cell production ID MAMMALIAN-CELLS; SLEEPING-BEAUTY; STEM-CELLS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; SITE SELECTION; IN-VIVO; DNA; MICE; MUTAGENESIS AB The transposon piggyBac is being used increasingly for genetic studies. Here, we describe modified versions of piggyBac transposase that have potentially wide-ranging applications, such as reversible transgenesis and modified targeting of insertions. piggyBac is distinguished by its ability to excise precisely, restoring the donor site to its pretransposon state. This characteristic makes piggyBac useful for reversible transgenesis, a potentially valuable feature when generating induced pluripotent stem cells without permanent alterations to genomic sequence. To avoid further genome modification following piggyBac excision by reintegration, we generated an excision competent/integration defective (Exc(+)Int(-)) transposase. Our findings also suggest the position of a target DNA-transposase interaction. Another goal of genome engineering is to develop reagents that can guide transgenes to preferred genomic regions. Others have shown that piggyBac transposase can be active when fused to a heterologous DNA-binding domain. An Exc(+)Int(-) transposase, the intrinsic targeting of which is defective, might also be a useful intermediate in generating a transposase whose integration activity could be rescued and redirected by fusion to a site-specific DNA-binding domain. We show that fusion to two designed zinc finger proteins rescued the Int(-) phenotype. Successful guided transgene integration into genomic DNA would have broad applications to gene therapy and molecular genetics. Thus, an Exc(+)Int(-) transposase is a potentially useful reagent for genome engineering and provides insight into the mechanism of transposase-target DNA interaction. C1 [Li, Xianghong; Craig, Nancy L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Li, Xianghong; Craig, Nancy L.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Burnight, Erin R.; McCray, Paul B., Jr.] Univ Iowa, Carver Coll Med, Genet Program, Iowa City, IA 52242 USA. [Cooney, Ashley L.; Staber, Janice; McCray, Paul B., Jr.; Sinn, Patrick L.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. [Malani, Nirav; Brady, Troy; Bushman, Frederic D.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Boston, MA 02129 USA. [Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. [Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wheelan, Sarah J.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat & Bioinformat, Baltimore, MD 21205 USA. RP Sinn, PL (reprint author), Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. EM patrick-sinn@uiowa.edu; ncraig@jhmi.edu OI Bushman, Frederic/0000-0003-4740-4056 FU Maryland Stem Cell Research Fund; National Institutes of Health (NIH) [T32 CA009216, DP1 GM105378, R01 GM088040, R01 HL-105821]; University of Iowa Center for Gene Therapy [NIH P30 DK-54759]; [AI 052845]; [AI082020] FX We thank Dr. Rupak Mitra and Dr. Courtney Busch for many discussions about piggyBac; Benjamin Brett, Dr. Todd Scheetz, and Dr. Tom Bair for their expert consultation; and Maureen R. Regan for technical assistance. This work was supported by a grant from the Maryland Stem Cell Research Fund (to N.L.C.). N.L.C. is an investigator of the Howard Hughes Medical Institute. This work was supported by Grants AI 052845 and AI082020 (to F. D. B.). J.D.S. was supported by National Institutes of Health (NIH) Grant T32 CA009216. J.K.J. was supported by NIH Director's Pioneer Award DP1 GM105378 and by NIH Grant R01 GM088040. This work was supported by the NIH Grant R01 HL-105821 (to P. L. S. and J.K.J.) and partially supported by the University of Iowa Center for Gene Therapy (NIH P30 DK-54759). NR 29 TC 40 Z9 44 U1 1 U2 29 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 JUN 18 PY 2013 VL 110 IS 25 BP E2279 EP E2287 DI 10.1073/pnas.1305987110 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 179DU UT WOS:000321500200009 PM 23723351 ER PT J AU Peng, J Li, QL Wigglesworth, K Rangarajan, A Kattamuri, C Peterson, RT Eppig, JJ Thompson, TB Matzuk, MM AF Peng, Jia Li, Qinglei Wigglesworth, Karen Rangarajan, Adithya Kattamuri, Chandramohan Peterson, Randall T. Eppig, John J. Thompson, Thomas B. Matzuk, Martin M. TI Reply to Mottershead et al.: GDF9:BMP15 heterodimers are potent regulators of ovarian functions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID MORPHOGENETIC PROTEIN 15; DIFFERENTIATION FACTOR-9; GROWTH C1 [Peng, Jia; Matzuk, Martin M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Peng, Jia; Matzuk, Martin M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Rangarajan, Adithya; Matzuk, Martin M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Ctr Drug Discovery, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA. [Li, Qinglei] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [Wigglesworth, Karen; Eppig, John J.] Jackson Lab, Bar Harbor, ME 04609 USA. [Kattamuri, Chandramohan; Thompson, Thomas B.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45221 USA. [Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Peterson, Randall T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Matzuk, MM (reprint author), Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. EM mmatzuk@bcm.edu FU NICHD NIH HHS [R01 HD023839, R37 HD033438, R01 HD033438] NR 6 TC 1 Z9 1 U1 0 U2 6 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 JUN 18 PY 2013 VL 110 IS 25 BP E2258 EP E2258 DI 10.1073/pnas.1304497110 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 179DU UT WOS:000321500200004 PM 23940843 ER PT J AU Kluk, MJ Ashworth, T Wang, HF Knoechel, B Mason, EF Morgan, EA Dorfman, D Pinkus, G Weigert, O Hornick, JL Chirieac, LR Hirsch, M Oh, DJ South, AP Leigh, IM Pourreyron, C Cassidy, AJ DeAngelo, DJ Weinstock, DM Krop, IE Dillon, D Brock, JE Lazar, AJF Peto, M Cho, RJ Stoeck, A Haines, BB Sathayanrayanan, S Rodig, S Aster, JC AF Kluk, Michael J. Ashworth, Todd Wang, Hongfang Knoechel, Birgit Mason, Emily F. Morgan, Elizabeth A. Dorfman, David Pinkus, Geraldine Weigert, Oliver Hornick, Jason L. Chirieac, Lucian R. Hirsch, Michelle Oh, David J. South, Andrew P. Leigh, Irene M. Pourreyron, Celine Cassidy, Andrew J. DeAngelo, Daniel J. Weinstock, David M. Krop, Ian E. Dillon, Deborah Brock, Jane E. Lazar, Alexander J. F. Peto, Myron Cho, Raymond J. Stoeck, Alexander Haines, Brian B. Sathayanrayanan, Sriram Rodig, Scott Aster, Jon C. TI Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry SO PLOS ONE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SQUAMOUS-CELL CARCINOMA; MARGINAL ZONE LYMPHOMA; GENE AMPLIFICATION; OVARIAN-CANCER; BREAST-CANCER; CODING GENOME; STEM-CELLS; B-CLL; T-ALL AB Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors), but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of patients for clinical trials. C1 [Kluk, Michael J.; Ashworth, Todd; Wang, Hongfang; Mason, Emily F.; Morgan, Elizabeth A.; Dorfman, David; Pinkus, Geraldine; Hornick, Jason L.; Chirieac, Lucian R.; Hirsch, Michelle; Oh, David J.; Dillon, Deborah; Brock, Jane E.; Rodig, Scott; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kluk, Michael J.; Ashworth, Todd; Wang, Hongfang; Mason, Emily F.; Morgan, Elizabeth A.; Dorfman, David; Pinkus, Geraldine; Hornick, Jason L.; Chirieac, Lucian R.; Hirsch, Michelle; Oh, David J.; Dillon, Deborah; Brock, Jane E.; Rodig, Scott; Aster, Jon C.] Harvard Univ, Sch Med, Boston, MA USA. [Knoechel, Birgit; Weigert, Oliver; DeAngelo, Daniel J.; Weinstock, David M.; Krop, Ian E.] Dana Farber Canc Inst, Dept Pediat Hematol, Boston, MA 02115 USA. [Knoechel, Birgit; Weigert, Oliver; DeAngelo, Daniel J.; Weinstock, David M.; Krop, Ian E.] Dana Farber Canc Inst, Dept Oncol & Med Oncol, Boston, MA 02115 USA. [South, Andrew P.; Leigh, Irene M.; Pourreyron, Celine; Cassidy, Andrew J.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Canc Res, Dundee DD1 9SY, Scotland. [South, Andrew P.; Leigh, Irene M.; Pourreyron, Celine; Cassidy, Andrew J.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Genet Core Serv Unit, Dundee DD1 9SY, Scotland. [Lazar, Alexander J. F.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Peto, Myron] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Cho, Raymond J.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Stoeck, Alexander; Haines, Brian B.; Sathayanrayanan, Sriram] Merck Oncol, Boston, MA USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jaster@rics.bwh.harvard.edu RI Lazar, Alexander/A-3416-2008; OI Lazar, Alexander/0000-0002-6395-4499; Cassidy, Andrew/0000-0003-4309-6981; Morgan, Elizabeth/0000-0001-5880-9337 FU NIH; Leukemia and Lymphoma Society; BWH Department of Pathology Robbins Award FX Supported by grants from the NIH and Leukemia and Lymphoma Society (JCA) and the BWH Department of Pathology Robbins Award (MJK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 37 Z9 38 U1 0 U2 5 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 JUN 18 PY 2013 VL 8 IS 6 AR UNSP e67306 DI 10.1371/journal.pone.0067306 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166SA UT WOS:000320576400182 PM 23825651 ER PT J AU Nakaya, T Ishiguro, K Belzil, C Rietsch, AM Yu, QY Mizuno, S Bronson, RT Geng, Y Nguyen, MD Akashi, K Sicinski, P Nakatani, Y AF Nakaya, Takeo Ishiguro, Kei-ichiro Belzil, Camille Rietsch, Anna M. Yu, Qunyan Mizuno, Shin-ichi Bronson, Roderick T. Geng, Yan Minh Dang Nguyen Akashi, Koichi Sicinski, Piotr Nakatani, Yoshihiro TI p600 Plays Essential Roles in Fetal Development SO PLOS ONE LA English DT Article ID END RULE PATHWAY; FOCAL ADHESION KINASE; AUXIN TRANSPORT; E7 ONCOPROTEIN; PROTEIN; MOUSE; IDENTIFICATION; TRANSFORMATION; GENES; HEART AB p600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development. C1 [Nakaya, Takeo; Ishiguro, Kei-ichiro; Rietsch, Anna M.; Yu, Qunyan; Geng, Yan; Sicinski, Piotr; Nakatani, Yoshihiro] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Nakaya, Takeo; Ishiguro, Kei-ichiro; Rietsch, Anna M.; Yu, Qunyan; Mizuno, Shin-ichi; Geng, Yan; Akashi, Koichi; Sicinski, Piotr; Nakatani, Yoshihiro] Harvard Univ, Sch Med, Boston, MA USA. [Nakaya, Takeo] Tokyo Med Univ, Translat Res Unit, Shinjuku Ku, Tokyo 1608402, Japan. [Nakaya, Takeo] Tokyo Med Univ, Dept Mol Pathol, Shinjuku Ku, Tokyo 1608402, Japan. [Ishiguro, Kei-ichiro] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo, Japan. [Belzil, Camille; Minh Dang Nguyen] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Mizuno, Shin-ichi; Akashi, Koichi] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Mizuno, Shin-ichi; Akashi, Koichi] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 812, Japan. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM yoshihiro_nakatani@dfci.harvard.edu FU National Institutes of Health [R01CA138866, R01CA108950]; Uehara foundation; Japan Society for the Promotion of Science; AIHS FX This work was supported by National Institutes of Health grants (R01CA138866 to YN and R01CA108950 to PS). TN was supported by Uehara foundation fellowship for research abroad. KI was supported by Japan Society for the Promotion of Science fellowship for research abroad, the Grant-in-Aid for Scientific Research on Priority Areas, a Grant in-Aid for Scientific Research on Innovative Areas and Grant in-Aid for Young Scientists. CB was supported by an AIHS doctoral scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2013 VL 8 IS 6 AR e66269 DI 10.1371/journal.pone.0066269 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166SA UT WOS:000320576400075 PM 23824717 ER PT J AU Hayes, JH Ollendorf, DA Pearson, SD Barry, MJ Kantoff, PW Lee, PA McMahon, PM AF Hayes, Julia H. Ollendorf, Daniel A. Pearson, Steven D. Barry, Michael J. Kantoff, Philip W. Lee, Pablo A. McMahon, Pamela M. TI Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer A Cost-Effectiveness Analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACTIVE SURVEILLANCE; RADICAL PROSTATECTOMY; CONTROLLED-TRIAL; MANAGEMENT; OUTCOMES; MORTALITY; THERAPY; RADIATION; BIOPSY; GRADE AB Background: Observation is underutilized among men with localized, low-risk prostate cancer. Objective: To assess the costs and benefits of observation versus initial treatment. Design: Decision analysis simulating treatment or observation. Data Sources: Medicare schedules, published literature. Target Population: Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 mu g/L, stage <= T2a, Gleason score <= 3 + 3). Time Horizon: Lifetime. Perspective: Societal. Intervention: Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). Outcome Measures: Quality-adjusted life expectancy and costs. Results of Base-Case Analysis: Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. Results of Sensitivity Analysis: Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. Limitation: Results depend on outcomes reported in the published literature, which is limited. Conclusion: Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Inst Technol Assessment, Lank Ctr Genitourinary Oncol,Inst Clin & Econ Rev, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hayes, JH (reprint author), Dana Farber Canc Inst, Dana 1230,450 Brookline Ave, Boston, MA 02115 USA. EM Julia_Hayes@dfci.harvard.edu FU National Cancer Institute; U.S. Department of Defense [W81XWH-09-1-0512]; Prostate Cancer Foundation; Institute for Clinical and Economic Review; National Cancer Institute at the National Institutes of Health [R25 CA92203-08]; Blue Shield of California Foundation; Agency for Healthcare Research and Quality; Health Dialog FX National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.; By grant R25 CA92203-08 (National Cancer Institute at the National Institutes of Health), grant W81XWH-09-1-0512 (U.S. Department of Defense), a Young Investigators Award to Dr. Hayes (Prostate Cancer Foundation), and funding to the Institute for Clinical and Economic Review from the Blue Shield of California Foundation.; Dr. Hayes: Grants (money to institution): U.S. Department of Defense, Prostate Cancer Foundation; Royalties: UpToDate. Dr. Ollendorf: Grants (money to institution): Blue Shield of California Foundation. Dr. Pearson: Consultancy: National Institutes of Health, Yale University; Employment: Massachusetts General Hospital; Grants/grants pending (money to institution): Agency for Healthcare Research and Quality. Dr. Barry: Board membership: Informed Medical Decisions Foundation; Employment: Informed Medical Decisions Foundation; Royalties (money to institution): Health Dialog. Dr. McMahon: Grants (money to institution): Blue Shield of California Foundation, Harvard Community Health Plan. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-085 7. NR 39 TC 42 Z9 42 U1 1 U2 13 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 JUN 18 PY 2013 VL 158 IS 12 BP 853 EP + DI 10.7326/0003-4819-158-12-201306180-00002 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 167PW UT WOS:000320645000013 PM 23778902 ER PT J AU Mahaffey, KW Wojdyla, D Hankey, GJ White, HD Nessel, CC Piccini, JP Patel, MR Berkowitz, SD Becker, RC Halperin, JL Singer, DE Califf, RM Fox, KAA Breithardt, G Hacke, W AF Mahaffey, Kenneth W. Wojdyla, Daniel Hankey, Graeme J. White, Harvey D. Nessel, Christopher C. Piccini, Jonathan P. Patel, Manesh R. Berkowitz, Scott D. Becker, Richard C. Halperin, Jonathan L. Singer, Daniel E. Califf, Robert M. Fox, Keith A. A. Breithardt, Guenter Hacke, Werner TI Clinical Outcomes With Rivaroxaban in Patients Transitioned From Vitamin K Antagonist Therapy A Subgroup Analysis of a Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ATRIAL-FIBRILLATION; WARFARIN; ANTICOAGULATION; PREVENTION; DABIGATRAN; HEMORRHAGE; RISK AB Background: In ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation. Objective: To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients. Design: Prespecified subgroup analysis. (ClinicalTrials.gov: NCT00403767) Setting: Global. Patients: 14 264 persons with atrial fibrillation. Measurements: Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients. Results: Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18]; interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58]; interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17]; interaction P = 0.003). Limitation: The trial was not designed to detect differences in these subgroups. Conclusion: The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. Royal Perth Hosp, Perth, WA, Australia. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1030, New Zealand. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. Bayer HealthCare Pharmaceut, Montville, NJ 07045 USA. Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. Hosp Univ Munster, Munster, Germany. Heidelberg Univ, Heidelberg, Germany. RP Mahaffey, KW (reprint author), Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM kenneth.mahaffey@dm.duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson Johnson; Bayer HealthCare; Johnson & Johnson Pharmaceutical Research and Development FX Johnson & Johnson and Bayer HealthCare.; By Johnson & Johnson Pharmaceutical Research and Development and Bayer HealthCare. NR 13 TC 19 Z9 20 U1 0 U2 5 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 JUN 18 PY 2013 VL 158 IS 12 BP 861 EP + DI 10.7326/0003-4819-158-12-201306180-00003 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 167PW UT WOS:000320645000014 PM 23778903 ER PT J AU Fu, RW Selph, S McDonagh, M Peterson, K Tiwari, A Chou, R Helfand, M AF Fu, Rongwei Selph, Shelley McDonagh, Marian Peterson, Kimberly Tiwari, Arpita Chou, Roger Helfand, Mark TI Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in Spine Fusion A Systematic Review and Meta-analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID LUMBAR INTERBODY FUSION; ANTERIOR CERVICAL DISKECTOMY; OFF-LABEL USE; RADIOGRAPHIC OUTCOMES; RETROGRADE EJACULATION; INTEGRATED ANALYSIS; RHBMP-2; SURGERY; AUTOGRAFT; ALLOGRAFT AB Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question. Purpose: To independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications. Data Sources: Individual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists. Study Selection: Randomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms. Data Extraction: Effectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria. Data Synthesis: Thirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting. Limitations: Outcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship. Conclusion: In spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did. C1 [Fu, Rongwei] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. Oregon State Univ, Corvallis, OR 97331 USA. RP Fu, RW (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code CSB669, Portland, OR 97239 USA. EM fur@ohsu.edu FU Yale University; Medtronic; Oregon Health & Science University FX Yale University and Medtronic.; By a research subcontract to Oregon Health & Science University under a sponsored research agreement between Yale University and Medtronic. NR 82 TC 151 Z9 152 U1 2 U2 20 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 JUN 18 PY 2013 VL 158 IS 12 BP 890 EP + DI 10.7326/0003-4819-158-12-201306180-00006 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 167PW UT WOS:000320645000017 PM 23778906 ER PT J AU Roush, GC Holford, TR Guddati, AK AF Roush, George C. Holford, Theodore R. Guddati, Achuta K. TI Chlorthalidone Versus Hydrochlorothiazide SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Roush, George C.] Univ Connecticut Sch Med, Bridgeport, CT USA. [Roush, George C.] St Vincents Med Ctr, Bridgeport, CT USA. [Holford, Theodore R.] Yale Univ Sch Publ Hlth, New Haven, CT USA. [Guddati, Achuta K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roush, GC (reprint author), Univ Connecticut Sch Med, Bridgeport, CT USA. NR 5 TC 3 Z9 3 U1 1 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 JUN 18 PY 2013 VL 158 IS 12 BP 920 EP 920 DI 10.7326/0003-4819-158-12-201306180-00014 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 167PW UT WOS:000320645000023 PM 23778913 ER PT J AU Braunwald, E Morrow, DA AF Braunwald, Eugene Morrow, David A. TI Unstable Angina: Is It Time for a Requiem? SO CIRCULATION LA English DT Article DE angina, unstable; troponin ID ACUTE CORONARY SYNDROMES; CARDIAC TROPONIN-I; ELEVATION MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; MEDICINE PRACTICE GUIDELINES; CLINICAL BIOCHEMISTRY; MINOR ELEVATIONS; NATIONAL ACADEMY; DECISION-MAKING; SENSITIVE ASSAY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org FU Accumetrics; Amgen; Athera; AstraZeneca; Beckman Coulter; BG Medicine; Bristol-Myers Squibb; Buhlmann Diagnostics; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Integrated Therapeutics; Johnson Johnson; Merck and Co; Merck-Schering Plow Joint Venture; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plow; Siemens; Singulex; Daiichi Sankyo; Genzyme; Amorcyte; Medicines Company; MC Communications; Ikaria; CardioRentis; Sanofi Aventis; Beckman-Coulter; Critical Diagnostics; Genentech; Gilead; Instrumentation Laboratories; Merck; Servier FX The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, Athera, AstraZeneca, Beckman Coulter, BG Medicine, Bristol-Myers Squibb, Buhlmann Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Johnson & Johnson, Merck and Co, Merck-Schering Plow Joint Venture, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plow, Siemens, and Singulex. Dr Braunwald has received consulting fees from Daiichi Sankyo, Genzyme, Amorcyte, The Medicines Company, MC Communications, Ikaria, CardioRentis, and Sanofi Aventis. Dr Morrow has received consulting fees from Beckman-Coulter, BG Medicine, Critical Diagnostics, Genentech, Gilead, Instrumentation Laboratories, Johnson & Johnson, Merck, Roche Diagnostics, and Servier. NR 45 TC 36 Z9 39 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 JUN 18 PY 2013 VL 127 IS 24 BP 2452 EP 2457 DI 10.1161/CIRCULATIONAHA.113.001258 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 168IM UT WOS:000320699100024 PM 23775194 ER PT J AU Clark, D McGiffin, DC Dell'Italia, LJ Ahmed, MI AF Clark, Donald, III McGiffin, David C. Dell'Italia, Louis J. Ahmed, Mustafa I. TI Submassive Pulmonary Embolism: Where's the Tipping Point? SO CIRCULATION LA English DT Article DE pulmonary embolism ID RIGHT-VENTRICULAR DYSFUNCTION; VENOUS THROMBOEMBOLISM; SURGICAL-TREATMENT; CONSECUTIVE PATIENTS; PROGNOSTIC VALUE; RISK-FACTORS; RIGHT HEART; EMBOLECTOMY; MANAGEMENT; HYPERTENSION C1 [Clark, Donald, III; Dell'Italia, Louis J.; Ahmed, Mustafa I.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [McGiffin, David C.] Univ Alabama Birmingham, Div Cardiothorac Surg, Dept Surg, Birmingham, AL 35294 USA. [Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Ahmed, MI (reprint author), Univ Alabama Birmingham, Div Cardiol, Dept Med, 434 BMR2,901 19th St South, Birmingham, AL 35294 USA. EM mahmed@uab.edu FU NIDDK NIH HHS [P30 DK079626] NR 36 TC 0 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 18 PY 2013 VL 127 IS 24 BP 2458 EP 2464 DI 10.1161/CIRCULATIONAHA.112.000859 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 168IM UT WOS:000320699100025 PM 23775195 ER PT J AU Dake, MD Ansel, GM Jaff, MR Ohki, T Saxon, RR Smouse, HB Snyder, SA O'Leary, EE Tepe, G Scheinert, D Zeller, T AF Dake, Michael D. Ansel, Gary M. Jaff, Michael R. Ohki, Takao Saxon, Richard R. Smouse, H. Bob Snyder, Scott A. O'Leary, Erin E. Tepe, Gunnar Scheinert, Dierk Zeller, Thomas CA Zilver PTX Investigators TI Sustained Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Lesions 2-Year Follow-Up From the Zilver PTX Randomized and Single-Arm Clinical Studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angioplasty; drug-eluting stent(s); paclitaxel-eluting stent(s); peripheral arterial disease ID SUPERFICIAL FEMORAL-ARTERY; BARE NITINOL STENTS; BALLOON ANGIOPLASTY; POPLITEAL ARTERIES; TRIAL; IMPLANTATION; DISEASE; CLAUDICATION; PERFORMANCE; RESTENOSIS AB Objectives A prospective, multinational randomized controlled trial (RCT) and a complementary single-arm study evaluated the 2-year safety and effectiveness of a paclitaxel-coated drug-eluting stent (DES) in patients with superficial femoral artery lesions. The RCT compared the DES with percutaneous transluminal angioplasty (PTA) and provisional bare-metal stent (BMS) placement. Background Local drug delivery for superficial femoral artery lesions has been investigated with the intent of limiting restenosis similarly to DES for the coronary arteries. One-year outcomes of DES in the superficial femoral artery are promising, but longer-term benefits have not been established. Methods In the RCT, patients were randomly assigned to primary DES implantation (n = 236) or PTA (n = 238). Acute PTA failure occurred in 120 patients, who underwent secondary randomization to DES (n = 61) or BMS (n = 59) placement. The single-arm study enrolled 787 patients with DES treatment. Results Compared with the control group, the primary DES group demonstrated significantly superior 2-year event-free survival (86.6% vs. 77.9%, p = 0.02) and primary patency (74.8% vs. 26.5%, p < 0.01). In addition, the provisional DES group exhibited superior 2-year primary patency compared with the provisional BMS group (83.4% vs. 64.1%, p < 0.01) and achieved higher sustained clinical benefit (83.9% vs. 68.4%, p = 0.05). Two-year freedom from target lesion revascularization with primary DES placement was 80.5% in the single-arm study and 86.6% in the RCT. Conclusions Two-year outcomes with the paclitaxel-eluting stent support its sustained safety and effectiveness in patients with femoropopliteal artery disease, including the long-term superiority of the DES to PTA and to provisional BMS placement. (Evaluation of the Zilver PTX Drug-Eluting Stent in the Above-the-Knee Femoropopliteal Artery; NCT00120406; Zilver (R) PTX (TM) Global Registry; NCT01094678) (C) 2013 by the American College of Cardiology Foundation C1 [Dake, Michael D.] Stanford Univ, Med Ctr, Dept Cardiothorac Surg, Stanford, CA 94305 USA. [Ansel, Gary M.] Riverside Methodist Hosp, Ctr Crit Limb Care, Columbus, OH 43214 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. [Ohki, Takao] Jikei Univ Hosp, Dept Surg, Tokyo, Japan. [Saxon, Richard R.] Tricity Med Ctr, Dept Diagnost Imaging & Intervent Radiol, Oceanside, CA USA. [Smouse, H. Bob] OSF St Francis Med Ctr, Dept Radiol, Peoria, IL USA. [Snyder, Scott A.; O'Leary, Erin E.] MED Inst Inc, W Lafayette, IN USA. [Tepe, Gunnar] Klinikum Rosenheim, Dept Radiol, Rosenheim, Germany. [Scheinert, Dierk] Pk Hosp, Dept Radiol, Ctr Vasc Med, Leipzig, Germany. [Zeller, Thomas] Herz Zentrum, Dept Angiol, Bad Krozingen, Germany. RP Dake, MD (reprint author), Stanford Univ, Sch Med, Dept Cardiothorac Surg, Falk Cardiovasc Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA. EM mddake@stanford.edu FU Cook Medical; Flexible Stenting Solutions; Cordis Endovascular; Sanofi-Aventis FX These studies were sponsored by Cook Medical. Dr. Dake is a member of the advisory boards of Abbott Vascular, W. L. Gore, TriVascular, and Vortex Medical and is a member of the board of directors of VIVA Physicians, a not-for-profit 501(c)(3) education and research organization, and has received speaking honoraria from Cook Medical. Dr. Ansel is a consultant for Cook Medical, Cordis Endovascular, C. R. Bard, W. L. Gore, and Flexible Stenting Solutions; has financial ownership in Flexible Stenting Solutions; has received payments for speakers' bureau appointments from Cook Medical, Cordis Endovascular, and W. L. Gore; and has received research grants from Cook Medical. Dr. Jaff is a member of the board of directors of VIVA Physicians. Dr. Ohki has received speaking honoraria from Cook Medical. Dr. Saxon is a member of the advisory board of Abbott Vascular and serves as a consultant for W. L. Gore; has received speaking honoraria from W. L. Gore; has received research grants from Cook Medical, W. L. Gore, Covidien, and Lutonix/C. R. Bard; and was an expert witness for a device unrelated to this study. Dr. Smouse is a consultant for Cook Medical. Drs. Snyder and O'Leary are paid employees of MED Institute, Inc., a contract research organization and Cook Group company. Dr. Tepe is a consultant for Cook Medical. Dr. Zeller is a member of the advisory boards of Medtronic-Invatec, W. L. Gore, Angioslide, Medtronic-Ardian, and Covidien; has received consulting fees or speaking honoraria from Sanofi-Aventis, C. R. Bard, Johnson & Johnson Cordis, Covidien, Boston Scientific Corporation, Straub Medical, Cook Medical, Invatec, Biotronik, Optimed, Pathway Medical, and W. L. Gore; and has received research grants from Cook Medical, Krauth Medical, Pathway Medical, Abbott Vascular, Johnson & Johnson Cordis, Angioslide, Ardian, Biotronik, Invatec, InnoRa, and W. L. Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 19 TC 141 Z9 147 U1 2 U2 8 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 JUN 18 PY 2013 VL 61 IS 24 BP 2417 EP 2427 DI 10.1016/j.jacc.2013.03.034 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167AJ UT WOS:000320602200005 PM 23583245 ER PT J AU Weinrauch, LA Desai, AS Skali, H D'Elia, JA AF Weinrauch, Larry A. Desai, Akshay S. Skali, Hicham D'Elia, John A. TI Risk Stratification of Resistant Hypertension in Chronic Kidney Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE ambulatory blood pressure monitoring; chronic kidney disease; resistant hypertension ID RENAL SYMPATHETIC DENERVATION; HIGH-BLOOD-PRESSURE; CONTROLLED-TRIAL; ARTERY STENOSIS; THERAPY; RECOMMENDATIONS; MANAGEMENT; DIAGNOSIS; HOME C1 [Weinrauch, Larry A.; D'Elia, John A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.; Desai, Akshay S.; Skali, Hicham] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Weinrauch, LA (reprint author), Harvard Univ, Sch Med, 521 Mt Auburn St, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu OI Skali, Hicham/0000-0002-5629-4138; Weinrauch, Larry/0000-0003-1357-9528 NR 19 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 18 PY 2013 VL 61 IS 24 BP 2468 EP 2470 DI 10.1016/j.jacc.2013.03.048 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167AJ UT WOS:000320602200012 PM 23623913 ER PT J AU Cook, AJ Gold, DR Li, Y AF Cook, Andrea J. Gold, Diane R. Li, Yi TI Spatial Cluster Detection for Longitudinal Outcomes Using Administrative Regions SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Asthma; Cluster detection; Cumulative residuals; Repeated measures; Wheeze ID CHILDREN AB This article proposes a new spatial cluster detection method for longitudinal outcomes that detects neighborhoods and regions with elevated rates of disease while controlling for individual level confounders. The proposed method, CumResPerm, utilizes cumulative geographic residuals through a permutation test to detect potential clusters which are defined as sets of administrative regions, such as a town or group of administrative regions. Previous cluster detection methods are not able to incorporate individual level data including covariate adjustment, while still being able to define potential clusters using informative neighborhood or town boundaries. Often, it is of interest to detect such spatial clusters because individuals residing in a town may have similar environmental exposures or socioeconomic backgrounds due to administrative reasons, such as zoning laws. Therefore, these boundaries can be very informative and more relevant than arbitrary clusters such as the standard circle or square. Application of the CumResPerm method will be illustrated by the Home Allergens and Asthma prospective cohort study analyzing the relationship between area or neighborhood residence and repeated measured outcome, occurrence of wheeze in the last six months, while taking into account mobile locations. C1 [Cook, Andrea J.] Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. [Cook, Andrea J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Gold, Diane R.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Gold, Diane R.] Harvard Univ, Sch Med, Boston, MA USA. [Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cook, AJ (reprint author), Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. EM cook.aj@ghc.org FU National Institutes of Health [RO1 AI/EHS 35786, RO1 CA95747] FX This work was supported by National Institutes of Health [RO1 AI/EHS 35786 to DRG; RO1 CA95747 to YL and AJC]. NR 18 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PD JUN 18 PY 2013 VL 42 IS 12 BP 2105 EP 2117 DI 10.1080/03610926.2011.605234 PG 13 WC Statistics & Probability SC Mathematics GA 135IK UT WOS:000318281600001 PM 23847392 ER PT J AU Danovitch, GM Chapman, J Capron, AM Levin, A Abbud, M Al Mousawi, M Bennett, W Budiani-Saberi, D Couser, W Dittmer, I Jha, V Lavee, J Martin, D Masri, M Naicker, S Takahara, S Tibell, A Shaheen, F Anantharaman, V Delmonico, FL AF Danovitch, Gabriel M. Chapman, Jeremy Capron, Alexander M. Levin, Adeera Abbud-Filho, Mario Al Mousawi, Mustafa Bennett, William Budiani-Saberi, Debra Couser, William Dittmer, Ian Jha, Vivek Lavee, Jacob Martin, Dominique Masri, Marwan Naicker, Saraladevi Takahara, Shiro Tibell, Annika Shaheen, Faissal Anantharaman, Vathsala Delmonico, Francis L. TI Organ Trafficking and Transplant Tourism: The Role of Global Professional Ethical Standards-The 2008 Declaration of Istanbul SO TRANSPLANTATION LA English DT Article DE Declaration of Istanbul; Organ trafficking; Transplant tourism ID DONATION; POLICY; CHINA; LAW; SOCIETY; ISRAEL; TRADE; INDIA AB By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals. Promulgation of the Declaration of Istanbul and the formation of the Declaration of Istanbul Custodian Group to promote and uphold its principles have demonstrated that concerted, strategic, collaborative, and persistent actions by professionals can deliver tangible changes. Over the past 5 years, the Declaration of Istanbul Custodian Group organized and encouraged cooperation among professional bodies and relevant international, regional, and national governmental organizations, which has produced significant progress in combating organ trafficking and transplant tourism around the world. At a fifth anniversary meeting in Qatar in April 2013, the DICG took note of this progress and set forth in a Communique a number of specific activities and resolved to further engage groups from many sectors in working toward the Declaration's objectives. C1 [Danovitch, Gabriel M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Chapman, Jeremy] Westmead Hosp, Westmead, NSW 2145, Australia. [Capron, Alexander M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Levin, Adeera] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Abbud-Filho, Mario] FAMERP HB FUNFARME, Inst Urol & Nephrol, Sao Paulo, Brazil. [Abbud-Filho, Mario] FAMERP HB FUNFARME, Sch Med, Sao Paulo, Brazil. [Al Mousawi, Mustafa] Hamed Al Essa Organ Transplant Ctr, Safat, Kuwait. [Bennett, William] Legacy Good Samaritan Hosp & Hlth Ctr, Portland, OR USA. [Budiani-Saberi, Debra] Coalit Organ Failure Solut, Bethesda, MD USA. [Couser, William] Univ Washington, Sch Med, Woodinville, WA USA. [Dittmer, Ian] Auckland City Hosp, Dept Renal Med, Auckland, New Zealand. [Jha, Vivek] Postgrad Inst Med Educ & Res, Dept Nephrol, Chandigarh 160012, India. [Lavee, Jacob] Tel Aviv Univ, Sackler Fac Med, Heart Transplantat Unit, Leviev Heart Ctr,Sheba Med Ctr, IL-69978 Tel Aviv, Israel. [Martin, Dominique] Univ Melbourne, Ctr Hlth & Soc, Carlton, Vic 3053, Australia. [Masri, Marwan] Transmed Life Res Inst, Beirut, Lebanon. [Naicker, Saraladevi] Univ Witwatersrand, Dept Internal Med, Johannesburg, South Africa. [Takahara, Shiro] Osaka Univ, Grad Sch Med, Dept Adv Technol Transplantat, Osaka, Japan. [Tibell, Annika] Karolinska Univ Hosp, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Shaheen, Faissal] Saudi Ctr Organ Transplantat, Riyadh, Saudi Arabia. [Anantharaman, Vathsala] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Delmonico, Francis L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. RP Danovitch, GM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Blvd, Los Angeles, CA 90095 USA. EM gdanovitch@mednet.ucla.edu OI Lavee, Jacob/0000-0002-3641-1114; Abbud-Filho, Mario/0000-0002-5079-9813 NR 29 TC 31 Z9 32 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2013 VL 95 IS 11 BP 1306 EP 1312 DI 10.1097/TP.0b013e318295ee7d PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299EE UT WOS:000330377400004 PM 23644753 ER PT J AU Zurowski, M McDonald, WM Fox, S Marsh, L AF Zurowski, Mateusz McDonald, William M. Fox, Susan Marsh, Laura TI Psychiatric comorbidities in dystonia: Emerging concepts SO MOVEMENT DISORDERS LA English DT Review DE dystonia; psychiatry; depression; anxiety; social phobia ID QUALITY-OF-LIFE; PRIMARY FOCAL DYSTONIA; IDIOPATHIC CERVICAL DYSTONIA; SPASMODIC TORTICOLLIS; GENERALIZED DYSTONIA; ANXIETY DISORDERS; MUTATION CARRIERS; DEPRESSION; MANAGEMENT; RECOGNITION AB Psychiatric disorders are highly prevalent in patients with dystonia and have a profound effect on quality of life. Patients with dystonia frequently meet criteria for anxiety disorders, especially social phobia, and major depressive disorder. Deficits in emotional processing have also been demonstrated in some dystonia populations. Onset of psychiatric disturbances in patients with dystonia often precedes onset of motor symptoms, suggesting that the pathophysiology of dystonia itself contributes to the genesis of psychiatric disturbances. This article examines the hypothesis that mood and anxiety disorders are intrinsic to the neurobiology of dystonia, citing the available literature, which is derived mostly from research on focal isolated dystonias. Limitations of studies are identified, and the role of emotional reactivity, especially in the context of pain secondary to dystonia, is recognized. Available evidence underscores the need to develop dystonia assessment tools that incorporate psychiatric measures. Such tools would allow for a better understanding of the full spectrum of dystonia presentations and facilitate research on the treatment of dystonia as well as the treatment of psychiatric illnesses in the context of dystonia. This article, solicited for a special Movement Disorders issue on novel research findings and emerging concepts in dystonia, addresses the following issues: (1) To what extent are psychiatric disturbances related to the pathophysiology of dystonia? (2) What is the impact of psychiatric disturbances on outcome measures of current assessment tools for dystonia? (3) How do psychiatric comorbidities influence the treatment of dystonia? Answers to these questions will lead to an increased appreciation of psychiatric disorders in dystonia, a better understanding of brain physiology, more nuanced research questions pertaining to this population, better clinical scales that can be used to further patient management and research, and improved patient outcomes. (C) 2013 Movement Disorder Society C1 [Zurowski, Mateusz] Univ Toronto, Dept Psychiat, Univ Hlth Network, Toronto, ON, Canada. [McDonald, William M.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Fox, Susan] Univ Toronto, Div Neurol, Univ Hlth Network, Toronto, ON, Canada. [Marsh, Laura] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Zurowski, M (reprint author), Univ Hlth Network, Dept Psychiat, Toronto Western Hosp, 7 Main,399 Bathurst St, Toronto, ON M5T 2S8, Canada. EM mateusz.zurowski@uhn.ca RI zurowski, mateusz/D-1536-2010 OI zurowski, mateusz/0000-0002-6407-4629 FU Dystonia Coalition [U54 NS065701, NS065701] FX This work was supported by the Dystonia Coalition U54 NS065701 (to Mateusz Zurowski) and by Dystonia Coalition grant NS065701 (William M. McDonald). NR 45 TC 13 Z9 13 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN 15 PY 2013 VL 28 IS 7 BP 914 EP 920 DI 10.1002/mds.25501 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 188ZH UT WOS:000322235700009 PM 23893448 ER PT J AU Tsytsarev, V Rao, B Maslov, KI Li, L Wang, LHV AF Tsytsarev, Vassiliy Rao, Bin Maslov, Konstantin I. Li, Li Wang, Lihong V. TI Photoacoustic and optical coherence tomography of epilepsy with high temporal and spatial resolution and dual optical contrasts SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Photoacoustic microscopy; Optical coherence tomography; Epileptic seizures; 4-Aminopyridine ID CEREBRAL-BLOOD-FLOW; IN-VIVO; HEMODYNAMIC-CHANGES; MICROSCOPY; SEIZURES; CORTEX; BRAIN; ACTIVATION; SIGNAL; FOCI AB Epilepsy mapping with high spatial and temporal resolution has great significance for both fundamental research on epileptic neurons and the clinical management of epilepsy. In this communication, we demonstrate for the first time in vivo epilepsy mapping with high spatial and temporal resolution and dual optical contrasts in an animal model. Through the variations of a depthresolved optical coherence tomography signal with optical scattering contrast, we observed that epileptic neuron activities modulated the optical refractive index of epileptic neurons and their surrounding tissue. Simultaneously, through neurovasculature coupling mechanisms and optical absorption contrast, we used photoacoustic signals to document the hemodynamic changes of the microvasculature surrounding the epileptic neurons. The epilepsy mapping results were confirmed by a simultaneously recorded electroencephalogram signal during epileptic seizure. Our new epilepsy mapping tool, with high temporal and spatial resolution and dual optical contrasts, may find many applications, such as drug development and epilepsy surgery. (C) 2013 Elsevier B.V. All rights reserved. C1 [Tsytsarev, Vassiliy; Rao, Bin; Maslov, Konstantin I.; Li, Li; Wang, Lihong V.] Washington Univ, Dept Biomed Engn, Opt Imaging Lab, St Louis, MO 63130 USA. [Tsytsarev, Vassiliy] Univ Maryland, Dept Anat & Neurobiol, Sch Med, Baltimore, MD 21201 USA. [Li, Li] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Wang, LHV (reprint author), Washington Univ, Dept Biomed Engn, 1 Brookings Dr, St Louis, MO 63130 USA. EM tsytsarev@umaryland.edu; raob@seas.wustl.edu; kimaslov@biomed.wustl.edu; li.li@mgh.harvard.edu; lhwang@seas.wustl.edu RI Rao, Bin/C-2499-2015; Wang, Lihong/A-7147-2009 OI Wang, Lihong/0000-0001-9783-4383 FU National Institutes of Health [R01 EB008085, R01 CA134539, U54 CA136398, R01 CA157277, R01 CA159959, DP1 EB016986] FX This work was sponsored in part by National Institutes of Health grants R01 EB008085, R01 CA134539, U54 CA136398, R01 CA157277, R01 CA159959, DP1 EB016986 (NIH Director's Pioneer Award). L.W. has a financial interest in Microphotoacoustics, Inc. and Endra, Inc., which, however, did not support this work. K.M. has a financial interest in Microphotoacoustics, Inc., which, however, did not support this work. NR 44 TC 14 Z9 14 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUN 15 PY 2013 VL 216 IS 2 BP 142 EP 145 DI 10.1016/j.jneumeth.2013.04.001 PG 4 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 174PP UT WOS:000321168200009 PM 23603664 ER PT J AU Duraiswamy, J Kaluza, KM Freeman, GJ Coukos, G AF Duraiswamy, Jaikumar Kaluza, Karen M. Freeman, Gordon J. Coukos, George TI Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors SO CANCER RESEARCH LA English DT Article ID CHRONIC VIRAL-INFECTION; SYNGENEIC MOUSE MODEL; HUMAN OVARIAN-CANCER; REGULATORY T; PROGRAMMED DEATH-1; DISTINCT MECHANISMS; ANTITUMOR-ACTIVITY; MYELOID-LEUKEMIA; IMMUNE ESCAPE; GROWTH-FACTOR AB Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. (c) 2013 AACR. C1 [Duraiswamy, Jaikumar; Kaluza, Karen M.; Coukos, George] Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Duraiswamy, Jaikumar; Kaluza, Karen M.; Coukos, George] Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Coukos, George] Univ Lausanne Hosp, Ludwig Ctr Canc Res, Dept Oncol, Lausanne, Switzerland. RP Coukos, G (reprint author), Ludwig Ctr Canc Res, Ch Boveresses 155, CH-1066 Lausanne, Switzerland. EM George.Coukos@chuv.ch FU NIH grant [2P50-CA083638]; SPORE-Pilot grant; [NIH-P01 AI056299] FX This work was supported by NIH grant 2P50-CA083638 (G. Coukos), SPORE-Pilot grant (to J. Duraiswamy), and NIH-P01 AI056299 (G.J. Freeman). NR 67 TC 187 Z9 196 U1 8 U2 57 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 JUN 15 PY 2013 VL 73 IS 12 BP 3591 EP 3603 DI 10.1158/0008-5472.CAN-12-4100 PG 13 WC Oncology SC Oncology GA 164AE UT WOS:000320380300012 PM 23633484 ER PT J AU Rice, WL Hou, S Kumar, ATN AF Rice, William L. Hou, Steven Kumar, Anand T. N. TI Resolution below the point spread function for diffuse optical imaging using fluorescence lifetime multiplexing SO OPTICS LETTERS LA English DT Article ID TOMOGRAPHY; DOMAIN; CONTRAST; SYSTEM AB We show that asymptotic lifetime-based fluorescence tomography can localize multiple-lifetime targets separated well below the diffuse point spread function of a turbid medium. This is made possible due to a complete diagonalization of the time domain forward problem in the asymptotic limit. We also show that continuous wave or direct time gate approaches to fluorescence tomography are unable to achieve this separation, indicating the unique advantage of a decay-amplitude-based approach for tomographic lifetime multiplexing with time domain data. (c) 2013 Optical Society of America C1 [Rice, William L.; Hou, Steven; Kumar, Anand T. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU National Institutes of Health [R01 EB015325] FX This work was supported by the National Institutes of Health Grant R01 EB015325. NR 14 TC 7 Z9 7 U1 0 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUN 15 PY 2013 VL 38 IS 12 BP 2038 EP 2040 DI 10.1364/OL.38.002038 PG 3 WC Optics SC Optics GA 163VX UT WOS:000320366500013 PM 23938969 ER PT J AU Singh, JA AF Singh, J. A. TI Intraarticular botulinum toxin reduced joint pain in patients with painful total knee or shoulder arthroplasty SO TOXICON LA English DT Meeting Abstract CT 7th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins (TOXINS) CY OCT 02-05, 2011 CL Santa Fe, NM C1 [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. EM jasvinder.md@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUN 15 PY 2013 VL 68 BP 121 EP 121 DI 10.1016/j.toxicon.2012.07.164 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 159VN UT WOS:000320075500152 ER PT J AU Pallin, DJ Binder, WD Allen, MB Lederman, M Parmar, S Filbin, MR Hooper, DC Camargo, CA AF Pallin, Daniel J. Binder, William D. Allen, Matthew B. Lederman, Molly Parmar, Siddharth Filbin, Michael R. Hooper, David C. Camargo, Carlos A., Jr. TI Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE cellulitis; community-associated methicillin-resistant Staphylococcus aureus; comparative effectiveness; trimethoprim-sulfamethoxazole; cephalexin ID RESISTANT STAPHYLOCOCCUS-AUREUS; SOFT-TISSUE INFECTIONS; EMERGENCY-DEPARTMENT; ANTIMICROBIAL THERAPY; SKIN INFECTIONS; RISK; COLONIZATION; GUIDELINES; CHILDREN AB Background. Community-associated methicillin-resistant S. aureus (CA-MRSA) is the most common organism isolated from purulent skin infections. Antibiotics are usually not beneficial for skin abscess, and national guidelines do not recommend CA-MRSA coverage for cellulitis, except purulent cellulitis, which is uncommon. Despite this, antibiotics targeting CA-MRSA are prescribed commonly and increasingly for skin infections, perhaps due, in part, to lack of experimental evidence among cellulitis patients. We test the hypothesis that antibiotics targeting CA-MRSA are beneficial in the treatment of cellulitis. Methods. We performed a randomized, multicenter, double-blind, placebo-controlled trial from 2007 to 2011. We enrolled patients with cellulitis, no abscesses, symptoms for <1 week, and no diabetes, immunosuppression, peripheral vascular disease, or hospitalization (clinicaltrials.gov NCT00676130). All participants received cephalexin. Additionally, each was randomized to trimethoprim-sulfamethoxazole or placebo. We provided 14 days of antibiotics and instructed participants to continue therapy for >= 1 week, then stop 3 days after they felt the infection to be cured. Our main outcome measure was the risk difference for treatment success, determined in person at 2 weeks, with telephone and medical record confirmation at 1 month. Results. We enrolled 153 participants, and 146 had outcome data for intent-to-treat analysis. Median age was 29, range 3-74. Of intervention participants, 62/73 (85%) were cured versus 60/73 controls (82%), a risk difference of 2.7% (95% confidence interval, -9.3% to 15%; P = .66). No covariates predicted treatment response, including nasal MRSA colonization and purulence at enrollment. Conclusions. Among patients diagnosed with cellulitis without abscess, the addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes overall or by subgroup. C1 [Pallin, Daniel J.; Allen, Matthew B.; Lederman, Molly; Parmar, Siddharth] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Boston Childrens Hosp, Div Emergency Med, Boston, MA USA. [Binder, William D.; Filbin, Michael R.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Allen, Matthew B.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lederman, Molly] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Hooper, David C.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), 75 Francis St,Neville House 304-D, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Brigham and Women's Hospital Department of Emergency Medicine; Harvard University, Boston, MA; Department of Emergency Medicine of Massachusetts General Hospital FX This work was supported by a grant from the Eleanor and Miles Shore Fellowship Program of the Brigham and Women's Hospital Department of Emergency Medicine; by the Milton Fund of Harvard University, Boston, MA; and by seed funding from the Department of Emergency Medicine of Massachusetts General Hospital. NR 30 TC 35 Z9 35 U1 0 U2 16 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 JUN 15 PY 2013 VL 56 IS 12 BP 1754 EP 1762 DI 10.1093/cid/cit122 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151NG UT WOS:000319466600012 PM 23457080 ER PT J AU Jena, AB AF Jena, Anupam B. TI Balancing Disease Eradication With the Emergence of Multidrug-Resistant HIV in Test-and-Treat Policies SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE human immunodeficiency virus; drug resistance; test and treat ID ANTIRETROVIRAL THERAPY; PREEXPOSURE PROPHYLAXIS; INFECTION; TRANSMISSION; PREVENTION; INITIATION; EPIDEMIC; COHORT C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp Boston, Dept Med, Boston, MA USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena.anupam@mgh.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 3 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 JUN 15 PY 2013 VL 56 IS 12 BP 1797 EP 1799 DI 10.1093/cid/cit159 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151NG UT WOS:000319466600019 PM 23487380 ER PT J AU Shyh-Chang, N Daley, GQ Cantley, LC AF Shyh-Chang, Ng Daley, George Q. Cantley, Lewis C. TI Stem cell metabolism in tissue development and aging SO DEVELOPMENT LA English DT Review DE Blastocyst metabolism; Pluripotent stem cells; Hematopoietic progenitors; Reprogramming; Metabolomics ID MITOCHONDRIAL PHOSPHATASE PTPMT1; HEMATOPOIETIC PROGENITORS; MOUSE EMBRYOS; SOMATIC-CELLS; PREIMPLANTATION EMBRYOS; CAENORHABDITIS-ELEGANS; MAMMALIAN DEVELOPMENT; GLUCOSE TRANSPORTERS; ANTIOXIDANT ENZYMES; ENERGY-METABOLISM AB Recent advances in metabolomics and computational analysis have deepened our appreciation for the role of specific metabolic pathways in dictating cell fate. Once thought to be a mere consequence of the state of a cell, metabolism is now known to play a pivotal role in dictating whether a cell proliferates, differentiates or remains quiescent. Here, we review recent studies of metabolism in stem cells that have revealed a shift in the balance between glycolysis, mitochondrial oxidative phosphorylation and oxidative stress during the maturation of adult stem cells, and during the reprogramming of somatic cells to pluripotency. These insights promise to inform strategies for the directed differentiation of stem cells and to offer the potential for novel metabolic or pharmacological therapies to enhance regeneration and the treatment of degenerative disease. C1 [Shyh-Chang, Ng; Daley, George Q.] Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Shyh-Chang, Ng; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shyh-Chang, Ng; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shyh-Chang, Ng; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA. [Cantley, Lewis C.] Cornell Weill Med Coll, Dept Med, New York, NY 10065 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Shyh-Chang, Ng/0000-0003-3138-9525 FU NSS Scholarship from the Agency for Science, Technology and Research, Singapore; National Institutes of Health (NIH); Ellison Medical Foundation; Alex's Lemonade Stand Foundation; Howard Hughes Medical Institute; NIH FX N.S.C. is supported by the NSS Scholarship from the Agency for Science, Technology and Research, Singapore. G.Q.D. is supported by the National Institutes of Health (NIH), the Ellison Medical Foundation and Alex's Lemonade Stand Foundation and is an investigator of the Howard Hughes Medical Institute. L.C.C. is supported by a grant from the NIH. Deposited in PMC for release after 12 months. NR 127 TC 122 Z9 126 U1 7 U2 79 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 15 PY 2013 VL 140 IS 12 BP 2535 EP 2547 DI 10.1242/dev.091777 PG 13 WC Developmental Biology SC Developmental Biology GA 154EY UT WOS:000319655800013 PM 23715547 ER PT J AU Kote-Jarai, Z Saunders, EJ Leongamornlert, DA Tymrakiewicz, M Dadaev, T Jugurnauth-Little, S Ross-Adams, H Al Olama, AA Benlloch, S Halim, S Russel, R Dunning, AM Luccarini, C Dennis, J Neal, DE Hamdy, FC Donovan, JL Muir, K Giles, GG Severi, G Wiklund, F Gronberg, H Haiman, CA Schumacher, F Henderson, BE Le Marchand, L Lindstrom, S Kraft, P Hunter, DJ Gapstur, S Chanock, S Berndt, SI Albanes, D Andriole, G Schleutker, J Weischer, M Canzian, F Riboli, E Key, TJ Travis, RC Campa, D Ingles, SA John, EM Hayes, RB Pharoah, P Khaw, KT Stanford, JL Ostrander, EA Signorello, LB Thibodeau, SN Schaid, D Maier, C Vogel, W Kibel, AS Cybulski, C Lubinski, J Cannon-Albright, L Brenner, H Park, JY Kaneva, R Batra, J Spurdle, A Clements, JA Teixeira, MR Govindasami, K Guy, M Wilkinson, RA Sawyer, EJ Morgan, A Dicks, E Baynes, C Conroy, D Bojesen, SE Kaaks, R Vincent, D Bacot, F Tessier, DC Easton, DF Eeles, RA AF Kote-Jarai, Zsofia Saunders, Edward J. Leongamornlert, Daniel A. Tymrakiewicz, Malgorzata Dadaev, Tokhir Jugurnauth-Little, Sarah Ross-Adams, Helen Al Olama, Ali Amin Benlloch, Sara Halim, Silvia Russel, Roslin Dunning, Alison M. Luccarini, Craig Dennis, Joe Neal, David E. Hamdy, Freddie C. Donovan, Jenny L. Muir, Ken Giles, Graham G. Severi, Gianluca Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A. Schumacher, Fredrick Henderson, Brian E. Le Marchand, Loic Lindstrom, Sara Kraft, Peter Hunter, David J. Gapstur, Susan Chanock, Stephen Berndt, Sonja I. Albanes, Demetrius Andriole, Gerald Schleutker, Johanna Weischer, Maren Canzian, Federico Riboli, Elio Key, Tim J. Travis, Ruth C. Campa, Daniele Ingles, Sue A. John, Esther M. Hayes, Richard B. Pharoah, Paul Khaw, Kay-Tee Stanford, Janet L. Ostrander, Elaine A. Signorello, Lisa B. Thibodeau, Stephen N. Schaid, Dan Maier, Christiane Vogel, Walther Kibel, Adam S. Cybulski, Cezary Lubinski, Jan Cannon-Albright, Lisa Brenner, Hermann Park, Jong Y. Kaneva, Radka Batra, Jyotsna Spurdle, Amanda Clements, Judith A. Teixeira, Manuel R. Govindasami, Koveela Guy, Michelle Wilkinson, Rosemary A. Sawyer, Emma J. Morgan, Angela Dicks, Ed Baynes, Caroline Conroy, Don Bojesen, Stig E. Kaaks, Rudolf Vincent, Daniel Bacot, Francois Tessier, Daniel C. Easton, Douglas F. Eeles, Rosalind A. CA COGS-CRUK GWAS-ELLIPSE Part UK Genetic Prostate Canc UK ProtecT Study Collaborators PRACTICAL Consortium TI Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression SO HUMAN MOLECULAR GENETICS LA English DT Article ID TELOMERE LENGTH; TERT-CLPTM1L LOCUS; WIDE ASSOCIATION; BREAST-CANCER; LUNG-CANCER; VARIANTS; HTERT; PROMOTER AB Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease. C1 [Kote-Jarai, Zsofia; Saunders, Edward J.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Jugurnauth-Little, Sarah; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A.; Sawyer, Emma J.; Morgan, Angela; Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, Sutton SM2 5NG, Surrey, England. [Ross-Adams, Helen; Halim, Silvia; Russel, Roslin] Cambridge Res Inst, Li Ka Shing Ctr, Canc Res UK, Cambridge CB2 0RE, England. [Al Olama, Ali Amin; Benlloch, Sara; Dunning, Alison M.; Luccarini, Craig; Dennis, Joe; Pharoah, Paul; Dicks, Ed; Baynes, Caroline; Conroy, Don; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge CB1 8RN, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Surg Oncol Uro Oncol S4, Cambridge CB2 2QQ, England. [Neal, David E.] Cambridge Res Inst, Li Ka Shing Ctr, Canc Res UK, Cambridge CB2 2QQ, England. [Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. [Hamdy, Freddie C.] Univ Oxford, Fac Med Sci, John Radcliffe Hosp, Oxford OX3 9DU, England. [Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol BS8 2PS, Avon, England. [Muir, Ken] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Ingles, Sue A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lindstrom, Sara; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Gapstur, Susan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Chanock, Stephen; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Schleutker, Johanna; Campa, Daniele] Univ Turku, Dept Medic Biochem & Genet, Inst Biomed Technol, Turku, Finland. [Schleutker, Johanna; Campa, Daniele] Univ Tampere, BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna; Campa, Daniele] FimLab Labs, Tampere, Finland. [Weischer, Maren; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-230 Herlev, Denmark. [Canzian, Federico; Kaaks, Rudolf] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England. [Key, Tim J.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Travis, Ruth C.; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Travis, Ruth C.; John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Hayes, Richard B.] NYU, Inst Canc, Langone Med Ctr, Div Epidemiol,Dept Environm Med, New York, NY USA. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Stanford, Janet L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Signorello, Lisa B.] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr,Vanderbilt Ingr, Nashville, TN 37212 USA. [Thibodeau, Stephen N.; Schaid, Dan] Mayo Clin, Rochester, MN USA. [Maier, Christiane; Vogel, Walther] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Maier, Christiane; Vogel, Walther] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02245 USA. [Cybulski, Cezary; Lubinski, Jan] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Div Genet Epidemiol, Dept Med, Salt Lake City, UT 84132 USA. [Cannon-Albright, Lisa] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Park, Jong Y.] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA. [Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, Sofia 1531, Bulgaria. [Kaneva, Radka] Med Univ Sofia, Dept Med Chem & Biochem, Sofia 1531, Bulgaria. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Australian Prostate Canc Res Ctr Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, P-4100 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. [Vincent, Daniel; Bacot, Francois; Tessier, Daniel C.] Ctr Innovat Genome Quebec, Montreal, PQ H3A 0G1, Canada. [Vincent, Daniel; Bacot, Francois; Tessier, Daniel C.] McGill Univ, Montreal, PQ H3A 0G1, Canada. RP Kote-Jarai, Z (reprint author), Inst Canc Res, Oncogenet Team, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. EM zsofia.kote-jarai@icr.ac.uk RI Batra, Jyotsna/B-4130-2011; Spurdle, Amanda/A-4978-2011; Albanes, Demetrius/B-9749-2015; Teixeira, Manuel/E-4885-2011; Campa, Daniele/K-1617-2016; Brenner, Hermann/B-4627-2017; OI Leongamornlert, Daniel/0000-0002-3486-3168; Hayes, Richard/0000-0002-0918-661X; albright, lisa/0000-0003-2602-3668; Dunning, Alison Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099; Clements, Judith/0000-0001-6026-1964; Ostrander, Elaine/0000-0001-6075-9738; Saunders, Ed/0000-0003-4343-3570; Eeles, Rosalind/0000-0002-3698-6241; Spurdle, Amanda/0000-0003-1337-7897; Dennis, Joe/0000-0003-4591-1214; Neal, David/0000-0002-6033-5086; Teixeira, Manuel/0000-0002-4896-5982; Campa, Daniele/0000-0003-3220-9944; Brenner, Hermann/0000-0002-6129-1572; Dadaev, Tokhir/0000-0002-8268-0438 FU European Commission [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]; National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [1 U19 CA 148537-01]; Institute of Cancer Research and The Everyman Campaign; Prostate Action; Orchid Cancer Appeal; National Cancer Research Network, UK; National Cancer Research Institute (NCRI), UK; NIHR; Royal Marsden NHS Foundation Trust FX This work was supported by European Commission's Seventh Framework Programme grant agreement No. 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). We would like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation (now Prostate Action), Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network, UK and The National Cancer Research Institute (NCRI), UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Funding to pay the Open Access publication charges for this article was provided by European Commission's Seventh Framework Programme grant agreement No. 223175 (HEALTH-F2-2009-223175). NR 25 TC 58 Z9 59 U1 2 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2013 VL 22 IS 12 BP 2520 EP 2528 DI 10.1093/hmg/ddt086 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 151AK UT WOS:000319432800017 PM 23535824 ER PT J AU Walsh, SR Wilck, MB Dominguez, DJ Zablowsky, E Bajimaya, S Gagne, LS Verrill, KA Kleinjan, JA Patel, A Zhang, Y Hill, H Acharyya, A Fisher, DC Antin, JH Seaman, MS Dolin, R Baden, LR AF Walsh, Stephen R. Wilck, Marissa B. Dominguez, David J. Zablowsky, Elise Bajimaya, Shringkhala Gagne, Lisa S. Verrill, Kelly A. Kleinjan, Jane A. Patel, Alka Zhang, Ying Hill, Heather Acharyya, Aruna Fisher, David C. Antin, Joseph H. Seaman, Michael S. Dolin, Raphael Baden, Lindsey R. TI Safety and Immunogenicity of Modified Vaccinia Ankara in Hematopoietic Stem Cell Transplant Recipients: A Randomized, Controlled Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE safety; immunogenicity; dose; stem cell transplant; modified vaccinia ankara; clinical trial ID SMALLPOX VACCINATION; VIRUS ANKARA; DRYVAX(R) CHALLENGE; INFECTIOUS-DISEASES; GENOMIC SEQUENCE; MVA; CANCER; STRAIN; IMMUNOTHERAPY; INDIVIDUALS AB Background. Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important. Methods. We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo. Results. MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon gamma enzyme-linked immunosorbent spot assay and were higher in the higher-dose group. Conclusions. MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population. Clinical Trials Registration. NCT00565929. C1 [Walsh, Stephen R.; Wilck, Marissa B.; Gagne, Lisa S.; Verrill, Kelly A.; Kleinjan, Jane A.; Patel, Alka; Dolin, Raphael; Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walsh, Stephen R.; Dominguez, David J.; Zablowsky, Elise; Bajimaya, Shringkhala; Seaman, Michael S.; Dolin, Raphael] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA. [Walsh, Stephen R.; Wilck, Marissa B.; Seaman, Michael S.; Dolin, Raphael; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA. [Fisher, David C.; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Ying; Hill, Heather; Acharyya, Aruna] EMMES Corp, Rockville, MD USA. RP Walsh, SR (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 3 Blackfan Cir, Boston, MA 02115 USA. EM srwalsh@bidmc.harvard.edu FU National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences (US Public Health Service) [U54 AI057159, U19 AI057330, UL1 RR025758, K23 AI085181] FX This work was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences (US Public Health Service grants U54 AI057159, U19 AI057330, UL1 RR025758, and K23 AI085181). NR 37 TC 11 Z9 12 U1 1 U2 4 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 JUN 15 PY 2013 VL 207 IS 12 BP 1888 EP 1897 DI 10.1093/infdis/jit105 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151PI UT WOS:000319472200014 PM 23482644 ER PT J AU Ashburner, J Go, A Reynolds, K Chang, YC Fang, M Applebaum, K Fredman, L Singer, D AF Ashburner, Jeffrey Go, Alan Reynolds, Kristi Chang, Yuchiao Fang, Margaret Applebaum, Kate Fredman, Lisa Singer, Daniel TI WARFARIN ANTICOAGULATION THERAPY AND MORTALITY FOLLOWING GASTROINTESTINAL HEMORRHAGE IN PATIENTS WITH ATRIAL FIBRILLATION IN CLINICAL CARE: THE ATRIA AND ATRIA-CVRN COHORTS. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Publ Hlth, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S127 EP S127 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300501 ER PT J AU Dunn, E Richmond, T Milliren, C Subramanian, SV AF Dunn, Erin Richmond, Tracy Milliren, Carly Subramanian, S. V. TI THE "MISSING LEVEL" PROBLEM IN MULTILEVEL STUDIES: EVIDENCE THAT CROSS-CLASSIFIED MULTILEVEL MODELS ARE PREFERRED TO TRADITIONAL MULTILEVEL MODELS. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Dunn, Erin; Richmond, Tracy; Milliren, Carly; Subramanian, S. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S153 EP S153 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300602 ER PT J AU Dunn, E McLaughlin, K Slopen, N Rosand, J Smoller, J AF Dunn, Erin McLaughlin, Katie Slopen, Natalie Rosand, Jonathan Smoller, Jordan TI ASSOCIATION BETWEEN DEVELOPMENTAL TIMING OF EXPOSURE TO CHILD MALTREATMENT AND SYMPTOMS OF DEPRESSION AND SUICIDALITY: EVIDENCE OF A SENSITIVE PERIOD? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Dunn, Erin; McLaughlin, Katie; Slopen, Natalie; Rosand, Jonathan; Smoller, Jordan] Massachusetts Gen Hosp, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S27 EP S27 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300108 ER PT J AU Fonda, J Lippa, S Fortier, C Milberg, W McGlinchey, R AF Fonda, Jennifer Lippa, Sara Fortier, Catherine Milberg, William McGlinchey, Regina TI POLYMORBIDITY: LOOKING BEYOND PTSD AND TBI IN RETURNING SERVICE MEMBERS AND VETERANS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Fonda, Jennifer; Lippa, Sara; Fortier, Catherine; Milberg, William; McGlinchey, Regina] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S29 EP S29 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300116 ER PT J AU Littman, AJ Thompson, ML Boyko, EJ Arterburn, DE AF Littman, Alyson J. Thompson, Mary Lou Boyko, Edward J. Arterburn, David E. TI USE OF BODY WEIGHTS FROM ELECTRONIC MEDICAL RECORDS: OPPORTUNITIES AND CHALLENGES. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Littman, Alyson J.; Thompson, Mary Lou; Boyko, Edward J.; Arterburn, David E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S72 EP S72 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300287 ER PT J AU Thwin, SS Clough-Gorr, K Raju, S Kosik, N Cho, K Hermos, J Gaziano, M AF Thwin, Soe Soe Clough-Gorr, Kerri Raju, Sanjay Kosik, Nicole Cho, Kelly Hermos, John Gaziano, Michael TI TREATMENT DECISION-MAKING IN VETERANS WITH EARLY STAGE PROSTATE CANCER. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Thwin, Soe Soe; Clough-Gorr, Kerri; Raju, Sanjay; Kosik, Nicole; Cho, Kelly; Hermos, John; Gaziano, Michael] VA Boston Healthcare Syst, Boston, MA 02130 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S176 EP S176 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300695 ER PT J AU Winston, C Lucero-Obusan, C Schirmer, P Holodniy, M AF Winston, Carla Lucero-Obusan, Cynthia Schirmer, Patricia Holodniy, Mark TI PREDICTING INFLUENZA ADMISSIONS AMONG VETERANS FROM TELEPHONE TRIAGE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 [Winston, Carla; Lucero-Obusan, Cynthia; Schirmer, Patricia; Holodniy, Mark] US Dept Vet Affairs, Palo Alto, CA 94304 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2013 VL 177 SU 11 BP S111 EP S111 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157BL UT WOS:000319870300439 ER PT J AU Albadawi, H Haurani, MJ Oklu, R Trubiano, JP Laub, PJ Yoo, HJ Watkins, MT AF Albadawi, Hassan Haurani, Mounir J. Oklu, Rahmi Trubiano, Jordan P. Laub, Peter J. Yoo, Hyung-Jin Watkins, Michael T. TI Differential effect of zoledronic acid on human vascular smooth muscle cells SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Vascular smooth muscle; Intimal hyperplasia; Bisphosphonates ID INTIMAL HYPERPLASIA; POLY(ADP-RIBOSE) POLYMERASE; ATP ANALOG; DNA-REPLICATION; CANCER-PATIENTS; BREAST-CANCER; IN-VITRO; BISPHOSPHONATE; RABBITS; CLODRONATE AB Introduction: The activation of human vascular smooth muscle cell proliferation, adhesion and migration is essential for intimal hyperplasia formation. These experiments were designed to test whether zoledronic acid (ZA) would modulate indices of human smooth muscle cell activation, exert differential effects on proliferating versus quiescent cells, and determine whether these effects were dependent on GTPase binding proteins prenylation. ZA was chosen for testing in these experiments because it is clinically used in humans with cancer, and has been shown to modulate rat smooth muscle cell proliferation and migration. Methods: Human aortic smooth muscle cells (HASMC) were cultured under either proliferating or growth arrest (quiescent) conditions in the presence or absence of ZA for 48 hours, whereupon the effect of ZA on HASMC proliferation, cellular viability, metabolic activity, and membrane integrity were compared. In addition, the effect of ZA on adhesion and migration were assessed in proliferating cells. The effect of increased concentration of ZA on the mevalonate pathway and genomic/cellular stress related poly-adenosine diphosphate ribose polymerase enzyme activity were assessed using the relative prenylation of Rap-1A/B protein and the formation of poly adenosine diphosphate-ribosylated protein, respectively. Results: There was a dose dependent inhibition of cellular proliferation, adhesion and migration following ZA treatment. ZA treatment decreased indices of cellular viability and significantly increased membrane injury in proliferating versus quiescent cells. This was correlated with the appearance of unprenylated Rap-1A protein and dose dependent down regulation of activity. Conclusions: These data suggest that ZA is effective in inhibiting HASMC proliferation, adhesion, and migration, which coincide with the appearance of unprenylated RAP-1A/B protein, thereby suggesting that the mevalonate pathway may play a role in the inhibition of HASMC activation. (C) 2013 Elsevier Inc. All rights reserved. C1 [Albadawi, Hassan; Haurani, Mounir J.; Trubiano, Jordan P.; Laub, Peter J.; Yoo, Hyung-Jin; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Vasc Intervent Radiol, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 440, Boston, MA 02114 USA. EM mtwatkins@partners.org RI Haurani, Mounir/F-5802-2012; OI Haurani, Mounir/0000-0003-3984-3366 FU National Institutes of Health [1R01AR055843]; American Diabetes Association; Pacific Vascular Research Foundation; Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX The authors acknowledge funding from the National Institutes of Health (1R01AR055843), the American Diabetes Association, the Pacific Vascular Research Foundation and the Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital (the Geneen Fund). M.W. is a Ronnie Isenberg Scholar in Academic Surgery at the Massachusetts General Hospital. NR 48 TC 3 Z9 3 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2013 VL 182 IS 2 BP 339 EP 346 DI 10.1016/j.jss.2012.10.033 PG 8 WC Surgery SC Surgery GA 143ZI UT WOS:000318907900030 PM 23164362 ER PT J AU Kuwahara, Y Mora-Blanco, EL Banine, F Rogers, AB Fletcher, C Sherman, LS Roberts, CWM Weissman, BE AF Kuwahara, Yasumichi Mora-Blanco, E. Lorena Banine, Fatima Rogers, Arlin B. Fletcher, Christopher Sherman, Larry S. Roberts, Charles W. M. Weissman, Bernard E. TI Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pediatric cancers; SWI; SNF complex; mouse models of cancer; SNF5/INI1 ID MALIGNANT RHABDOID TUMOR; CENTRAL-NERVOUS-SYSTEM; STEM-CELL; TARGETED DISRUPTION; MUTATIONAL ANALYSIS; T-ANTIGEN; IN-VIVO; HSNF5/INI1; CANCER; SNF5 AB Malignant rhabdoid tumors (MRTs) are rare, aggressive cancers occuring in young children primarily through inactivation of the SNF5(INI1, SMARCB1) tumor suppressor gene. We and others have demonstrated that mice heterozygous for a Snf5 null allele develop MRTs with partial penetrance. We have also shown that Snf5+/ mice that lack expression of the pRb family, due to TgT121 transgene expression, develop MRTs with increased penetrance and decreased latency. Here, we report that altering the genetic background has substantial effects upon MRT development in Snf5+/- and TgT121;Snf5+/ mice, with a mixed F1 background resulting in increased latency and the appearance of brain tumors. We also report the establishment of the first mouse MRT cell lines that recapitulate many features of their human counterparts. Our studies provide further insight into the genetic influences on MRT development as well as provide valuable new cell culture and genetically engineered mouse models for the study of CNS-MRT etiology. C1 [Kuwahara, Yasumichi; Rogers, Arlin B.; Weissman, Bernard E.] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Mora-Blanco, E. Lorena; Roberts, Charles W. M.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mora-Blanco, E. Lorena; Roberts, Charles W. M.] Harvard Univ, Boston, MA 02115 USA. [Banine, Fatima; Sherman, Larry S.] Oregon Hlth & Sci Univ, Natl Primate Res Ctr, Div Neurosci, Beaverton, OR USA. [Rogers, Arlin B.; Weissman, Bernard E.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Fletcher, Christopher] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Weissman, BE (reprint author), Univ N Carolina, Lineberger Canc Ctr, Room 32-048, Chapel Hill, NC 27599 USA. EM weissman@med.unc.edu FU PHS [R01CA091048, R01CA113794, U01CA105423, RR00163]; Garrett B. Smith Foundation; Cure AT/RT Now fund; Children's Tumor Foundation FX We wish to thank Mr. Nisarg Desai for excellent help with the genotyping studies and the UNC-Lineberger Animal Studies Core for their help with the in vivo tumorigenicity studies. The work was supported by PHS awards R01CA091048 (B. E. W.), R01CA113794 and U01CA105423 (C. W. M. R.) and RR00163 (L. S. S.). Dr. Roberts also gratefully acknowledges support from The Garrett B. Smith Foundation and the Cure AT/RT Now fund. Dr. Sherman also gratefully acknowledges support from the Children's Tumor Foundation. NR 49 TC 0 Z9 0 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2013 VL 132 IS 12 BP 2767 EP 2777 DI 10.1002/ijc.27976 PG 11 WC Oncology SC Oncology GA 126DV UT WOS:000317593100006 PM 23197309 ER PT J AU Francis, SA Daly, C Heydari, B Abbasi, S Shah, RV Kwong, RY AF Francis, Sanjeev A. Daly, Caroline Heydari, Bobak Abbasi, Siddique Shah, Ravi V. Kwong, Raymond Y. TI Cost-effectiveness analysis for imaging techniques with a focus on cardiovascular magnetic resonance SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Review ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; HEART-DISEASE; UNITED-STATES; CHEST-PAIN; STRESS MRI; CE-MARC; DIAGNOSIS; HEALTH; ANGIOGRAPHY AB With the need for healthcare cost-containment, increased scrutiny will be placed on new medical therapeutic or diagnostic technologies. Several challenges exist for a new diagnostic test to demonstrate cost-effectiveness. New diagnostic tests differ from therapeutic procedures due to the fact that diagnostic tests do not generally directly affect long-term patient outcomes. Instead, the results of diagnostic tests can influence management decisions for patients and by this route, diagnostic tests indirectly affect long-term outcomes. The benefits from a specific diagnostic technology depend therefore not only on its performance characteristics, but also on other factors such as prevalence of disease, and effectiveness of existing treatments for the disease of interest. We review the concepts and theories of cost-effectiveness analyses (CEA) as they apply to diagnostic tests in general. The limitations of CEA across different study designs and geographic regions are discussed, and we also examine the strengths and weakness of the existing publications where CMR was the focus of CEA compared to other diagnostic options. C1 [Heydari, Bobak; Abbasi, Siddique; Shah, Ravi V.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Francis, Sanjeev A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Daly, Caroline] St James Hosp, Div Cardiol, Dublin 8, Ireland. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. EM rykwong@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 NR 51 TC 11 Z9 11 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD JUN 14 PY 2013 VL 15 AR 52 DI 10.1186/1532-429X-15-52 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 180FK UT WOS:000321578800001 PM 23767423 ER PT J AU Campbell, KN Wong, JS Gupta, R Asanuma, K Sudol, M He, JC Mundel, P AF Campbell, Kirk N. Wong, Jenny S. Gupta, Ritu Asanuma, Katsuhiko Sudol, Marius He, John Cijiang Mundel, Peter TI Yes-associated Protein (YAP) Promotes Cell Survival by Inhibiting Proapoptotic Dendrin Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMAIN-CONTAINING PROTEIN; WW DOMAIN; INDUCED APOPTOSIS; RAT-BRAIN; HIPPO; PODOCYTES; PATHWAY; KIBRA; DROSOPHILA; GENE AB Kidney podocytes are highly specialized terminally differentiated cells that form the final barrier to urinary protein loss. Podocytes are a target for injury by metabolic, autoimmune, hereditary, inflammatory, and other stressors. Persistence of podocyte injury leads to podocyte death and loss, which results in progressive kidney damage and ultimately kidney failure. Dendrin is a dual compartment protein with proapoptotic signaling properties. Nuclear relocation of dendrin in response to glomerular injury promotes podocyte apoptosis. Here we show that Yes-associated protein (YAP), a downstream target of Hippo kinases and an inhibitor of apoptosis, is expressed in the nucleus of podocytes. The WW domains of YAP mediate the interaction with the PPXY motifs of dendrin. This interaction is functionally relevant because YAP binding to dendrin reduces dendrin-dependent, staurosporine-induced apoptosis in co-transfected HEK293 cells. Moreover gene silencing of YAP in podocytes increases adriamycin-induced podocyte apoptosis. It also increases staurosporine-induced caspase-3/7 activity, which is rescued by dendrin depletion in YAP knockdown cells. Our findings elucidate YAP binding to dendrin as a prosurvival mechanism. The antiapoptotic signaling properties of YAP in podocytes could hold significance in the quest for targeted therapeutics aimed at preventing podocyte loss. C1 [Campbell, Kirk N.; Wong, Jenny S.; Sudol, Marius; He, John Cijiang] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. [Gupta, Ritu] Yale New Haven Med Ctr, Dept Med, New Haven, CT 06511 USA. [Asanuma, Katsuhiko] Kyoto Univ, Grad Sch Med, Med Innovat Ctr, Lab Kidney Res,TMK Project, Kyoto 6068501, Japan. [Sudol, Marius] Weis Ctr Res, Danville, PA 17822 USA. [Mundel, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. [Mundel, Peter] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Campbell, KN (reprint author), Mt Sinai Sch Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM kirk.campbell@mssm.edu; mundel.peter@mgh.harvard.edu FU National Institutes of Health [DK57683, DK062472, DK09368201, DK081617]; NephCure Young Investigator grant; PA Breast Cancer Coalition [60707, 920093]; Geisinger Clinic FX This work was supported, in whole or in part, by National Institutes of Health Grants DK57683, DK062472, and DK09368201 (to P. M.), National Institutes of Health Grant DK081617 (to K. N. C.). This work was also supported by a NephCure Young Investigator grant (to K. N. C.) and by PA Breast Cancer Coalition Grants 60707 and 920093 and by a grant from the Geisinger Clinic (to M. S.). NR 38 TC 12 Z9 12 U1 1 U2 3 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 JUN 14 PY 2013 VL 288 IS 24 BP 17057 EP 17062 DI 10.1074/jbc.C113.457390 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164AH UT WOS:000320380600002 PM 23667252 ER PT J AU Onal, M Piemontese, M Xiong, JH Wang, YY Han, L Ye, SQ Komatsu, M Selig, M Weinstein, RS Zhao, HB Jilka, RL Almeida, M Manolagas, SC O'Brien, CA AF Onal, Melda Piemontese, Marilina Xiong, Jinhu Wang, Yiying Han, Li Ye, Shiqiao Komatsu, Masaaki Selig, Martin Weinstein, Robert S. Zhao, Haibo Jilka, Robert L. Almeida, Maria Manolagas, Stavros C. O'Brien, Charles A. TI Suppression of Autophagy in Osteocytes Mimics Skeletal Aging SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRABECULAR BONE LOSS; OSTEOCLAST FORMATION; TARGETED DELETION; RANKL EXPRESSION; OXIDATIVE STRESS; BMP ANTAGONIST; MICE; CELLS; GENE; OSTEOPOROSIS AB Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66(shc) phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging. C1 [Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. [Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. [Komatsu, Masaaki] Tokyo Metropolitan Inst Med Sci, Prot Metab Project, Tokyo 1568506, Japan. [Selig, Martin] Massachusetts Gen Hosp, Pathol Serv, Electron Microscopy Unit, Boston, MA 02114 USA. [Selig, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP O'Brien, CA (reprint author), Univ Arkansas Med Sci, 4301 W Markham St,MS 587, Little Rock, AR 72205 USA. EM caobrien@uams.edu RI xiong, jinhu/E-1849-2011; Liu, Juan/J-5155-2015; Ye, Shiqiao/N-2873-2015 OI Ye, Shiqiao/0000-0003-1529-7102 FU National Institutes of Health [AG13918, AR049794]; Central Arkansas Veteran's Healthcare System [1I01BX000294]; UAMS Translational Research Institute [UL1RR029884]; UAMS tobacco settlement funds FX This work was supported by National Institutes of Health Grants AG13918 (to S. C. M.) and AR049794 (to C. A. O.) and the Central Arkansas Veteran's Healthcare System (Merit Review 1I01BX000294, to C. A. O.). Additional support was provided by the UAMS Translational Research Institute (UL1RR029884) and by UAMS tobacco settlement funds. NR 53 TC 43 Z9 45 U1 1 U2 14 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 JUN 14 PY 2013 VL 288 IS 24 BP 17432 EP 17440 DI 10.1074/jbc.M112.444190 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164AH UT WOS:000320380600035 PM 23645674 ER PT J AU Zhang, YY Wang, JF Wheat, J Chen, X Jin, S Sadrzadeh, H Fathi, AT Peterson, RT Kung, AL Sweetser, DA Yeh, JRJ AF Zhang, Yiyun Wang, Jianfeng Wheat, Justin Chen, Xi Jin, Shan Sadrzadeh, Hossein Fathi, Amir T. Peterson, Randall T. Kung, Andrew L. Sweetser, David A. Yeh, Jing-Ruey Joanna TI AML1-ETO mediates hematopoietic self-renewal and leukemogenesis through a COX/beta-catenin signaling pathway SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; NONSTEROIDAL ANTIINFLAMMATORY DRUG; BETA-CATENIN; STEM-CELLS; REGULATES EXPRESSION; COLORECTAL-CANCER; LONG-TERM; DIFFERENTIATION; TRANSLOCATION; DISEASE AB Developing novel therapies that suppress self-renewal of leukemia stem cells may reduce the likelihood of relapses and extend long-term survival of patients with acute myelogenous leukemia (AML). AML1-ETO (AE) is an oncogene that plays an important role in inducing self-renewal of hematopoietic stem/progenitor cells (HSPCs), leading to the development of leukemia stem cells. Previously, using a zebrafish model of AE and a whole-organism chemical suppressor screen, we have discovered that AE induces specific hematopoietic phenotypes in embryonic zebrafish through a cyclooxygenase (COX)-2 and beta-catenin-dependent pathway. Here, we show that AE also induces expression of the Cox-2 gene and activates beta-catenin in mouse bone marrow cells. Inhibition of COX suppresses beta-catenin activation and serial replating of AE(+) mouse HSPCs. Genetic knockdown of beta-catenin also abrogates the clonogenic growth of AE(+) mouse HSPCs and human leukemia cells. In addition, treatment with nimesulide, a COX-2 selective inhibitor, dramatically suppresses xenograft tumor formation and inhibits in vivo progression of human leukemia cells. In summary, our data indicate an important role of a COX/beta-catenin-dependent signaling pathway in tumor initiation, growth, and self-renewal, and in providing the rationale for testing potential benefits from common COX inhibitors as a part of AML treatments. C1 [Zhang, Yiyun; Jin, Shan; Peterson, Randall T.; Yeh, Jing-Ruey Joanna] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Zhang, Yiyun; Wang, Jianfeng; Jin, Shan; Fathi, Amir T.; Peterson, Randall T.; Sweetser, David A.; Yeh, Jing-Ruey Joanna] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wang, Jianfeng; Wheat, Justin; Chen, Xi; Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. [Wang, Jianfeng; Wheat, Justin; Chen, Xi; Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Med Genet, Boston, MA 02114 USA. [Sadrzadeh, Hossein; Fathi, Amir T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Peterson, Randall T.; Kung, Andrew L.] Broad Inst, Cambridge, MA USA. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Yeh, JRJ (reprint author), 149 13th St,149-4201, Charlestown, MA 02129 USA. EM dsweetser@partners.org; jyeh1@partners.org FU National Institutes of Health [K01 AG031300, R01 CA140188, R01 CA115772, T32 CA071345]; Hundai Hope on Wheels; Mattina Proctor Foundation; Massachusetts General Hospital Claflin Distinguished Scholar Award FX This work was supported by grants from the National Institutes of Health (K01 AG031300 [J.-R.J.Y.], R01 CA140188 [J.-R.J.Y., D. A. S., R. T. P., and Y.Z.], R01 CA115772 [D. A. S., X. C., and J.W.], and T32 CA071345 [J.W.]); Hundai Hope on Wheels (D. A. S.); the Mattina Proctor Foundation (D. A. S.); and the Massachusetts General Hospital Claflin Distinguished Scholar Award (J.-R.J.Y.). NR 50 TC 17 Z9 19 U1 2 U2 11 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 JUN 13 PY 2013 VL 121 IS 24 BP 4906 EP 4916 DI 10.1182/blood-2012-08-447763 PG 11 WC Hematology SC Hematology GA 184NB UT WOS:000321896300018 PM 23645839 ER PT J AU DiNardo, CD Propert, KJ Loren, AW Paietta, E Sun, ZX Levine, RL Straley, KS Yen, K Patel, JP Agresta, S Abdel-Wahab, O Perl, AE Litzow, MR Rowe, JM Lazarus, HM Fernandez, HF Margolis, DJ Tallman, MS Luger, SM Carroll, M AF DiNardo, Courtney D. Propert, Kathleen J. Loren, Alison W. Paietta, Elisabeth Sun, Zhuoxin Levine, Ross L. Straley, Kimberly S. Yen, Katharine Patel, Jay P. Agresta, Samuel Abdel-Wahab, Omar Perl, Alexander E. Litzow, Mark R. Rowe, Jacob M. Lazarus, Hillard M. Fernandez, Hugo F. Margolis, David J. Tallman, Martin S. Luger, Selina M. Carroll, Martin TI Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia SO BLOOD LA English DT Article ID IDH2 MUTATIONS; PROGNOSTIC-SIGNIFICANCE; MOLECULAR ALTERATIONS; ONCOLOGY-GROUP; AML; DIFFERENTIATION; PREVALENCE; FREQUENT; GROWTH; GENES AB Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate (2HG), but the clinical utility of 2HG has not been established. We studied whether 2HG measurements in acute myeloid leukemia (AML) patients correlate with IDH mutations, and whether diagnostic or remission 2HG measurements predict survival. Sera from 223 de novo AML patients were analyzed for 2HG concentration by reverse-phase liquid chromatography-mass spectrometry. Pretreatment 2HG levels ranged from 10 to 30 000 ng/mL and were elevated in IDH-mutants (median, 3004 ng/mL), compared to wild-type IDH (median, 61 ng/mL) (P < .0005). 2HG levels did not differ among IDH1 or IDH2 allelic variants. In receiver operating characteristic analysis, a discriminatory level of 700 ng/mL optimally segregated patients with and without IDH mutations, and on subsequent mutational analysis of the 13 IDH wild-type samples with 2HG levels >700 ng/mL, 9 were identified to have IDH mutations. IDH-mutant patients with 2HG levels >200 at complete remission had shorter overall survival compared to 2HG <= 200 ng/mL (hazard ratio, 3.9; P = .02). We establish a firm association between IDH mutations and serum 2HG concentration in AML, and confirm that serum oncometabolite measurements provide useful diagnostic and prognostic information that can improve patient selection for IDH-targeted therapies. C1 [DiNardo, Courtney D.; Propert, Kathleen J.; Loren, Alison W.; Perl, Alexander E.; Margolis, David J.; Luger, Selina M.; Carroll, Martin] Univ Penn, Philadelphia, PA 19104 USA. [Paietta, Elisabeth] Montefiore Med Ctr, Albert Einstein Coll Med, North Div, Bronx, NY 10467 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Levine, Ross L.; Patel, Jay P.; Abdel-Wahab, Omar; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Straley, Kimberly S.; Yen, Katharine; Agresta, Samuel] Agios, Cambridge, MA USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Fernandez, Hugo F.] H Lee Moffitt Canc Inst, Tampa, FL USA. RP Carroll, M (reprint author), Hosp Univ Penn, Div Hematol Oncol, Rm 708 BRB 2-3, Philadelphia, PA 19146 USA. EM carroll2@mail.med.upenn.edu OI Abdel-Wahab, Omar/0000-0002-3907-6171 FU National Institutes of Health Cancer Clinical Epidemiology Training Grant [T32 CA 009679]; National Institutes of Health National Cancer Institute Grant [RO1 CA149566]; VA Merit Award [1I01BX000918] FX This work was supported by the National Institutes of Health Cancer Clinical Epidemiology Training Grant (T32 CA 009679) (C. D. D.) and by the National Institutes of Health National Cancer Institute Grant (RO1 CA149566) and VA Merit Award 1I01BX000918 (M.C.). NR 37 TC 55 Z9 57 U1 1 U2 10 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 JUN 13 PY 2013 VL 121 IS 24 BP 4917 EP 4924 DI 10.1182/blood-2013-03-493197 PG 8 WC Hematology SC Hematology GA 184NB UT WOS:000321896300019 PM 23641016 ER PT J AU Wharton, W Gleason, CE Miller, VM Asthana, S AF Wharton, Whitney Gleason, Carey E. Miller, Virginia M. Asthana, Sanjay TI Rationale and design of the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS cognitive and affective sub study (KEEPS Cog) SO BRAIN RESEARCH LA English DT Article DE Hormone therapy; Clinical trial; KEEPS; Estrogen; Alzheimer's disease; Cognition; Menopause ID CONJUGATED EQUINE ESTROGENS; HORMONE REPLACEMENT THERAPY; HEALTH INITIATIVE MEMORY; ORAL MICRONIZED PROGESTERONE; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; ALZHEIMER-DISEASE; CACHE COUNTY AB This manuscript describes the study design and rationalle for the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective ancillary study (KEEPS Cog). KEEPS is a multicenter, randomized, double-blinded, placebo-controlled trial, designed to test the hypothesis that low-dose hormone therapy (HT) initiated in recently postmenopausal women will reduce the progression of subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC) over four years. The KEEPS Cog ancillary study was designed to assess potential estrogenic treatment effects on cognition and mood. We present the KEEPS trial in the context of issues raised by the Women's Health Initiative (WHI) and the Women's Health Initiative Memory Study (WHIMS). Here we also describe the most recent results and ongoing HT-related research studies designed to address similar issues. This article is part of a Special Issue entitled Hormone Therapy. (C) 2013 Published by Elsevier B.V. C1 [Wharton, Whitney; Gleason, Carey E.; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Gleason, Carey E.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Wharton, Whitney; Gleason, Carey E.; Asthana, Sanjay] Wisconsin Alzheimers Dis Res Ctr ADRC, Madison, WI 53792 USA. [Miller, Virginia M.] Mayo Clin, Rochester, MN 55905 USA. RP Wharton, W (reprint author), Univ Wisconsin, Dept Med & Publ Hlth, 2500 Overlook Terrace,VA Hosp GRECC D4243, Madison, WI 53705 USA. EM wlwharto@medicine.wisc.edu FU NIA NIH HHS [P50 AG033514] NR 32 TC 20 Z9 21 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 13 PY 2013 VL 1514 SI SI BP 12 EP 17 DI 10.1016/j.brainres.2013.04.011 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 180KV UT WOS:000321595000003 PM 23603409 ER PT J AU Liu, Y Quang, P Braggio, E Ngo, H Badalian-Very, G Flores, L Zhang, Y Sacco, A Maiso, P Azab, AK Azab, F Carrasco, R Rollins, BJ Roccaro, AM Ghobrial, IM AF Liu, Yang Phong Quang Braggio, Esteban Hai Ngo Badalian-Very, Gayane Flores, Ludmila Zhang, Yong Sacco, Antonio Maiso, Patricia Azab, Abdel Kareem Azab, Feda Carrasco, Ruben Rollins, Barrett J. Roccaro, Aldo M. Ghobrial, Irene M. TI Novel Tumor Suppressor Function of Glucocorticoid-Induced TNF Receptor GITR in Multiple Myeloma SO PLOS ONE LA English DT Article ID NF-KAPPA-B; NK CELLS; T-CELLS; SUPERFAMILY; PATHWAY; ACTIVATION; BIOLOGY; LIGAND; CANCER; NEUROBLASTOMA AB Glucocorticoid-induced TNF receptor (GITR) plays a crucial role in modulating immune response and inflammation, however the role of GITR in human cancers is poorly understood. In this study, we demonstrated that GITR is inactivated during tumor progression in Multiple Myeloma (MM) through promoter CpG island methylation, mediating gene silencing in primary MM plasma cells and MM cell lines. Restoration of GITR expression in GITR deficient MM cells led to inhibition of MM proliferation in vitro and in vivo and induction of apoptosis. These findings were supported by the presence of induction of p21 and PUMA, two direct downstream targets of p53, together with modulation of NF-kappa B in GITR-overexpressing MM cells. Moreover, the unbalanced expression of GITR in clonal plasma cells correlated with MM disease progression, poor prognosis and survival. These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression. C1 [Liu, Yang; Phong Quang; Hai Ngo; Badalian-Very, Gayane; Flores, Ludmila; Zhang, Yong; Sacco, Antonio; Maiso, Patricia; Azab, Abdel Kareem; Azab, Feda; Carrasco, Ruben; Rollins, Barrett J.; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02114 USA. [Braggio, Esteban] Mayo Clin, Coll Med, Div Haematol, Dept Med, Scottsdale, AZ USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02114 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU NIH [R01CA125690, R01CA133799] FX This work was supported by NIHR01CA125690 and R01CA133799 NR 38 TC 5 Z9 5 U1 0 U2 5 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 JUN 13 PY 2013 VL 8 IS 6 AR e66982 DI 10.1371/journal.pone.0066982 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172XB UT WOS:000321038800009 PM 23785514 ER PT J AU Elkins, JM Wang, J Deng, XM Pattison, MJ Arthur, JSC Erazo, T Gomez, N Lizcano, JM Gray, NS Knapp, S AF Elkins, Jonathan M. Wang, Jing Deng, Xianming Pattison, Michael J. Arthur, J. Simon C. Erazo, Tatiana Gomez, Nestor Lizcano, Jose M. Gray, Nathanael S. Knapp, Stefan TI X-ray Crystal Structure of ERK5 (MAPK7) in Complex with a Specific Inhibitor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TARGETED DELETION; SIGNALING PATHWAY; MEK5-ERK5 PATHWAY; PROSTATE-CANCER; BREAST-CANCER; GROWTH-FACTOR; EXPRESSION; BMK1/ERK5; IDENTIFICATION AB The protein kinase ERK5 (MAPK7) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role mediating cell proliferation, survival, epithelial-mesenchymal transition, and angiogenesis. To date, no three-dimensional structure has been published that would allow rational design of inhibitors. To address this, we determined the X-ray crystal structure of the human ERK5 kinase domain in complex with a highly specific benzo[e]pyrimido[5,4-b]diazepine-6(11H)-one inhibitor. The structure reveals that specific residue differences in the ATP-binding site, compared to the related ERKs p38s and JNKs, allow for the development of ERK5-specific inhibitors. The selectivity of previously observed ERK5 inhibitors can also be rationalized using this structure, which provides a template for future development of inhibitors with potential for treatment of disease. C1 [Elkins, Jonathan M.; Wang, Jing; Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford OX3 7DQ, England. [Knapp, Stefan] Univ Oxford, TDI, Oxford OX3 7FZ, England. [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Pattison, Michael J.; Arthur, J. Simon C.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Pattison, Michael J.; Arthur, J. Simon C.] Univ Dundee, Coll Life Sci, Div Cell Signaling & Immunol, Dundee DD1 5EH, Scotland. [Erazo, Tatiana; Gomez, Nestor; Lizcano, Jose M.] Univ Autonoma Barcelona, Inst Neurociencies, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain. RP Knapp, S (reprint author), Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England. EM stefan.knapp@sgc.ox.ac.uk RI Gomez, Nestor/I-2522-2015; OI Gomez, Nestor/0000-0002-1348-2737; Pattison, Michael/0000-0001-7588-2560; Elkins, Jon/0000-0003-2858-8929; Arthur, Simon/0000-0002-8135-1958; lizcano, jose m/0000-0002-3154-5383; Knapp, Stefan/0000-0001-5995-6494 FU SGC [1097737]; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada; GlaxoSmithKline; Pfizer; Eli Lilly; Takeda; AbbVie; Novartis Research Foundation; Ontario Ministry of Research and Innovation; Wellcome Trust [092809/Z/10/Z] FX J.M.E., J.W., and S.K. are grateful for financial support by the SGC, a registered charity (No. 1097737) that receives funds from the Canadian Institutes for Health Research, the Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline, Pfizer, Eli Lilly, Takeda, AbbVie, the Novartis Research Foundation, the Ontario Ministry of Research and Innovation, and the Wellcome Trust (No. 092809/Z/10/Z). NR 46 TC 9 Z9 9 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JUN 13 PY 2013 VL 56 IS 11 BP 4413 EP 4421 DI 10.1021/jm4000837 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 167OI UT WOS:000320640900017 PM 23656407 ER PT J AU Bartsch, P Swenson, ER AF Baertsch, Peter Swenson, Erik R. TI Acute High-Altitude Illnesses SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MOUNTAIN-SICKNESS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; PULMONARY-EDEMA; CEREBRAL EDEMA; EXERCISE PERFORMANCE; NORMOBARIC HYPOXIA; DOUBLE-BLIND; PREVENTION; DEXAMETHASONE AB A 45-year-old healthy man wishes to climb Mount Kilimanjaro (5895 m) in a 5-day period, starting at 1800 m. The results of a recent exercise stress test were normal; he runs 10 km 4 or 5 times per week and finished a marathon in less than 4 hours last year. He wants to know how he can prevent becoming ill at high altitude and whether training or sleeping under normobaric hypoxic conditions in the weeks before the ascent would be helpful. What would you advise? C1 [Baertsch, Peter] Univ Clin, Dept Internal Med, Div Sports Med 7, D-69120 Heidelberg, Germany. [Swenson, Erik R.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. RP Bartsch, P (reprint author), Univ Clin, Dept Internal Med, Div Sports Med 7, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM peter.bartsch@med.uni-heidelberg.de FU Merck Sharp Dohme; Bayer HealthCare; Linde Group FX Dr. Bartsch reports receiving lecture fees from Merck Sharp & Dohme and Bayer HealthCare and payment to his institution for meeting expenses from the Linde Group. No other potential conflict of interest relevant to this article was reported. NR 50 TC 92 Z9 94 U1 8 U2 44 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 JUN 13 PY 2013 VL 368 IS 24 BP 2294 EP 2302 DI 10.1056/NEJMcp1214870 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 161YN UT WOS:000320230500005 PM 23758234 ER PT J AU Cole, AJ Eskandar, E Mela, T Noebels, JL Gonzalez, RG McGuone, D AF Cole, Andrew J. Eskandar, Emad Mela, Theofanie Noebels, Jeffrey L. Gonzalez, R. Gilberto McGuone, Declan TI Case 18-2013: A 32-Year-Old Woman with Recurrent Episodes of Altered Consciousness Oligoastrocytoma, WHO grade II of IV, associated with temporal-lobe seizures and ictal asystole (arrhythmogenic epilepsy) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LONG-QT SYNDROME; BRADYCARDIA; SYNCOPE; IDENTIFICATION; STIMULATION; LOBECTOMY; GENETICS; DEATH; TERM C1 [Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Mela, Theofanie] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [McGuone, Declan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Eskandar, Emad] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Mela, Theofanie] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [McGuone, Declan] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Clarus Ventures; Concert Pharmaceuticals; Sage Pharmaceuticals FX Dr. Cole reports receiving consulting fees from Clarus Ventures, Concert Pharmaceuticals, and Sage Pharmaceuticals. Dr. Eskandar reports payment to his institution for a patent on a device for deep-brain stimulation for enhancing learning, motivation, and memory. No other potential conflict of interest relevant to this article was reported. NR 32 TC 2 Z9 2 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 13 PY 2013 VL 368 IS 24 BP 2304 EP 2312 DI 10.1056/NEJMcpc1215969 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 161YN UT WOS:000320230500008 PM 23758236 ER PT J AU Hunt, KA Mistry, V Bockett, NA Ahmad, T Ban, M Barker, JN Barrett, JC Blackburn, H Brand, O Burren, O Capon, F Compston, A Gough, SCL Jostins, L Kong, Y Lee, JC Lek, M MacArthur, DG Mansfield, JC Mathew, CG Mein, CA Mirza, M Nutland, S Onengut-Gumuscu, S Papouli, E Parkes, M Rich, SS Sawcer, S Satsangi, J Simmonds, MJ Trembath, RC Walker, NM Wozniak, E Todd, JA Simpson, MA Plagnol, V van Heel, DA AF Hunt, Karen A. Mistry, Vanisha Bockett, Nicholas A. Ahmad, Tariq Ban, Maria Barker, Jonathan N. Barrett, Jeffrey C. Blackburn, Hannah Brand, Oliver Burren, Oliver Capon, Francesca Compston, Alastair Gough, Stephen C. L. Jostins, Luke Kong, Yong Lee, James C. Lek, Monkol MacArthur, Daniel G. Mansfield, John C. Mathew, Christopher G. Mein, Charles A. Mirza, Muddassar Nutland, Sarah Onengut-Gumuscu, Suna Papouli, Efterpi Parkes, Miles Rich, Stephen S. Sawcer, Steven Satsangi, Jack Simmonds, Matthew J. Trembath, Richard C. Walker, Neil M. Wozniak, Eva Todd, John A. Simpson, Michael A. Plagnol, Vincent van Heel, David A. TI Negligible impact of rare autoimmune-locus coding-region variants on missing heritability SO NATURE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; PSORIASIS SUSCEPTIBILITY LOCI; RHEUMATOID-ARTHRITIS; COMMON VARIANTS; LOW-FREQUENCY; GENES; RISK; ARCHITECTURE; REVEALS AB Genome-wide association studies(GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute(1,2). To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set(3-5). This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis(6) (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect(7-10). C1 [Hunt, Karen A.; Mistry, Vanisha; Bockett, Nicholas A.; van Heel, David A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England. [Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter EX2 5DW, Devon, England. [Ban, Maria; Compston, Alastair; Sawcer, Steven] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 0QQ, England. [Barker, Jonathan N.; Capon, Francesca; Mathew, Christopher G.; Mirza, Muddassar; Papouli, Efterpi; Simpson, Michael A.] Kings Coll London, Sch Med, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England. [Barrett, Jeffrey C.; Blackburn, Hannah] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Brand, Oliver; Gough, Stephen C. L.; Simmonds, Matthew J.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Burren, Oliver; Nutland, Sarah; Walker, Neil M.; Todd, John A.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 0XY, England. [Jostins, Luke] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Kong, Yong] Yale Univ, WM Keck Fdn Biotechnol Resource Lab, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. [Lee, James C.; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Med, Cambridge CB2 0QQ, England. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Mansfield, John C.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Mein, Charles A.; Wozniak, Eva] Queen Mary Univ London, Barts & London Sch Med & Dent, John Vane Sci Ctr, Genome Ctr, London EC1M 6BQ, England. [Onengut-Gumuscu, Suna; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Trembath, Richard C.] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 2AT, England. [Plagnol, Vincent] UCL, Genet Inst, London WC1E 6BT, England. RP van Heel, DA (reprint author), Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England. EM v.plagnol@ucl.ac.uk; d.vanheel@qmul.ac.uk RI Capon, Francesca/F-4763-2011; Simpson, Michael/F-4737-2011; Todd, John/A-3542-2010; Mathew, Christopher/G-3434-2015; OI Barrett, Jeffrey/0000-0002-1152-370X; Trembath, Richard/0000-0003-0550-3400; Lee, James/0000-0001-5711-9385; Capon, Francesca/0000-0003-2432-5793; Simpson, Michael/0000-0002-8539-8753; Mathew, Christopher/0000-0003-4178-1838; Walker, Neil/0000-0001-9796-7688; Simmonds, Matt/0000-0003-3154-3510; van Heel, David/0000-0002-0637-2265; Plagnol, Vincent/0000-0002-5597-9215; Kong, Yong/0000-0002-2881-5274; Burren, Oliver/0000-0002-3388-5760 FU Medical Research Council [MRC G1001158]; Coeliac UK; MRC [G0601387]; National Institutes for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London; Cambridge NIHR Biomedical Research Centre; Wellcome Trust [076113/C/04/Z, 068545/Z/02, 068181, JDRF 4-2001-1008, WT061858]; NIHR [RP-PG-0310-1002]; UK MRC [G0000934]; British Society for Paediatric Endocrinology and Diabetes FX The study was primarily funded by the Medical Research Council (MRC G1001158 to D. A. v. H and V. P.), with further funding from Coeliac UK (to D. A. v. H). We thank C. Wijmenga and G. Trynka for sharing ImmunoChip data, and the International Multiple Sclerosis Genomics Consortium for ImmunoChip data and samples. J.N.B. and R. C. T. are supported by MRC grant G0601387. This research was supported by the National Institutes for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The study was supported by the Cambridge NIHR Biomedical Research Centre. We thank E. Gray and D. Jones (Wellcome Trust Sanger Institute) for sample preparation. We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS-CC collection), funded by the Wellcome Trust grant 076113/C/04/Z and by NIHR programme grant to NHS Blood and Transplant (RP-PG-0310-1002). The collection was established as part of the Wellcome Trust Case Control Consortium(WTCCC). We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the UK MRC grant G0000934 and the Wellcome Trust grant 068545/Z/02. We thank nurses and doctors for recruiting autoimmune thyroid disease (AITD) subjects into the AITD National Collection, funded by the Wellcome Trust grant 068181. We acknowledge use of DNA from the Cambridge BioResource. We acknowledge use of DNA from the Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Case-Series (GRID), funded by JDRF and the Wellcome Trust (grant references JDRF 4-2001-1008 and WT061858). The subjects were recruited in the UK by D. Dunger and his team with support from the British Society for Paediatric Endocrinology and Diabetes. The samples were prepared and provided by the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, University of Cambridge, UK. Psoriasis samples used were based on the WTCCC2 GWAS clinical panel, for which we thank D. Burden, C. Griffiths, M. Cork and R. McManus. Finally, we would like to thank all autoimmune disease and control subjects for participating in this study. NR 30 TC 98 Z9 98 U1 1 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 2013 VL 498 IS 7453 BP 232 EP + DI 10.1038/nature12170 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 162RR UT WOS:000320283400049 PM 23698362 ER PT J AU Shalek, AK Satija, R Adiconis, X Gertner, RS Gaublomme, JT Raychowdhury, R Schwartz, S Yosef, N Malboeuf, C Lu, DN Trombetta, JJ Gennert, D Gnirke, A Goren, A Hacohen, N Levin, JZ Park, H Regev, A AF Shalek, Alex K. Satija, Rahul Adiconis, Xian Gertner, Rona S. Gaublomme, Jellert T. Raychowdhury, Raktima Schwartz, Schraga Yosef, Nir Malboeuf, Christine Lu, Diana Trombetta, John J. Gennert, Dave Gnirke, Andreas Goren, Alon Hacohen, Nir Levin, Joshua Z. Park, Hongkun Regev, Aviv TI Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells SO NATURE LA English DT Article ID MESSENGER-RNA-SEQ; GENE-EXPRESSION; LEVEL; RESPONSES; PROTEINS; PATHWAY; DRUG AB Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output(1-5), with important functional consequences(4,5). Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs1,2 or proteins(5,6) simultaneously, because genomic profiling methods(3) could not be applied to single cells until very recently(7-10). Here we use single-cell RNA sequencing to investigate heterogeneity in the response of mouse bone-marrow-derived dendritic cells (BMDCs) to lipopolysaccharide. We find extensive, and previously unobserved, bimodal variation in messenger RNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs; other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit, involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits. C1 [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Satija, Rahul; Adiconis, Xian; Raychowdhury, Raktima; Schwartz, Schraga; Yosef, Nir; Malboeuf, Christine; Lu, Diana; Trombetta, John J.; Gennert, Dave; Gnirke, Andreas; Goren, Alon; Hacohen, Nir; Levin, Joshua Z.; Park, Hongkun; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Goren, Alon] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Goren, Alon] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. [Goren, Alon] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02140 USA. RP Park, H (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM Hongkun_Park@harvard.edu; aregev@broad.mit.edu OI Shalek, Alex K./0000-0001-5670-8778; Schwartz, Schraga/0000-0002-3671-9709 FU National Institutes of Health (NIH) [1F32HD075541-01, U54 AI057159, DP2 OD002230, 5DP1OD003893-03, DP1OD003958-01]; Charles H. Hood Foundation; NIH CEGS Award [1P50HG006193-01]; Broad Institute; HHMI; Klarman Cell Observatory at the Broad Institute FX We thank N. Chevrier, C. Villani, M. Jovanovic, M. Bray and J. Shuga for scientific discussions; N. Friedman and E. Lander for comments on the manuscript; B. Tilton, T. Rogers and M. Tam for assistance with cell sorting; J. Bochicchio, E. Shefler and C. Guiducci for project management; the Broad Genomics Platform for all sequencing work; K. Fitzgerald for the Irf7-/- bone marrow; and L. Gaffney for help with artwork. Work was supported by a National Institutes of Health (NIH) Postdoctoral Fellowship (1F32HD075541-01, to R. S.), a Charles H. Hood Foundation Postdoctoral Fellowship (to A. Goren), an NIH grant (U54 AI057159, to N. H.), an NIH New Innovator Award (DP2 OD002230, to N. H.), an NIH CEGS Award (1P50HG006193-01, to H. P., A. R. and N. H.), NIH Pioneer Awards (5DP1OD003893-03 to H. P., DP1OD003958-01 to A. R.), the Broad Institute (to H. P. and A. R.), HHMI (to A. R.), and the Klarman Cell Observatory at the Broad Institute (to A.R.). NR 30 TC 309 Z9 315 U1 15 U2 165 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 2013 VL 498 IS 7453 BP 236 EP 240 DI 10.1038/nature12172 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 162RR UT WOS:000320283400050 PM 23685454 ER PT J AU Floyd, SR Pacold, ME Huang, QY Clarke, SM Lam, FC Cannell, IG Bryson, BD Rameseder, J Lee, MJ Blake, EJ Fydrych, A Ho, R Greenberger, BA Chen, GC Maffa, A Del Rosario, AM Root, DE Carpenter, AE Hahn, WC Sabatini, DM Chen, CC White, FM Bradner, JE Yaffe, MB AF Floyd, Scott R. Pacold, Michael E. Huang, Qiuying Clarke, Scott M. Lam, Fred C. Cannell, Ian G. Bryson, Bryan D. Rameseder, Jonathan Lee, Michael J. Blake, Emily J. Fydrych, Anna Ho, Richard Greenberger, Benjamin A. Chen, Grace C. Maffa, Amanda Del Rosario, Amanda M. Root, David E. Carpenter, Anne E. Hahn, William C. Sabatini, David M. Chen, Clark C. White, Forest M. Bradner, James E. Yaffe, Michael B. TI The bromodomain protein Brd4 insulates chromatin from DNA damage signalling SO NATURE LA English DT Article ID P-TEFB; GAMMA-H2AX; ACTIVATION; TRANSCRIPTION; REPAIR; BREAKS AB DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death(1). Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response(2). Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage. C1 [Floyd, Scott R.; Pacold, Michael E.; Huang, Qiuying; Clarke, Scott M.; Lam, Fred C.; Cannell, Ian G.; Bryson, Bryan D.; Rameseder, Jonathan; Lee, Michael J.; Blake, Emily J.; Fydrych, Anna; Ho, Richard; Greenberger, Benjamin A.; Chen, Grace C.; Maffa, Amanda; Del Rosario, Amanda M.; White, Forest M.; Yaffe, Michael B.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Floyd, Scott R.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Pacold, Michael E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Pacold, Michael E.; Sabatini, David M.] Whitehead Inst, Cambridge, MA 02139 USA. [Root, David E.; Carpenter, Anne E.; Hahn, William C.; Sabatini, David M.; Bradner, James E.; Yaffe, Michael B.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Hahn, William C.; Chen, Clark C.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chen, Clark C.; Yaffe, Michael B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [White, Forest M.; Yaffe, Michael B.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Yaffe, Michael B.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Yaffe, MB (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM myaffe@mit.edu OI Lee, Michael/0000-0003-3378-6196 FU Koch Institute; Center for Environmental Health Sciences National Institutes of Health [P30-CA14051, ES-002109]; SPARC; Holman Pathway Research Resident Seed Grant; American Society for Radiation Oncology Junior Faculty Career Research Training Award; Burroughs Wellcome Career Award for Medical Scientists; [R01-ES15339]; [1-U54-CA112967-04]; [R21-NS063917] FX We thank H. Le, T. R. Jones and M. Vokes for assistance with screening and image analysis. We thank C. Whittaker, S. Hoersch and M. Moran for computing and data analysis assistance; C. Reinhardt, C. Ellson and A. Gardino for manuscript editing; and P. Filippakopoulos and S. Knapp for discussions. This work was partially supported by the Koch Institute and Center for Environmental Health Sciences National Institutes of Health Core Grants P30-CA14051 and ES-002109; and by grants R01-ES15339, 1-U54-CA112967-04 and R21-NS063917; a SPARC grant to M.B.Y.; and a Holman Pathway Research Resident Seed Grant, American Society for Radiation Oncology Junior Faculty Career Research Training Award, Klarman Scholar, Koch Institute Clinical Investigator Award, and Burroughs Wellcome Career Award for Medical Scientists to S.R.F. NR 22 TC 74 Z9 78 U1 4 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 2013 VL 498 IS 7453 BP 246 EP + DI 10.1038/nature12147 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 162RR UT WOS:000320283400052 PM 23728299 ER PT J AU Cohen, NR Lobritz, MA Collins, JJ AF Cohen, Nadia R Lobritz, Michael A. Collins, James J. TI Microbial Persistence and the Road to Drug Resistance SO CELL HOST & MICROBE LA English DT Review ID MYCOBACTERIUM-TUBERCULOSIS PERSISTENCE; MEDIATE ANTIBIOTIC TOLERANCE; SMALL-MOLECULE INHIBITORS; PLASMODIUM-FALCIPARUM; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS; BACTERICIDAL ANTIBIOTICS; BIOFILM FORMATION; STRESS-RESPONSE AB Microbial drug persistence is a widespread phenomenon in which a subpopulation of microorganisms is able to survive antimicrobial treatment without acquiring resistance-conferring genetic changes. Microbial persisters can cause recurrent or intractable infections, and, like resistant mutants, they carry an increasing clinical burden. In contrast to heritable drug resistance, however, the biology of persistence is only beginning to be unraveled. Persisters have traditionally been thought of as metabolically dormant, nondividing cells. As discussed in this review, increasing evidence suggests that persistence is in fact an actively maintained state, triggered and enabled by a network of intracellular stress responses that can accelerate processes of adaptive evolution. Beyond shedding light on the basis of persistence, these findings raise the possibility that persisters behave as an evolutionary reservoir from which resistant organisms can emerge. As persistence and its consequences come into clearer focus, so too does the need for clinically useful persister-eradication strategies. C1 [Cohen, Nadia R; Lobritz, Michael A.; Collins, James J.] Boston Univ, Howard Hughes Med Inst, Boston, MA 02215 USA. [Cohen, Nadia R; Lobritz, Michael A.; Collins, James J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Cohen, Nadia R; Lobritz, Michael A.; Collins, James J.] Boston Univ, Ctr Synthet Biol, Boston, MA 02215 USA. [Cohen, Nadia R; Lobritz, Michael A.; Collins, James J.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. [Lobritz, Michael A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Collins, James J.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Collins, JJ (reprint author), Boston Univ, Howard Hughes Med Inst, Boston, MA 02215 USA. EM jcollins@bu.edu FU Wyss Institute Clinical Fellowship program; Howard Hughes Medical Institute FX We thank Drs. Kara Lassen, Ahmad S. Khalil, Peter Belenky, and Rebecca S. Shapiro for critical input and reading of the manuscript. This work was supported by funding from the Wyss Institute Clinical Fellowship program and the Howard Hughes Medical Institute. NR 115 TC 68 Z9 71 U1 10 U2 56 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD JUN 12 PY 2013 VL 13 IS 6 BP 632 EP 642 DI 10.1016/j.chom.2013.05.009 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AA1IY UT WOS:000330851000004 PM 23768488 ER PT J AU Morfini, GA Bosco, DA Brown, H Gatto, R Kaminska, A Song, YY Molla, L Baker, L Marangoni, MN Berth, S Tavassoli, E Bagnato, C Tiwari, A Hayward, LJ Pigino, GF Watterson, DM Huang, CF Banker, G Brown, RH Brady, ST AF Morfini, Gerardo A. Bosco, Daryl A. Brown, Hannah Gatto, Rodolfo Kaminska, Agnieszka Song, Yuyu Molla, Linda Baker, Lisa Marangoni, M. Natalia Berth, Sarah Tavassoli, Ehsan Bagnato, Carolina Tiwari, Ashutosh Hayward, Lawrence J. Pigino, Gustavo F. Watterson, D. Martin Huang, Chun-Fang Banker, Gary Brown, Robert H., Jr. Brady, Scott T. TI Inhibition of Fast Axonal Transport by Pathogenic SOD1 Involves Activation of p38 MAP Kinase SO PLOS ONE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DEGENERATION; ZINC SUPEROXIDE-DISMUTASE; SQUID GIANT-AXON; PROTEIN-KINASE; MOUSE MODEL; CYTOPLASMIC DYNEIN; IN-VIVO; NEUROFILAMENT PROTEIN; HEXANUCLEOTIDE REPEAT AB Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT) deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS. C1 [Morfini, Gerardo A.; Gatto, Rodolfo; Kaminska, Agnieszka; Song, Yuyu; Marangoni, M. Natalia; Berth, Sarah; Tavassoli, Ehsan; Pigino, Gustavo F.; Brady, Scott T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60607 USA. [Morfini, Gerardo A.; Brown, Hannah; Kaminska, Agnieszka; Song, Yuyu; Molla, Linda; Baker, Lisa; Marangoni, M. Natalia; Berth, Sarah; Pigino, Gustavo F.; Brady, Scott T.] Marine Biol Lab, Woods Hole, MA 02543 USA. [Bosco, Daryl A.; Hayward, Lawrence J.; Brown, Robert H., Jr.] Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01655 USA. [Tiwari, Ashutosh] Michigan Technol Univ, Dept Chem, Houghton, MI 49931 USA. [Brown, Hannah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Watterson, D. Martin] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chicago, IL 60611 USA. [Watterson, D. Martin] Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. [Huang, Chun-Fang; Banker, Gary] Oregon Hlth & Sci Univ, Jungers Ctr Neurosci Res, Portland, OR 97201 USA. [Bagnato, Carolina] Natl Univ Rio Negro, Dept Nat Sci & Engn, Rio Negro, Argentina. RP Morfini, GA (reprint author), Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60607 USA. EM gmorfini@uic.edu; stbrady@uic.edu RI Tiwari, Ashutosh/A-7458-2008; OI Tiwari, Ashutosh/0000-0001-7373-349X; Song, Yuyu/0000-0002-9196-1610; Watterson, Daniel/0000-0001-7605-5866 FU Marine Biological Laboratory; NIH [NS066942A, R01NS44170, NS23868, NS23320, NS41170, MH066179, R01AG031311, R01NS055951, U01NS05225, R01NS050557, 1RC1NS068391, 1RC2NS070342, R01NS067206]; Howard Hughes Medical Institute-USE [52006287]; Muscular Dystrophy Association (MDA); ALS Association; ALS/CVS Therapy Alliance; Angel Fund; DeBourgknecht Fund for ALS Research; P2ALS; Project ALS FX Support was provided by 2007/2008 Marine Biological Laboratory summer fellowships and NIH (NS066942A) grants to GM; Howard Hughes Medical Institute-USE Grant #52006287 to Hunter College of CUNY (LM); Muscular Dystrophy Association (MDA) and NIH (R01NS44170) grants to LJH; MDA and NIH (NS23868, NS23320, NS41170) grants to STB; NIH grant MH066179 to GB; NIH grants R01AG031311 and R01NS055951 to DMW; NIH (U01NS05225, R01NS050557, 1RC1NS068391, 1RC2NS070342) grants to RHB; R01NS067206 to DAB; ALS Association grants to GM, AT, RHB, and STB; and ALS/CVS Therapy Alliance grants to RHB, GM, AT, LJH, and DAB. RHB and AT received support from the Angel Fund. RHB also received support from the DeBourgknecht Fund for ALS Research, P2ALS and Project ALS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 24 Z9 25 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 12 PY 2013 VL 8 IS 6 AR e65235 DI 10.1371/journal.pone.0065235 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 163FW UT WOS:000320322400010 PM 23776455 ER PT J AU Mehndiratta, MM Singhal, AB Chaturvedi, S Sivakumar, MR Moonis, M AF Mehndiratta, Man Mohan Singhal, Aneesh B. Chaturvedi, Seemant Sivakumar, M. R. Moonis, Majaz TI MEETING THE CHALLENGES OF STROKE IN INDIA SO NEUROLOGY LA English DT Editorial Material C1 [Mehndiratta, Man Mohan] GB Pant Hosp, Dept Neurol, New Delhi, India. [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chaturvedi, Seemant] Wayne State Univ, Dept Neurol, Detroit, MI USA. [Moonis, Majaz] Univ Massachusetts, Dept Neurol, Worcester, MA 01605 USA. RP Mehndiratta, MM (reprint author), GB Pant Hosp, Dept Neurol, New Delhi, India. EM mmehndi@hotmail.com NR 3 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 11 PY 2013 VL 80 IS 24 BP 2246 EP 2247 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 304FW UT WOS:000330733500017 PM 23751917 ER PT J AU Giza, CC Kutcher, JS Ashwal, S Barth, J Getchius, TSD Gioia, GA Gronseth, GS Guskiewicz, K Mandel, S Manley, G McKeag, DB Thurman, DJ Zafonte, R AF Giza, Christopher C. Kutcher, Jeffrey S. Ashwal, Stephen Barth, Jeffrey Getchius, Thomas S. D. Gioia, Gerard A. Gronseth, Gary S. Guskiewicz, Kevin Mandel, Steven Manley, Geoffrey McKeag, Douglas B. Thurman, David J. Zafonte, Ross TI Summary of evidence-based guideline update: Evaluation and management of concussion in sports Report of the Guideline Development Subcommittee of the American Academy of Neurology SO NEUROLOGY LA English DT Article ID TRAUMATIC BRAIN-INJURY; COLLEGIATE FOOTBALL PLAYERS; HIGH-SCHOOL; STANDARDIZED ASSESSMENT; NCAA CONCUSSION; RUGBY PLAYERS; EPIDEMIOLOGY; RECOVERY; RISK; PREDICTORS AB Objective: To update the 1997 American Academy of Neurology (AAN) practice parameter regarding sports concussion, focusing on 4 questions: 1) What factors increase/decrease concussion risk? 2) What diagnostic tools identify those with concussion and those at increased risk for severe/prolonged early impairments, neurologic catastrophe, or chronic neurobehavioral impairment? 3) What clinical factors identify those at increased risk for severe/prolonged early postconcussion impairments, neurologic catastrophe, recurrent concussions, or chronic neurobehavioral impairment? 4) What interventions enhance recovery, reduce recurrent concussion risk, or diminish long-term sequelae? The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: We systematically reviewed the literature from 1955 to June 2012 for pertinent evidence. We assessed evidence for quality and synthesized into conclusions using a modified Grading of Recommendations Assessment, Development and Evaluation process. We used a modified Delphi process to develop recommendations. Results: Specific risk factors can increase or decrease concussion risk. Diagnostic tools to help identify individuals with concussion include graded symptom checklists, the Standardized Assessment of Concussion, neuropsychological assessments, and the Balance Error Scoring System. Ongoing clinical symptoms, concussion history, and younger age identify those at risk for postconcussion impairments. Risk factors for recurrent concussion include history of multiple concussions, particularly within 10 days after initial concussion. Risk factors for chronic neurobehavioral impairment include concussion exposure and APOE epsilon 4 genotype. Data are insufficient to show that any intervention enhances recovery or diminishes long-term sequelae postconcussion. Practice recommendations are presented for preparticipation counseling, management of suspected concussion, and management of diagnosed concussion. C1 [Giza, Christopher C.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Pediat Neurol, Los Angeles, CA 90095 USA. [Kutcher, Jeffrey S.] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA. [Ashwal, Stephen] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Ashwal, Stephen] Loma Linda Univ, Dept Neurol, Loma Linda, CA 92350 USA. [Barth, Jeffrey] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA. [Getchius, Thomas S. D.] Amer Acad Neurol, Ctr Hlth Policy, Minneapolis, MN USA. [Gioia, Gerard A.] George Washington Univ, Sch Med, Dept Pediat & Psychiat, Washington, DC USA. [Gronseth, Gary S.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS USA. [Guskiewicz, Kevin] Univ N Carolina, Matthew Geller Sport Related Traumat Brain Injury, Chapel Hill, NC USA. [Mandel, Steven] Neurol & Neurophysiol Associates PC, Philadelphia, PA USA. [Manley, Geoffrey] UCSF Med Ctr, San Francisco, CA USA. [McKeag, Douglas B.] Indiana Univ, Ctr Sports Med, Dept Family Med, Indianapolis, IN 46204 USA. [Thurman, David J.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Zafonte, Ross] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Phys Med & Rehabil,Spaulding Rehabil Hosp, Cambridge, MA 02138 USA. RP Giza, CC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Pediat Neurol, Los Angeles, CA 90095 USA. FU American Academy of Neurology FX This evidence-based guideline was funded by the American Academy of Neurology. No author received honoraria or financial support to develop this document. NR 40 TC 237 Z9 240 U1 18 U2 59 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 11 PY 2013 VL 80 IS 24 BP 2250 EP 2257 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 304FW UT WOS:000330733500019 PM 23508730 ER PT J AU Singhal, T Venna, N AF Singhal, Tarun Venna, Nagagopal TI Mystery Case: Frontal meningoencephalocele causing recurrent bacterial meningitis SO NEUROLOGY LA English DT Editorial Material C1 [Singhal, Tarun; Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, Div Gen Neurol, Boston, MA 02114 USA. RP Venna, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Gen Neurol, Boston, MA 02114 USA. EM nvenna1@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 11 PY 2013 VL 80 IS 24 BP E250 EP E250 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 304FW UT WOS:000330733500001 PM 23751922 ER PT J AU Bouix, S Pasternak, O Rathi, Y Pelavin, PE Zafonte, R Shenton, ME AF Bouix, Sylvain Pasternak, Ofer Rathi, Yogesh Pelavin, Paula E. Zafonte, Ross Shenton, Martha E. TI Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-Concussive Symptoms following Mild Traumatic Brain Injury SO PLOS ONE LA English DT Article ID PRINCIPAL EIGENVECTOR MEASUREMENTS; TENSOR IMAGING FINDINGS; MINOR HEAD-INJURY; FRACTIONAL ANISOTROPY; MEAN DIFFUSIVITY; MRI; DTI; REPRODUCIBILITY; DEGENERATION; 1.5T AB A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject's diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: "load'' (number of abnormal regions) and "severity'' (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging. C1 [Bouix, Sylvain; Pasternak, Ofer; Rathi, Yogesh; Pelavin, Paula E.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Zafonte, Ross] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Shenton, Martha E.] Vet Affairs Boston Healthcare Syst, Dept Psychiat, Brockton Div, Brockton, MA USA. RP Bouix, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM sylvain@bwh.harvard.edu OI Bouix, Sylvain/0000-0003-1326-6054 FU Center for Integration of Medicine and Innovative Technology Soldier in Medicine Award; National Institute of Health [R01 MH082918, R01 NS078337, NAMIC-U54 EB005149]; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium; Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX This work was supported in part by the Center for Integration of Medicine and Innovative Technology Soldier in Medicine Award [to S.B.], by the National Institute of Health [R01 MH082918 to S.B., R01 NS078337 to M.E.S., NAMIC-U54 EB005149 to M.E.S.] and by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD to M.E.S., S.B., O.P., Y.R. and R.Z.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 30 Z9 30 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2013 VL 8 IS 6 AR e66205 DI 10.1371/journal.pone.0066205 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 169CU UT WOS:000320755400120 PM 23776631 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Use of biologics in a patient with rheumatoid arthritis refractory to methotrexate SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID THERAPY; RISK; MALIGNANCIES; METAANALYSIS; ABATACEPT; EFFICACY; AGENTS C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg & Med Acute care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Ctr Surg & Med Acute care Res & Transit C SMART, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 NR 15 TC 2 Z9 2 U1 0 U2 0 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 11 PY 2013 VL 185 IS 9 BP 793 EP 795 DI 10.1503/cmaj.121607 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 180YQ UT WOS:000321635600036 PM 23460636 ER PT J AU Shah, RV Goldfine, AB AF Shah, Ravi V. Goldfine, Allison B. TI Response to Letter Regarding Article, "Statins and Risk of New-Onset Diabetes Mellitus" SO CIRCULATION LA English DT Letter ID THERAPY; METAANALYSIS; TRIALS C1 [Shah, Ravi V.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Shah, RV (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 11 PY 2013 VL 127 IS 23 BP E838 EP E838 DI 10.1161/CIRCULATIONAHA.113.001664 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160YR UT WOS:000320156900006 PM 23905169 ER PT J AU Sun, L Zhu, LL Lu, P Yuen, T Li, JH Ma, RS Baliram, R Moonga, SS Liu, P Zallone, A New, MI Davies, TF Zaidi, M AF Sun, Li Zhu, Ling-Ling Lu, Ping Yuen, Tony Li, Jianhua Ma, Risheng Baliram, Ramkumari Moonga, Surinder S. Liu, Peng Zallone, Alberta New, Maria I. Davies, Terry F. Zaidi, Mone TI Genetic confirmation for a central role for TNF alpha in the direct action of thyroid stimulating hormone on the skeleton SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone metabolism; thyroid disease; bone density ID MARROW STROMAL CELLS; BONE LOSS; OSTEOCLAST PRECURSORS; THYROTROPIN RECEPTOR; POSTMENOPAUSAL WOMEN; TRANSGENIC MICE; IN-VIVO; TSH; EXPRESSION; OXYTOCIN AB Clinical data showing correlations between low thyroid-stimulating hormone (TSH) levels and high bone turnover markers, low bone mineral density, and an increased risk of osteoporosis-related fractures are buttressed by mouse genetic and pharmacological studies identifying a direct action of TSH on the skeleton. Here we show that the skeletal actions of TSH deficiency are mediated, in part, through TNF alpha. Compound mouse mutants generated by genetically deleting the Tnf alpha gene on a Tshr(-/-) (homozygote) or Tshr(+/-) (heterozygote) background resulted in full rescue of the osteoporosis, low bone formation, and hyperresorption that accompany TSH deficiency. Studies using ex vivo bone marrow cell cultures showed that TSH inhibits and stimulates TNF alpha production from macrophages and osteoblasts, respectively. TNF alpha, in turn, stimulates osteoclastogenesis but also enhances the production in bone marrow of a variant TSH beta. This locally produced TSH suppresses osteoclast formation in a negative feedback loop. We speculate that TNF alpha elevations due to low TSH signaling in human hyperthyroidism contribute to the bone loss that has traditionally been attributed solely to high thyroid hormone levels. C1 [Sun, Li; Zhu, Ling-Ling; Lu, Ping; Yuen, Tony; Li, Jianhua; Ma, Risheng; Baliram, Ramkumari; Moonga, Surinder S.; Liu, Peng; Zallone, Alberta; New, Maria I.; Davies, Terry F.; Zaidi, Mone] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA. [Sun, Li; Zhu, Ling-Ling; Lu, Ping; Yuen, Tony; Li, Jianhua; Ma, Risheng; Baliram, Ramkumari; Moonga, Surinder S.; Liu, Peng; Zallone, Alberta; New, Maria I.; Davies, Terry F.; Zaidi, Mone] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Yuen, Tony; New, Maria I.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Ma, Risheng; Baliram, Ramkumari; Davies, Terry F.] James J Peters Vet Affairs Med Ctr, Thyroid Res Unit, Bronx, NY 10468 USA. [Zallone, Alberta] Univ Bari, Dept Human Anat & Histol, I-70124 Bari, Italy. RP New, MI (reprint author), Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA. EM maria.new@mssm.edu; mone.zaidi@mssm.edu FU National Institutes of Health [DK80459, AG23176, AG40132]; Department of Veterans Affairs; Maria I. New Children's Hormone Research Foundation; Chinese University of Hong Kong FX We thank Dr. Jay Cao for help with microtomography measurements. This work was supported by National Institutes of Health Grants DK80459 (to L. S., T. F. D., and M.Z.), AG23176 (to M.Z.), and AG40132 (to M.Z.). T. F. D. acknowledges support from the Department of Veterans Affairs (Veterans Affairs Merit Award). M.I.N. is supported by the Maria I. New Children's Hormone Research Foundation and the Chinese University of Hong Kong. NR 38 TC 8 Z9 10 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 JUN 11 PY 2013 VL 110 IS 24 BP 9891 EP 9896 DI 10.1073/pnas.1308336110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171LM UT WOS:000320930100068 PM 23716650 ER PT J AU Slater, LH Hett, EC Clatworthy, AE Mark, KG Hung, DT AF Slater, Louise H. Hett, Erik C. Clatworthy, Anne E. Mark, Kevin G. Hung, Deborah T. TI CCT chaperonin complex is required for efficient delivery of anthrax toxin into the cytosol of host cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TCP-1; TRiC ID BOTULINUM C2 TOXIN; PROTECTIVE ANTIGEN; LETHAL FACTOR; MEMBRANE TRANSLOCATION; PROTEIN TRANSLOCATION; DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; IN-VITRO; RECEPTOR; ACTIN AB Bacterial toxins have evolved successful strategies for coopting host proteins to access the cytosol of host cells. Anthrax lethal factor (LF) enters the cytosol through pores in the endosomal membrane formed by anthrax protective antigen. Although in vitro models using planar lipid bilayers have shown that translocation can occur in the absence of cellular factors, recent studies using intact endosomes indicate that host factors are required for translocation in the cellular environment. In this study, we describe a high-throughput shRNA screen to identify host factors required for anthrax lethal toxin-induced cell death. The cytosolic chaperonin complex chaperonin containing t-complex protein 1 (CCT) was identified, and subsequent studies showed that CCT is required for efficient delivery of LF and related fusion proteins into the cytosol. We further show that knockdown of CCT inhibits the acid-induced delivery of LF and the fusion protein LFN-Bla (N terminal domain of LF fused to beta-lactamase) across the plasma membrane of intact cells. Together, these results suggest that CCT is required for efficient delivery of enzymatically active toxin to the cytosol and are consistent with a direct role for CCT in translocation of LF through the protective antigen pore. C1 [Slater, Louise H.; Hett, Erik C.; Clatworthy, Anne E.; Mark, Kevin G.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Slater, Louise H.; Hett, Erik C.; Clatworthy, Anne E.; Mark, Kevin G.; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Slater, Louise H.; Hett, Erik C.; Clatworthy, Anne E.; Mark, Kevin G.; Hung, Deborah T.] Broad Inst, Infect Dis Initiat, Cambridge, MA 02142 USA. [Slater, Louise H.; Hett, Erik C.; Clatworthy, Anne E.; Mark, Kevin G.; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu FU National Institutes of Health (NIH) National Research Service [F32AI084323]; NIH [U54 AI057159] FX We thank A. Barker and A. McCluskey for help with production and purification of PA, LF, and LFN-Bla; and the Broad Institute RNAi screening platform for technical help. E. C. H. was supported by National Institutes of Health (NIH) National Research Service Award Fellowship F32AI084323. This work was supported, in part, by NIH Grant U54 AI057159 to the New England Center of Excellence/Biodefense and Emerging Infectious Diseases (D.T.H.). NR 44 TC 7 Z9 7 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 2013 VL 110 IS 24 BP 9932 EP 9937 DI 10.1073/pnas.1302257110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171LM UT WOS:000320930100075 PM 23716698 ER PT J AU Cywes-Bentley, C Skurnik, D Zaidi, T Roux, D DeOliveira, RB Garrett, WS Lu, X O'Malley, J Kinzel, K Zaidi, T Rey, A Perrin, C Fichorova, RN Kayatani, AKK Maira-Litran, T Gening, ML Tsvetkov, YE Nifantiev, NE Bakaletz, LO Pelton, SI Golenbock, DT Pier, GB AF Cywes-Bentley, Colette Skurnik, David Zaidi, Tanweer Roux, Damien DeOliveira, Rosane B. Garrett, Wendy S. Lu, Xi O'Malley, Jennifer Kinzel, Kathryn Zaidi, Tauqeer Rey, Astrid Perrin, Christophe Fichorova, Raina N. Kayatani, Alexander K. K. Maira-Litran, Tomas Gening, Marina L. Tsvetkov, Yury E. Nifantiev, Nikolay E. Bakaletz, Lauren O. Pelton, Stephen I. Golenbock, Douglas T. Pier, Gerald B. TI Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunotherapy; infectious diseases; malaria; carbohydrates; animal models ID POLY-N-ACETYLGLUCOSAMINE; HUMAN MONOCLONAL-ANTIBODIES; STAPHYLOCOCCUS-AUREUS; SURFACE POLYSACCHARIDE; CONJUGATE VACCINES; UNITED-STATES; DISPERSIN-B; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; STREPTOCOCCUS-PNEUMONIAE; NEISSERIA-MENINGITIDIS AB Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A beta-(1 -> 6)-linked poly-N-acetyl-D-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e. g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology. C1 [Cywes-Bentley, Colette; Skurnik, David; Zaidi, Tanweer; Roux, Damien; Lu, Xi; O'Malley, Jennifer; Kinzel, Kathryn; Zaidi, Tauqeer; Maira-Litran, Tomas; Pier, Gerald B.] Harvard Univ, Sch Med, Dept Med, Div Infect Dis,Brigham & Womens Hosp, Boston, MA 02115 USA. [DeOliveira, Rosane B.; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Complex Dis, Boston, MA 02115 USA. [Rey, Astrid; Perrin, Christophe] Sanofi Res & Dev, Therapeut Strateg Unit, Infect Dis, F-31270 Toulouse, France. [Fichorova, Raina N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Genital Tract Biol,Dept Obstet Gynecol & Repr, Boston, MA 02115 USA. [Kayatani, Alexander K. K.] Walter Reed Army Inst Res, Mil Malaria Res Program, Vaccine Branch, Silver Spring, MD 20910 USA. [Gening, Marina L.; Tsvetkov, Yury E.; Nifantiev, Nikolay E.] ND Zelinskii Inst Organ Chem, Lab Glycoconjugate Chem, Moscow 119991, Russia. [Bakaletz, Lauren O.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Bakaletz, Lauren O.] Ohio State Univ, Coll Med, Columbus, OH 43205 USA. [Pelton, Stephen I.] Boston Univ, Med Ctr, Dept Pediat Infect Dis, Boston, MA 02118 USA. RP Pier, GB (reprint author), Harvard Univ, Sch Med, Dept Med, Div Infect Dis,Brigham & Womens Hosp, Boston, MA 02115 USA. EM gpier@rics.bwh.harvard.edu RI Roux, Damien/C-5618-2014; Fichorova, Raina/G-9969-2014; Roux, Damien/L-3671-2014; OI Roux, Damien/0000-0002-6103-6416; Roux, Damien/0000-0002-6103-6416; Pier, Gerald/0000-0002-9112-2331; Pelton, Stephen/0000-0003-4862-5344 FU NIAID [AI46706, AI057159, U54 AI057159, 5R01AI079085-04, RO1AI079293] FX We gratefully acknowledge the following individuals for supplying microbial strains or tissue samples: Dr. Peter Rice (University of Massachusetts Medical School); Dr. Lee Wetzler (Boston University Medical School); Drs. Daniel Milner, Eric Rubin, and Marc Lipsitch (Harvard School of Public Health), Drs. Richard Malley and Michael Wessels (Children's Hospital, Harvard Medical School); Dr. Darren Higgins (Harvard Medical School); Drs. Laurie Comstock, Maria Chatzidaki-Livanis, Neeraj (Neil) Surana, and Lynn Bry (Brigham and Women's Hospital, Harvard Medical School); Dr. Yung-Fu Chang (Cornell College of Veterinary Medicine); Dr. Joanna Goldberg (University of Virginia Medical School); Drs. Stanley Spinola and Margaret Bauer (Indiana University Medical School); Dr. Darlene Miller (Bascom-Palmer Eye Institute, University of Miami); Dr. Arturo Casadevall (Albert Einstein College of Medicine); Dr. Janet Yother (University of Alabama, Birmingham); Dr. Sandra Richter (University of Iowa); Dr. Janet Lindow (University of Vermont); Dr. Alan Cross (University of Maryland School of Medicine); Dr. Kwang Sik Kim (The Johns Hopkins University School of Medicine); Dr. Rachel McLoughlin (University College Dublin); and Dr. Johannes Huebner (Ludwig Maximilians University). We also gratefully acknowledge the technical expertise and help of Ms. Maria Ericsson with electron microscopy and Ms. Ariana Huebner with laboratory experiments. This work was supported by NIAID Grants AI46706 and AI057159, a component of Award U54 AI057159. The work with T. vaginalis was supported by NIAID Grant 5R01AI079085-04 and the work with P. berghei was supported by NIAID Grant RO1AI079293. NR 58 TC 41 Z9 42 U1 0 U2 21 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 JUN 11 PY 2013 VL 110 IS 24 BP E2209 EP E2218 DI 10.1073/pnas.1303573110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171LM UT WOS:000320930100011 PM 23716675 ER PT J AU Yao, JK Dougherty, GG Reddy, RD Matson, WR Kaddurah-Daouk, R Keshavan, MS AF Yao, Jeffrey K. Dougherty, George G. Reddy, Ravinder D. Matson, Wayne R. Kaddurah-Daouk, Rima Keshavan, Matcheri S. TI Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE schizophrenia; first-episode psychosis; neuroleptic-naive; oxidative stress; purine catabolism; monoamine neurotransmitters ID SERUM URIC-ACID; NEUROLOGIC EXAMINATION ABNORMALITIES; MULTIPLE-SCLEROSIS PATIENTS; NEUROLEPTIC-NAIVE PATIENTS; REDOX-ACTIVE COMPOUNDS; SEROTONERGIC RESPONSIVITY; LIQUID-CHROMATOGRAPHY; PLASMA ANTIOXIDANTS; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE AB Schizophrenia (SZ) is a biochemically complex disorder characterized by widespread defects in multiple metabolic pathways whose dynamic interactions, until recently, have been difficult to examine. Rather, evidence for these alterations has been collected piecemeal, limiting the potential to inform our understanding of the interactions amongst relevant biochemical pathways. We herein review perturbations in purine and neurotransmitter metabolism observed in early SZ using a metabolomic approach. Purine catabolism is an underappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. We have observed a homeostatic imbalance of purine catabolism in first-episode neuroleptic-naive patients with SZ (FENNS). Precursor and product relationships within purine pathways are tightly correlated. Although some of these correlations persist across disease or medication status, others appear to be lost among FENNS suggesting that steady formation of the antioxidant uric acid (UA) via purine catabolism is altered early in the course of illness. As is the case for within-pathway correlations, there are also significant cross-pathway correlations between respective purine and tryptophan (TRP) pathway metabolites. By contrast, purine metabolites show significant cross-pathway correlation only with tyrosine, and not with its metabolites. Furthermore, several purine metabolites (UA, guanosine, or xanthine) are each significantly correlated with 5-hydroxyindoleacetic acid (5-HIAA) in healthy controls, but not in FENNS at baseline or 4-week after antipsychotic treatment. Taken together, the above findings suggest that purine catabolism strongly associates with the TRP pathways leading to serotonin (5-hydroxytryptamine, 5-HT) and kynurenine metabolites. The lack of a significant correlation between purine metabolites and 5-HIAA, suggests alterations in key 5-HT pathways that may both be modified by and contribute to oxidative stress via purine catabolism in FENNS. C1 [Yao, Jeffrey K.; Dougherty, George G.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.; Dougherty, George G.; Reddy, Ravinder D.; Keshavan, Matcheri S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, 7180 Highland Dr,151U-H, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory RD; VA Pittsburgh Healthcare System [MH58141, MH64118, MH45203, MH 45156, R24 GM078233, c UL1 RR024153, M01 RR00056]; Metabolomics Research Network; Stanley Medical Research Institute; NARSAD FX This review is based upon work supported in part by the grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory R&D [Merit Reviews (Jeffrey K. Yao) and Senior Research Career Scientist Award (Jeffrey K. Yao)], VA Pittsburgh Healthcare System (Jeffrey K. Yao, George G. Dougherty, Ravinder D. Reddy), National Institute of Health [MH58141 (Jeffrey K. Yao), MH64118 (Ravinder D. Reddy), MH45203 and MH 45156 (Matcheri S. Keshavan), R24 GM078233 (Rima Kaddurah-Daouk), c UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR00056], Metabolomics Research Network (Rima Kaddurah-Daouk); Stanley Medical Research Institute (Rima Kaddurah-Daouk), and NARSAD (Rima Kaddurah-Daouk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 99 TC 10 Z9 10 U1 1 U2 14 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JUN 11 PY 2013 VL 7 AR 90 DI 10.3389/fncel.2013.00090 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 170JM UT WOS:000320846200001 PM 23781173 ER PT J AU Bhat-Nakshatri, P Song, EK Collins, NR Uversky, VN Dunker, AK O'Malley, BW Geistlinger, TR Carroll, JS Brown, M Nakshatri, H AF Bhat-Nakshatri, Poornima Song, Eun-Kyung Collins, Nikail R. Uversky, Vladimir N. Dunker, A. Keith O'Malley, Bert W. Geistlinger, Tim R. Carroll, Jason S. Brown, Myles Nakshatri, Harikrishna TI Interplay between estrogen receptor and AKT in Estradiol-induced alternative splicing SO BMC MEDICAL GENOMICS LA English DT Article ID GROWTH-FACTOR RECEPTOR-2; GENOME-WIDE ASSOCIATION; BREAST-CANCER; MESSENGER-RNA; GENE-EXPRESSION; BINDING-SITES; ALPHA BINDING; SR PROTEINS; FAS LIGAND; ACTIVATION AB Background: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERa) and their ligands promote alternative splicing. The endogenous targets of ERa: estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERa on E2-induced splicing are unknown. Methods: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERa binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. Results: We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERa cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERa binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERa and splicing factors, influenced ERa: E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ERa-dependent overexpression of FGFR2, whereas resistance to fulvestrant was associated with ERa-dependent isoform switching, which correlated with altered response to KGF. Conclusion: E2 may partly alter cellular proteome through alternative splicing uncoupled to its effects on transcription initiation and aberration in E2-induced alternative splicing events may influence response to anti-estrogens. C1 [Bhat-Nakshatri, Poornima; Song, Eun-Kyung; Collins, Nikail R.; Nakshatri, Harikrishna] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Nakshatri, Harikrishna] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Uversky, Vladimir N.; Dunker, A. Keith] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Dunker, A. Keith] Indiana Univ, Sch Informat, Sch Med Program Bioinformat, Dept Mol & Cellular Biol, Indianapolis, IN 46202 USA. [O'Malley, Bert W.] Baylor Coll Med, Dept Med Oncol, Houston, TX 77030 USA. [Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geistlinger, Tim R.] Amyris, Emeryville, CA 94608 USA. [Carroll, Jason S.] Univ Cambridge, Cambridge Res Inst, Cambridge CB2 0RE, England. [Carroll, Jason S.] Univ Cambridge, Canc Res UK, Dept Oncol, Cambridge CB2 0RE, England. RP Nakshatri, H (reprint author), Indiana Univ Sch Med, Dept Surg, 980 West Walnut St, Indianapolis, IN 46202 USA. EM hnakshat@iupui.edu RI Uversky, Vladimir/F-4515-2011; OI Uversky, Vladimir/0000-0002-4037-5857; Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [CA89153]; Susan G. Komen for the Cure grant [SAC110025]; Korea Science & Engineering Foundation FX This work is supported by a grant from the National Institutes of Health (CA89153) and Susan G. Komen for the Cure grant SAC110025. E-K. Song was supported by a post-doctoral fellowship from the Korea Science & Engineering Foundation. NR 61 TC 8 Z9 8 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD JUN 11 PY 2013 VL 6 AR 21 DI 10.1186/1755-8794-6-21 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 166RT UT WOS:000320575500001 PM 23758675 ER PT J AU Stirman, SW Miller, CJ Toder, K Calloway, A AF Stirman, Shannon Wiltsey Miller, Christopher J. Toder, Katherine Calloway, Amber TI Development of a framework and coding system for modifications and adaptations of evidence-based interventions SO IMPLEMENTATION SCIENCE LA English DT Article DE Implementation; Modification; Adaptation; Sustainability ID COGNITIVE PROCESSING THERAPY; HIV PREVENTION INTERVENTIONS; PROGRAM FIDELITY; HEALTH-PROGRAMS; SUSTAINABILITY; MODEL; IMPLEMENTATION; ADHERENCE; PTSD; FACILITATORS AB Background: Evidence-based interventions are frequently modified or adapted during the implementation process. Changes may be made to protocols to meet the needs of the target population or address differences between the context in which the intervention was originally designed and the one into which it is implemented [Addict Behav 2011, 36(6):630-635]. However, whether modification compromises or enhances the desired benefits of the intervention is not well understood. A challenge to understanding the impact of specific types of modifications is a lack of attention to characterizing the different types of changes that may occur. A system for classifying the types of modifications that are made when interventions and programs are implemented can facilitate efforts to understand the nature of modifications that are made in particular contexts as well as the impact of these modifications on outcomes of interest. Methods: We developed a system for classifying modifications made to interventions and programs across a variety of fields and settings. We then coded 258 modifications identified in 32 published articles that described interventions implemented in routine care or community settings. Results: We identified modifications made to the content of interventions, as well as to the context in which interventions are delivered. We identified 12 different types of content modifications, and our coding scheme also included ratings for the level at which these modifications were made (ranging from the individual patient level up to a hospital network or community). We identified five types of contextual modifications (changes to the format, setting, or patient population that do not in and of themselves alter the actual content of the intervention). We also developed codes to indicate who made the modifications and identified a smaller subset of modifications made to the ways that training or evaluations occur when evidence-based interventions are implemented. Rater agreement analyses indicated that the coding scheme can be used to reliably classify modifications described in research articles without overly burdensome training. Conclusions: This coding system can complement research on fidelity and may advance research with the goal of understanding the impact of modifications made when evidence-based interventions are implemented. Such findings can further inform efforts to implement such interventions while preserving desired levels of program or intervention effectiveness. C1 [Stirman, Shannon Wiltsey] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Stirman, Shannon Wiltsey; Miller, Christopher J.] VA Boston Healthcare Syst, Boston, MA USA. [Stirman, Shannon Wiltsey] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Toder, Katherine] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Miller, Christopher J.] VA Ctr Org Leadership & Management Res, Boston, MA USA. [Calloway, Amber] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP Stirman, SW (reprint author), Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. EM sws@bu.edu FU National Institute of Mental Health [R00 MH 01800, R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI) FX The preparation of this article was supported through funding from the National Institute of Mental Health (R00 MH 01800) [Dr. Stirman]. At the time that this study was being conducted, Dr. Stirman was a Fellow at the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St. Louis, which is funded through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). We wish to thank Jennifer Gamarra and Andrea DeVito for their assistance with the preparation of this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Veterans Affairs. NR 55 TC 41 Z9 41 U1 3 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JUN 10 PY 2013 VL 8 AR 65 DI 10.1186/1748-5908-8-65 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 168OH UT WOS:000320714900001 PM 23758995 ER PT J AU Watanabe, H Meyerson, M AF Watanabe, Hideo Meyerson, Matthew TI Hopping between Differentiation States in Lung Adenocarcinoma SO CANCER CELL LA English DT Editorial Material ID NKX2-1; GATA6 AB The work by Cheung and colleagues, in this issue of Cancer Cell, demonstrates another example of how lineage-specific transcriptional regulators of differentiation, GATA6 and HOPX, can control the fate of lung adenocarcinoma progression. C1 [Watanabe, Hideo; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Watanabe, Hideo; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Watanabe, Hideo; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Watanabe, H (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM hideo_watanabe@dfci.harvard.edu FU NCI NIH HHS [R01 CA109038] NR 11 TC 5 Z9 5 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN 10 PY 2013 VL 23 IS 6 BP 707 EP 709 DI 10.1016/j.ccr.2013.05.013 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 163QB UT WOS:000320350900001 PM 23763994 ER PT J AU Buchwalter, G Hickey, MM Cromer, A Selfors, LM Gunawardane, RN Frishman, J Jeselsohn, R Lim, E Chi, D Fu, XY Schiff, R Brown, M Brugge, JS AF Buchwalter, Gilles Hickey, Michele M. Cromer, Anne Selfors, Laura M. Gunawardane, Ruwanthi N. Frishman, Jason Jeselsohn, Rinath Lim, Elgene Chi, David Fu, Xiaoyong Schiff, Rachel Brown, Myles Brugge, Joan S. TI PDEF Promotes Luminal Differentiation and Acts as a Survival Factor for ER-Positive Breast Cancer Cells SO CANCER CELL LA English DT Article ID ETS TRANSCRIPTION FACTOR; GENE-EXPRESSION PATTERNS; GENOME-WIDE ANALYSIS; FACTOR MESSENGER-RNA; MAMMARY-GLAND; IN-VIVO; RECEPTOR; TUMORS; EPITHELIUM; INVASION AB Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. PDEF levels strongly correlate with estrogen receptor (ER)-positive luminal breast cancer, and PDEF transcription is inversely regulated by ER and GATA3. Furthermore, PDEF is essential for luminal breast cancer cell survival and is required in models of endocrine resistance. These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy. C1 [Buchwalter, Gilles; Frishman, Jason; Jeselsohn, Rinath; Lim, Elgene; Chi, David; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Buchwalter, Gilles; Frishman, Jason; Jeselsohn, Rinath; Lim, Elgene; Chi, David; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Buchwalter, Gilles; Frishman, Jason; Jeselsohn, Rinath; Lim, Elgene; Chi, David; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Hickey, Michele M.; Cromer, Anne; Selfors, Laura M.; Gunawardane, Ruwanthi N.; Brugge, Joan S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Fu, Xiaoyong; Schiff, Rachel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77054 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu; joan_brugge@hms.harvard.edu OI Lim, Elgene/0000-0001-8065-8838; Brown, Myles/0000-0002-8213-1658 FU DOD Breast Cancer Research Program Postdoctoral Fellowship [W81XWH-10-1-0029]; Association pour la Recherche contre le Cancer; Susan G. Komen for the Cure [KG080737]; Breast Cancer Research Foundation; NCI [P01 CA080111]; NIDDK [R01 DK074967] FX We are grateful to Housheng Hansen He for help with gene expression analysis and the Nikon Imaging Center at Harvard Medical School, the DF/HCC Rodent Histopathology Core, the Developmental Studies Hybridoma Bank at the University of Iowa, and members of the Brugge and Brown laboratories for technical assistance and helpful discussions. This work was supported by a DOD Breast Cancer Research Program Postdoctoral Fellowship (W81XWH-10-1-0029 to M.M.H.), fellowships from the Association pour la Recherche contre le Cancer (to G.B.) and Susan G. Komen for the Cure (KG080737 to G.B.), and grants from the Breast Cancer Research Foundation (to J.S.B.), the NCI (P01 CA080111 to M.B.), and NIDDK (R01 DK074967 to M.B.). NR 49 TC 18 Z9 19 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN 10 PY 2013 VL 23 IS 6 BP 753 EP 767 DI 10.1016/j.ccr.2013.04.026 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 163QB UT WOS:000320350900009 PM 23764000 ER PT J AU Chen, LF Monti, S Juszczynski, P Ouyang, J Chapuy, B Neuberg, D Doench, JG Bogusz, AM Habermann, TM Dogan, A Witzig, TE Kutok, JL Rodig, SJ Golub, T Shipp, MA AF Chen, Linfeng Monti, Stefano Juszczynski, Przemyslaw Ouyang, Jing Chapuy, Bjoern Neuberg, Donna Doench, John G. Bogusz, Agata M. Habermann, Thomas M. Dogan, Ahmet Witzig, Thomas E. Kutok, Jeffery L. Rodig, Scott J. Golub, Todd Shipp, Margaret A. TI SYK Inhibition Modulates Distinct PI3K/AKT-Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas SO CANCER CELL LA English DT Article ID NF-KAPPA-B; HEMATOPOIETIC PROGENITOR CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; THERAPEUTIC TARGET; GENE-EXPRESSION; LIPID RAFTS; PRE-BCR; DEREGULATION; ACTIVATION AB B cell receptor (BCR) signaling pathway components represent promising treatment targets in diffuse large B cell lymphoma (DLBCL) and additional B cell tumors. BCR signaling activates spleen tyrosine kinase (SYK) and downstream pathways including PI3K/AKT and NF-kappa B. In previous studies, chemical SYK blockade selectively decreased BCR signaling and induced apoptosis of BCR-dependent DLBCLs. Herein, we characterize distinct SYK/PI3K-dependent survival pathways in DLBCLs with high or low baseline NF-KB activity including selective repression of the pro-apoptotic HRK protein in NF-kappa B-low tumors. We also define SYK/PI3K-dependent cholesterol biosynthesis as a feed-forward mechanism of maintaining the integrity of BCRs in lipid rafts in DLBCLs with low or high NF-kappa B. In addition, SYK amplification and PTEN deletion are identified as selective genetic alterations in primary "BCR"-type DLBCLs. C1 [Chen, Linfeng; Juszczynski, Przemyslaw; Ouyang, Jing; Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02215 USA. [Monti, Stefano; Doench, John G.; Golub, Todd] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA. [Bogusz, Agata M.; Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Habermann, Thomas M.; Witzig, Thomas E.] Mayo Clin, Dept Med, Rochester, MN 55905 USA. [Dogan, Ahmet] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM margaret_shipp@dfci.harvard.edu OI Monti, Stefano/0000-0002-9376-0660; Doench, John/0000-0002-3707-9889 FU NIH [P01CA092625, LLS SCOR 7391, LLS SCOR 7009] FX This work was supported by NIH grants P01CA092625, LLS SCOR 7391, and LLS SCOR 7009. NR 49 TC 37 Z9 44 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN 10 PY 2013 VL 23 IS 6 BP 826 EP 838 DI 10.1016/j.ccr.2013.05.002 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 163QB UT WOS:000320350900014 PM 23764004 ER PT J AU Bekelman, JE Kim, M Emanuel, EJ AF Bekelman, Justin E. Kim, Miranda Emanuel, Ezekiel J. TI Toward Accountable Cancer Care SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID MEDICARE C1 [Bekelman, Justin E.] Univ Penn, Abramson Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel J.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel J.] Univ Penn, Wharton Sch Business, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Kim, Miranda] Dana Farber Harvard Canc Ctr, Harvard Joint Ctr Radiat Therapy, Boston, MA USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Sch Med, Perelman Ctr Adv Med, Abramson Canc Ctr, 4 West,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU NCI NIH HHS [K07 CA163616] NR 7 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 10 PY 2013 VL 173 IS 11 BP 958 EP 959 DI 10.1001/jamainternmed.2013.635 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 159MT UT WOS:000320050200005 PM 23699890 ER PT J AU Flood, KL MacLennan, PA McGrew, D Green, D Dodd, C Brown, CJ AF Flood, Kellie L. MacLennan, Paul A. McGrew, Deborah Green, Darlene Dodd, Cindy Brown, Cynthia J. TI Effects of an Acute Care for Elders Unit on Costs and 30-Day Readmissions SO JAMA INTERNAL MEDICINE LA English DT Article ID HOSPITALIZED OLDER PATIENTS; ONCOLOGY-ACUTE CARE; FUNCTIONAL DECLINE; CONTROLLED TRIAL; HEALTH-CARE; HIGH-RISK; OUTCOMES; ADULTS; INTERVENTION; MOBILITY AB Importance: Providing high-quality care while containing cost is essential for the economic stability of our health care system. The United States is experiencing a rapidly growing elderly population. The Acute Care for Elders (ACE) unit interdisciplinary team model of care has been shown to improve outcomes in hospitalized older adults. The University of Alabama at Birmingham ACE unit incorporates evidence-based care processes. We hypothesized that the ACE model would also reduce costs. Objective: To examine variable direct costs from an interdisciplinary ACE compared with a multidisciplinary usual care (UC) unit. Design: Retrospective cohort study. Setting: Tertiary care academic medical center. Participants: Hospitalists' patients aged 70 years or older spending the entirety of their hospitalization in either the ACE or UC unit in fiscal year 2010. Main Outcome Measures: Using administrative data, we analyzed variable direct costs for ACE and UC patients. We also conducted a subset analysis restricted to the 25 most common diagnosis related groups (DRGs) shared by ACE and UC patients. Generalized linear regression was used to estimate cost ratios and 95% confidence intervals adjusted for age, sex, comorbidity score, and case mix index (CMI). Results: A total of 818 hospitalists' patients met inclusion criteria: 428 from the ACE and 390 from the UC unit. For this study group (all DRGs), the mean (SD) variable direct cost per patient was $2109 ($1870) for ACE and $2480 ($2113) for UC (P=.009). Adjusted cost ratios revealed significant cost savings for patients with low (0.82; 95% CI, 0.72-0.94) or moderate (0.74; 95% CI, 0.620.89) CMI scores; care was cost neutral for patients with high CMI scores (1.13; 95% CI, 0.93-1.37). Significantly fewer ACE patients than UC patients were readmitted within 30 days of discharge (7.9% vs 12.8%; P=.02). Subset analysis of the 25 most common DRGs revealed a significantly reduced mean (SD) variable direct cost per patient for ACE compared with UC patients ($1693 [$1063] vs $2138 [$1431]; P<.001); cost ratios for total (0.78; 95% CI, 0.70-0.87) and daily (0.89; 95% CI, 0.85-0.94) variable direct costs remained significant after adjustment. Conclusions and Relevance: The ACE unit team model reduces costs and 30-day readmissions. In an era when improving care processes while reducing costs is a vital objective for the Medicare program and our nation as a whole, the ACE model meets these goals. C1 [Flood, Kellie L.; Brown, Cynthia J.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [MacLennan, Paul A.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [McGrew, Deborah; Green, Darlene; Dodd, Cindy] Univ Alabama Birmingham, Birmingham Hosp, Birmingham, AL 35294 USA. [Brown, Cynthia J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Flood, KL (reprint author), Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, 1720 2nd Ave S,CH-19,Room 219, Birmingham, AL 35294 USA. EM kflood@uabmc.edu NR 33 TC 21 Z9 22 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 10 PY 2013 VL 173 IS 11 BP 981 EP 987 DI 10.1001/jamainternmed.2013.524 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 159MT UT WOS:000320050200010 PM 23609002 ER PT J AU Hung, WW Ross, JS Farber, J Siu, AL AF Hung, William W. Ross, Joseph S. Farber, Jeffrey Siu, Albert L. TI Evaluation of the Mobile Acute Care of the Elderly (MACE) Service SO JAMA INTERNAL MEDICINE LA English DT Article ID HOSPITALIZED OLDER PATIENTS; UNITED-STATES; MULTICOMPONENT INTERVENTION; FUNCTIONAL OUTCOMES; MEDICAL UNIT; SYSTEM; VALIDATION; COMMUNITY; DELIRIUM; SCORES AB Importance: Older adults are particularly vulnerable to adverse events during hospitalization for acute medical problems. The Mobile Acute Care of the Elderly (MACE) service is a novel model of care delivered by an interdisciplinary team, designed to deliver specialized care to hospitalized older adults to improve patient outcomes. Objective: To evaluate the impact of the MACE service when compared with general medical service (usual care). Design: Prospective, matched cohort study. Setting: The Mount Sinai Hospital, an urban tertiary acute care hospital. Participants: Patients aged 75 years or older admitted because of an acute illness to either the MACE service or usual care. Patients were matched for age, diagnosis, and ability to ambulate independently. Exposures: Admission to the MACE service when compared with admission to usual care. Main Outcome Measures: Patient outcomes included incidence of adverse events, including falls, pressure ulcers, restraint use, and catheter-associated urinary tract infections, along with length of stay, rehospitalization within 30 days, functional status at 30 days, and patient satisfaction during care transitions, measured with the 3-item Care Transition Measure. Results: A total of 173 matched pairs of patients were recruited. The mean (SD) age was 85.2 (5.3) and 84.7 (5.4) years in the MACE and usual-care groups, respectively. After adjustment for confounders, patients in the MACE group were less likely to experience adverse events (9.5% vs 17.0%; adjusted odds ratio, 0.11; 95% CI, 0.01-0.88; P=.04) and had shorter hospital stays (0.8 days, 95% CI, 0.7-0.9; P=.001) than patients receiving usual care. Patients in the MACE group were not less likely to have a lower rate of rehospitalization within 30 days than those in the usual-care group (odds ratio, 0.91; 95% CI, 0.39-2.10; P=.83). Functional status did not differ between the 2 groups. Care Transition Measure scores were 7.4 points (95% CI, 2.9-11.9; P=.001) higher in the MACE group. Conclusions and Relevance: Admission to the MACE service was associated with lower rates of adverse events, shorter hospital stays, and better satisfaction. This model has the potential to improve care outcomes among hospitalized older adults. C1 [Hung, William W.; Farber, Jeffrey; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Bronx, NY USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Bronx, NY USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM william.hung@mssm.edu FU Medtronic, Inc; National Institute on Aging [K08 AG032886]; American Federation for Aging Research through the Paul B. Beeson Career Development Award Program; John A. Hartford Center of Excellence; Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine [P30-AG028741]; Centers for Medicare & Medicaid Services; Pew Charitable Trusts FX Dr Ross reports that he is a member of a scientific advisory board for FAIR Health, Inc, and receives grant funding from Medtronic, Inc, to develop methods of clinical trial data sharing, from the Centers for Medicare & Medicaid Services to develop and maintain performance measures used for public reporting, and from the Pew Charitable Trusts to examine regulatory issues at the US Food and Drug Administration. Dr Ross is supported by the National Institute on Aging (grant K08 AG032886) and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program.; Support for this project was provided by the John A. Hartford Center of Excellence and in part by the Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine (grant P30-AG028741). NR 28 TC 9 Z9 9 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 10 PY 2013 VL 173 IS 11 BP 990 EP 996 DI 10.1001/jamainternmed.2013.478 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 159MT UT WOS:000320050200012 PM 23608775 ER PT J AU Linos, E Parvataneni, R Stuart, SE Boscardin, WJ Landefeld, CS Chren, MM AF Linos, Eleni Parvataneni, Rupa Stuart, Sarah E. Boscardin, W. John Landefeld, C. Seth Chren, Mary-Margaret TI Treatment of Nonfatal Conditions at the End of Life Nonmelanoma Skin Cancer SO JAMA INTERNAL MEDICINE LA English DT Article ID MOHS MICROGRAPHIC SURGERY; BASAL-CELL CARCINOMA; UNITED-STATES; CARE; COHORT AB Importance: Nonmelanoma skin cancer (NMSC) is the most common cancer and predominantly affects older patients. Because NMSCs do not typically affect survival or short-term quality of life, the decision about whether and how to treat patients with limited life expectancy (LLE) is challenging, especially for asymptomatic tumors. Objective: To compare treatment patterns and clinical outcomes of patients with NMSC with and without LLE. Design, Setting, and Participants: A prospective cohort study of 1536 consecutive patients diagnosed with NMSC at 2 dermatology clinics: a university-based private practice and a Veterans Affairs Medical Center in San Francisco, California. Patients were recruited in 1999 through 2000 and followed up for a median of 9 years. A total of 1360 patients with 1739 tumors (90%) were included in the final analysis. Limited life expectancy was defined as patients either 85 years or older at the time of diagnosis or patients with multiple comorbidities (Charlson Comorbidity Index of >= 3). Treatment options included no treatment, destruction, or 2 types of surgery-elliptical excision or Mohs surgery. Main Outcomes and Measures: Treatment type. Results: Most NMSCs (69%) were treated surgically, regardless of patient life expectancy. The choice of surgery was not influenced by patient prognosis in univariate or multivariable models adjusted for tumor and patient characteristics. Many patients with LLE (43%) died within 5 years, none of NMSC. Tumor recurrence was rare (3.7% at 5 years [95% CI, 2.6%-4.7%]) in all patients. Although serious complications were unusual, approximately 20% of patients with LLE reported complications of therapy, compared with 15% of other patients. Conclusions and Relevance: Most NMSCs are treated surgically, regardless of the patient's life expectancy. Given the very low tumor recurrence rates and high mortality from causes unrelated to NMSC in patients with LLE, clinicians should consider whether these patients would prefer less invasive treatment strategies. C1 [Linos, Eleni; Parvataneni, Rupa; Stuart, Sarah E.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. RP Linos, E (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Room N421,Mail Code Box 0808, San Francisco, CA 94143 USA. EM linose@derm.ucsf.edu RI Linos, Eleni/C-4392-2014; OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU National Center for Research Resources [KL2RR024130]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [R01 AR 054983, K24 AR052667]; American Skin Association; Dermatology Foundation FX This study was supported in part by Award KL2RR024130 from the National Center for Research Resources (Dr Linos), by grants R01 AR 054983 and K24 AR052667 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (Dr Chren), and by a Career Development Award from the American Skin Association and Dermatology Foundation (Dr Linos). NR 23 TC 17 Z9 17 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN 10 PY 2013 VL 173 IS 11 BP 1006 EP 1012 DI 10.1001/jamainternmed.2013.639 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 159MT UT WOS:000320050200016 PM 23699934 ER PT J AU Stone, RM AF Stone, Richard M. TI Consolidation Chemotherapy for Adults With AML in First Remission: Is There a Best Choice? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HIGH-DOSE CYTARABINE; GROUP-B; THERAPY; MUTATIONS; CANCER; INTENSIFICATION; YOUNGER; AGE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU Novartis FX Research Funding: Richard M. Stone, Novartis NR 22 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2013 VL 31 IS 17 BP 2067 EP 2069 DI 10.1200/JCO.2013.48.6886 PG 3 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400009 PM 23630213 ER PT J AU Marcucci, G Maharry, KS Metzeler, KH Volinia, S Wu, YZ Mrozek, K Nicolet, D Kohlschmidt, J Whitman, SP Mendler, JH Schwind, S Becker, H Eisfeld, AK Carroll, AJ Powell, BL Kolitz, JE Garzon, R Caligiuri, MA Stone, RM Bloomfield, CD AF Marcucci, Guido Maharry, Kati S. Metzeler, Klaus H. Volinia, Stefano Wu, Yue-Zhong Mrozek, Krzysztof Nicolet, Deedra Kohlschmidt, Jessica Whitman, Susan P. Mendler, Jason H. Schwind, Sebastian Becker, Heiko Eisfeld, Ann-Kathrin Carroll, Andrew J. Powell, Bayard L. Kolitz, Jonathan E. Garzon, Ramiro Caligiuri, Michael A. Stone, Richard M. Bloomfield, Clara D. TI Clinical Role of microRNAs in Cytogenetically Normal Acute Myeloid Leukemia: miR-155 Upregulation Independently Identifies High-Risk Patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RESISTANCE MODULATOR PSC-833; PARTIAL TANDEM DUPLICATION; AGE 60 YEARS; GROUP-B; OLDER PATIENTS; EXPRESSION SIGNATURES; PROGNOSTIC-SIGNIFICANCE; DISTINCT GENE; EUROPEAN LEUKEMIANET; CANCER AB Purpose To evaluate the impact of miR-155 on the outcome of adults with cytogenetically normal (CN) acute myeloid leukemia (AML) in the context of other clinical and molecular prognosticators and to gain insight into the leukemogenic role of this microRNA. Patients and Methods We evaluated 363 patients with primary CN-AML. miR-155 levels were measured in pretreatment marrow and blood by NanoString nCounter assays that quantified the expression of the encoding gene MIR155HG. All molecular prognosticators were assessed centrally. miR-155-associated gene and microRNA expression profiles were derived using microarrays. Results Considering all patients, high miR-155 expression was associated with a lower complete remission (CR) rate (P < .001) and shorter disease-free survival (P = .001) and overall survival (OS; P < .001) after adjusting for age. In multivariable analyses, high miR-155 expression remained an independent predictor for a lower CR rate (P = .007) and shorter OS (P < .001). High miR-155 expressers had approximately 50% reduction in the odds of achieving CR and 60% increase in the risk of death compared with low miR-155 expressers. Although high miR-155 expression was not associated with a distinct microRNA expression profile, it was associated with a gene expression profile enriched for genes involved in cellular mechanisms deregulated in AML (eg, apoptosis, nuclear factor-kappa B activation, and inflammation), thereby supporting a pivotal and unique role of this microRNA in myeloid leukemogenesis. Conclusion miR-155 expression levels are associated with clinical outcome independently of other strong clinical and molecular predictors. The availability of emerging compounds with antagonistic activity to microRNAs in the clinic provides the opportunity for future therapeutic targeting of miR-155 in AML. (C) 2013 by American Society of Clinical Oncology C1 [Marcucci, Guido; Maharry, Kati S.; Metzeler, Klaus H.; Volinia, Stefano; Wu, Yue-Zhong; Mrozek, Krzysztof; Nicolet, Deedra; Kohlschmidt, Jessica; Whitman, Susan P.; Mendler, Jason H.; Schwind, Sebastian; Becker, Heiko; Eisfeld, Ann-Kathrin; Garzon, Ramiro; Caligiuri, Michael A.; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Maharry, Kati S.; Nicolet, Deedra; Kohlschmidt, Jessica] Mayo Clin, Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Kolitz, Jonathan E.] Monter Canc Ctr, Lake Success, NY USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marcucci, G (reprint author), Ohio State Univ, Ctr Comprehens Canc, Biomed Res Tower 460 W 12th Ave, Columbus, OH 43210 USA. EM guido.marcucci@osumc.edu RI Metzeler, Klaus/C-2118-2009; Garzon, Ramiro/E-3104-2011; Mrozek, Krzysztof/A-3142-2008; OI Metzeler, Klaus/0000-0003-3920-7490; Mendler, Jason/0000-0001-5605-5324; Volinia, Stefano/0000-0003-0910-3893 FU National Cancer Institute (Bethesda, MD) [CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657, CA140158]; Coleman Leukemia Research Foundation; Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation; Pelotonia Fellowship Program; Conquer Cancer Foundation FX Supported in part by National Cancer Institute (Bethesda, MD) Grants No. CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657, and CA140158; the Coleman Leukemia Research Foundation; the Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation (H.B.); the Pelotonia Fellowship Program (A.-K.E.); and the Conquer Cancer Foundation (J.H.M.). NR 48 TC 75 Z9 80 U1 0 U2 10 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 JUN 10 PY 2013 VL 31 IS 17 BP 2086 EP 2093 DI 10.1200/JCO.2012.45.6228 PG 8 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400014 PM 23650424 ER PT J AU Shepherd, FA Domerg, C Hainaut, P Janne, PA Pignon, JP Graziano, S Douillard, JY Brambilla, E Le Chevalier, T Seymour, L Bourredjem, A Teuff, G Pirker, R Filipits, M Rosell, R Kratzke, R Bandarchi, B Ma, XL Capelletti, M Soria, JC Tsao, MS AF Shepherd, Frances A. Domerg, Caroline Hainaut, Pierre Jaenne, Pasi A. Pignon, Jean-Pierre Graziano, Stephen Douillard, Jean-Yves Brambilla, Elizabeth Le Chevalier, Thierry Seymour, Lesley Bourredjem, Abderrahmane Le Teuff, Gwenael Pirker, Robert Filipits, Martin Rosell, Rafael Kratzke, Robert Bandarchi, Bizhan Ma, Xiaoli Capelletti, Marzia Soria, Jean-Charles Tsao, Ming-Sound TI Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non-Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID K-RAS ONCOGENE; METASTATIC COLORECTAL-CANCER; VINORELBINE PLUS CISPLATIN; GROWTH-FACTOR RECEPTOR; MOLECULAR BIOMARKERS; PHASE-III; ADENOCARCINOMA; ACTIVATION; EGFR; RESISTANCE AB Purpose We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non-small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT. (C) 2013 by American Society of Clinical Oncology C1 [Shepherd, Frances A.; Bandarchi, Bizhan; Tsao, Ming-Sound] Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Shepherd, Frances A.; Bandarchi, Bizhan; Tsao, Ming-Sound] Univ Toronto, Toronto, ON, Canada. [Seymour, Lesley] Queens Univ, Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. [Domerg, Caroline; Pignon, Jean-Pierre; Le Chevalier, Thierry; Bourredjem, Abderrahmane; Le Teuff, Gwenael; Soria, Jean-Charles] Inst Gustave Roussy, Paris, France. [Domerg, Caroline; Pignon, Jean-Pierre; Le Chevalier, Thierry; Bourredjem, Abderrahmane; Le Teuff, Gwenael; Soria, Jean-Charles] Univ Paris 11, Paris, France. [Hainaut, Pierre; Ma, Xiaoli] Int Agcy Res Canc, F-69372 Lyon, France. [Douillard, Jean-Yves] Inst Cancerol Ouest, St Herblain, France. [Brambilla, Elizabeth] Univ Grenoble 1, INSERM, U823, Inst Albert Bonniot, Grenoble, France. [Jaenne, Pasi A.; Capelletti, Marzia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Graziano, Stephen] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Pirker, Robert; Filipits, Martin] Med Univ Vienna, Vienna, Austria. [Rosell, Rafael] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Badalona, Spain. [Kratzke, Robert] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Shepherd, FA (reprint author), Princess Margaret Hosp, Dept Med Oncol & Hematol, Room 5-103,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM frances.shepherd@uhn.on.ca RI Brambilla, Elisabeth/L-8796-2013; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU Ligue Nationale Contre le Cancer (France); Programme National d'Excellence Spe'cialise cancer du poumon de l'Institut National du Cancer (INCa) (France); National Cancer Institute (United States); Canadian Cancer Society Research Institute (Canada) FX Supported by la Ligue Nationale Contre le Cancer (France), le Programme National d'Excellence Spe'cialise cancer du poumon de l'Institut National du Cancer (INCa) (France), the National Cancer Institute (United States), the Canadian Cancer Society Research Institute (Canada), and an unrestricted grant from Sanofi. NR 40 TC 76 Z9 76 U1 0 U2 8 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 JUN 10 PY 2013 VL 31 IS 17 BP 2173 EP U168 DI 10.1200/JCO.2012.48.1390 PG 10 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400026 PM 23630215 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Normalizing Tumor Microenvironment to Treat Cancer: Bench to Bedside to Biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERSTITIAL FLUID PRESSURE; METASTATIC BREAST-CANCER; FACTOR RECEPTOR-2 BLOCKADE; ANTI-ANGIOGENIC THERAPY; PHASE-I TRIAL; SOLID TUMORS; ANTIANGIOGENIC THERAPY; BLOOD-FLOW; VASCULAR NORMALIZATION AB For almost four decades, my work has focused on one challenge: improving the delivery and efficacy of anticancer therapeutics. Working on the hypothesis that the abnormal tumor microenvironment-characterized by hypoxia and high interstitial fluid pressure-fuels tumor progression and treatment resistance, we developed an array of sophisticated imaging technologies and animal models as well as mathematic models to unravel the complex biology of tumors. Using these tools, we demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and extracellular matrix associated with tumors are abnormal, which together create a hostile tumor microenvironment. We next hypothesized that agents that induce normalization of the microenvironment can improve treatment outcome. Indeed, we demonstrated that judicious use of antiangiogenic agents-originally designed to starve tumors-could transiently normalize tumor vasculature, alleviate hypoxia, increase delivery of drugs and antitumor immune cells, and improve the outcome of various therapies. Our trials of antiangiogenics in patients with newly diagnosed and recurrent glioblastoma supported this concept. They revealed that patients whose tumor blood perfusion increased in response to cediranib survived 6 to 9 months longer than those whose blood perfusion did not increase. The normalization hypothesis also opened doors to treating various nonmalignant diseases characterized by abnormal vasculature, such as neurofibromatosis type 2. More recently, we discovered that antifibrosis drugs capable of normalizing the tumor microenvironment can improve the delivery and efficacy of nano-and molecular medicines. Our current efforts are directed at identifying predictive biomarkers and more-effective strategies to normalize the tumor microenvironment for enhancing anticancer therapies. (C) 2013 by American Society of Clinical Oncology C1 [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02115 USA. EM jain@steele.mgh.harvard.edu RI Arumugam, Thirumagal/C-3408-2014 FU National Cancer Institute; National Science Foundation; Department of Defense Breast Cancer Research; American Cancer Society; National Foundation for Cancer Research; Goldhirsh Foundation; Brain Tumor Society; AstraZeneca; DuPont-Merck; Enzon; Genentech; Hybritech; ImClone; Medimmune; Miravant; Roche FX Supported by grants from the National Cancer Institute (1980 to present), National Science Foundation (1976-1999), Department of Defense Breast Cancer Research Program (1996-2002; 2010 to present), American Cancer Society (1980-1992), National Foundation for Cancer Research (1998 to present), Goldhirsh Foundation (2002-2006), and Brain Tumor Society (2006-2008) and by grants from AstraZeneca, DuPont-Merck, Enzon, Genentech, Hybritech, ImClone, Medimmune, Miravant, Roche. NR 173 TC 239 Z9 246 U1 18 U2 138 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 JUN 10 PY 2013 VL 31 IS 17 BP 2205 EP U210 DI 10.1200/JCO.2012.46.3653 PG 15 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400029 PM 23669226 ER PT J AU Joyce, CE Novina, CD AF Joyce, Cailin E. Novina, Carl D. TI miR-155 in Acute Myeloid Leukemia: Not Merely a Prognostic Marker? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MICRORNA EXPRESSION; TRANSCRIPTION FACTOR; TARGETS; SIGNATURE; CANCER; PU.1 C1 [Joyce, Cailin E.] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. RP Joyce, CE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 23 TC 4 Z9 4 U1 0 U2 5 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 JUN 10 PY 2013 VL 31 IS 17 BP 2219 EP 2221 DI 10.1200/JCO.2012.48.3180 PG 3 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400030 PM 23650419 ER PT J AU Mayer, EL Lin, NU AF Mayer, Erica L. Lin, Nancy U. TI Questionable Validity of Cardiac Risk Score on the Basis of the NSABP B-31 Model Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID BREAST-CANCER; TRASTUZUMAB C1 [Mayer, Erica L.; Lin, Nancy U.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Mayer, EL (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 6 TC 0 Z9 0 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 JUN 10 PY 2013 VL 31 IS 17 BP 2225 EP 2226 DI 10.1200/JCO.2012.48.3719 PG 2 WC Oncology SC Oncology GA 160FZ UT WOS:000320104400036 PM 23901420 ER PT J AU McDavid, A Crane, PK Newton, KM Crosslin, DR McCormick, W Weston, N Ehrlich, K Hart, E Harrison, R Kukull, WA Rottscheit, C Peissig, P Stefanski, E McCarty, CA Zuvich, RL Ritchie, MD Haines, JL Denny, JC Schellenberg, GD de Andrade, M Kullo, I Li, RL Mirel, D Crenshaw, A Bowen, JD Li, G Tsuang, D McCurry, S Teri, L Larson, EB Jarvik, GP Carlson, CS AF McDavid, Andrew Crane, Paul K. Newton, Katherine M. Crosslin, David R. McCormick, Wayne Weston, Noah Ehrlich, Kelly Hart, Eugene Harrison, Robert Kukull, Walter A. Rottscheit, Carla Peissig, Peggy Stefanski, Elisha McCarty, Catherine A. Zuvich, Rebecca Lynn Ritchie, Marylyn D. Haines, Jonathan L. Denny, Joshua C. Schellenberg, Gerard D. de Andrade, Mariza Kullo, Iftikhar Li, Rongling Mirel, Daniel Crenshaw, Andrew Bowen, James D. Li, Ge Tsuang, Debby McCurry, Susan Teri, Linda Larson, Eric B. Jarvik, Gail P. Carlson, Chris S. TI Enhancing the Power of Genetic Association Studies through the Use of Silver Standard Cases Derived from Electronic Medical Records SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CATEGORICAL-DATA; COMMON VARIANTS; MISCLASSIFICATION; DIAGNOSIS; CRITERIA; LINKAGE; CD2AP AB The feasibility of using imperfectly phenotyped "silver standard" samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square test of independence using either research-quality case/control samples alone, or augmented with silver standard data. The subset of the parameter space where inclusion of silver standard samples increases statistical power is identified. A case study of dementia subjects identified from electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network, combined with subjects from two studies specifically targeting dementia, verifies these results. C1 [McDavid, Andrew; Carlson, Chris S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Crane, Paul K.; McCormick, Wayne; Larson, Eric B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Newton, Katherine M.; Weston, Noah; Ehrlich, Kelly; Hart, Eugene; Harrison, Robert; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Crosslin, David R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kukull, Walter A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Rottscheit, Carla; Peissig, Peggy] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. [Stefanski, Elisha] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA. [Zuvich, Rebecca Lynn; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [de Andrade, Mariza] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Kullo, Iftikhar] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Li, Rongling] NHGRI, NIH, Bethesda, MD 20892 USA. [Mirel, Daniel; Crenshaw, Andrew] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Bowen, James D.] Swedish Med Ctr, Dept Neurol, Seattle, WA USA. [Li, Ge; Tsuang, Debby] Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. [Tsuang, Debby] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McCurry, Susan; Teri, Linda] Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Jarvik, Gail P.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Jarvik, Gail P.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. RP McDavid, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM amcdavid@fhcrc.org RI Crane, Paul/C-8623-2014; Jarvik, Gail/N-6476-2014; Tsuang, Debby/L-7234-2016; OI Jarvik, Gail/0000-0002-6710-8708; Tsuang, Debby/0000-0002-4716-1894; Kukull, Walter/0000-0001-8761-9014; Crane, Paul/0000-0003-4278-7465; McDavid, Andrew/0000-0002-6581-1213 FU National Institutes of Health (NIH) [HG004610, AG06781, U01HG004438] FX This study was funded by National Institutes of Health (NIH) award HG004610, AG06781 (Group Health Cooperative) and U01HG004438. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 7 Z9 7 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 10 PY 2013 VL 8 IS 6 AR e63481 DI 10.1371/journal.pone.0063481 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164VY UT WOS:000320440500003 PM 23762230 ER PT J AU Rao, VR Neogi, U Talboom, JS Padilla, L Rahman, M Fritz-French, C Gonzalez-Ramirez, S Verma, A Wood, C Ruprecht, RM Ranga, U Azim, T Joska, J Eugenin, E Shet, A Bimonte-Nelson, H Tyor, WR Prasad, VR AF Rao, Vasudev R. Neogi, Ujjwal Talboom, Joshua S. Padilla, Ligia Rahman, Mustafizur Fritz-French, Cari Gonzalez-Ramirez, Sandra Verma, Anjali Wood, Charles Ruprecht, Ruth M. Ranga, Udaykumar Azim, Tasnim Joska, John Eugenin, Eliseo Shet, Anita Bimonte-Nelson, Heather Tyor, William R. Prasad, Vinayaka R. TI Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence SO RETROVIROLOGY LA English DT Article DE Clade C HIV-1; Subtype C HIV-1; HIV-1 Tat; Tat dicysteine; Neuropathogenesis; SCID-HIVE mouse model; HIV-1 Tat C31S polymorphism; Neuroaids; HIV dementia ID TYPE-1 SUBTYPE-C; IMMUNODEFICIENCY-VIRUS ENCEPHALITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; RADIAL-ARM MAZE; MOLECULAR CLONE; SCID MICE; NEUROCOGNITIVE DISORDERS; CHEMOTACTIC PROTEIN-1; NEURONAL INJURY; WORKING-MEMORY AB Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. Therefore, we focused our study on the variations seen in tat gene and its contribution to HIV associated neuropathogenesis. Results: A phylogenetic analysis of tat sequences of Southern African (South Africa and Zambia) HIV isolates with those from the geographically distant Southeast Asian (India and Bangladesh) isolates revealed that Southern African tat sequences are distinct from Southeast Asian isolates. The proportion of HIV - 1C variants with an intact dicysteine motif in Tat protein (C30C31) was significantly higher in the Southern African countries compared to Southeast Asia and broadly paralleled the high incidence of HAD in these countries. Neuropathogenic potential of a Southern African HIV-1C isolate (from Zambia; HIV-1C(1084i)), a HIV-1C isolate (HIV-1(IndieC1)) from Southeast Asia and a HIV-1B isolate (HIV-1(ADA)) from the US were tested using in vitro assays to measure neurovirulence and a SCID mouse HIV encephalitis model to measure cognitive deficits. In vitro assays revealed that the Southern African isolate, HIV-1C(1084i) exhibited increased monocyte chemotaxis and greater neurotoxicity compared to Southeast Asian HIV-1C. In neurocognitive tests, SCID mice injected with MDM infected with Southern African HIV-1C(1084i) showed greater cognitive dysfunction similar to HIV-1B but much higher than those exposed to Southeast Asian HIV - 1C. Conclusions: We report here, for the first time, that HIV-1C from Southern African countries is genetically distinct from Southeast Asian HIV-1C and that it exhibits a high frequency of variants with dicysteine motif in a key neurotoxic HIV protein, Tat. Our results indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat. C1 [Rao, Vasudev R.; Prasad, Vinayaka R.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Neogi, Ujjwal; Shet, Anita] St Johns Med Coll & Hosp, Dept Microbiol & Pediat, Div Clin Virol, Bangalore, Karnataka, India. [Talboom, Joshua S.; Bimonte-Nelson, Heather] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Talboom, Joshua S.; Bimonte-Nelson, Heather] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Padilla, Ligia; Tyor, William R.] Atlanta VA Med Ctr, Decatur, GA USA. [Rahman, Mustafizur; Azim, Tasnim] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Fritz-French, Cari; Tyor, William R.] Emory Univ, Grad Div Biol & Biomed Sci, Immunol & Mol Pathol Program, Atlanta, GA 30322 USA. [Gonzalez-Ramirez, Sandra; Wood, Charles; Tyor, William R.] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA. [Gonzalez-Ramirez, Sandra; Wood, Charles; Tyor, William R.] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Verma, Anjali; Ranga, Udaykumar] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Bangalore 560012, Karnataka, India. [Joska, John] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Eugenin, Eliseo] Publ Hlth Res Inst, Newark, NJ USA. [Eugenin, Eliseo] UMDNJ, Dept Microbiol & Mol Genet, Newark, NJ USA. [Tyor, William R.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Prasad, VR (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM vinayaka.prasad@einstein.yu.edu RI rahman, mustafizur/E-6918-2010; Neogi, Ujjwal/E-4274-2012; OI Neogi, Ujjwal/0000-0002-0844-3338; Shet, Anita/0000-0002-7204-8164 FU NIH [R01 MH083579, D43 TW001403, P01 AI048240, NS74903, GM103509, R01 MH096625, T32 AI060547] FX This work was mainly supported by NIH R01 MH083579 (V. R. P.) and NIH D43 TW001403 (V. R. P.). The work was also supported by NIH P01 AI048240 (R. M. R.), NIH NS74903 & NIH GM103509 (to C. W.), NIH R01 MH096625 (to E. E.) and NIH T32 AI060547 (to S. G.). The authors wish to thank the Einstein/Montefiore Center for AIDS Research (P30 AI051519) for the use of BSL3/Clinical Virology Core services; Jasmeen Dara and Arthur Ruiz for reading the manuscript, Milka Rodriguez and Jayashree Nandi for technical assistance and Susan Engelbrecht for help with sequencing the Cape Town samples. NR 61 TC 20 Z9 20 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUN 8 PY 2013 VL 10 AR 61 DI 10.1186/1742-4690-10-61 PG 16 WC Virology SC Virology GA 167BE UT WOS:000320604400001 PM 23758766 ER PT J AU Nahrendorf, M Swirski, FK AF Nahrendorf, Matthias Swirski, Filip K. TI Monocyte and Macrophage Heterogeneity in the Heart SO CIRCULATION RESEARCH LA English DT Review DE healing; heart failure; macrophages; monocytes; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; PREDICT CARDIOVASCULAR EVENTS; GENE-EXPRESSION PROFILES; HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; BONE-MARROW; IN-VIVO; ATHEROSCLEROTIC LESIONS; INFLAMMATORY MONOCYTES; RHEUMATOID-ARTHRITIS AB Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The cells and their subsets pursue distinct functions in steady-state and disease, and their tenure may range between hours and months. Some subsets are highly inflammatory, whereas others support tissue repair. This review discusses current concepts of lineage relationships and crosstalk of systems, highlights open questions, and describes tools for studying monocyte and macrophage subsets in the murine and human heart. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu; fswirski@mgh.harvard.edu FU National Heart, Lung, and Blood Institute; National Institutes of Health; Department of Health and Human Services [R01HL095612, R01HL095629, R01HL096576, HHSN268201000044C] FX This work has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the Department of Health and Human Services (R01HL095612, R01HL095629, R01HL096576, Contract No. HHSN268201000044C). NR 95 TC 94 Z9 99 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JUN 7 PY 2013 VL 112 IS 12 BP 1624 EP 1633 DI 10.1161/CIRCRESAHA.113.300890 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 298UV UT WOS:000330350900019 PM 23743228 ER PT J AU Miyamoto, DT Viswanathan, AN AF Miyamoto, David T. Viswanathan, Akila N. TI Concurrent Chemoradiation for Vaginal Cancer SO PLOS ONE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; HIGH-DOSE-RATE; CERVICAL-CANCER; PREOPERATIVE CHEMORADIATION; INTERSTITIAL BRACHYTHERAPY; RADIATION-THERAPY; CHEMOTHERAPY; VULVA; OUTCOMES AB Background: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT) or concurrent chemoradiation therapy (CRT). Methods: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS) and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. Results: The median age at diagnosis was 61 years (range, 18-92 years) and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p=0.037; 3-yr DFS = 43% vs. 73%, log-rank p=0.011). Twenty-three patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group (p=0.027). With regard to the sites of first relapse, 10 patients (14%) had local only, 4 (6%) had local and regional, 9 (13%) had regional only, 1 (1%) had regional and distant, and 2 (3%) had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04)). Conclusions: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients. C1 [Miyamoto, David T.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU St. Laurent Family Fund FX This research was supported by a donation to Dr Viswanathan by the St. Laurent Family Fund. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 9 Z9 9 U1 0 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 JUN 7 PY 2013 VL 8 IS 6 AR e65048 DI 10.1371/journal.pone.0065048 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173QU UT WOS:000321094800016 PM 23762284 ER PT J AU Adams, SV Ahnen, DJ Baron, JA Campbell, PT Gallinger, S Grady, WM LeMarchand, L Lindor, NM Potter, JD Newcomb, PA AF Adams, Scott V. Ahnen, Dennis J. Baron, John A. Campbell, Peter T. Gallinger, Steven Grady, William M. LeMarchand, Loic Lindor, Noralane M. Potter, John D. Newcomb, Polly A. TI Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Colorectal cancer; Inflammatory bowel disease; Outcomes research; Cancer survival; Inflammation ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POPULATION-BASED DANISH; C-REACTIVE PROTEIN; ULCERATIVE-COLITIS; CROHNS-DISEASE; MICROSATELLITE INSTABILITY; 5-AMINOSALICYLATE USE; INTESTINAL CANCER; RISK; PROGNOSIS AB AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD- associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC. (C) 2013 Baishideng. All rights reserved. C1 [Adams, Scott V.; Grady, William M.; Potter, John D.; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Ahnen, Dennis J.] Denver VA Med Ctr, Dept Med, Denver, CO 80045 USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO 80045 USA. [Baron, John A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Dept Intramural Res, Atlanta, GA 30303 USA. [Gallinger, Steven] Univ Toronto, Div Gen Surg, Toronto, ON M5G 2C4, Canada. [LeMarchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. RP Adams, SV (reprint author), Fred Hutchinson Canc Res Ctr, M3-B232,POB 19024, Seattle, WA 98109 USA. EM sadams@fhcrc.org RI Gallinger, Steven/E-4575-2013; OI Potter, John/0000-0001-5439-1500 FU The American Society of Preventive Oncology/Prevent Cancer Foundation/American Society for Clinical Oncology Cancer Prevention Research Fellowship; Australasian Colorectal Cancer Family Registry [U01 CA097735]; Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; University of Hawaii Colorectal Cancer Family Registry [U01 CA074806]; University of California, Irvine Informatics Center [U01 CA078296] FX Supported by The American Society of Preventive Oncology/Prevent Cancer Foundation/American Society for Clinical Oncology Cancer Prevention Research Fellowship to SVA; the Australasian Colorectal Cancer Family Registry, No. U01 CA097735; the Familial Colorectal Neoplasia Collaborative Group, No. U01 CA074799; the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, No. U01 CA074800; the Ontario Registry for Studies of Familial Colorectal Cancer, No. U01 CA074783; the Seattle Colorectal Cancer Family Registry, No. U01 CA074794; the University of Hawaii Colorectal Cancer Family Registry, No. U01 CA074806; and the University of California, Irvine Informatics Center, No. U01 CA078296 NR 45 TC 7 Z9 7 U1 0 U2 6 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUN 7 PY 2013 VL 19 IS 21 BP 3241 EP 3248 DI 10.3748/wjg.v19.i21.3241 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 163YQ UT WOS:000320375000007 PM 23745025 ER PT J AU Cho, J Ibbott, G Gillin, M Gonzalez-Lepera, C Min, CH Zhu, XP El Fakhri, G Paganetti, H Mawlawi, O AF Cho, Jongmin Ibbott, Geoffrey Gillin, Michael Gonzalez-Lepera, Carlos Min, Chul Hee Zhu, Xuping El Fakhri, Georges Paganetti, Harald Mawlawi, Osama TI Determination of elemental tissue composition following proton treatment using positron emission tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BEAM RANGE VERIFICATION; MONTE-CARLO SIMULATIONS; CT NUMBERS; IN-BEAM; THERAPY; PET; DISTRIBUTIONS; RADIOTHERAPY; IRRADIATION; UNCERTAINTIES AB Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of H-1, C-12, N-14, and O-16 was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm; the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated C-12 and O-16 sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of C-12 + O-16 and calculate the relative elemental composition of C-12 and O-16. A Monte Carlo simulation was also used to determine the elemental composition of the C-12 + O-16 section. The calculated compositions of the C-12 + O-16 section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition (C-12 and O-16) maps that corresponded to the proton-activated regions. We compared the C-12 and O-16 compositions of seven ROIs that corresponded to the vitreous humor, adipose/face mask, adipose tissue, and brain tissue with ICRU 46 elemental composition data. The C-12 and O-16 compositions of the C-12 + O-16 phantom section were estimated to within a maximum difference of 3.6% for the near monoenergetic and SOBP beams over an 8 cm depth range. On the other hand, the Monte Carlo simulation estimated the corresponding C-12 and O-16 compositions in the C-12 + O-16 section to within a maximum difference of 3.4%. For the patients, the C-12 and O-16 compositions in the seven ROIs agreed with the ICRU elemental composition data, with a mean (maximum) difference of 9.4% (15.2%). The C-12 and O-16 compositions of the phantom and patients were estimated with relatively small differences. PET imaging may be useful for determining the tissue elemental composition and thereby improving proton treatment planning and verification. C1 [Cho, Jongmin] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. [Cho, Jongmin] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Gonzalez-Lepera, Carlos] Univ Texas MD Anderson Canc Ctr, Dept Nucl Med, Houston, TX 77030 USA. [Min, Chul Hee] Yonsei Univ, Coll Hlth Sci, Dept Radiol Sci, Wonju 220710, Kangwon Do, South Korea. [Zhu, Xuping; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Zhu, Xuping; El Fakhri, Georges; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mawlawi, Osama] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. RP Cho, J (reprint author), Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. EM jcho2@mdanderson.org FU National Institutes of Health through MD Anderson's Cancer Center Support Grant [CA016672] FX The authors thank Pablo Yepes at Rice University and Uwe Titt in the Department of Radiation Physics, Tinsu Pan in the Department of Imaging Physics, Francesco Stingo in the Department of Biostatistics, and the Department of Scientific Publications at the MD Anderson Cancer Center. This research is supported in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant (CA016672). NR 35 TC 6 Z9 6 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2013 VL 58 IS 11 BP 3815 EP 3835 DI 10.1088/0031-9155/58/11/3815 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 144UN UT WOS:000318966200021 PM 23681070 ER PT J AU Apostolou, E Ferrari, F Walsh, RM Bar-Nur, O Stadtfeld, M Cheloufi, S Stuart, HT Polo, JM Ohsumi, TK Borowsky, ML Kharchenko, PV Park, PJ Hochedlinger, K AF Apostolou, Effie Ferrari, Francesco Walsh, Ryan M. Bar-Nur, Ori Stadtfeld, Matthias Cheloufi, Sihem Stuart, Hannah T. Polo, Jose M. Ohsumi, Toshiro K. Borowsky, Mark L. Kharchenko, Peter V. Park, Peter J. Hochedlinger, Konrad TI Genome-wide Chromatin Interactions of the Nanog Locus in Pluripotency, Differentiation, and Reprogramming SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; CHROMOSOMAL REARRANGEMENTS; TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; GROUND-STATE; ES CELLS; MOUSE; ORGANIZATION; MEDIATOR; COMPLEX AB The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential interactions with other parts of the genome remain largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture sequencing. This network was rearranged during differentiation and restored in induced pluripotent stem cells. A large fraction of Nanog-interacting loci were bound by Mediator or cohesin in pluripotent cells. Depletion of these proteins from ESCs resulted in a disruption of contacts and the acquisition of a differentiation-specific interaction pattern prior to obvious transcriptional and phenotypic changes. Similarly, the establishment of Nanog interactions during reprogramming often preceded transcriptional upregulation of associated genes, suggesting a causative link. Our results document a complex, pluripotency-specific chromatin "interactome'' for Nanog and suggest a functional role for long-range genomic interactions in the maintenance and induction of pluripotency. C1 [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA. [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Apostolou, Effie; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ferrari, Francesco; Kharchenko, Peter V.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kharchenko, Peter V.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, 10 Shattuck St, Boston, MA 02115 USA. EM peter_park@harvard.edu; khochedlinger@helix.mgh.harvard.edu RI Ferrari, Francesco/H-5007-2012; OI Ferrari, Francesco/0000-0002-9811-3753; Stadtfeld, Matthias/0000-0002-5852-9906 FU JCCF; HHMI; NIH [RC2HL102815, K25AG037596, DP2OD003266, R01HD058013] FX We acknowledge Peter Fraser, Frank Grosveld, Jane Skok, and Job Dekker for comments and suggestions. We thank Mariann Miscinai and Triantiafyllos Paparountas for discussing bioinformatics analysis, Eda Yildirim and Berni Peyer for advice about FISH experiments, and all members of the Hochedlinger and Park groups for suggestions. E.A. was supported by post-doctoral fellowships from JCCF and HHMI. P.J.P. was supported by a Sloan Research Fellowship and NIH (RC2HL102815), P.V.K was supported by NIH (K25AG037596), and K.H. was supported by NIH (DP2OD003266 and R01HD058013). NR 62 TC 79 Z9 80 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JUN 6 PY 2013 VL 12 IS 6 BP 699 EP 712 DI 10.1016/j.stem.2013.04.013 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VH UT WOS:000329569900013 PM 23665121 ER PT J AU Yang, YM Gupta, SK Kim, KJ Powers, BE Cerqueira, A Wainger, BJ Ngo, HD Rosowski, KA Schein, PA Ackeifi, CA Arvanites, AC Davidow, LS Woolf, CJ Rubin, LL AF Yang, Yin M. Gupta, Shailesh K. Kim, Kevin J. Powers, Berit E. Cerqueira, Antonio Wainger, Brian J. Ngo, Hien D. Rosowski, Kathryn A. Schein, Pamela A. Ackeifi, Courtney A. Arvanites, Anthony C. Davidow, Lance S. Woolf, Clifford J. Rubin, Lee L. TI A Small Molecule Screen in Stem-Cell-Derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS SO CELL STEM CELL LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOUSE MODEL; C-JUN; MATRIX METALLOPROTEINASES; DISEASE PROGRESSION; SIGNALING PATHWAY; PROTEIN-KINASE; SURVIVAL; DEATH AB Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe a new small molecule survival screen carried out using MNs from both wild-type and mutant SOD1 mouse embryonic stem cells. Among the hits we found, kenpaullone had a particularly impressive ability to prolong the healthy survival of both types of MNs that can be attributed to its dual inhibition of GSK-3 and HGK kinases. Furthermore, kenpaullone also strongly improved the survival of human MNs derived from ALS-patient-induced pluripotent stem cells and was more active than either of two compounds, olesoxime and dexpramipexole, that recently failed in ALS clinical trials. Our studies demonstrate the value of a stem cell approach to drug discovery and point to a new paradigm for identification and preclinical testing of future ALS therapeutics. C1 [Yang, Yin M.; Gupta, Shailesh K.; Kim, Kevin J.; Powers, Berit E.; Cerqueira, Antonio; Ngo, Hien D.; Rosowski, Kathryn A.; Schein, Pamela A.; Ackeifi, Courtney A.; Rubin, Lee L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Yang, Yin M.; Gupta, Shailesh K.; Kim, Kevin J.; Powers, Berit E.; Cerqueira, Antonio; Ngo, Hien D.; Rosowski, Kathryn A.; Schein, Pamela A.; Ackeifi, Courtney A.; Arvanites, Anthony C.; Davidow, Lance S.; Rubin, Lee L.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rosowski, Kathryn A.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, Program Neurobiol, Boston, MA 02115 USA. [Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Rubin, LL (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM lee_rubin@harvard.edu OI Kim, Kevin/0000-0002-7015-5871 FU ALS Association; New York Stem Cell Foundation; NINDS [P01NS066888] FX We are grateful to K. Eggan for providing mouse ESCs and human ESCs and iPSCs, G. Daley for providing the TDP-43 human iPSCs, and B. Doble and J. Woodgett for providing mouse GSK-KO ESC lines. We would also like to thank B. Tilton and P. Rogers for assistance with FACS; K. Kotkow, A. D. Sinor-Anderson, N. Makhortova, M. Hayhurst, K. Krumholz, G. Boulting, J. Ichida, E. Kiskinis, and A. Blumenstein for providing reagents and helpful discussions; and J. LaLonde for editorial assistance. This work was supported by the ALS Association, the New York Stem Cell Foundation, NINDS (P01NS066888), and the Harvard Stem Cell Institute. L.L.R. is a founder of iPierian Inc. and a member of its Scientific Advisory Board. NR 58 TC 109 Z9 114 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JUN 6 PY 2013 VL 12 IS 6 BP 713 EP 726 DI 10.1016/j.stem.2013.04.003 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VH UT WOS:000329569900014 PM 23602540 ER PT J AU Tulpule, A Kelley, JM Lensch, MW McPherson, J Park, IH Hartung, O Nakamura, T Schlaeger, TM Shimamura, A Daley, GQ AF Tulpule, Asmin Kelley, James M. Lensch, M. William McPherson, Jade Park, In Hyun Hartung, Odelya Nakamura, Tomoka Schlaeger, Thorsten M. Shimamura, Akiko Daley, George Q. TI Pluripotent Stem Cell Models of Shwachman-Diamond Syndrome Reveal a Common Mechanism for Pancreatic and Hematopoietic Dysfunction SO CELL STEM CELL LA English DT Article ID MARROW FAILURE SYNDROMES; SBDS GENE; MUTATIONS; DIFFERENTIATION; GENERATION; FEATURES; PROTEIN; DEATH; RNA AB Shwachman-Diamond syndrome (SDS), a rare autosomal- recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction, is caused by mutations in the Shwachman-Bodian- Diamond syndrome (SBDS) gene. We created human pluripotent stem cell models of SDS through knockdown of SBDS in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two patients with SDS. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis, and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. Protease-mediated autodigestion provides a mechanistic link between the pancreatic and hematopoietic phenotypes in SDS, highlighting the utility of hESCs and iPSCs in obtaining novel insights into human disease. C1 [Tulpule, Asmin; Lensch, M. William; McPherson, Jade; Hartung, Odelya; Schlaeger, Thorsten M.; Shimamura, Akiko; Daley, George Q.] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Tulpule, Asmin; Daley, George Q.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kelley, James M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Tulpule, Asmin; Lensch, M. William; McPherson, Jade; Hartung, Odelya; Schlaeger, Thorsten M.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lensch, M. William; Daley, George Q.] Howard Hughes Med Inst, New Haven, CT 06520 USA. [Park, In Hyun] Yale Stem Cell Ctr, New Haven, CT 06520 USA. [Nakamura, Tomoka; Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA. [Shimamura, Akiko] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Shimamura, Akiko] Univ Washington, Seattle, WA 98105 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU Manton Center for Orphan Disease Research (BCH); NIH [P30 DK056465-10, R01 HL079582-11, R24 DK092760, RC4 DK09091, U01 HL100001, UL1 DE019582]; Roche Foundation for Anemia Research FX We thank Shuibing Chen (Weill Cornell Medical College) and Doug Melton (Harvard University) for their help with pancreatic differentiation protocols and Roderick Bronson (Harvard University) for his histopathological expertise. Harry Kozakewich (Boston Children's Hospital [BCH]) provided SDS patient slides. This work was supported by the Manton Center for Orphan Disease Research (BCH); NIH grants P30 DK056465-10, R01 HL079582-11, R24 DK092760, RC4 DK09091, U01 HL100001, and UL1 DE019582; and the Roche Foundation for Anemia Research. G.Q.D. is an investigator of the Howard Hughes Medical Institute. NR 32 TC 29 Z9 30 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JUN 6 PY 2013 VL 12 IS 6 BP 727 EP 736 DI 10.1016/j.stem.2013.04.002 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VH UT WOS:000329569900015 PM 23602541 ER PT J AU Wan, YZ Wu, CJ AF Wan, Youzhong Wu, Catherine J. TI SF3B1 mutations in chronic lymphocytic leukemia SO BLOOD LA English DT Review ID SPLICING FACTOR SF3B; PRE-MESSENGER-RNA; MYELODYSPLASTIC SYNDROMES; CLINICAL-SIGNIFICANCE; RING SIDEROBLASTS; RECURRENT MUTATIONS; CLONAL EVOLUTION; CANCER GENES; MACHINERY; PATHWAY AB SF3B1 is a critical component of the splicing machinery, which catalyzes the removal of introns from precursor messenger RNA (mRNA). Next-generation sequencing studies have identified mutations in SF3B1 in chronic lymphocytic leukemia (CLL) at high frequency. In CLL, SF3B1 mutation is associated with more aggressive disease and shorter survival, and recent studies suggest that it can be incorporated into prognostic schema to improve the prediction of disease progression. Mutations in SF3B1 are predominantly subclonal genetic events in CLL, and hence are likely later events in the progression of CLL. Evidence of altered pre-mRNA splicing has been detected in CLL cases with SF3B1 mutations. Although the causative link between SF3B1 mutation and CLL pathogenesis remains unclear, several lines of evidence suggest SF3B1 mutation might be linked to genomic stability and epigenetic modification. C1 [Wan, Youzhong; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Wan, Youzhong; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Room 420,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org FU Leukemia and Lymphoma Society; Blavatnik Family Foundation; Lymphoma Research Foundation; National Institutes of Health National Heart, Lung, and Blood Institute [1RO1HL103532-01, 1RO1HL116452-01]; National Cancer Institute [1R01CA155010-01A1]; Leukemia Lymphoma Translational Research Program Award; American Association of Cancer Research: Stand Up To Cancer Innovative Research Grant FX Y.W. is supported by a fellowship from the Leukemia and Lymphoma Society. C.J.W. acknowledges support from the Blavatnik Family Foundation, the Lymphoma Research Foundation, and the National Institutes of Health National Heart, Lung, and Blood Institute (1RO1HL103532-01, 1RO1HL116452-01) and National Cancer Institute (1R01CA155010-01A1), and is a recipient of a Leukemia Lymphoma Translational Research Program Award and an American Association of Cancer Research: Stand Up To Cancer Innovative Research Grant. NR 49 TC 32 Z9 32 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 6 PY 2013 VL 121 IS 23 BP 4627 EP 4634 DI 10.1182/blood-2013-02-427641 PG 8 WC Hematology SC Hematology GA 184MW UT WOS:000321895700006 PM 23568491 ER PT J AU Higgins, PC Prigerson, HG AF Higgins, Philip C. Prigerson, Holly G. TI Caregiver Evaluation of the Quality of End-Of-Life Care (CEQUEL) Scale: The Caregiver's Perception of Patient Care Near Death SO PLOS ONE LA English DT Article ID EXPLORATORY FACTOR-ANALYSIS; BEREAVED FAMILY-MEMBERS; INITIAL VALIDATION; TERMINAL ILLNESS; CANCER-PATIENTS; MENTAL-HEALTH; MEDICAL-CARE; COMMUNICATION; PROVIDERS; PERSPECTIVES AB Purpose: End-of-life (EOL) measures are limited in capturing caregiver assessment of the quality of EOL care. Because none include caregiver perception of patient suffering or prolongation of death, we sought to develop and validate the Caregiver Evaluation of Quality of End-of-Life Care (CEQUEL) scale to include these dimensions of caregiver-perceived quality of EOL care. Patients and Methods: Data were derived from Coping with Cancer (CwC), a multisite, prospective, longitudinal study of advanced cancer patients and their caregivers (N = 275 dyads). Caregivers were assessed before and after patient deaths. CEQUEL's factor structure was examined; reliability was evaluated using Cronbach's alpha, and convergent validity by the strength of associations between CEQUEL scores and key EOL outcomes. Results: Factor analysis revealed four distinct factors: Prolongation of Death, Perceived Suffering, Shared Decision-Making, and Preparation for the Death. Each item loaded strongly on only a single factor. The 13-item CEQUEL and its subscales showed moderate to acceptable Cronbach's alpha (range: 0.52-0.78). 53% of caregivers reported patients suffering more than expected. Higher CEQUEL scores were positively associated with therapeutic alliance (rho =. 13; p <=.05) and hospice enrollment (z = -2.09; p <=.05), and negatively associated with bereaved caregiver regret (rho = -.36, p <=.001) and a diagnosis of Posttraumatic Stress Disorder (z = -2.06; p <=.05). Conclusion: CEQUEL is a brief, valid measure of quality of EOL care from the caregiver's perspective. It is the first scale to include perceived suffering and prolongation of death. If validated in future work, it may prove a useful quality indicator for the delivery of EOL care and a risk indicator for poor bereavement adjustment. C1 [Higgins, Philip C.] Boston Coll, Grad Sch Social Work, Chestnut Hill, MA 02167 USA. [Higgins, Philip C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Higgins, Philip C.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu FU American Cancer Society [DSW1009403SW]; National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA156732]; Center for Psychosocial Epidemiology and Outcomes Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to PCH: DSW1009403SW from the American Cancer Society; and to HGP: MH63892 from the National Institute of Mental Health and CA106370 and CA156732 from the National Cancer Institute; and the Center for Psychosocial Epidemiology and Outcomes Research, 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 62 TC 6 Z9 6 U1 1 U2 19 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 JUN 6 PY 2013 VL 8 IS 6 AR e66066 DI 10.1371/journal.pone.0066066 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173SK UT WOS:000321099000125 PM 23762467 ER PT J AU Zhang, Y Schuff, N Camacho, M Chao, LL Fletcher, TP Yaffe, K Woolley, SC Madison, C Rosen, HJ Miller, BL Weiner, MW AF Zhang, Yu Schuff, Norbert Camacho, Monica Chao, Linda L. Fletcher, Thomas P. Yaffe, Kristine Woolley, Susan C. Madison, Catherine Rosen, Howard J. Miller, Bruce L. Weiner, Michael W. TI MRI Markers for Mild Cognitive Impairment: Comparisons between White Matter Integrity and Gray Matter Volume Measurements SO PLOS ONE LA English DT Article ID MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; POSTERIOR CINGULATE; ENTORHINAL CORTEX; ABNORMAL INTEGRITY; DIAGNOSTIC UTILITY; STRUCTURAL MRI; FIBER TRACTS; DIFFUSION AB The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy. C1 [Zhang, Yu; Schuff, Norbert; Camacho, Monica; Chao, Linda L.; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Zhang, Yu; Schuff, Norbert; Camacho, Monica; Chao, Linda L.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Fletcher, Thomas P.] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Psychiat Neurol & Epidemiol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Woolley, Susan C.; Madison, Catherine] Calif Pacific Med Ctr, Dept Neurol, San Francisco, CA USA. [Rosen, Howard J.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Zhang, Y (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. EM Yu.Zhang@ucsf.edu FU National Institutes of Health/National Institute on Aging [P01AG19724, P01AG12435]; NIH/National Center for Research Resources [P41RR023953] FX This research was supported in part by National Institutes of Health/National Institute on Aging grants P01AG19724, P01AG12435 and grant from NIH/National Center for Research Resources P41RR023953, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 22 Z9 23 U1 2 U2 19 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 JUN 6 PY 2013 VL 8 IS 6 AR e66367 DI 10.1371/journal.pone.0066367 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173SK UT WOS:000321099000132 PM 23762488 ER PT J AU Callen, E Di Virgilio, M Kruhlak, MJ Nieto-Soler, M Wong, N Chen, HT Faryabi, RB Polato, F Santos, M Starnes, LM Wesemann, DR Lee, JE Tubbs, A Sleckman, BP Daniel, JA Ge, K Alt, FW Fernandez-Capetillo, O Nussenzweig, MC Nussenzweig, A AF Callen, Elsa Di Virgilio, Michela Kruhlak, Michael J. Nieto-Soler, Maria Wong, Nancy Chen, Hua-Tang Faryabi, Robert B. Polato, Federica Santos, Margarida Starnes, Linda M. Wesemann, Duane R. Lee, Ji-Eun Tubbs, Anthony Sleckman, Barry P. Daniel, Jeremy A. Ge, Kai Alt, Frederick W. Fernandez-Capetillo, Oscar Nussenzweig, Michel C. Nussenzweig, Andre TI 53BP1 Mediates Productive and Mutagenic DNA Repair through Distinct Phosphoprotein Interactions SO CELL LA English DT Article ID CLASS SWITCH RECOMBINATION; LYSINE-4 METHYLTRANSFERASE COMPLEX; STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; END RESECTION; BRCT-DOMAIN; DYSFUNCTIONAL TELOMERES; B-CELLS; PTIP; RIF1 AB The DNA damage response (DDR) protein 53BP1 protects DNA ends from excessive resection in G1, and thereby favors repair by nonhomologous end-joining (NHEJ) as opposed to homologous recombination (HR). During S phase, BRCA1 antagonizes 53BP1 to promote HR. The pro-NHEJ and antirecombinase functions of 53BP1 are mediated in part by RIF1, the only known factor that requires 53BP1 phosphorylation for its recruitment to double-strand breaks (DSBs). Here, we show that a 53BP1 phosphomutant, 53BP1(8A), comprising alanine substitutions of the eight most N-terminal S/TQ phosphorylation sites, mimics 53BP1 deficiency by restoring genome stability in BRCA1-deficient cells yet behaves like wild-type 53BP1 with respect to immunoglobulin class switch recombination (CSR). 53BP1(8A) recruits RIF1 but fails to recruit the DDR protein PTIP to DSBs, and disruption of PTIP phenocopies 53BP1(8A). We conclude that 53BP1 promotes productive CSR and suppresses mutagenic DNA repair through distinct phosphodependent interactions with RIF1 and PTIP. C1 [Callen, Elsa; Wong, Nancy; Chen, Hua-Tang; Faryabi, Robert B.; Polato, Federica; Santos, Margarida; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Di Virgilio, Michela; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Di Virgilio, Michela; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Nieto-Soler, Maria; Fernandez-Capetillo, Oscar] Spanish Natl Canc Res Ctr CNIO, Gen Instabil Grp, Madrid 28029, Spain. [Santos, Margarida; Daniel, Jeremy A.] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark. [Wesemann, Duane R.; Alt, Frederick W.] Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Wesemann, Duane R.; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Lee, Ji-Eun; Ge, Kai] NIDDKD, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Tubbs, Anthony; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Nussenzweig, A (reprint author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Lee, Ji-Eun/F-7891-2011; Faryabi, Robert/H-3544-2015; Fernandez-Capetillo, Oscar/H-3508-2015; Daniel, Jeremy/S-4729-2016; OI Lee, Ji-Eun/0000-0002-3768-7016; Faryabi, Robert/0000-0002-7931-2175; Fernandez-Capetillo, Oscar/0000-0002-2690-6885; Daniel, Jeremy/0000-0002-1981-5571; Tubbs, Anthony/0000-0002-5605-8231; Ge, Kai/0000-0002-7442-5138 FU NIH [AI89972]; American Association of Allergy Asthma and Immunology and CSL Behring; Career Award for Medical Scientists (Burroughs Wellcome Fund); Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; Department of Defense grant [BC102335] FX We thank all members of the A. Nussenzweig lab and Davide Robbiani for discussions; Titia de Lange for RIF1f/f mice; Susan Sharrow for flow cytometry; and Sandy Chang for the TRF2 shRNA construct. M.C.N., F.W.A and O.F.-C. are HHMI investigators. D.R.W. was supported by NIH grants AI89972, the American Association of Allergy Asthma and Immunology and CSL Behring, and a Career Award for Medical Scientists (Burroughs Wellcome Fund). This work was supported by the Intramural Research Program of the NIH, the National Cancer Institute, and the Center for Cancer Research, and by a Department of Defense grant to A.N. (BC102335). NR 53 TC 109 Z9 112 U1 2 U2 33 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 6 PY 2013 VL 153 IS 6 BP 1266 EP 1280 DI 10.1016/j.cell.2013.05.023 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158NQ UT WOS:000319979200012 PM 23727112 ER PT J AU Galbraith, MD Allen, MA Bensard, CL Wang, XX Schwinn, MK Qin, B Long, HW Daniels, DL Hahn, WC Dowell, RD Espinosa, JM AF Galbraith, Matthew D. Allen, Mary A. Bensard, Claire L. Wang, Xiaoxing Schwinn, Marie K. Qin, Bo Long, Henry W. Daniels, Danette L. Hahn, William C. Dowell, Robin D. Espinosa, Joaquin M. TI HIF1A Employs CDK8-Mediator to Stimulate RNAPII Elongation in Response to Hypoxia SO CELL LA English DT Article ID BROMODOMAIN PROTEIN BRD4; POLYMERASE-II CTD; TRANSCRIPTION ELONGATION; P-TEFB; COMPLEX; CDK8; RECRUITMENT; COACTIVATOR; INITIATION; BINDING AB The transcription factor HIF1A is a key mediator of the cellular response to hypoxia. Despite the importance of HIF1A in homeostasis and various pathologies, little is known about how it regulates RNA polymerase II (RNAPII). We report here that HIF1A employs a specific variant of the Mediator complex to stimulate RNAPII elongation. The Mediator-associated kinase CDK8, but not the paralog CDK19, is required for induction of many HIF1A target genes. HIF1A induces binding of CDK8-Mediator and the super elongation complex (SEC), containing AFF4 and CDK9, to alleviate RNAPII pausing. CDK8 is dispensable for HIF1A chromatin binding and histone acetylation, but it is essential for binding of SEC and RNAPII elongation. Global analysis of active RNAPII reveals that hypoxia-inducible genes are paused and active prior to their induction. Our results provide a mechanistic link between HIF1A and CDK8, two potent oncogenes, in the cellular response to hypoxia. C1 [Galbraith, Matthew D.; Allen, Mary A.; Bensard, Claire L.; Espinosa, Joaquin M.] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Galbraith, Matthew D.; Allen, Mary A.; Bensard, Claire L.; Dowell, Robin D.; Espinosa, Joaquin M.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Allen, Mary A.; Dowell, Robin D.] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA. [Wang, Xiaoxing; Qin, Bo; Long, Henry W.; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wang, Xiaoxing; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Schwinn, Marie K.; Daniels, Danette L.] Promega Corp, Madison, WI 53711 USA. [Qin, Bo] Tongji Univ, Dept Bioinformat, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. RP Espinosa, JM (reprint author), Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. EM joaquin.espinosa@colorado.edu OI DOWELL, ROBIN/0000-0001-7665-9985 FU NSF [MCB-0842974, MCB-1243522]; NIH [RO1CA117907, RO1CA140545]; Butcher Seed Grant; Boettcher Foundation's Webb-Waring Biomedical Research program; DoD Breast Cancer Postdoctoral Fellowship [W81XWH-10-1-0062, 2T15LM009451] FX We thank Dr. Shilatifard for AFF4 antibody, Dr. Taatjes and Dr. Lin for HeLa nuclear extracts and MED15 antibody, and Edward Head for helpful discussions. This work was supported primarily by NSF grants MCB-0842974 and MCB-1243522, and also by NIH RO1CA117907 grant (J.M.E.), a Butcher Seed Grant (J.M.E, R.D.D.), the Boettcher Foundation's Webb-Waring Biomedical Research program (R.D.D.), DoD Breast Cancer Postdoctoral Fellowship W81XWH-10-1-0062 (X.W.), 2T15LM009451 (M.A.A.), and NIH RO1CA140545 (W.C.H.). J.M.E. is an HHMI Early Career Scientist. W.C.H. is a consultant for Novartis. Promega Corporation is the commercial owner by assignment of patents of the HaloTag technology and its applications. NR 40 TC 67 Z9 68 U1 1 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 6 PY 2013 VL 153 IS 6 BP 1327 EP 1339 DI 10.1016/j.cell.2013.04.048 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158NQ UT WOS:000319979200016 PM 23746844 ER PT J AU Oates, EC Rossor, AM Hafezparast, M Gonzalez, M Speziani, F MacArthur, DG Lek, M Cottenie, E Scoto, M Foley, AR Hurles, M Houlden, H Greensmith, L Auer-Grumbach, M Pieber, TR Strom, TM Schule, R Herrmann, DN Sowden, JE Acsadi, G Menezes, MP Clarke, NF Zuchner, S Muntoni, F North, KN Reilly, MM AF Oates, Emily C. Rossor, Alexander M. Hafezparast, Majid Gonzalez, Michael Speziani, Fiorella MacArthur, Daniel G. Lek, Monkol Cottenie, Ellen Scoto, Mariacristina Foley, A. Reghan Hurles, Matthew Houlden, Henry Greensmith, Linda Auer-Grumbach, Michaela Pieber, Thomas R. Strom, Tim M. Schule, Rebecca Herrmann, David N. Sowden, Janet E. Acsadi, Gyula Menezes, Manoj P. Clarke, Nigel F. Zuechner, Stephan Muntoni, Francesco North, Kathryn N. Reilly, Mary M. CA UK10K TI Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BICAUDAL-D; TRANSPORT; OOGENESIS; NEURONS; GENOME; FORM AB Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP. BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex, which facilitates trafficking of cellular cargos that are critical to motor neuron development and maintenance. We demonstrate that mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex, which might result in the perturbation of BICD2-dynein-dynactin-mediated trafficking, and impair neurite outgrowth. These findings provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterize BICD2-associated diseases, and underscore the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons. C1 [Oates, Emily C.; Menezes, Manoj P.; Clarke, Nigel F.; North, Kathryn N.] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia. [Oates, Emily C.; Menezes, Manoj P.; Clarke, Nigel F.] Univ Sydney, Fac Med, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Rossor, Alexander M.; Cottenie, Ellen; Houlden, Henry; Greensmith, Linda; Reilly, Mary M.] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England. [Hafezparast, Majid] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England. [Gonzalez, Michael; Speziani, Fiorella; Zuechner, Stephan] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA. [Gonzalez, Michael; Speziani, Fiorella; Zuechner, Stephan] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [MacArthur, Daniel G.; Lek, Monkol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.; Lek, Monkol] Broad Inst Harvard & MIT, Boston, MA 02142 USA. [Scoto, Mariacristina; Foley, A. Reghan; Muntoni, Francesco] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England. [Hurles, Matthew] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Houlden, Henry] UCL Inst Neurol, Neurogenet Lab, London WC1N 3BG, England. [Greensmith, Linda] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. [Auer-Grumbach, Michaela] Med Univ Vienna, Div Orthopaed, A-1090 Vienna, Austria. [Pieber, Thomas R.] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, A-8036 Graz, Austria. [Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Strom, Tim M.] Tech Univ Munich, Inst Human Genet, D-85748 Garching, Germany. [Schule, Rebecca] Univ Tubingen, Hertie Inst Clin Brain Res, D-72074 Tubingen, Germany. [Schule, Rebecca] Univ Tubingen, Ctr Neurol, Dept Neurodegenerat Dis, D-72074 Tubingen, Germany. [Herrmann, David N.; Sowden, Janet E.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Herrmann, David N.] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. [Acsadi, Gyula] Connecticut Childrens Med Ctr, Dept Neurol, Hartford, CT 06106 USA. [North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [North, Kathryn N.] Univ Melbourne, Dept Paediat, Parkville, Vic 3010, Australia. RP North, KN (reprint author), Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia. EM kathryn.north@mcri.edu.au RI Houlden, Henry/C-1532-2008; North, Kathryn/K-6476-2012 OI Houlden, Henry/0000-0002-2866-7777; North, Kathryn/0000-0003-0841-8009 FU National Human Genome Research Institute, National Institutes of Health [U54 HG003067]; Inherited Neuropathies Consortium (Rare Disease Clinical Research Network, National Institute of Neurological Disorders and Stroke) [1U54NS0657]; Wellcome Trust [WT091310] FX We would like to thank Leigh Waddell for coordination of AUS1 exome samples, Katy Eichinger for research evaluation of USA1, and Garth Nicholson, Marina Kennerson, Giovanni Stevanin, and Matthew Harms for further investigating additional BICD2 variants that ultimately did not segregate with the disease phenotype in their kindreds. AUS1 exome sequencing was supported by a grant from the National Human Genome Research Institute, National Institutes of Health (Medical Sequencing Program grant U54 HG003067 to E.S. Lander, the principal investigator at the Broad Institute of Harvard and MIT). Genetic testing of AUSTRAI1, UK1, USA1, and GERMANY1 was supported by the Inherited Neuropathies Consortium (Rare Disease Clinical Research Network, National Institute of Neurological Disorders and Stroke 1U54NS0657). The study makes use of data (from sample set NM5061932 [UK2]) generated by the UK10K Consortium with funding from the Wellcome Trust (award WT091310). Investigators who contributed to the generation of these data are listed at www.UK10K.org. Funding sources for individual authors are summarized in the Supplemental Acknowledgments. NR 21 TC 51 Z9 53 U1 0 U2 10 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 JUN 6 PY 2013 VL 92 IS 6 BP 965 EP 973 DI 10.1016/j.ajhg.2013.04.018 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 164MX UT WOS:000320415300013 PM 23664120 ER PT J AU Lapenta, OM Minati, L Fregni, F Boggio, PS AF Lapenta, Olivia M. Minati, Ludovico Fregni, Felipe Boggio, Paulo S. TI Je pense donc je fais: transcranial direct current stimulation modulates brain oscillations associated with motor imagery and movement observation SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE tDCS; EEG; mu rhythm; motor imagery; action observation; primary motor cortex ID MU-RHYTHM; MAGNETIC STIMULATION; CORTICOSPINAL EXCITABILITY; HOMEOSTATIC PLASTICITY; STROKE PATIENTS; EEG EVIDENCE; CORTEX; SIMULATION; HUMANS; TASK AB Motor system neural networks are activated during movement imagery, observation and execution, with a neural signature characterized by suppression of the Mu rhythm. In order to investigate the origin of this neurophysiological marker, we tested whether transcranial direct current stimulation (tDCS) modifies Mu rhythm oscillations during tasks involving observation and imagery of biological and non-biological movements. We applied tDCS (anodal, cathodal, and sham) in 21 male participants (mean age 23.8 +/- 3.06), over the left M1 with a current of 2 mA for 20 min. Following this, we recorded the EEG at C3, C4, and Cz and surrounding C3 and C4 electrodes. Analyses of C3 and C4 showed significant effects for biological vs. non-biological movement (p = 0.005), and differential hemisphere effects according to the type of stimulation (p = 0.04) and type of movement (p = 0.02). Analyses of surrounding electrodes revealed significant interaction effects considering type of stimulation and imagery or observation of biological or non-biological movement (p = 0.03). The main findings of this study were (1) Mu desynchronization during biological movement of the hand region in the contralateral hemisphere after sham tDCS; (2) polarity-dependent modulation effects of tDCS on the Mu rhythm, i.e., anodal tDCS led to Mu synchronization while cathodal tDCS led to Mu desynchronization during movement observation and imagery (3) specific focal and opposite inter-hemispheric effects, i.e., contrary effects for the surrounding electrodes during imagery condition and also for inter-hemispheric electrodes (C3 vs. C4). These findings provide insights into the cortical oscillations during movement observation and imagery. Furthermore, it shows that tDCS can be highly focal when guided by a behavioral task. C1 [Lapenta, Olivia M.; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Ctr Hlth & Biol Sci, BR-01241001 Sao Paulo, Brazil. [Minati, Ludovico] Fdn IRCCS Ist Neurol Carlo Besta, UO Direz Sci, Milan, Italy. [Fregni, Felipe] Harvard Univ, Lab Neuromodulat, Sch Med, Spaulding Rehabil Hosp,Massachusetts Gen Hosp, Boston, MA USA. RP Boggio, PS (reprint author), Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Rua Piaui,181,10 Andar, BR-01241001 Sao Paulo, Brazil. EM boggio@mackenzie.br RI Boggio, Paulo/K-6272-2012 OI Boggio, Paulo/0000-0002-6109-0447 FU CNPq researcher grant [304164/2012-7]; Master grant (CAPES-PROSUP-IES modality I) FX Paulo S. Boggio is supported by a CNPq researcher grant (304164/2012-7). Olivia M. Lapenta was supported by a Master grant (CAPES-PROSUP-IES modality I). NR 57 TC 13 Z9 13 U1 1 U2 10 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JUN 6 PY 2013 VL 7 AR 256 DI 10.3389/fnhum.2013.00256 PG 9 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 158TP UT WOS:000319996400001 PM 23761755 ER PT J AU Hoo, GWS AF Hoo, Guy W. Soo TI In Prone Ventilation, One Good Turn Deserves Another SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; FAILURE C1 [Hoo, Guy W. Soo] Vet Affairs Greater Los Angeles Healthcare Syst, West Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect 111Q, Los Angeles, CA USA. [Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hoo, GWS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, West Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect 111Q, Los Angeles, CA USA. NR 10 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 2013 VL 368 IS 23 BP 2227 EP 2228 DI 10.1056/NEJMe1304349 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 158DN UT WOS:000319948900012 ER PT J AU Greka, A Dekker, JP Calderwood, SB AF Greka, Anna Dekker, John P. Calderwood, Stephen B. TI Case 4-2013: A Man with Acute Flank Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Greka, Anna; Dekker, John P.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greka, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 2013 VL 368 IS 23 BP 2237 EP 2237 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 158DN UT WOS:000319948900026 PM 23738559 ER PT J AU Bagci-Onder, T Agarwal, A Flusberg, D Wanningen, S Sorger, P Shah, K AF Bagci-Onder, T. Agarwal, A. Flusberg, D. Wanningen, S. Sorger, P. Shah, K. TI Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors SO ONCOGENE LA English DT Article DE live-cell imaging; DR4/5; TRAIL; GBM; neural stem cell; dual luciferase imaging ID HISTONE DEACETYLASE INHIBITORS; PHASE-II TRIAL; INDUCED APOPTOSIS; CANCER-CELLS; UP-REGULATION; DOWN-REGULATION; STEM-CELLS; IN-VIVO; S-TRAIL; GLIOMA AB Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and its efficacy has been tested in pre-clinical models by delivering it systemically as a purified ligand or via engineered stem cells (SC). However, about 50% of tumor lines are resistant to TRAIL and overcoming TRAIL resistance in aggressive tumors, such as glioblastoma-multiforme (GBM), and understanding the molecular dynamics of TRAIL-based combination therapies are critical to broadly use TRAIL as a therapeutic agent. In this study, we developed death receptor (DR)4/5-reporters that offer an imaging-based platform to identify agents that act in concert with a potent, secretable variant of TRAIL (S-TRAIL) by monitoring changes in DR4/5 expression. Utilizing these reporters, we show a differential regulation of DR4/5 when exposed to a panel of clinically relevant agents. A histone deacetylase inhibitor, MS-275, resulted in upregulation of DR4/5 in all GBM cell lines, and these changes could be followed in real time both in vitro and in vivo in mice bearing tumors and they correlated with increased TRAIL sensitivity. To further assess the dynamics of combinatorial strategies that overcome resistance of tumors to SC released S-TRAIL, we also engineered tumor cells to express live-cell caspase-reporters and SCs to express S-TRAIL. Utilizing DR4/5 and caspase reporters in parallel, we show that MS-275 sensitizes TRAIL-resistant GBM cells to stem cell (SC) delivered S-TRAIL by changing the time-to-death in vitro and in vivo. This study demonstrates the effectiveness of a combination of real-time reporters of TRAIL-induced apoptosis pathway in evaluating the efficacy of SC-TRAIL-based therapeutics and may have implications in targeting a broad range of cancers. C1 [Bagci-Onder, T.; Agarwal, A.; Wanningen, S.; Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Bagci-Onder, T.; Agarwal, A.; Wanningen, S.; Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Flusberg, D.; Sorger, P.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02114 USA. [Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Shah, K.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. EM kshah@mgh.harvard.edu FU American Cancer Society; NIH [CA138922, NS071197, CA139980]; James McDonnell Foundation FX We thank Dr Shi-Yon Sun for providing pDR4 and pDR5 basic constructs; real-time PCR core facility of Neuroscience Department, Massachusetts General Hospital; flow cytometry core facility of Ragon Institute, Massachusetts General Hospital; and Nikon Imaging Center, Harvard Medical School for technical help and equipments. This work was supported by American Cancer Society (KS), NIH grants CA138922, NS071197 (KS), CA139980 (PKS) and the James McDonnell Foundation (KS). There are no competing financial interests to disclose. NR 39 TC 14 Z9 14 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 6 PY 2013 VL 32 IS 23 BP 2818 EP 2827 DI 10.1038/onc.2012.304 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 163WR UT WOS:000320369100002 PM 22824792 ER PT J AU Choi, S Chatzigeorgiou, M Taylor, KP Schafer, WR Kaplan, JM AF Choi, Seungwon Chatzigeorgiou, Marios Taylor, Kelsey P. Schafer, William R. Kaplan, Joshua M. TI Analysis of NPR-1 Reveals a Circuit Mechanism for Behavioral Quiescence in C. elegans SO NEURON LA English DT Article ID PIGMENT-DISPERSING FACTOR; SLEEP-LIKE STATE; CAENORHABDITIS-ELEGANS; SOCIAL-BEHAVIOR; DROSOPHILA-MELANOGASTER; NEURAL CIRCUIT; NEUROPEPTIDE; NEURONS; SYSTEM; GENE AB Animals undergo periods of behavioral quiescence and arousal in response to environmental, circadian, or developmental cues. During larval molts, C. elegans undergoes a period of profound behavioral quiescence termed lethargus. Locomotion quiescence during lethargus was abolished in mutants lacking a neuropeptide receptor (NPR-1) and was reduced in mutants lacking NPR-1 ligands (FLP-18 and FLP-21). Wild-type strains are polymorphic for the npr-1 gene, and their lethargus behavior varies correspondingly. Locomotion quiescence and arousal were mediated by decreased and increased secretion of an arousal neuropeptide (PDF-1) from central neurons. PDF receptors (PDFR-1) expressed in peripheral mechanosensory neurons enhanced touch-evoked calcium transients. Thus, a central circuit stimulates arousal from lethargus by enhancing the sensitivity of peripheral mechanosensory neurons in the body. These results define a circuit mechanism controlling a developmentally programmed form of quiescence. C1 [Choi, Seungwon; Taylor, Kelsey P.; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Choi, Seungwon; Taylor, Kelsey P.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Choi, Seungwon; Taylor, Kelsey P.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Chatzigeorgiou, Marios; Schafer, William R.] MRC, Mol Biol Lab, Div Cell Biol, Cambridge CB2 0QH, England. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU Kwanjeong Educational Foundation; [NIH DK80215]; [MRC MC-A022-5PB9] FX We thank the following for strains, advice, reagents, and comments on the manuscript: Cori Bargmann for NPR-1 sensory rescue and rat TRPV1 transgenes, Mario de Bono for flp-18 mutants, the Caenorhabditis Genetics Center (CGC) and S. Mitani for strains, and members of the Kaplan lab for comments on the manuscript. This work was supported by a Kwanjeong Educational Foundation Predoctoral Fellowship (S.C.), and by research grants to J.K. (NIH DK80215), and to W.S. (MRC MC-A022-5PB9). NR 51 TC 31 Z9 35 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 5 PY 2013 VL 78 IS 5 BP 869 EP 880 DI 10.1016/j.neuron.2013.04.002 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 168YH UT WOS:000320743400013 PM 23764289 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Ipsilateral lower extremity joint involvement increases the risk of poor pain and function outcomes after hip or knee arthroplasty SO BMC MEDICINE LA English DT Article DE Arthroplasty; Ipsilateral; Joint replacement; Outcomes; Risk factors; Total hip replacement; Total knee replacement ID CLINICAL RATING SYSTEM; REPLACEMENT; PREDICTORS; TRENDS AB Background: Poor pain and function outcomes are undesirable after an elective surgery such as total hip or knee arthroplasty (THA/TKA). Recent studies have indicated that the presence of contralateral joint influences outcomes of THA/TKA, however the impact of ipsilateral knee/hip involvement on THA/TKA outcomes has not been explored. The objective of this study was to assess the association of ipsilateral knee/hip joint involvement on short-term and medium-term pain and function outcomes after THA/TKA. Methods: In this retrospective study of prospectively collected data, we used the data from the Mayo Clinic Total Joint Registry to assess the association of ipsilateral knee or hip joint involvement with moderate to severe pain and moderate to severe activity limitation at 2-year and 5-year follow-up after primary and revision THA and TKA using multivariable-adjusted logistic regression analyses. Results: At 2 years, 3,823 primary THA, 4,701 primary TKA, 1,218 revision THA and 725 revision TKA procedures were studied. After adjusting for multiple covariates, ipsilateral knee pain was significantly associated with outcomes after primary THA (all P values <0.01): (1) moderate to severe pain: at 2 years, odds ratio (OR), 2.3 (95% confidence interval (CI) 1.5 to 3.6); at 5 years, OR 1.8 (95% CI 1.1 to 2.7); (2) moderate to severe activity limitation: at 2 years, OR 3.1 (95% CI 2.3 to 4.3); at 5 years, OR 3.6 (95% CI 2.6 to 5.0). Ipsilateral hip pain was significantly associated with outcomes after primary TKA (all P values <0.01): (1) moderate to severe pain: at 2 years, OR 3.3 (95% CI 2.3 to 4.7); at 5 years, OR 1.8 (95% CI 1.1 to 2.7); (2) moderate to severe activity limitation: at 2 years, OR 3.6 (95% CI 2.6 to 4.9); at 5 years, OR 2.2 (95% CI 1.6 to 3.2). Similar associations were noted for revision THA and TKA patients. Conclusions: To the best of our knowledge, this is the first study showing that the presence of ipsilateral joint involvement after THA or TKA is strongly associated with poor pain and function outcomes. A potential way to improve outcomes is to address ipsilateral lower extremity joint involvement. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 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 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Mayo Clinic Orthopedic Surgery research funds; National Institutes of Health (NIH) Clinical Translational Science Award [1 KL2 RR024151-01]; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Aging and National Cancer Institute FX This study was supported by research funds 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 and National Cancer Institute. The funding agencies played no role in the design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. This study was presented as an oral abstract presentation at the 2012 American College of Rheumatology Annual meeting in Washington, DC in November 2012. NR 22 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD JUN 5 PY 2013 VL 11 AR 144 DI 10.1186/1741-7015-11-144 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 163GF UT WOS:000320323300001 PM 23738845 ER PT J AU Iannotti, JP Deutsch, A Green, A Rudicel, S Christensen, J Marraffino, S Rodeo, S AF Iannotti, Joseph P. Deutsch, Allen Green, Andrew Rudicel, Sally Christensen, Jared Marraffino, Shannon Rodeo, Scott TI Time to Failure After Rotator Cuff Repair A Prospective Imaging Study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTHROSCOPIC REPAIR; FUNCTIONAL OUTCOMES; FATTY DEGENERATION; SHOULDER; TEARS; ROW; ULTRASOUND; INTEGRITY; TRENDS; MODEL AB Background: Failure of tendon healing after a rotator cuff repair is demonstrated by magnetic resonance imaging (MRI) as a fluid-filled defect within the tendon. The frequency of, and factors associated with, failure of the tendon repair to heal have been the focus of many clinical studies. The timing of when these defects occur has not been previously studied in a large prospectively defined patient population, to our knowledge. It was our hypothesis that the majority of failures occur within twelve weeks after surgery. Methods: One hundred and thirteen patients were enrolled in a multi-institutional prospective study. All patients had a standardized arthroscopic repair of a full-thickness tear of 1 to 4 cm as well as sequential MRI studies at six intervals from two weeks to fifty-two weeks. MRIs were reviewed at the time of imaging by the treating surgeon. Standardized patient-oriented clinical data were collected, physical examination was performed, and strength measurements were made preoperatively and postoperatively. Results: The treating surgeons diagnosed a recurrent tear with MRI in nineteen (17%) of the 113 patients within one year after surgery. The mean time to the retear was 19.2 weeks. There was a linear increase in retears over the first twenty-six weeks after surgery, and one additional tear was diagnosed between twenty-six and fifty-two weeks after repair. Conclusions: Retears primarily occur between six and twenty-six weeks after arthroscopic rotator cuff repair, and few additional tears occur thereafter. A substantial number of retears occur between twelve and twenty-six weeks after repair. C1 [Iannotti, Joseph P.] Cleveland Clin, Cleveland, OH 44195 USA. Kelsey Seabold Clin, Houston, TX 77025 USA. Univ Orthoped, Providence, RI USA. Hosp Special Surg, New York, NY 10021 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CORE Inst, Phoenix, AZ USA. Everett Clin, Everett, WA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Texas Orthoped Specialists, Bedford, TX USA. UCSF, San Francisco, CA USA. Yale Univ, New Haven, CT USA. RP Iannotti, JP (reprint author), Cleveland Clin, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM iannotj@ccf.org FU Pfizer Pharmaceuticals FX This study was funded by Pfizer Pharmaceuticals. They provided support for defining the study protocol and provided all resources for monitoring data collection from each enrollment site, monitoring study data, central data collection, and analysis. No support was provided to any author for review of data or for preparation of this manuscript. NR 26 TC 46 Z9 48 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN 5 PY 2013 VL 95A IS 11 BP 965 EP 971 DI 10.2106/JBJS.L.00708 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 161TU UT WOS:000320217000002 PM 23780533 ER PT J AU Harms, AS Cao, SW Rowse, AL Thome, AD Li, XR Mangieri, LR Cron, RQ Shacka, JJ Raman, C Standaert, DG AF Harms, Ashley S. Cao, Shuwen Rowse, Amber L. Thome, Aaron D. Li, Xinru Mangieri, Leandra R. Cron, Randy Q. Shacka, John J. Raman, Chander Standaert, David G. TI MHCII Is Required for alpha-Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneratione SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; MOUSE MODEL; CEREBROSPINAL-FLUID; BRAIN; GAMMA; CHAIN; INTERLEUKIN-1-BETA; INFLAMMATION; EXPRESSION AB Accumulation of alpha-synuclein (alpha-syn) in the brain is a core feature of Parkinson disease (PD) and leads to microglial activation, production of inflammatory cytokines and chemokines, T-cell infiltration, and neurodegeneration. Here, we have used both an in vivo mouse model induced by viral overexpression of alpha-syn as well as in vitro systems to study the role of the MHCII complex in alpha-syn-induced neuroinflammation and neurodegeneration. We find that in vivo, expression of full-length human alpha-syncauses striking induction of MHCII expression by microglia, while knock-out of MHCII prevents alpha-syn-induced microglial activation, antigen presentation, IgG deposition, and the degeneration of dopaminergic neurons. In vitro, treatment of microglia with aggregated alpha-syn leads to activation of antigen processing and presentation of antigen sufficient to drive CD4 T-cell proliferation and to trigger cytokine release. These results indicate a central role for microglial MHCII in the activation of both the innate and adaptive immune responses to alpha-syn in PD and suggest that the MHCII signaling complex may be a target of neuroprotective therapies for the disease. C1 [Harms, Ashley S.; Cao, Shuwen; Thome, Aaron D.; Li, Xinru; Standaert, David G.] Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, Birmingham, AL 35294 USA. [Rowse, Amber L.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mangieri, Leandra R.; Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Cron, Randy Q.] Childrens Hosp Alabama, Dept Pediat, Div Rheumatol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Raman, Chander] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. RP Standaert, DG (reprint author), Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, 1719 6th Ave South,CIRC 516, Birmingham, AL 35294 USA. EM dstandaert@uab.edu RI Cao, Shuwen/E-1924-2016 FU RJG Foundation; University of Alabama (UAB) Comprehensive Arthritis, Musculoskeletal, and Autoimmunity Center (CAMAC) Comprehensive Flow Cytometry Core (NIH) [P30 AR48311]; UAB Animal Resources Program (NIH) [G20 RR025858, G20 RR022807-01]; NIH [T32 AR007450-30] FX The work from these studies is generously supported by the RJG Foundation, the University of Alabama (UAB) Comprehensive Arthritis, Musculoskeletal, and Autoimmunity Center (CAMAC) Comprehensive Flow Cytometry Core (NIH Grant P30 AR48311), the UAB Animal Resources Program (NIH Grants G20 RR025858 and G20 RR022807-01), and NIH Grant T32 AR007450-30. We thank Dr. Chad Steele for his help with the multiplex ELISA assay at University of Alabama at Birmingham. NR 39 TC 56 Z9 58 U1 3 U2 19 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 JUN 5 PY 2013 VL 33 IS 23 BP 9592 EP 9600 DI 10.1523/JNEUROSCI.5610-12.2013 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 158IS UT WOS:000319963300003 PM 23739956 ER PT J AU Seal, KH Stein, MB AF Seal, Karen H. Stein, Murray B. TI Preventing the Pain of PTSD SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; MORPHINE; OPIOIDS; FEAR; IRAQ AB A selective opioid receptor agonist prevents fear memory consolidation in the amygdala in a mouse model of posttraumatic stress disorder (Andero et al.). C1 [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA 92103 USA. RP Stein, MB (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. EM mstein@ucsd.edu NR 10 TC 2 Z9 2 U1 1 U2 5 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 JUN 5 PY 2013 VL 5 IS 188 AR 188fs22 DI 10.1126/scitranslmed.3006635 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 158LK UT WOS:000319972300002 PM 23740896 ER PT J AU Maggard-Gibbons, M Maglione, M Livhits, M Ewing, B Maher, AR Hu, JH Li, ZP Shekelle, PG AF Maggard-Gibbons, Melinda Maglione, Margaret Livhits, Masha Ewing, Brett Maher, Alicia Ruelaz Hu, Jianhui Li, Zhaoping Shekelle, Paul G. TI Bariatric Surgery for Weight Loss and Glycemic Control in Nonmorbidly Obese Adults With Diabetes A Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID Y GASTRIC BYPASS; BODY-MASS INDEX; RANDOMIZED-CONTROLLED-TRIAL; LIFE-STYLE INTERVENTIONS; BMI LESS-THAN-35 KG/M(2); LONG-TERM EFFECTIVENESS; GLUCAGON-LIKE PEPTIDE-1; 10-YEAR FOLLOW-UP; THAN 35 KG/M(2); SLEEVE GASTRECTOMY AB Importance Bariatric surgery is beneficial in persons with a body mass index (BMI) of 35 or greater with obesity-related comorbidities. There is interest in using these procedures in persons with lower BMI and diabetes. Objective To assess the association between bariatric surgery vs nonsurgical treatments and weight loss and glycemic control among patients with diabetes or impaired glucose tolerance and BMI of 30 to 35. Evidence Review PubMed, EMBASE, and Cochrane Library databases were searched from January 1985 through September 2012. Of 1291 screened articles, we included 32 surgical studies, 11 systematic reviews on nonsurgical treatments, and 11 large nonsurgical studies published after those reviews. Weight loss, metabolic outcomes, and adverse events were abstracted by 2 independent reviewers. Findings Three randomized clinical trials (RCTs) (N=290; including 1 trial of 150 patients with type 2 diabetes and mean BMI of 37, 1 trial of 80 patients without diabetes [38% with metabolic syndrome] and BMI of 30 to 35, and 1 trial of 60 patients with diabetes and BMI of 30 to 40 [13 patients with BMI <35]) found that surgery was associated with greater weight loss (range, 14.4-24 kg) and glycemic control (range, 0.9-1.43 point improvements in hemoglobin A(1c) levels) during 1 to 2 years of follow-up than nonsurgical treatment. Indirect comparisons of evidence from observational studies of bariatric procedures (n approximate to 600 patients) and meta-analyses of nonsurgical therapies (containing more than 300 RCTs) support this finding at 1 or 2 years of follow-up. However, there are no robust surgical data beyond 5 years of follow-up on outcomes of diabetes, glucose control, or macrovascular and microvascular outcomes. In contrast, some RCT data of nonsurgical therapies show benefits at 10 years of follow-up or more. Surgeon-reported adverse events were low (eg, hospital deaths of 0.3%-1.0%), but data were from select centers and surgeons. Long-term adverse events are unknown. Conclusions and Relevance Current evidence suggests that, when compared with nonsurgical treatments, bariatric surgical procedures in patients with a BMI of 30 to 35 and diabetes are associated with greater short-term weight loss and better intermediate glucose outcomes. Evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this population until more data are available about long-term outcomes and complications of surgery. C1 [Maggard-Gibbons, Melinda; Maglione, Margaret; Ewing, Brett; Maher, Alicia Ruelaz; Hu, Jianhui; Shekelle, Paul G.] Rand Hlth, Santa Monica, CA USA. [Maggard-Gibbons, Melinda; Livhits, Masha] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Maggard-Gibbons, Melinda; Livhits, Masha; Li, Zhaoping; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Maggard-Gibbons, Melinda] Olive View UCLA Med Ctr, Dept Surg, Sylmar, CA 91342 USA. [Maher, Alicia Ruelaz] Akasha Ctr Integrat Med, Santa Monica, CA USA. RP Maggard-Gibbons, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, CHS 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu FU AHRQ [290-2007-10062I]; US Department of Health and Human Services FX This project was funded under the contract 290-2007-10062I from the AHRQ and US Department of Health and Human Services. NR 84 TC 97 Z9 99 U1 2 U2 34 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 5 PY 2013 VL 309 IS 21 BP 2250 EP 2261 DI 10.1001/jama.2013.4851 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 156YC UT WOS:000319859200029 PM 23736734 ER PT J AU Demberg, T Brocca-Cofano, E Kuate, S Aladi, S Vargas-Inchaustegui, DA Venzon, D Kalisz, I Kalyanaraman, VS Lee, EM Pal, R DiPasquale, J Ruprecht, RM Montefiori, DC Srivastava, I Barnett, SW Robert-Guroff, M AF Demberg, Thorsten Brocca-Cofano, Egidio Kuate, Seraphin Aladi, Stanley Vargas-Inchaustegui, Diego A. Venzon, David Kalisz, Irene Kalyanaraman, V. S. Lee, Eun Mi Pal, Ranajit DiPasquale, Janet Ruprecht, Ruth M. Montefiori, David C. Srivastava, Indresh Barnett, Susan W. Robert-Guroff, Marjorie TI Impact of antibody quality and anamnestic response on viremia control post-challenge in a combined Tat/Env vaccine regimen in rhesus macaques SO VIROLOGY LA English DT Article DE HIV vaccine; HIV Tat; HIV Envelope; Rhesus macaque; SHIV challenge; ADCC ID VIRUS SHIV89.6P CHALLENGE; CELLS IN-VITRO; PROTECTIVE EFFICACY; IMMUNE-RESPONSES; DENDRITIC CELLS; REPLICATION-COMPETENT; ANTIRETROVIRAL THERAPY; RECOMBINANT VACCINES; HIV-1 INFECTION; MESSENGER-RNA AB Previously, priming rhesus macaques with Adenovirus type 5 host range mutant-recombinants encoding Tat and Env and boosting with Tat and Env protein in MPL-SE controlled chronic viremia by 4 logs following homologous intravenous SHIV89.6P, challenge. Here we evaluated Tat, Env, and Tat/Env regimens for immunogenicity and protective efficacy using clade C Env, alum adjuvant, and a heterologous intrarectal SHIV1157ipd3N4 challenge. Despite induction of strong cellular and humoral immunity, Tat/Env group T and B-cell memory responses were not significantly enhanced over Tat- or Env-only groups. Lack of viremia control post-challenge was attributed to lower avidity Env antibodies and no anamnestic ADCC response or SHIV1157ipd3N4 neutralizing antibody development post-challenge. Poor biologic activity of the Tat immunogen may have impaired Tat immunity. In the absence of sterilizing immunity, strong anamnestic responses to heterologous virus can help control viremia. Both antibody breadth and optimal adjuvanticity are needed to elicit high-quality antibody for protective efficacy. Published by Elsevier Inc. C1 [Demberg, Thorsten; Brocca-Cofano, Egidio; Kuate, Seraphin; Aladi, Stanley; Vargas-Inchaustegui, Diego A.; DiPasquale, Janet; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Kalisz, Irene; Kalyanaraman, V. S.; Lee, Eun Mi; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC 27705 USA. [Srivastava, Indresh; Barnett, Susan W.] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA. RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU NIH [P01AI048240]; Intramural Research Program of the National Institutes of Health; National Cancer Institute FX We thank Dr. Deborah Weiss, James Treece and all the veterinary staff at ABL for excellent care of our animals and performance of all animal technical procedures. The following reagent was obtained from the AIDS Research and Reference Reagent program, DAIDS, NIAID, NIH: HIV Tat clade B consensus peptides, complete set. This work was supported in part by NIH grant P01AI048240 to R.M.R and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 46 TC 7 Z9 7 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2013 VL 440 IS 2 BP 210 EP 221 DI 10.1016/j.virol.2013.02.024 PG 12 WC Virology SC Virology GA 141VT UT WOS:000318755300012 PM 23528732 ER PT J AU Chaudhuri, D Sancak, Y Mootha, VK Clapham, DE AF Chaudhuri, Dipayan Sancak, Yasemin Mootha, Vamsi K. Clapham, David E. TI MCU encodes the pore conducting mitochondrial calcium currents SO ELIFE LA English DT Article ID ESSENTIAL COMPONENT; CA2+ UPTAKE; UNIPORTER; CHANNELS; PROTEIN AB Mitochondrial calcium (Ca2+) import is a well-described phenomenon regulating cell survival and ATP production. Of multiple pathways allowing such entry, the mitochondrial Ca2+ uniporter is a highly Ca2+-selective channel complex encoded by several recently-discovered genes. However, the identity of the pore-forming subunit remains to be established, since knockdown of all the candidate uniporter genes inhibit Ca2+ uptake in imaging assays, and reconstitution experiments have been equivocal. To definitively identify the channel, we use whole-mitoplast voltage-clamping, the technique that originally established the uniporter as a Ca2+ channel. We show that RNAi-mediated knockdown of the mitochondrial calcium uniporter (MCU) gene reduces mitochondrial Ca2+ current (I-MiCa), whereas overexpression increases it. Additionally, a classic feature of I-MiCa, its sensitivity to ruthenium red inhibition, can be abolished by a point mutation in the putative pore domain without altering current magnitude. These analyses establish that MCU encodes the pore-forming subunit of the uniporter channel. C1 [Chaudhuri, Dipayan] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chaudhuri, Dipayan; Clapham, David E.] Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA USA. [Sancak, Yasemin; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sancak, Yasemin; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sancak, Yasemin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Clapham, DE (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA USA. EM dclapham@enders.tch.harvard.edu FU National Institutes of Health [F32HL107021, R24DK080261]; Helen Hay Whitney Foundation; Howard Hughes Medical Institute FX National Institutes of Health F32HL107021 Dipayan Chaudhuri; National Institutes of Health R24DK080261 Vamsi K Mootha; Helen Hay Whitney Foundation Yasemin Sancak; Howard Hughes Medical Institute David E Clapham NR 14 TC 51 Z9 52 U1 0 U2 3 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 4 PY 2013 VL 2 AR e00704 DI 10.7554/eLife.00704 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274OP UT WOS:000328616200004 PM 23755363 ER PT J AU Tilly, JL Sinclair, DA AF Tilly, Jonathan L. Sinclair, David A. TI Germline Energetics, Aging, and Female Infertility SO CELL METABOLISM LA English DT Review ID ASSISTED REPRODUCTIVE TECHNOLOGIES; MUSCLE MITOCHONDRIAL-FUNCTION; CALORIE RESTRICTION; STEM-CELLS; HUMAN OOCYTES; MATERNAL AGE; LIFE-SPAN; CHROMOSOME-ABNORMALITIES; MOUSE OOCYTES; HUMAN EMBRYOS AB The role of metabolism in ovarian aging is poorly described, despite the fact that ovaries fail earlier than most other organs. Growing interest in ovarian function is being driven by recent evidence that mammalian females routinely generate new oocytes during adult life through the activity of germline stem cells. In this perspective, we overview the female reproductive system as a powerful and clinically relevant model to understand links between aging and metabolism, and we discuss new concepts for how oocytes and their precursor cells might be altered metabolically to sustain or increase ovarian function and fertility in women. C1 [Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Tilly, Jonathan L.] Harvard Univ, Dept Obstet Gynecol & Reprod Biol, Sch Med, Boston, MA 02115 USA. [Sinclair, David A.] Harvard Univ, Glenn Labs Biol Mech Aging, Sch Med, Boston, MA 02115 USA. [Sinclair, David A.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. [Sinclair, David A.] Univ New S Wales, Sydney, NSW 2052, Australia. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM jtilly@partners.org; david_sinclair@hms.harvard.edu OI Sinclair, David/0000-0002-9936-436X FU Method to Extend Research in Time (MERIT) Award from the National Institute on Aging [NIH R37-AG012279]; Glenn Foundation for Medical Research; Henry and Vivian Rosenberg Philanthropic Fund; NIH [R01-AG028730]; Ellison Medical Foundation; Juvenile Diabetes Foundation; United Mitochondrial Disease Foundation FX Work conducted by the lab of J.L.T. was supported by a Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (NIH R37-AG012279), the Glenn Foundation for Medical Research, and the Henry and Vivian Rosenberg Philanthropic Fund. Work conducted by the lab of D. A. S. was supported by NIH grant R01-AG028730, the Ellison Medical Foundation, the Glenn Foundation for Medical Research, the Juvenile Diabetes Foundation, the United Mitochondrial Disease Foundation, and a philanthropic gift from R. Shulsky-David. The authors thank D. C. Woods for helpful discussions and citation of work from preliminary studies conducted with J.L.T. Interest is declared by J.L.T. in intellectual property described in U. S. Patent 7,955,846, related to work discussed herein; J.L.T. and D. A. S. are cofounders of OvaScience, Inc. (Cambridge, MA); D. A. S. is a cofounder of and consultant to Cohbar (Washington, DC) and Sirtris, a GlaxoSmithKline company (Cambridge, MA). NR 158 TC 32 Z9 35 U1 1 U2 27 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JUN 4 PY 2013 VL 17 IS 6 BP 838 EP 850 DI 10.1016/j.cmet.2013.05.007 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242UC UT WOS:000326266900008 PM 23747243 ER PT J AU Ezzat, S Zheng, L Florez, JC Stefan, N Mayr, T Hliang, MM Jablonski, K Harden, M Stancakova, A Laakso, M Haring, HU Ullrich, A Asa, SL AF Ezzat, Shereen Zheng, Lei Florez, Jose C. Stefan, Norbert Mayr, Thomas Hliang, Maw Maw Jablonski, Kathleen Harden, Maegan Stancakova, Alena Laakso, Markku Haring, Hans-Ulrich Ullrich, Axel Asa, Sylvia L. TI The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes SO CELL METABOLISM LA English DT Article ID GROWTH-FACTOR RECEPTOR-4; ADAPTER PROTEIN GRB14; FGFR4 ARG388 ALLELE; BETA-CELL FUNCTION; BREAST-CANCER; SUSCEPTIBILITY LOCI; ARG(388) ALLELE; FACTOR-I; PROGRESSION; ACTIVATION AB The fibroblast growth factor receptor 4 (FGFR4)-R388 single-nucleotide polymorphism has been associated with cancer risk and prognosis. Here we show that the FGFR4-R388 allele yields a receptor variant that preferentially promotes STAT3/5 signaling. This STAT activation transcriptionally induces Grb14 in pancreatic endocrine cells to promote insulin secretion. Knockin mice with the FGFR4 variant allele develop pancreatic islets that secrete more insulin, a feature that is reversed through Grb14 deletion and enhanced with FGF19 administration. We also show in humans that the FGFR4-R388 allele enhances islet function and may protect against type 2 diabetes. These data support a common genetic link underlying cancer and hyperinsulinemia. C1 [Ezzat, Shereen; Zheng, Lei; Hliang, Maw Maw; Asa, Sylvia L.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res & Diabet, Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.; Harden, Maegan] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02142 USA. [Stefan, Norbert; Haring, Hans-Ulrich] Univ Tubingen, D-72076 Tubingen, Germany. [Mayr, Thomas; Ullrich, Axel] Max Planck Inst Biochem, Dept Mol Biol, D-82152 Martinsried, Germany. [Jablonski, Kathleen] George Washington Univ, Biostat Ctr, Rockville, MD 20852 USA. [Stancakova, Alena; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland. RP Ezzat, S (reprint author), Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. EM shereen.ezzat@utoronto.ca OI Stefan, Norbert/0000-0002-2186-9595 FU Canadian Institutes of Health Research [CIHR-MOP-125981]; Raymond and Beverly Sackler Foundation; Ontario Ministry of Health and Long-Term Care (OMHLTC); Heisenberg-Grant from the Deutsche Forschungsgemeinschaft [STE 1096/1-1]; Academy of Finland; Finnish Diabetes Research Foundation; Finnish Cardiovascular Research Foundation; EVO grant from the Kuopio University Hospital [5263]; [R01 DK072041] FX The authors would like to thank Anastasia Diamandis for technical assistance and Vuk Stambolic for helpful discussions. This work was supported by the Canadian Institutes of Health Research (CIHR-MOP-125981), the Raymond and Beverly Sackler Foundation, and the Ontario Ministry of Health and Long-Term Care (OMHLTC). The views expressed do not necessarily reflect those of the OMHLTC. N.S. is supported by a Heisenberg-Grant from the Deutsche Forschungsgemeinschaft (STE 1096/1-1). M. L. is supported by the Academy of Finland, the Finnish Diabetes Research Foundation, The Finnish Cardiovascular Research Foundation, and an EVO grant from the Kuopio University Hospital (5263). Genetic studies in the DPP are funded by R01 DK072041 to J.C.F. J.C.F. has received consulting honoraria from Novartis, Lilly, and Pfizer. NR 57 TC 8 Z9 10 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JUN 4 PY 2013 VL 17 IS 6 BP 929 EP 940 DI 10.1016/j.cmet.2013.05.002 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242UC UT WOS:000326266900016 PM 23747250 ER PT J AU Csordas, G Golenar, T Seifert, EL Kamer, KJ Sancak, Y Perocchi, F Moffat, C Weaver, D Perez, SD Bogorad, R Koteliansky, V Adijanto, J Mootha, VK Hajnoczky, GR AF Csordas, Gyoergy Golenar, Tuende Seifert, Erin L. Kamer, Kimberli J. Sancak, Yasemin Perocchi, Fabiana Moffat, Cynthia Weaver, David Perez, Sergio de la Fuente Bogorad, Roman Koteliansky, Victor Adijanto, Jeffrey Mootha, Vamsi K. Hajnoczky, Gyoergy TI MICU1 Controls Both the Threshold and Cooperative Activation of the Mitochondrial Ca2+ Uniporter SO CELL METABOLISM LA English DT Article ID RAT-LIVER MITOCHONDRIA; ENDOPLASMIC-RETICULUM; CALCIUM UNIPORTER; ESSENTIAL COMPONENT; INNER MEMBRANE; CHANNELS; SIGNALS; METABOLISM; PROTEIN; MECHANISMS AB Mitochondrial Ca2+ uptake via the uniporter is central to cell metabolism, signaling, and survival. Recent studies identified MCU as the uniporter's likely pore and MICU1, an EF-hand protein, as its critical regulator. How this complex decodes dynamic cytoplasmic [Ca2+] ([Ca2+](c)) signals, to tune out small [Ca2+](c) increases yet permit pulse transmission, remains unknown. We report that loss of MICU1 in mouse liver and cultured cells causes mitochondrial Ca2+ accumulation during small [Ca2+](c) elevations but an attenuated response to agonist-induced [Ca2+](c) pulses. The latter reflects loss of positive cooperativity, likely via the EF-hands. MICU1 faces the intermembrane space and responds to [Ca2+](c) changes. Prolonged MICU1 loss leads to an adaptive increase in matrix Ca2+ binding, yet cells show impaired oxidative metabolism and sensitization to Ca2+ overload. Collectively, the data indicate that MICU1 senses the [Ca2+](c) to establish the uniporter's threshold and gain, thereby allowing mitochondria to properly decode different inputs. C1 [Csordas, Gyoergy; Golenar, Tuende; Seifert, Erin L.; Moffat, Cynthia; Weaver, David; Perez, Sergio de la Fuente; Adijanto, Jeffrey; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Kamer, Kimberli J.; Sancak, Yasemin; Perocchi, Fabiana; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sancak, Yasemin; Perocchi, Fabiana; Mootha, Vamsi K.] Harvard Univ, Dept Syst Biol, Med Sch &, Cambridge, MA 02142 USA. [Sancak, Yasemin; Perocchi, Fabiana; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Bogorad, Roman] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Koteliansky, Victor] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA. [Perocchi, Fabiana] Univ Munich, Gene Ctr, D-81377 Munich, Germany. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu; gyorgy.hajnoczky@jefferson.edu OI Kamer, Kimberli/0000-0001-8728-7793 FU NIH [DK080261, DK051526] FX We thank Olga Goldberger for technical assistance, and B. R. Bettencourt, K. Charisse, S. Kuchimanchi, and A. Akinc of Alnylam Pharmaceuticals for siRNA design, synthesis, and formulation. This work was supported by NIH grants DK080261 (to V. K. M.) and DK051526 (to G. H.). V. K. was formerly an employee at and received compensation from Alnylam Pharmaceuticals. NR 48 TC 104 Z9 107 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JUN 4 PY 2013 VL 17 IS 6 BP 976 EP 987 DI 10.1016/j.cmet.2013.04.020 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242UC UT WOS:000326266900020 PM 23747253 ER PT J AU DesRoches, CM Audet, AM Painter, M Donelan, K AF DesRoches, Catherine M. Audet, Anne-Marie Painter, Michael Donelan, Karen TI Meeting Meaningful Use Criteria and Managing Patient Populations A National Survey of Practicing Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ELECTRONIC HEALTH RECORD; CARE; INCENTIVES; SYSTEMS AB Background: Meaningful use, as defined by the Centers for Medicare & Medicaid Services, will require the aggregation of patient data to enable population assessment. Little is known about the proportion of physicians who are able to meet meaningful use criteria or their use of electronic health records (EHRs) to manage patient populations. Objective: To evaluate physicians' reports of EHR adoption and ease of use and their ability to use EHRs for patient panel management. Design: National mailed survey of practicing physicians (response rate of 60%). Setting: Late 2011 and early 2012. Participants: 1820 primary care physicians and specialists in office-based practices. Measurements: Proportion of physicians who have a basic EHR and meet meaningful use criteria and ease of use of computerized systems designed for patient population management tasks. Results: A total of 43.5% of physicians reported having a basic EHR, and 9.8% met meaningful use criteria. Computerized systems for managing patient populations were not widespread; fewer than one half of respondents reported the presence of computerized systems for any of the patient population management tasks included in the survey. Physicians with such functionalities reported that these systems varied in ease of use. Physicians with an EHR that met meaningful use criteria were significantly more likely than those not meeting the standard to rate panel management tasks as easy. Limitation: Ease-of-use measures are subjective. Conclusion: Few physicians could meet meaningful use criteria in early 2012 and using computerized systems for the panel management tasks was difficult. Results support the growing evidence that using the basic data input capabilities of an EHR does not translate into the greater opportunity that these technologies promise. C1 [DesRoches, Catherine M.] Mathemat Policy Res, Cambridge, MA 02139 USA. Commonwealth Fund, New York, NY USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP DesRoches, CM (reprint author), Mathemat Policy Res, 955 Massachusetts Ave,Suite 800, Cambridge, MA 02139 USA. EM cdesroches@mathematica-mpr.com FU Robert Wood Johnson Foundation [68812]; Commonwealth Fund [20110087] FX By the Robert Wood Johnson Foundation (grant 68812) and the Commonwealth Fund (grant 20110087). NR 22 TC 29 Z9 29 U1 1 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 4 PY 2013 VL 158 IS 11 BP 791 EP + DI 10.7326/0003-4819-158-11-201306040-00003 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 164AA UT WOS:000320379800002 PM 23732712 ER PT J AU Kalantarian, S Ruskin, JN AF Kalantarian, Shadi Ruskin, Jeremy N. TI Cognitive Impairment Associated With Atrial Fibrillation RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Kalantarian, Shadi; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kalantarian, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 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 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 4 PY 2013 VL 158 IS 11 BP 849 EP 849 DI 10.7326/0003-4819-158-11-201306040-00016 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 164AA UT WOS:000320379800012 PM 23732721 ER PT J AU Hsu, JC Li, YM Marcus, GM Hsue, PY Scherzer, R Grunfeld, C Shlipak, MG AF Hsu, Jonathan C. Li, Yongmei Marcus, Gregory M. Hsue, Priscilla Y. Scherzer, Rebecca Grunfeld, Carl Shlipak, Michael G. TI Atrial Fibrillation and Atrial Flutter in Human Immunodeficiency Virus-Infected Persons Incidence, Risk Factors, and Association With Markers of HIV Disease Severity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE arrhythmia; atrial fibrillation; epidemiology; HIV infection; risk factors ID ANTIRETROVIRAL THERAPY ERA; CARDIOVASCULAR EVENTS; KIDNEY-FUNCTION; LIFETIME RISK; HEART; INFLAMMATION; PREVALENCE; VETERANS; COHORT; ATHEROSCLEROSIS AB Objectives The purpose of this study was to investigate the associations of traditional risk factors and longitudinal measures of human immunodeficiency virus (HIV) disease severity with risk of incident atrial fibrillation (AF) in a contemporary cohort of HIV-infected individuals. Background Cardiovascular disease is common in HIV-infected persons; however, the most common cardiac arrhythmia, AF, has not been adequately studied in this population. Methods We studied a national sample of 30,533 HIV-infected veterans followed in the Veterans Affairs HIV Clinical Case Registry from 1996 to 2011. We examined the independent associations of demographic characteristics, time-updated comorbidities, and time-updated clinical measurements including CD4(+) cell count and viral load with the outcome of incident AF using proportional hazards regression for multivariable analysis. Results Over a median follow-up of 6.8 years, 780 (2.6%) patients developed AF. After multivariable adjustment for traditional risk factors, a lower CD4(+) cell count (<200 compared with >350 cells/mm(3); hazard ratio [HR]: 1.4; 95% confidence interval [CI]: 1.1 to 1.8; p = 0.018) and higher viral load (>100,000 compared with <500 copies/ml; HR: 1.7; 95% CI: 1.2 to 2.4; p = 0.002) were independently associated with increased risk of incident AF. Additional risk factors independently associated with risk of AF included older age, White race, coronary artery disease, congestive heart failure, alcoholism, proteinuria, reduced kidney function, and hypothyroidism. Conclusions In a large HIV-infected cohort, markers of HIV disease severity represented by low CD4(+) cell count and high viral load, assessed by multiple time-updated measures, were independently associated with development of AF. (C) 2013 by the American College of Cardiology Foundation C1 [Hsu, Jonathan C.; Marcus, Gregory M.] Univ Calif San Francisco, Sect Cardiac Electrophysiol, Div Cardiol, Dept Med, San Francisco, CA 94143 USA. [Li, Yongmei; Scherzer, Rebecca; Grunfeld, Carl; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Li, Yongmei; Scherzer, Rebecca; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hsue, Priscilla Y.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. RP Hsu, JC (reprint author), Univ Calif San Francisco, Sect Cardiac Electrophysiol, Div Cardiol, Dept Med, 500 Parnassus Ave,MUE 434,Box 1354, San Francisco, CA 94143 USA. EM jonhsumd@gmail.com OI Hsu, Jonathan/0000-0002-1523-573X FU National Institutes of Health, University of California, San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research [P30-AI027763]; St. Jude Medical; Baylis; Medical, Gilead; SentreHeart Inc; Tobira FX This research was supported by a grant from the National Institutes of Health, University of California, San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research, P30-AI027763. Dr. Marcus receives speaker's fees from St. Jude Medical; is a consultant for InCarda; and receives research support from Baylis; Medical, Gilead, and SentreHeart Inc. Dr. Hsue is an advisor for Gilead and Pfizer; and has received research support from Tobira. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 33 TC 20 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 4 PY 2013 VL 61 IS 22 BP 2288 EP 2295 DI 10.1016/j.jacc.2013.03.022 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 166ZV UT WOS:000320600700010 PM 23563125 ER PT J AU Zhao, LB Lu, YT Li, FQ Wu, K Hou, S Yu, JH Shen, QL Wu, DX Song, M OuYang, WH Luo, Z Lee, T Fang, XH Shao, C Xu, X Garcia, MA Chung, LWK Rettig, M Tseng, HR Posadas, EM AF Zhao, Libo Lu, Yi-Tsung Li, Fuqiang Wu, Kui Hou, Shuang Yu, Juehua Shen, Qinglin Wu, Dongxia Song, Min OuYang, Wei-Han Luo, Zheng Lee, Tom Fang, Xiaohong Shao, Chen Xu, Xun Garcia, Mitch A. Chung, Leland W. K. Rettig, Matthew Tseng, Hsian-Rong Posadas, Edwin M. TI High-Purity Prostate Circulating Tumor Cell Isolation by a Polymer Nanofiber-Embedded Microchip for Whole Exome Sequencing SO ADVANCED MATERIALS LA English DT Article DE electrospun nanomaterials; microfluidics; circulating tumor cell; whole exome sequencing; prostate cancer ID CANCER PATIENTS; BREAST-CANCER; CAPTURE; PROGRESSION; ENRICHMENT; BLOOD C1 [Zhao, Libo; Fang, Xiaohong] Chinese Acad Sci, Key Lab Mol Nanostruct & Nanotechnol, Inst Chem, Beijing 100190, Peoples R China. [Lu, Yi-Tsung; Chung, Leland W. K.; Posadas, Edwin M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Med, Urol Oncol Program, Los Angeles, CA 90048 USA. [Lu, Yi-Tsung; Chung, Leland W. K.; Posadas, Edwin M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Med, Urooncol Res Program, Los Angeles, CA 90048 USA. [Zhao, Libo; Hou, Shuang; Yu, Juehua; Shen, Qinglin; Wu, Dongxia; Song, Min; Luo, Zheng; Lee, Tom; Tseng, Hsian-Rong] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, CIMI, CNSI, Los Angeles, CA 90095 USA. [Rettig, Matthew] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Los Angeles, CA 90095 USA. [Rettig, Matthew] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90095 USA. [Rettig, Matthew] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA USA. [Li, Fuqiang; Wu, Kui; Xu, Xun] BGI ShenZhen, Shenzhen 518083, Peoples R China. [OuYang, Wei-Han; Garcia, Mitch A.] CytoLumina Technol Corp, Walnut, CA 91789 USA. [Shao, Chen] Fourth Mil Med Univ, Dept Urol, Xijing Hosp, Xian 710032, Peoples R China. RP Xu, X (reprint author), BGI ShenZhen, 2nd F,Bldg 11, Shenzhen 518083, Peoples R China. EM xuxun@genomics.cn; mgarcia@cytolumina.com; Leland.Chung@cshs.org; MRettig@mednet.ucla.edu; HRTseng@mednet.ucla.edu; Edwin.Posadas@csmc.edu RI Tseng, Hsian-Rong/G-2222-2010; Zhao, Libo/G-2421-2010 FU NIH/NCI [R21 CA151159, R33 CA157396]; DoD Idea Award [W81XWH-11-1-0422]; PCF Young Investigator Award; Prostate Cancer Foundation (PCF) FX The research endeavors at UCLA were supported by a Creativity Award from Prostate Cancer Foundation (PCF), and research grants (R21 CA151159 and R33 CA157396) from NIH/NCI Innovative Molecular Analysis Technologies (IMAT) Program. The research endeavors at Cedars Sinai Medical Center were supported by DoD Idea Award (W81XWH-11-1-0422) and PCF Young Investigator Award. NR 26 TC 58 Z9 59 U1 14 U2 160 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD JUN 4 PY 2013 VL 25 IS 21 BP 2897 EP 2902 DI 10.1002/adma.201205237 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 157MG UT WOS:000319899700002 PM 23529932 ER PT J AU Viswanathan, J Haapasalo, A Kurkinen, KMA Natunen, T Makinen, P Bertram, L Soininen, H Tanzi, RE Hiltunen, M AF Viswanathan, Jayashree Haapasalo, Annakaisa Kurkinen, Kaisa M. A. Natunen, Teemu Makinen, Petra Bertram, Lars Soininen, Hilkka Tanzi, Rudolph E. Hiltunen, Mikko TI Ubiquilin-1 Modulates gamma-Secretase-Mediated epsilon-Site Cleavage in Neuronal Cells SO BIOCHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; PRESENILIN/GAMMA-SECRETASE; TRANSMEMBRANE DOMAIN; INTRACELLULAR DOMAIN; ALZHEIMERS-DISEASE; NOTCH; APP; FE65; PROTEASOME; INTERACTS AB Ubiquilin-1 is an Alzheimer's disease-associated protein, which is known to modulate amyloid precursor protein (APP) processing, amyloid-beta (A beta) secretion, and presenilin-1 (PS1) accumulation. Here, we aim to elucidate the molecular mechanisms by which full-length transcript variant 1 of ubiquilin-1 (TV1) affects APP processing and gamma-secretase function in human neuroblastoma cells stably overexpressing APP (SH-SY5Y-APP751). We found that TV1 overexpressing significant increased the level of APP intracellular domain (AICD) generation. However, there was no increase in the levels of secreted A beta 40, A beta 42, or total A beta, suggesting that ubiquilin-1 in particular enhances gamma-secretase-mediated epsilon-site cleavage. This is supported by the finding that TV1 also significantly increased the level of intracellular domain generation of another gamma-secretase substrate, leukocyte common antigen-related (LAR) phosphatase. However, in these cells, the increase in AICD levels was abolished, suggesting a preference of the gamma-secretase for LAR over APP. TV2, another ubiquilin-1 variant that lacks the protein fragment encoded by exon 8, did not increase the level of AICD generation like TV1 did. The subcellular and plasma membrane localization of APP or gamma-secretase complex components PS1 and nicastrin was not altered in TV1-overexpressing cells. Moreover, the effects of TV1 were not mediated by altered expression or APP binding of FE6S, an adaptor protein thought to regulate AICD generation and stability. These data suggest that ubiquilin-1 modulates gamma-secretase-mediated epsilon-site cleave and thus may play role in regulating gamma-secretase cleavage of various substrates. C1 [Viswanathan, Jayashree; Haapasalo, Annakaisa; Kurkinen, Kaisa M. A.; Natunen, Teemu; Makinen, Petra; Soininen, Hilkka; Hiltunen, Mikko] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio 70211, Finland. [Viswanathan, Jayashree; Haapasalo, Annakaisa; Kurkinen, Kaisa M. A.; Natunen, Teemu; Makinen, Petra; Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Hiltunen, M (reprint author), Univ Eastern Finland, Inst Clin Med Neurol, POB 1627, Kuopio 70211, Finland. EM mikko.hiltunen@uef.fi RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU EC FP6; Health Research Council of the Academy of Finland; EVO of Kuopio University Hospital [5772708]; Cure Alzheimer's Fund; Sigrid Juselius Foundation; strategic funding of the University of Eastern Finland (UEF-Brain); [MEST-CT-2005-019217] FX This study was supported by EC FP6, MEST-CT-2005-019217, the Health Research Council of the Academy of Finland, EVO Grant 5772708 of Kuopio University Hospital, Cure Alzheimer's Fund, Sigrid Juselius Foundation, and the strategic funding of the University of Eastern Finland (UEF-Brain). NR 48 TC 6 Z9 6 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 4 PY 2013 VL 52 IS 22 BP 3899 EP 3912 DI 10.1021/bi400138p PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160DM UT WOS:000320097200012 PM 23663107 ER PT J AU Wylie, BJ Kalilani-Phiri, L Madanitsa, M Membe, G Nyirenda, O Mawindo, P Kuyenda, R Malenga, A Masonbrink, A Makanani, B Thesing, P Laufer, MK AF Wylie, Blair J. Kalilani-Phiri, Linda Madanitsa, Mwayi Membe, Gladys Nyirenda, Osward Mawindo, Patricia Kuyenda, Redson Malenga, Albert Masonbrink, Abbey Makanani, Bonus Thesing, Phillip Laufer, Miriam K. TI Gestational age assessment in malaria pregnancy cohorts: a prospective ultrasound demonstration project in Malawi SO MALARIA JOURNAL LA English DT Article DE Malaria in pregnancy; Ultrasound; Foetal biometry; Preterm delivery; Small for gestational age; Ballard examination ID LOCAL HEALTH-WORKERS; THAI-BURMESE BORDER; FALCIPARUM-MALARIA; BIRTH-WEIGHT; DIAMETER MEASUREMENT; NEWBORN-INFANT; BALLARD SCORE; MENSTRUAL AGE; FETAL-GROWTH; REFUGEE CAMP AB Background: Malaria during pregnancy is associated with an increased risk for low birth weight (< 2500 grams). Distinguishing infants that are born premature (< 37 weeks) from those that are growth-restricted (less than the 10th percentile at birth) requires accurate assessment of gestational age. Where ultrasound is accessible, sonographic confirmation of gestational age is more accurate than menstrual dating. The goal was to pilot the feasibility and utility of adding ultrasound to an observational pregnancy malaria cohort. Methods: In July 2009, research staff (three mid-level clinical providers, one nurse) from The Blantyre Malaria Project underwent an intensive one-week ultrasound training to perform foetal biometry. Following an additional four months of practice and remote image review, subjects from an ongoing cohort were recruited for ultrasound to determine gestational age. Gestational age at delivery established by ultrasound was compared with postnatal gestational age assessment (Ballard examination). Results: One hundred and seventy-eight women were enrolled. The majority of images were of good quality (94.3%, 509/540) although a learning curve was apparent with 17.5% (24/135) images of unacceptable quality in the first 25% of scans. Ultrasound was used to date 13% of the pregnancies when menstrual dates were unknown and changed the estimated gestational age for an additional 25%. There was poor agreement between the gestational age at delivery as established by the ultrasound protocol compared to that determined by the Ballard examination (bias 0.8 weeks, limits of agreement -3.5 weeks to 5.1 weeks). The distribution of gestational ages by Ballard suggested a clustering of gestational age around the mean with 87% of the values falling between 39 and 41 weeks. The distribution of gestational age by ultrasound confirmed menstrual dates was more typical. Using ultrasound confirmed dates as the gold standard, 78.5% of preterm infants were misclassified as term and 26.8% of small-for gestational age infants misclassified as appropriately grown by Ballard. Conclusion: Ultrasound should be strongly considered in prospective malaria studies with obstetric endpoints to confirm gestational age and avoid misclassification of infants as premature or growth-restricted. The use of ultrasound does require a significant investment of time to maintain quality image acquisition. C1 [Wylie, Blair J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Kalilani-Phiri, Linda; Madanitsa, Mwayi; Membe, Gladys; Makanani, Bonus] Univ Malawi, Coll Med, Blantyre, Malawi. [Nyirenda, Osward; Mawindo, Patricia; Kuyenda, Redson; Malenga, Albert; Thesing, Phillip] Queen Elizabeth Cent Hosp, Blantyre Malaria Project, Blantyre 3, Malawi. [Masonbrink, Abbey; Thesing, Phillip] New York Dept Hlth, New York, NY USA. [Thesing, Phillip] City Cincinnati Hlth Dept, Cincinnati, OH USA. [Masonbrink, Abbey; Laufer, Miriam K.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Massachusetts 55 Fruit St Boston, Boston, MA 02114 USA. EM bwylie@partners.org FU Doris Duke Charitable Foundation [2008042]; National Institutes of Health [K23 ES021471]; SoundCaring Program (Sonosite(TM), Inc, Bothell, Washington, USA) FX The ultrasound machine used during the project was donated by the Vincent Department of Obstetrics and Gynecology at the Massachusetts General Hospital with a matching grant from the SoundCaring Program (Sonosite (TM), Inc, Bothell, Washington, USA). Research was supported by the Doris Duke Charitable Foundation grant number 2008042 (to MKL) and by the National Institutes of Health grant number K23 ES021471 (to BJW). We are especially grateful to the pregnant women who participated in this trial and have supported our work at the Ndirande research clinic for over a decade. NR 42 TC 8 Z9 8 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD JUN 4 PY 2013 VL 12 AR 183 DI 10.1186/1475-2875-12-183 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 160LO UT WOS:000320121200001 PM 23734718 ER PT J AU Hamilton, RT Bhattacharya, A Walsh, ME Shi, Y Wei, R Zhang, YQ Rodriguez, KA Buffenstein, R Chaudhuri, AR Van Remmen, H AF Hamilton, Ryan T. Bhattacharya, Arunabh Walsh, Michael E. Shi, Yun Wei, Rochelle Zhang, Yiqiang Rodriguez, Karl A. Buffenstein, Rochelle Chaudhuri, Asish R. Van Remmen, Holly TI Elevated Protein Carbonylation, and Misfolding in Sciatic Nerve from db/db and Sod1(-/-) Mice: Plausible Link between Oxidative Stress and Demyelination SO PLOS ONE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PERIPHERAL MYELIN PROTEIN-22; ALDOSE REDUCTASE INHIBITION; ALZHEIMERS-DISEASE BRAIN; DIABETIC-NEUROPATHY; LIPID-PEROXIDATION; SKELETAL-MUSCLE; CONDUCTION-VELOCITY; NITROSATIVE STRESS; ADVANCED GLYCATION AB Diabetic peripheral polyneuropathy is associated with decrements in motor/sensory neuron myelination, nerve conduction and muscle function; however, the mechanisms of reduced myelination in diabetes are poorly understood. Chronic elevation of oxidative stress may be one of the potential determinants for demyelination as lipids and proteins are important structural constituents of myelin and highly susceptible to oxidation. The goal of the current study was to determine whether there is a link between protein oxidation/misfolding and demyelination. We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1 2/2) mouse model of in vivo oxidative stress. Both experimental models displayed a significant decrement in nerve conduction, increase in tail distal motor latency as well as reduced myelin thickness and fiber/axon diameter. Further biochemical studies demonstrated that oxidative stress is likely to be a potential key player in the demyelination process as both models exhibited significant elevation in protein carbonylation and alterations in protein conformation. Since peripheral myelin protein 22 (PMP22) is a key component of myelin sheath and has been found mutated and aggregated in several peripheral neuropathies, we predicted that an increase in carbonylation and aggregation of PMP22 may be associated with demyelination in dbdb mice. Indeed, PMP22 was found to be carbonylated and aggregated in sciatic nerves of dbdb mice. Sequence-driven hydropathy plot analysis and in vitro oxidation-induced aggregation of purified PMP22 protein supported the premise for oxidation-dependent aggregation of PMP22 in dbdb mice. Collectively, these data strongly suggest for the first time that oxidation-mediated protein misfolding and aggregation of key myelin proteins may be linked to demyelination and reduced nerve conduction in peripheral neuropathies. C1 [Hamilton, Ryan T.; Bhattacharya, Arunabh; Walsh, Michael E.; Shi, Yun; Zhang, Yiqiang; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Rodriguez, Karl A.; Buffenstein, Rochelle; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hamilton, Ryan T.; Bhattacharya, Arunabh; Shi, Yun; Wei, Rochelle; Zhang, Yiqiang; Rodriguez, Karl A.; Buffenstein, Rochelle; Chaudhuri, Asish R.; Van Remmen, Holly] Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Chaudhuri, Asish R.; Van Remmen, Holly] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Chaudhuri, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM chaudhuria@uthscsa.edu; vanremmen@uthscsa.edu FU National Service Research Award; Program project at the National Institute of Aging [AG20591]; University of Michigan Grant; Go Grant at the National institute of Aging project [RCA2AG036613]; Glenn Award (Research in Biological Mechanisms of Aging); Ellison Medical Foundation [AGSS-178006]; Glenn Foundation for Medical Research FX Funding provided by T32 AG021890-08 (NIA) National Service Research Award to Postdoctoral Fellow Training Grant on the Biology of Aging to Steven N. Austad for trainees (RTH, KAR) AG20591 Program project at the National Institute of Aging (HV) (Project 2: Does Superoxide-Induced Mitochondrial Dysfunction Lead to Muscle Atrophy?) University of Michigan Grant (Subcontract), RCA2AG036613 Go Grant at the National institute of Aging project 8 (WW and HV) (Effect of rapa on removal of protein by the autophagic and/or proteasomal pathways) under (AR) (Can rapamycin retard aging?), Glenn Award (Research in Biological Mechanisms of Aging) (http://glennfoundation.org/), AGSS-178006 (RB is PI) Ellison Medical Foundation (Genomic Stability in the Naked Mole-Rat: A Role for Cancer Resistance and Extended Longevity) (http://www.ellisonfoundation.org/), and Glenn Foundation for Medical Research (RB is PI). (Comparative biological mechanisms of aging, insights from the longest lived rodent, the naked mole-rat) (http://glennfoundation.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 17 Z9 17 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 4 PY 2013 VL 8 IS 6 AR e65725 DI 10.1371/journal.pone.0065725 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 158IE UT WOS:000319961900075 PM 23750273 ER PT J AU Jiang, W Zhang, DH Bursac, N Zhang, Y AF Jiang, Wei Zhang, Donghui Bursac, Nenad Zhang, Yi TI WNT3 Is a Biomarker Capable of Predicting the Definitive Endoderm Differentiation Potential of hESCs SO STEM CELL REPORTS LA English DT Article ID EMBRYONIC STEM-CELLS; INSULIN-PRODUCING CELLS; EFFICIENT DIFFERENTIATION; PROGENITORS; PROPENSITY; EXPRESSION; LINES AB Generation of functional cells from human pluripotent stem cells (PSCs) through in vitro differentiation is a promising approach for drug screening and cell therapy. However, the observed large and unavoidable variation in the differentiation potential of different human embryonic stem cell (hESC)/induced PSC (iPSC) lines makes the selection of an appropriate cell line for the differentiation of a particular cell lineage difficult. Here, we report identification of WNT3 as a biomarker capable of predicting definitive endoderm (DE) differentiation potential of hESCs. We show that the mRNA level of WNT3 in hESCs correlates with their DE differentiation efficiency. In addition, manipulations of hESCs through WNT3 knockdown or overexpression can respectively inhibit or promote DE differentiation in a WNT3 level-dependent manner. Finally, analysis of several hESC lines based on their WNT3expression levels allowed accurate prediction of their DE differentiation potential. Collectively, our study supports the notion that WNT3 can serve as a biomarker for predicting DE differentiation potential of hESCs. C1 [Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Zhang, Donghui; Bursac, Nenad] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. RP Jiang, W (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 25 Shattuck St, Boston, MA 02115 USA. EM wei.jiang@childrens.harvard.edu; yzhang@genetics.med.harvard.edu RI Jiang, Wei/J-7993-2012; zhang, donghui/I-5130-2013 OI Jiang, Wei/0000-0002-6463-7356; FU NIH [U01-DK089565, R01-HL104326, R21-HL095069]; JDRF postdoctoral fellowship FX We thank Dr. Edouard Stanley (Monash University) for the MEL-1 (MG3) and HES3 cell lines, Dr. Sean Wu (Stanford University) for the iPSC JT16 line, and Mr. Damian Sendler for a critical reading of the manuscript. This work was supported by NIH grants U01-DK089565 to Y.Z. and R01-HL104326 and R21-HL095069 to N.B. W.J. is supported by a JDRF postdoctoral fellowship. Y.Z. is an investigator of the Howard Hughes Medical Institute. The authors declare no competing financial interests. NR 20 TC 20 Z9 21 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD JUN 4 PY 2013 VL 1 IS 1 BP 46 EP 52 DI 10.1016/j.stemcr.2013.03.003 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1SI UT WOS:000336632000007 PM 24052941 ER PT J AU Ascierto, PA Grimaldi, AM Acquavella, N Borgognoni, L Calabro, L Cascinelli, N Cesano, A Del Vecchio, M Eggermont, AM Faries, M Ferrone, S Fox, BA Gajewski, TF Galon, J Gnjatic, S Gogas, H Kashani-Sabet, M Kaufman, HL Larkin, J Lo, RS Mantovani, A Margolin, K Melief, C McArthur, G Palmieri, G Puzanov, I Ribas, A Seliger, B Sosman, J Suenaert, P Tarhini, AA Trinchieri, G Vidal-Vanaclocha, F Wang, E Ciliberto, G Mozzillo, N Marincola, FM Thurin, M AF Ascierto, Paolo A. Grimaldi, Antonio M. Acquavella, Nicolas Borgognoni, Lorenzo Calabro, Luana Cascinelli, Natale Cesano, Alessandra Del Vecchio, Michele Eggermont, Alexander M. Faries, Mark Ferrone, Soldano Fox, Bernard A. Gajewski, Thomas F. Galon, Jerome Gnjatic, Sacha Gogas, Helen Kashani-Sabet, Mohammed Kaufman, Howard L. Larkin, James Lo, Roger S. Mantovani, Alberto Margolin, Kim Melief, Cornelis McArthur, Grant Palmieri, Giuseppe Puzanov, Igor Ribas, Antoni Seliger, Barbara Sosman, Jeff Suenaert, Peter Tarhini, Ahmad A. Trinchieri, Giorgio Vidal-Vanaclocha, Fernando Wang, Ena Ciliberto, Gennaro Mozzillo, Nicola Marincola, Francesco M. Thurin, Magdalena TI Future perspectives in melanoma research. Meeting report from the "Melanoma Bridge. Napoli, December 2nd-4th 2012" SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID ADJUVANT INTERFERON THERAPY; SENTINEL LYMPH-NODES; HIGH-RISK MELANOMA; RANDOMIZED CONTROLLED-TRIAL; STAGE-III MELANOMA; T-CELL RESPONSES; METASTATIC MELANOMA; ANTITUMOR-ACTIVITY; PEGYLATED INTERFERON-ALPHA-2B; BRAF(V600E) INHIBITION AB Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third "Melanoma Research: " A bridge from Naples to the World" meeting, shortened as " Bridge Melanoma Meeting" took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients. C1 [Ascierto, Paolo A.; Grimaldi, Antonio M.; Ciliberto, Gennaro; Mozzillo, Nicola] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy. [Acquavella, Nicolas] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Borgognoni, Lorenzo] SM Annunziata Hosp, Reg Melanoma Refferral Ctr, Florence, Italy. [Calabro, Luana] Univ Hosp Siena, Ist Toscano Tumori, Siena, Italy. [Cascinelli, Natale] WHO, Melanoma Program, Milan, Italy. [Cesano, Alessandra] Nodality Inc, San Francisco, CA USA. [Del Vecchio, Michele] Ist Nazl Tumori, Fdn IRCCS, Dept Med Oncol, I-20133 Milan, Italy. [Eggermont, Alexander M.] Canc Inst Gustave Roussy, Paris, France. [Faries, Mark] John Wayne Canc Inst, Santa Monica, CA USA. [Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Fox, Bernard A.] Providence Portland Med Ctr, Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Gajewski, Thomas F.] Univ Chicago, Chicago, IL 60637 USA. [Galon, Jerome] INSERM, Lab Integrat Canc Immunol, U872, F-75006 Paris, France. [Galon, Jerome] Univ Paris 05, Paris, France. [Galon, Jerome] Univ Paris 06, Ctr Rech Cordeliers, Paris, France. [Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA. [Gogas, Helen] Univ Athens, Sch Med, Dept Med 1, GR-11527 Athens, Greece. [Kashani-Sabet, Mohammed] Calif Pacific Med Ctr, Res Inst, Ctr Melanoma Res & Treatment, San Francisco, CA USA. [Kaufman, Howard L.] Rush Univ, Chicago, IL 60612 USA. [Larkin, James] Royal Marsden NHS Fdn Trust, London, England. [Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lo, Roger S.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Mantovani, Alberto] Humanitas Clin & Res Inst, Rozzano, Italy. [Margolin, Kim] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Melief, Cornelis] Leiden Univ, Med Ctr, Leiden, Netherlands. [Melief, Cornelis] ISA Pharmaceut, Leiden, Netherlands. [McArthur, Grant] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Tumor Immunol Programme, Los Angeles, CA 90095 USA. [Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06108 Halle, Germany. [Sosman, Jeff] Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN USA. [Suenaert, Peter] GlaxoSmithKline Vaccines, Global Early Clin Dev, Clin Immunotherapeut, Immunotherapeut, Rixensart, Belgium. [Tarhini, Ahmad A.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Vidal-Vanaclocha, Fernando] CEU San Pablo Univ, Inst Appl Mol Med IMMA, Madrid 28668, Spain. [Vidal-Vanaclocha, Fernando] HM Hosp, Sch Med, Madrid 28668, Spain. [Wang, Ena] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. [Thurin, Magdalena] NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. RP Ascierto, PA (reprint author), Fdn G Pascale, Ist Nazl Tumori, Naples, Italy. EM paolo.ascierto@gmail.com RI Del Vecchio, Michele/K-1584-2016; OI Palmieri, Giuseppe/0000-0002-4350-2276; Del Vecchio, Michele/0000-0001-9060-2512; Ciliberto, Gennaro/0000-0003-2851-8605; Mantovani, Alberto/0000-0001-5578-236X FU Cancer Research Institute/Ludwig Institute for Cancer Research Cancer Vaccine Collaborative FX The meeting was supported by Fondazione Melanoma Onlus and the Society of ImmunoTherapy of Cancer (SITC). A special thanks to 3P Solution of Napoli for their support and cooperation in organizing the meeting and to Michael Hoetzel for providing us with the group picture from the meeting. Sacha Gnjatic would like to acknowledge the Cancer Research Institute/Ludwig Institute for Cancer Research Cancer Vaccine Collaborative for grant support. All Authors would like to dedicate this manuscript to the memory of Natale Cascinelli who devoted his life to the research and care of melanoma patients and was an example for all of us. NR 115 TC 12 Z9 12 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 3 PY 2013 VL 11 AR 137 DI 10.1186/1479-5876-11-137 PG 28 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 162ZQ UT WOS:000320305200001 PM 23731854 ER PT J AU Menzaghi, C Bacci, S Salvemini, L Mendonca, C Palladino, G Fontana, A De Bonis, C Marucci, A Goheen, E Prudente, S Morini, E Rizza, S Kanagaki, A Fini, G Mangiacotti, D Federici, M De Cosmo, S Pellegrini, F Doria, A Trischitta, V AF Menzaghi, Claudia Bacci, Simonetta Salvemini, Lucia Mendonca, Christine Palladino, Giuseppe Fontana, Andrea De Bonis, Concetta Marucci, Antonella Goheen, Elizabeth Prudente, Sabrina Morini, Eleonora Rizza, Stefano Kanagaki, Alyssa Fini, Grazia Mangiacotti, Davide Federici, Massimo De Cosmo, Salvatore Pellegrini, Fabio Doria, Alessandro Trischitta, Vincenzo TI Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes SO PLOS ONE LA English DT Article ID CORONARY-ARTERY-DISEASE; HEART-DISEASE; MYOCARDIAL-INFARCTION; ADIPOSE-TISSUE; INSULIN-RESISTANCE; HORMONE RESISTIN; RISK; MARKER; ASSOCIATION; ADIPONECTIN AB Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. Results: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.101.64) and 1.99 (1.552.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.101.56) and all-cause mortality (HR per SD increment = 1.16; 1.061.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). Conclusions: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry. C1 [Menzaghi, Claudia; Salvemini, Lucia; Palladino, Giuseppe; De Bonis, Concetta; Marucci, Antonella; Morini, Eleonora; Fini, Grazia; Mangiacotti, Davide; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Bacci, Simonetta; De Cosmo, Salvatore] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy. [Mendonca, Christine; Goheen, Elizabeth; Kanagaki, Alyssa; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Fontana, Andrea; Pellegrini, Fabio] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy. [Prudente, Sabrina; Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Mendel Lab, Rome, Italy. [Rizza, Stefano; Federici, Massimo] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. [Pellegrini, Fabio] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Unit Biostat, I-66030 Santa Maria Imbaro, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. RP Menzaghi, C (reprint author), IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. EM c.menzaghi@operapadrepio.it; v.trischitta@operapadrepio.it RI Prudente, Sabrina/H-2886-2016; Fontana, Andrea/J-8584-2016; Trischitta, Vincenzo/K-1487-2016; Salvemini, Lucia/K-2121-2016; Federici, Massimo/G-9940-2012; marucci, antonella/B-8722-2017 OI Prudente, Sabrina/0000-0001-9220-8981; Menzaghi, Claudia/0000-0002-7438-8955; Fontana, Andrea/0000-0002-6660-5315; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; Salvemini, Lucia/0000-0001-8776-9477; Federici, Massimo/0000-0003-4989-5194; marucci, antonella/0000-0001-8131-8317 FU Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST; PO Puglia FESR; Italian Ministry of Health [RC2011, RC2012]; European Foundation for the Study of Diabetes/Pfizer; National Institutes of Health [HL073168]; EFSD/Pfizer FX This research was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006 and PO Puglia FESR 2007-2013, Italian Ministry of Health grants RC2011, RC2012, European Foundation for the Study of Diabetes/Pfizer grant (CM) and National Institutes of Health grant HL073168 (AD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; CM received funding from the EFSD/Pfizer. MF is a PLOS ONE Editorial Board member. 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. NR 40 TC 27 Z9 27 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 3 PY 2013 VL 8 IS 6 AR UNSP e64729 DI 10.1371/journal.pone.0064729 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157CD UT WOS:000319872300025 ER PT J AU Price, JC Pollock, LM Rudd, ML Fogoros, SK Mohamed, H Hanigan, CL Le Gallo, M Zhang, SY Cruz, P Cherukuri, PF Hansen, NF McManus, KJ Godwin, AK Sgroi, DC Mullikin, JC Merino, MJ Hieter, P Bell, DW AF Price, Jessica C. Pollock, Lana M. Rudd, Meghan L. Fogoros, Sarah K. Mohamed, Hassan Hanigan, Christin L. Le Gallo, Matthieu Zhang, Suiyuan Cruz, Pedro Cherukuri, Praveen F. Hansen, Nancy F. McManus, Kirk J. Godwin, Andrew K. Sgroi, Dennis C. Mullikin, James C. Merino, Maria J. Hieter, Philip Bell, Daphne W. CA NIH Intramural Sequencing Ctr NISC TI Sequencing of Candidate Chromosome Instability Genes in Endometrial Cancers Cancers Reveals Somatic Mutations in ESCO1, CHTF18, and MRE11A SO PLOS ONE LA English DT Article ID SISTER-CHROMATID COHESION; CTF18-REPLICATION FACTOR-C; ANTIGEN LOADER COMPLEX; DNA MISMATCH REPAIR; MICROSATELLITE INSTABILITY; S-PHASE; SACCHAROMYCES-CEREVISIAE; COLORECTAL CANCERS; CONSERVED PROTEIN; HUMAN-CELLS AB Most endometrial cancers can be classified histologically as endometrioid, serous, or clear cell. Non-endometrioid endometrial cancers (NEECs; serous and clear cell) are the most clinically aggressive of the three major histotypes and are characterized by aneuploidy, a feature of chromosome instability. The genetic alterations that underlie chromosome instability in endometrial cancer are poorly understood. In the present study, we used Sanger sequencing to search for nucleotide variants in the coding exons and splice junctions of 21 candidate chromosome instability genes, including 19 genes implicated in sister chromatid cohesion, from 24 primary, microsatellite-stable NEECs. Somatic mutations were verified by sequencing matched normal DNAs. We subsequently resequenced mutated genes from 41 additional NEECs as well as 42 endometrioid ECs (EECs). We uncovered nonsynonymous somatic mutations in ESCO1, CHTF18, and MRE11A in, respectively, 3.7% (4 of 107), 1.9% (2 of 107), and 1.9% (2 of 107) of endometrial tumors. Overall, 7.7% (5 of 65) of NEECs and 2.4% (1 of 42) of EECs had somatically mutated one or more of the three genes. A subset of mutations are predicted to impact protein function. The co-occurrence of somatic mutations in ESCO1 and CHTF18 was statistically significant (P = 0.0011, two-tailed Fisher's exact test). This is the first report of somatic mutations within ESCO1 and CHTF18 in endometrial tumors and of MRE11A mutations in microsatellite-stable endometrial tumors. Our findings warrant future studies to determine whether these mutations are driver events that contribute to the pathogenesis of endometrial cancer. C1 [Price, Jessica C.; Pollock, Lana M.; Rudd, Meghan L.; Fogoros, Sarah K.; Mohamed, Hassan; Hanigan, Christin L.; Le Gallo, Matthieu; Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; NIH Intramural Sequencing Ctr NISC] NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Zhang, Suiyuan; Cruz, Pedro; Cherukuri, Praveen F.; Hansen, Nancy F.; Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [McManus, Kirk J.] Univ Manitoba, Manitoba Inst Cell Biol, Dept Biochem & Med Genet, Winnipeg, MB, Canada. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Ctr Canc, Kansas City, KS 66103 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Merino, Maria J.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hieter, Philip] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov FU National Human Genome Research Institute at NIH; NIH [CA016519, RO1-1CA112021-01]; Canadian Institutes of Health Research (CIHR) [MOP-38096]; Manitoba Health Research Council (MHRC); CIHR/MHRC RPP New Investigator award; NCI SPORE in breast cancer at Massachusetts General Hospital; Avon Foundation; [U01 CA113916]; [R01 CA140323] FX This work was funded, in part, by the Intramural Research Program of the National Human Genome Research Institute at NIH (DWB, JCM); NIH grant CA016519 (PH); Canadian Institutes of Health Research (CIHR) grant MOP-38096 (PH); Manitoba Health Research Council (MHRC) grant (KJM); CIHR/MHRC RPP New Investigator award (KJM); U01 CA113916 and R01 CA140323 (AKG); NIH RO1-1CA112021-01 (DCS); the NCI SPORE in breast cancer at Massachusetts General Hospital (DCS); and the Avon Foundation (DCS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 7 Z9 7 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 3 PY 2013 VL 8 IS 6 AR e63313 DI 10.1371/journal.pone.0063313 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157CD UT WOS:000319872300008 ER PT J AU Rehman, H Krishnasamy, Y Haque, K Thurman, RG Lemasters, JJ Schnellmann, RG Zhong, Z AF Rehman, Hasibur Krishnasamy, Yasodha Haque, Khujista Thurman, Ronald G. Lemasters, John J. Schnellmann, Rick G. Zhong, Zhi TI Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats SO PLOS ONE LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; PROXIMAL TUBULE CELLS; HUMAN SKELETAL-MUSCLE; ACUTE KIDNEY INJURY; MAMMALIAN-CELLS; DIETARY GLYCINE; PROTEIN-KINASE; PERMEABILITY TRANSITION; METABOLIC REGULATOR AB Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-beta (AS-beta) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-beta, ND3, COX-IV, mtDNA copy number, PGC-1 alpha mRNA and protein, decreased acetylated PGC-1 alpha, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB. C1 [Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Lemasters, John J.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Thurman, Ronald G.; Zhong, Zhi] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Zhong, Z (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. EM zhong@musc.edu FU National Institutes of Health [DK70844, DK37034, GM 084147]; South Carolina COBRE in Oxidants, Redox Balance and Stress Signaling [P20 GM103542] FX This study was supported, in part, by Grants DK70844, DK37034, and GM 084147 from the National Institutes of Health and South Carolina COBRE in Oxidants, Redox Balance and Stress Signaling [P20 GM103542]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 13 Z9 13 U1 0 U2 15 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 JUN 3 PY 2013 VL 8 IS 6 AR e65029 DI 10.1371/journal.pone.0065029 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157CD UT WOS:000319872300044 ER PT J AU Garfin, PM Min, D Bryson, JL Serwold, T Edris, B Blackburn, CC Richie, ER Weinberg, KI Manley, NR Sage, J Viatour, P AF Garfin, Phillip M. Min, Dullei Bryson, Jerrod L. Serwold, Thomas Edris, Badreddin Blackburn, Clare C. Richie, Ellen R. Weinberg, Kenneth I. Manley, Nancy R. Sage, Julien Viatour, Patrick TI Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; RETINOBLASTOMA GENE FAMILY; CORTICAL EPITHELIAL-CELLS; TRANSGENIC MICE; CYCLIN D1; TRANSCRIPTIONAL REGULATION; POSITIVE SELECTION; IN-VIVO; DIFFERENTIATION; PROLIFERATION AB Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow-independent mechanism, identifying a novel pathway to target to increase thymic function in patients. C1 [Garfin, Phillip M.; Min, Dullei; Weinberg, Kenneth I.; Sage, Julien; Viatour, Patrick] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Edris, Badreddin; Sage, Julien; Viatour, Patrick] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Bryson, Jerrod L.; Manley, Nancy R.] Univ Georgia, Dept Genet, Athens, GA 30602 USA. [Serwold, Thomas] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Blackburn, Clare C.] Univ Edinburgh, Sch Biol Sci, Inst Stem Cell Res, Med Res Council Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland. [Richie, Ellen R.] Univ Texas MD Anderson Canc Ctr, Depat Mol Carcinogenesis, Div Sci Pk Res, Smithville, TX 78957 USA. RP Sage, J (reprint author), Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. EM julsage@stanford.edu RI Blackburn, Clare/B-2847-2009 OI Blackburn, Clare/0000-0002-6326-640X FU Lucile Packard Foundation for Children's Health; Leukemia and Lymphoma Society; Human Frontier Science Program; European Molecular Biology Organization; Fonds de la Recherche Scientifique; Leon Fredericq Foundation; California Institute of Regenerative Medicine grant [TG2-01159]; Alex's Lemonade Stand Foundation for Childhood Cancer; Paul F. Glenn Laboratories for the Biology of Aging at Stanford University FX This work was supported by the Lucile Packard Foundation for Children's Health and the Leukemia and Lymphoma Society (to J. Sage), as well as fellowships from Human Frontier Science Program, the European Molecular Biology Organization, the Fonds de la Recherche Scientifique, the Leon Fredericq Foundation (to P. Viatour), and the California Institute of Regenerative Medicine grant number TG2-01159 (to P.M. Garfin). This work was also supported by the Alex's Lemonade Stand Foundation for Childhood Cancer and the Paul F. Glenn Laboratories for the Biology of Aging at Stanford University. NR 63 TC 17 Z9 18 U1 1 U2 10 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 JUN 3 PY 2013 VL 210 IS 6 BP 1087 EP 1097 DI 10.1084/jem.20121716 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 156FS UT WOS:000319807800004 PM 23669396 ER PT J AU Ferree, S Neuhaus, V Mudgal, CS AF Ferree, S. Neuhaus, V. Mudgal, C. S. TI Mouse wrist SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Letter ID TENOSYNOVITIS C1 [Ferree, S.; Neuhaus, V.; Mudgal, C. S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Ferree, S (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. EM cmudgal@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 EI 2043-6289 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD JUN PY 2013 VL 38 IS 5 BP 568 EP 569 DI 10.1177/1753193412453427 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AF3DY UT WOS:000334592900028 PM 22976874 ER PT J AU Cordeiro, CA Moreira, PR Bessa, TF Costa, GC Dutra, WO Campos, WR Orefice, F Young, LH Teixeira, AL AF Cordeiro, Cynthia A. Moreira, Paula R. Bessa, Thais F. Costa, Germano C. Dutra, Walderez O. Campos, Wesley R. Orefice, Fernando Young, Lucy H. Teixeira, Antonio L. TI Interleukin-6 gene polymorphism (-174 G/C) is associated with toxoplasmic retinochoroiditis SO ACTA OPHTHALMOLOGICA LA English DT Article DE uveitis; toxoplasmosis; polymorphism; interleukin-6 ID OCULAR TOXOPLASMOSIS; PERIODONTAL-DISEASE; ALZHEIMERS-DISEASE; PROTECTIVE ROLE; AQUEOUS-HUMOR; PLASMA-LEVELS; IL-6 GENE; TNF-ALPHA; UVEITIS; GONDII AB Abstract. Purpose: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans. Methods: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -174 of IL-6 (-174G/C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes. Results: There was a significant difference in the genotype (chi(2) = 12.9, p = 0.001) and allele (chi(2) = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence. Conclusions: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR. C1 [Cordeiro, Cynthia A.; Teixeira, Antonio L.] Univ Fed Minas Gerais, Sch Med, Dept Internal Med, Belo Horizonte, MG, Brazil. [Cordeiro, Cynthia A.; Young, Lucy H.] Massachusetts Eye & Ear Infirm, Retina Dept, Boston, MA 02114 USA. [Cordeiro, Cynthia A.; Orefice, Fernando] Brazilian Ctr Visual Sci, Belo Horizonte, MG, Brazil. [Moreira, Paula R.; Bessa, Thais F.; Costa, Germano C.; Dutra, Walderez O.] Univ Fed Minas Gerais, Inst Biol Sci, Dept Morphol, Belo Horizonte, MG, Brazil. [Dutra, Walderez O.] SRI Int, Ctr Infect Dis Res, Biosci Div, Trop Dis Res Program, Menlo Pk, CA 94025 USA. [Campos, Wesley R.] Univ Fed Minas Gerais, Sch Med, Dept Ophthalmol, Belo Horizonte, MG, Brazil. RP Cordeiro, CA (reprint author), Rua Espirito Santo 2701 Apt 801, BR-30160032 Belo Horizonte, MG, Brazil. EM cordeiro.cy@gmail.com FU CNPq, Brazil [163183/20112] FX This work was supported by grant from CNPq (163183/20112), Brazil. The funding sources did not have any role in the data collection, analysis, and manuscript writing. NR 38 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD JUN PY 2013 VL 91 IS 4 BP E311 EP E314 DI 10.1111/aos.12046 PG 4 WC Ophthalmology SC Ophthalmology GA AF0FE UT WOS:000334387500013 PM 23336844 ER PT J AU Basu, P Shah, NJ Farhat, S Siriki, R Mittimanj, K Rahaman, M Atluri, S AF Basu, P. Shah, N. J. Farhat, S. Siriki, R. Mittimanj, K. Rahaman, M. Atluri, S. TI EFFECT OF N ACETYLCYSTEINE (NAC) IN HYPOXIA INDUCED LIVER INJURY (HILI)-A RANDOMIZED PLACEBO CONTROL CLINICAL TRIAL SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Basu, P.; Siriki, R.; Mittimanj, K.; Rahaman, M.; Atluri, S.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, Flushing, NY USA. [Shah, N. J.] James J Peters VA Med Ctr, Mt Sinai Sch Med, New York, NY USA. [Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A184 EP A184 DI 10.1136/gutjnl-2013-304907.418 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600312 ER PT J AU Basu, P Shah, NJ Farhat, S Siriki, R Mittimanj, K Rahaman, M Atluri, S AF Basu, P. Shah, N. J. Farhat, S. Siriki, R. Mittimanj, K. Rahaman, M. Atluri, S. TI ROMIPLOSTIM'S EFFECT TO OPTIMIZE SVR WITH TELAPRAVIR, RIBAVIRIN, AND PEG INTERFERON-ALFA 2A IN THROMBOCYTOPENIC CIRRHOTICS WITH CHRONIC HEPATITIS C. A PLACEBO CONTROLLED PROSPECTIVE CLINICAL TRIAL: RESTRAINT C TRIAL SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Basu, P.; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Basu, P.; Siriki, R.; Mittimanj, K.; Rahaman, M.; Atluri, S.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, Flushing, NY USA. [Shah, N. J.] James J Peters VA Med Ctr, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A183 EP A183 DI 10.1136/gutjnl-2013-304907.416 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600310 ER PT J AU Basu, P Shah, NJ Farhat, S Siriki, R Mittimanj, K Rahaman, M Atluri, S AF Basu, P. Shah, N. J. Farhat, S. Siriki, R. Mittimanj, K. Rahaman, M. Atluri, S. TI TELAPREVIR WITH ADJUSTED DOSE OF RIBAVIRIN IN NAIVE CHC-G1: EFFICACY AND TREATMENT IN CHC IN HEMODIALYSIS POPULATION. TARGET C (RCT) SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Basu, P.; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Basu, P.; Siriki, R.; Mittimanj, K.; Rahaman, M.; Atluri, S.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, Flushing, NY USA. [Shah, N. J.] James J Peters VA Med Ctr, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A182 EP A182 DI 10.1136/gutjnl-2013-304907.414 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600308 ER PT J AU Basu, P Shah, NJ Farhat, S Siriki, R Mittimanj, K Atluri, S Rahaman, M AF Basu, P. Shah, N. J. Farhat, S. Siriki, R. Mittimanj, K. Atluri, S. Rahaman, M. TI CURCUMIN, ANTI-OXIDANT, AND PIOGLITAZONE THERAPY WITH INCLUSION OF VITAMIN E IN NON ALCOHOLIC FATTY LIVER DISEASE-A RANDOMIZED OPEN LABEL PLACEBO CONTROLLED CLINICAL PROSPECTIVE TRIAL (CAPTIVE) SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Basu, P.; Siriki, R.; Mittimanj, K.; Atluri, S.; Rahaman, M.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, Flushing, NY USA. [Basu, P.; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Shah, N. J.] Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A23 EP A23 DI 10.1136/gutjnl-2013-304907.052 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600047 ER PT J AU Canavan, C Corey, K Hur, C AF Canavan, C. Corey, K. Hur, C. TI DEFINING CIRRHOSIS WITH FIBROSCAN FOR ENTRY TO HEPATOCELLULAR CARCINOMA SURVEILLANCE IN CHRONIC HEPATITIS C: A UK COST EFFECTIVENESS ANALYSIS SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Canavan, C.] Univ Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG7 2RD, England. [Corey, K.; Hur, C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hur, C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A35 EP A35 DI 10.1136/gutjnl-2013-304907.080 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600070 ER PT J AU Pai, M Yang, J Zhang, X Jin, Z Wang, D Senturk, H Lakhtakia, S Reddy, DN Kahaleh, M Habib, N Brugge, WR AF Pai, M. Yang, J. Zhang, X. Jin, Z. Wang, D. Senturk, H. Lakhtakia, S. Reddy, D. N. Kahaleh, M. Habib, N. Brugge, W. R. TI ENDOSCOPIC ULTRASOUND GUIDED RADIOFREQUENCY ABLATION (EUS-RFA) FOR PANCREATIC DUCTAL ADENOCARCINOMA SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY JUN 24-27, 2013 CL Glasgow, SCOTLAND SP British Soc Gastroenterol C1 [Pai, M.; Habib, N.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, HPB Unit, London, England. [Yang, J.; Zhang, X.] Hangzhou First Peoples Hosp, GI Dept, Hangzhou, Zhejiang, Peoples R China. [Jin, Z.; Wang, D.] Second Mil Med Univ, Changhai Hosp, Digest Endoscopy Ctr, Shanghai, Peoples R China. [Senturk, H.] Bezmi Alem Univ, Istanbul, Turkey. [Lakhtakia, S.; Reddy, D. N.] Asian Inst Gastroenterol, Hyderabad, Andhra Pradesh, India. [Kahaleh, M.] Weill Cornell Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10065 USA. [Habib, N.] EMcision Ltd, London, England. [Brugge, W. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 6 Z9 6 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2013 VL 62 SU 1 BP A153 EP A153 DI 10.1136/gutjnl-2013-304907.344 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6SF UT WOS:000331227600276 ER PT J AU Ahluwalia, S Bekelman, D Prendergast, TJ Huynh, AK Lorenz, K AF Ahluwalia, Sangeeta Bekelman, David Prendergast, Thomas J. Huynh, Alexis K. Lorenz, Karl TI CROSSING BOUNDARIES: WHAT IS NEEDED TO REALIZE A COMPREHENSIVE MODEL OF ADVANCE CARE PLANNING? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ahluwalia, Sangeeta; Huynh, Alexis K.; Lorenz, Karl] Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Ahluwalia, Sangeeta] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Bekelman, David] VA Denver, Denver, CO USA. [Bekelman, David] Univ Colorado, Denver, CO 80202 USA. [Prendergast, Thomas J.] VA Portland, Portland, OR USA. [Lorenz, Karl] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S56 EP S57 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300133 ER PT J AU Arora, V Kumar, R Farnan, JM Levy, A Shah, N AF Arora, Vineet Kumar, Rupali Farnan, Jeanne M. Levy, Andrew Shah, Neel TI GOTMEDS? DESIGNING AND PILOTING AN INTERACTIVE MODULE FOR TRAINEES ON REDUCING DRUG COSTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Arora, Vineet; Kumar, Rupali; Farnan, Jeanne M.; Levy, Andrew] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Shah, Neel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S464 EP S465 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302417 ER PT J AU Arreola-Owen, OA Warde, CM Gomez, AG AF Arreola-Owen, Olivia A. Warde, Carole M. Gomez, Arthur G. TI A PILOT PRIMARY CARE RESIDENCY TRACK: EDUCATION AND LEADERSHIP IN PATIENT-ALIGNED CARE TEAMS (ELPACT) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Arreola-Owen, Olivia A.] Cedars Sinai Internal Med Residency, Los Angeles, CA USA. [Warde, Carole M.; Gomez, Arthur G.] Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S452 EP S452 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302389 ER PT J AU Ashburner, JM Grant, RW Jernigan, M Borowsky, LH Atlas, SJ AF Ashburner, Jeffrey M. Grant, Richard W. Jernigan, Michael Borowsky, Leila H. Atlas, Steven J. TI THE MEDICATION METRONOME: A HEALTH IT SYSTEM TO IMPROVE MEDICATION MANAGEMENT AND LABORATORY MONITORING FOR CHRONIC DISEASES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ashburner, Jeffrey M.; Grant, Richard W.; Jernigan, Michael; Borowsky, Leila H.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S447 EP S447 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302378 ER PT J AU Ashburner, JM Go, AS Reynolds, K Chang, YC Fang, M Fredman, L Singer, DE AF Ashburner, Jeffrey M. Go, Alan S. Reynolds, Kristi Chang, Yuchiao Fang, Margaret Fredman, Lisa Singer, Daniel E. TI WARFARIN ANTICOAGULATION THERAPY AND MORTALITY FOLLOWING GASTROINTESTINAL HEMORRHAGE IN PATIENTS WITH ATRIAL FIBRILLATION IN CLINICAL CARE: THE ATRIA AND ATRIA-CVRN COHORTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ashburner, Jeffrey M.; Chang, Yuchiao; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Pasadena, CA 91101 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ashburner, Jeffrey M.; Fang, Margaret; Fredman, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S240 EP S240 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301326 ER PT J AU Ashburner, JM Ward, CE Levy, D Zai, A Grant, RW Atlas, SJ AF Ashburner, Jeffrey M. Ward, Charlotte E. Levy, Douglas Zai, Adrian Grant, Richard W. Atlas, Steven J. TI IMPACT OF A POPULATION MANAGEMENT SYSTEM ON PHYSICIAN PERCEIVED TIME DEVOTED TO PREVENTIVE CANCER SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ashburner, Jeffrey M.; Ward, Charlotte E.; Levy, Douglas; Zai, Adrian; Grant, Richard W.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S100 EP S100 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300239 ER PT J AU Atlas, SJ Estey, G Ashburner, JM Rao, P He, W Chueh, H AF Atlas, Steven J. Estey, Gregory Ashburner, Jeffrey M. Rao, Priya He, Wei Chueh, Henry TI PATIENT ATTRIBUTION TO CARE PROVIDERS IN A PRIMARY CARE NETWORK: COMPARING RETROSPECTIVE AND PROSPECTIVE ALGORITHMS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Atlas, Steven J.; Estey, Gregory; Ashburner, Jeffrey M.; Rao, Priya; He, Wei; Chueh, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S444 EP S444 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302372 ER PT J AU Atlas, SJ Ashburner, JM Zai, A Chang, YC Percac-Lima, S Levy, D Grant, RW AF Atlas, Steven J. Ashburner, Jeffrey M. Zai, Adrian Chang, Yuchiao Percac-Lima, Sanja Levy, Douglas Grant, Richard W. TI THE ROLE OF THE PCP IN PREVENTIVE CANCER SCREENING USING A NOVEL POPULATION MANAGEMENT SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Atlas, Steven J.; Ashburner, Jeffrey M.; Zai, Adrian; Chang, Yuchiao; Percac-Lima, Sanja; Levy, Douglas; Grant, Richard W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S212 EP S212 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301263 ER PT J AU Bachhuber, M Patel, S O'Brien, B AF Bachhuber, Melissa Patel, Shalini O'Brien, Bridget TI A HOME VISIT CURRICULUM TO FOSTER INTERPROFESSIONAL LEARNING AND IMPROVE CARE COORDINATION FOR HIGH-RISK PATIENTS IN TRAINEE PRIMARY CARE CONTINUITY CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Bachhuber, Melissa; Patel, Shalini; O'Brien, Bridget] UCSF, San Francisco, CA USA. [Bachhuber, Melissa; Patel, Shalini; O'Brien, Bridget] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S451 EP S451 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302386 ER PT J AU Baggett, TP Rigotti, NA AF Baggett, Travis P. Rigotti, Nancy A. TI SMOKING-ATTRIBUTABLE MORTALITY AMONG HOMELESS ADULTS IN BOSTON SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Baggett, Travis P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S182 EP S183 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301194 ER PT J AU Baggett, TP Lebrun-Harris, LA Rigotti, NA AF Baggett, Travis P. Lebrun-Harris, Lydie A. Rigotti, Nancy A. TI HOMELESSNESS, CIGARETTE SMOKING, AND DESIRE TO QUIT: A NATIONAL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Baggett, Travis P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Lebrun-Harris, Lydie A.] Hlth Resources & Serv Adm, Rockville, MD USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S89 EP S89 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300212 ER PT J AU Barocas, J Brennan, M Crnich, C Hess, T Sethi, A Sosman, JM AF Barocas, Joshua Brennan, Meghan Crnich, Christopher Hess, Timothy Sethi, Ajay Sosman, James M. TI SELF-AUDIT INCREASES CLINICIAN-DRIVEN UNIVERSAL HIV SCREENING AMONG INTERNAL MEDICINE RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Barocas, Joshua; Brennan, Meghan; Crnich, Christopher; Hess, Timothy; Sethi, Ajay; Sosman, James M.] Univ Wisconsin, Madison, WI USA. [Brennan, Meghan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S178 EP S178 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301183 ER PT J AU Bekelman, D Nowels, CT Main, D Heidenreich, P Hattler, B Lorenz, K Meek, P McBryde, C Hooker, S AF Bekelman, David Nowels, Carolyn T. Main, Debbi Heidenreich, Paul Hattler, Brack Lorenz, Karl Meek, Paula McBryde, Connor Hooker, Stephanie TI PILOT CLINICAL TRIAL OF A COLLABORATIVE CARE INTERVENTION TO IMPROVE SYMPTOMS AND QUALITY OF LIFE IN CHRONIC HEART FAILURE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Bekelman, David; Hattler, Brack; McBryde, Connor] VA Eastern Colorado Heath Care Syst, Denver, CO USA. [Bekelman, David; Nowels, Carolyn T.; Hattler, Brack; McBryde, Connor] Univ Colorado, Sch Med, Aurora, CO USA. [Main, Debbi; Hooker, Stephanie] Univ Colorado, Denver, CO 80202 USA. [Meek, Paula] Univ Colorado, Coll Nursing, Aurora, CO USA. [Heidenreich, Paul] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Lorenz, Karl] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S149 EP S149 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301113 ER PT J AU Bokhour, BG Solomon, J Laws, MB Gifford, AL Goetz, MB AF Bokhour, Barbara G. Solomon, Jeffrey Laws, Michael B. Gifford, Allen L. Goetz, Matthew B. TI THE IMPACT OF AN HIV ADHERENCE INFORMATICS INTERVENTION ON PATIENT-PROVIDER COMMUNICATION ABOUT ART ADHERENCE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Bokhour, Barbara G.; Solomon, Jeffrey; Gifford, Allen L.] ENRM Vet Affairs Med Ctr, Bedford, MA USA. [Bokhour, Barbara G.; Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Goetz, Matthew B.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S217 EP S217 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301274 ER PT J AU Bradley, K Rubinsky, AD Au, D Bryson, CL Achtmeyer, C Williams, E Lapham, G Chavez, L Kivlahan, D AF Bradley, Katharine Rubinsky, Anna D. Au, David Bryson, Christopher L. Achtmeyer, Carol Williams, Emily Lapham, Gwendolyn Chavez, Laura Kivlahan, Daniel TI VALIDATING ALCOHOL SCREENING SCORES AS PATIENT-REPORTED OUTCOME MEASURES - RESULTS OF THE MONITOR STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Bradley, Katharine; Rubinsky, Anna D.; Au, David; Bryson, Christopher L.; Achtmeyer, Carol; Williams, Emily; Lapham, Gwendolyn; Chavez, Laura] VA Puget Sound, Seattle, WA USA. [Bradley, Katharine] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [Au, David; Bryson, Christopher L.; Williams, Emily] Univ Washington, Seattle, WA 98195 USA. [Kivlahan, Daniel] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S236 EP S236 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301317 ER PT J AU Brown, RT Ahalt, C Steinman, MA Williams, B AF Brown, Rebecca T. Ahalt, Cyrus Steinman, Michael A. Williams, Brie TI HANDS ON THE HOOD, GRANDPA: ASSESSING THE NEED FOR GERIATRICS HEALTH TRAINING AMONG POLICE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Brown, Rebecca T.; Ahalt, Cyrus; Steinman, Michael A.; Williams, Brie] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S84 EP S84 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300199 ER PT J AU Burke, R Guo, RX Misky, GJ AF Burke, Robert Guo, Ruixin Misky, Gregory J. TI IDENTIFYING KEYS TO SUCCESS FOR REDUCING READMISSIONS: USING THE IDEAL TRANSITION IN CARE FRAMEWORK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Burke, Robert] Denver VA Med Ctr, Denver, CO USA. [Burke, Robert; Guo, Ruixin; Misky, Gregory J.] Univ Colorado, Sch Med, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S94 EP S94 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300225 ER PT J AU Burke, R Whitfield, E Prochazka, AV AF Burke, Robert Whitfield, Emily Prochazka, Allan V. TI EFFECT OF A HOSPITALIST-RUN POST-DISCHARGE CLINIC ON ADVERSE POST-DISCHARGE OUTCOMES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Burke, Robert; Whitfield, Emily; Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO USA. [Burke, Robert; Prochazka, Allan V.] Univ Colorado, Sch Med, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S69 EP S69 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300162 ER PT J AU Carlini, SV Klinger, E Gonzalez, I Linder, JA Park, ER Kontos, E Rigotti, NA Haas, J AF Carlini, Sara V. Klinger, Elissa Gonzalez, Irina Linder, Jeffrey A. Park, Elyse R. Kontos, Emily Rigotti, Nancy A. Haas, Jennifer TI ACCURACY OF RACE/ETHNICITY AND LANGUAGE PREFERENCE IN AN ELECTRONIC HEALTH RECORD SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Carlini, Sara V.; Klinger, Elissa; Gonzalez, Irina; Linder, Jeffrey A.; Haas, Jennifer] Brigham & Womens Hosp, Boston, MA 02115 USA. [Park, Elyse R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kontos, Emily; Haas, Jennifer] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S16 EP S16 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300036 ER PT J AU Chang, E Chung, B Gilmore, J Tang, LQ Morgan, A Wells, KB AF Chang, Evelyn Chung, Bowen Gilmore, James Tang, Lingqi Morgan, Anna Wells, Kenneth B. TI COMORBID DEPRESSION AND SUBSTANCE ABUSE IN SAFETY-NET CLIENTS OF HEALTH AND COMMUNITY-BASED AGENCIES IN LOS ANGELES: CLINICAL NEEDS AND SERVICE USE PATTERNS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Chang, Evelyn] VA Greater Los Angeles, Los Angeles, CA USA. [Wells, Kenneth B.] RAND Corp, Santa Monica, CA USA. [Chung, Bowen; Tang, Lingqi; Wells, Kenneth B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Gilmore, James] Behav Hlth Serv Inc, Los Angeles, CA USA. [Morgan, Anna] Harbor UCLA, Torrance, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S48 EP S49 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300115 ER PT J AU Chang, E Wells, KB Young, AS Stockdale, SE Fickel, J Johnson, M Jou, K Rubenstein, LV AF Chang, Evelyn Wells, Kenneth B. Young, Alexander S. Stockdale, Susan E. Fickel, Jacqueline Johnson, Megan Jou, Kevin Rubenstein, Lisa V. TI ACHIEVING COMMUNICATION BETWEEN PRIMARY CARE AND MENTAL HEALTH: WHY IS IT SO DIFFICULT, EVEN IN THE VA? A QUALITY IMPROVEMENT APPROACH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Chang, Evelyn] VA Greater Los Angeles, Los Angeles, CA USA. [Young, Alexander S.; Stockdale, Susan E.; Fickel, Jacqueline; Johnson, Megan; Jou, Kevin; Rubenstein, Lisa V.] VA Greater Los Angeles, North Hills, CA USA. [Wells, Kenneth B.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Wells, Kenneth B.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S17 EP S17 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300039 ER PT J AU Cohen, B Shi, Y Neylan, T Seal, KH AF Cohen, Beth Shi, Ying Neylan, Thomas Seal, Karen H. TI OFF-LABEL ANTIPSYCHOTIC PRESCRIPTIONS IN IRAQ AND AFGHANISTAN VETERANS WITH POSTTRAUMATIC STRESS DISORDER IN VA HEALTHCARE, 2001-2011 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Cohen, Beth; Shi, Ying; Neylan, Thomas; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cohen, Beth; Neylan, Thomas; Seal, Karen H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S131 EP S132 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301072 ER PT J AU Cohen, B Neylan, T Bertenthal, D Yaffe, K AF Cohen, Beth Neylan, Thomas Bertenthal, Daniel Yaffe, Kristine TI ASSOCIATION OF POSTTRAUMATIC STRESS DISORDER AND INCIDENT CEREBROVASCULAR DISEASE IN A VETERANS ADMINISTRATION POPULATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Cohen, Beth; Neylan, Thomas; Bertenthal, Daniel; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Cohen, Beth; Neylan, Thomas; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S28 EP S28 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300066 ER PT J AU Darby, A Ahalt, C Cenzer, IS Sudore, RL Williams, B AF Darby, Anna Ahalt, Cyrus Cenzer, Irena Stijacic Sudore, Rebecca L. Williams, Brie TI EVALUATING A MODIFIED INFORMED CONSENT FOR OLDER ADULTS IN CORRECTIONAL RESEARCH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Darby, Anna] Mt Sinai Sch Med, New York, NY USA. [Ahalt, Cyrus; Cenzer, Irena Stijacic; Sudore, Rebecca L.; Williams, Brie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cenzer, Irena Stijacic; Sudore, Rebecca L.; Williams, Brie] San Francisco VA Med Ctr, San Francisco, CA USA. RI Darby, Alistair/I-6485-2012 OI Darby, Alistair/0000-0002-3786-6209 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S74 EP S74 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300174 ER PT J AU DeBiasi, R Adusumalli, S Schainfeld, R Jaff, MR AF DeBiasi, Ralph Adusumalli, Srinath Schainfeld, Robert Jaff, Michael R. TI ATHEROSCLEROTIC RENAL ARTERY STENOSIS (ARAS): WHO SHOULD BE SCREENED AND BY WHOM? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [DeBiasi, Ralph; Adusumalli, Srinath; Schainfeld, Robert; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S30 EP S30 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300072 ER PT J AU Edelman, EJ Gordon, KS Lo Re, V Skanderson, M Fiellin, DA Justice, AC AF Edelman, E. J. Gordon, Kirsha S. Lo Re, Vincent Skanderson, Melissa Fiellin, David A. Justice, Amy C. TI ACETAMINOPHEN RECEIPT AMONG HIV-INFECTED PATIENTS WITH ADVANCED HEPATIC FIBROSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Edelman, E. J.; Fiellin, David A.; Justice, Amy C.] Yale Univ, New Haven, CT USA. [Gordon, Kirsha S.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lo Re, Vincent] Univ Penn, Philadelphia, PA 19104 USA. [Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RI Lo Re, Vincent/N-7817-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S16 EP S17 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300038 ER PT J AU Edwards, ST Mafi, JN Landon, BE AF Edwards, Samuel T. Mafi, John N. Landon, Bruce E. TI SPECIALISTS AS PRIMARY CARE PHYSICIANS: PATIENT CHARACTERISTICS AND QUALITY OF CARE OF VISITS TO GENERALIST AND SPECIALIST PHYSICIANS SELF-IDENTIFIED AS PRIMARY CARE PHYSICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Edwards, Samuel T.] Boston VA Healthcare Syst, Boston, MA USA. [Edwards, Samuel T.; Mafi, John N.] Harvard Univ, Sch Med, Boston, MA USA. [Mafi, John N.; Landon, Bruce E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Landon, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S184 EP S185 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301198 ER PT J AU Edwards, ST Prentice, J Li, DL Simon, SR Cooper, D Edes, T Pizer, SD AF Edwards, Samuel T. Prentice, Julia Li, Donglin Simon, Steven R. Cooper, Dayna Edes, Thomas Pizer, Steven D. TI PREDICTORS OF EARLY ENROLLMENT IN HOME BASED PRIMARY CARE AMONG VETERANS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Edwards, Samuel T.; Prentice, Julia; Li, Donglin; Simon, Steven R.; Pizer, Steven D.] Boston VA Healthcare Syst, Boston, MA USA. [Edwards, Samuel T.] Harvard Univ, Sch Med, Boston, MA USA. [Prentice, Julia; Pizer, Steven D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Prentice, Julia; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cooper, Dayna; Edes, Thomas] Vet Hlth Adm, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S151 EP S152 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301119 ER PT J AU Edwards, ST Neri, PM Volk, LA Schiff, GD Bates, DW AF Edwards, Samuel T. Neri, Pamela M. Volk, Lynn A. Schiff, Gordon D. Bates, David W. TI NOTE QUALITY AND QUALITY OF CARE: IS THERE AN ASSOCIATION? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Edwards, Samuel T.] VA Boston Healthcare Syst, Boston, MA USA. [Edwards, Samuel T.; Schiff, Gordon D.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Neri, Pamela M.; Volk, Lynn A.] Partners Healthcare Syst, Wellesley, MA USA. [Schiff, Gordon D.; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S130 EP S130 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301070 ER PT J AU Elman, SA Wang, LD Bachorik, AE Huppert, LA Palaniappa, NC Simchoni, N Spinelli, MA Thomas, DC Berman, R Meah, YS AF Elman, Scott A. Wang, Linda Bachorik, Alexandra E. Huppert, Laura A. Palaniappa, Nandini C. Simchoni, Noa Spinelli, Matthew A. Thomas, David C. Berman, Rebecca Meah, Yasmin S. TI STUDENT-RUN CLINICS AS MEDICAL STUDENT SCHOLARLY HOMES FOR GENERAL INTERNAL MEDICINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Elman, Scott A.; Huppert, Laura A.; Berman, Rebecca] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Linda; Bachorik, Alexandra E.; Palaniappa, Nandini C.; Simchoni, Noa; Spinelli, Matthew A.; Thomas, David C.; Meah, Yasmin S.] Icahn Sch Med Mt Sinai, New York, NY USA. [Berman, Rebecca] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S188 EP S188 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301206 ER PT J AU Eng, JA Hatoun, J Liu, C Blum-Smith, L Shea, S Suen, W AF Eng, Jessica A. Hatoun, Jonathan Liu, Constance Blum-Smith, Laura Shea, Sandra Suen, Winnie TI RESIDENT ATTITUDES, KNOWLEDGE AND BEHAVIORS REGARDING AN ELECTRONIC INCIDENT REPORTING SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Eng, Jessica A.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Eng, Jessica A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hatoun, Jonathan; Liu, Constance; Suen, Winnie] Boston Med Ctr, Boston, MA USA. [Hatoun, Jonathan] Boston Childrens Hosp, Boston, MA USA. [Blum-Smith, Laura; Shea, Sandra] Comm Interns & Residents, New York, NY USA. [Suen, Winnie] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S171 EP S171 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301166 ER PT J AU Eng, JA Hunter, CJ Cantino, LB Yuan, C Lai, S Kalmar, E Boscardin, CK Handley, MA Gonzales, R Ackerman, S AF Eng, Jessica A. Hunter, Cecily J. Cantino, Laura B. Yuan, Caterina Lai, Sunny Kalmar, Evie Boscardin, Christy K. Handley, Margaret A. Gonzales, Ralph Ackerman, Sara TI LET'S TALK! PATIENT ATTITUDES ABOUT TELEPHONE-BASED ALTERNATIVES TO FOLLOW-UP OFFICE VISITS WITH SPECIALISTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Eng, Jessica A.; Hunter, Cecily J.; Cantino, Laura B.; Yuan, Caterina; Lai, Sunny; Kalmar, Evie; Boscardin, Christy K.; Handley, Margaret A.; Gonzales, Ralph] UCSF Sch Med, San Francisco, CA USA. [Eng, Jessica A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerman, Sara] UCSF Sch Nursing, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S114 EP S115 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301034 ER PT J AU Fairfield, K Gerstein, B Levin, CA McNaughton-Collins, M AF Fairfield, Kathleen Gerstein, Bethany Levin, Carrie A. McNaughton-Collins, Mary TI DECISIONS ABOUT MEDICATION USE AND CANCER SCREENING AMONG ELDERLY ADULTS IN THE UNITED STATES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Fairfield, Kathleen] Maine Med Ctr, Portland, ME 04102 USA. [McNaughton-Collins, Mary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gerstein, Bethany; Levin, Carrie A.; McNaughton-Collins, Mary] Informed Med Decis Fdn, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S57 EP S57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300134 ER PT J AU Flickinger, TE Saha, S Moore, RD Beach, MC AF Flickinger, Tabor E. Saha, Somnath Moore, Richard D. Beach, Mary Catherine TI HIGHER QUALITY COMMUNICATION AND RELATIONSHIPS ARE ASSOCIATED WITH IMPROVED PATIENT ENGAGEMENT IN HIV CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Flickinger, Tabor E.; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S88 EP S88 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300210 ER PT J AU Fraser, T Strom, JB Park, L AF Fraser, Traci Strom, Jordan B. Park, Lee TI EXUDATIVE PLEURAL EFFUSION IN A HAITIAN MAN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Fraser, Traci; Strom, Jordan B.; Park, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S325 EP S325 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302072 ER PT J AU Fu, S Roth, C Battaglia, C Nelson, D Farmer, M Do, T Goldstein, M Kavathekar, R Widome, R Hagedorne, H Zillich, A AF Fu, Steven Roth, Craig Battaglia, Catherine Nelson, David Farmer, Melissa Do, Tam Goldstein, Michael Kavathekar, Rahul Widome, Rachel Hagedorne, Hildi Zillich, Alan TI A RANDOMIZED TRIAL OF TWO APPROACHES TO TRAINING VETERANS AFFAIRS (VA) MEDICAL HOME HEALTHCARE PROVIDERS ON MOTIVATIONAL INTERVIEWING FOR TOBACCO CESSATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Fu, Steven; Roth, Craig; Nelson, David; Do, Tam; Kavathekar, Rahul; Widome, Rachel; Hagedorne, Hildi] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Zillich, Alan] Roudebush VA Med Ctr, Indianapolis, IN USA. [Battaglia, Catherine] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Farmer, Melissa] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goldstein, Michael] VHA Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S7 EP S8 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300017 ER PT J AU Gerber, MR Pineles, S Japuntich, S Bean-Mayberry, B King, M Haskell, SG AF Gerber, Megan R. Pineles, Suzanne Japuntich, Sandra Bean-Mayberry, Bevanne King, Matthew Haskell, Sally G. TI HORMONE THERAPY USE IN WOMEN VETERANS ACCESSING VA CARE: A NATIONAL CROSS-SECTIONAL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Gerber, Megan R.; Pineles, Suzanne; Japuntich, Sandra; King, Matthew] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Gerber, Megan R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles Healthcare Sys, Los Angeles, CA USA. [Haskell, Sally G.] VA Connecticut Healthcare Syst West Haven Campus, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S89 EP S90 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300213 ER PT J AU Gopalan, A Tahirovic, E Moss, H Troxel, AB Zhu, JS Volpp, KG AF Gopalan, Anjali Tahirovic, Emin Moss, Haley Troxel, Andrea B. Zhu, Jingsan Volpp, Kevin G. TI A RANDOMIZED, CONTROLLED TRIAL OF ALTERNATIVE FORMS OF FEEDBACK ON GLYCEMIC CONTROL IN PATIENTS WITH POORLY CONTROLLED DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Gopalan, Anjali; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Tahirovic, Emin; Moss, Haley; Troxel, Andrea B.; Zhu, Jingsan; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gopalan, Anjali] Robert Wood Johnson Clin Scholars Program, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S13 EP S13 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300030 ER PT J AU Halm, E Tiro, J Nelson, C Batchelor, K Xuan, L Cosenza, C Sepucha, KR AF Halm, Ethan Tiro, Jasmin Nelson, Colin Batchelor, Kim Xuan, Lei Cosenza, Carol Sepucha, Karen R. TI DEVELOPMENT OF AN INSTRUMENT TO MEASURE THE QUALITY OF TREATMENT DECISIONS FOR ASYMPTOMATIC CAROTID ARTERY DISEASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Halm, Ethan; Tiro, Jasmin; Batchelor, Kim; Xuan, Lei] Univ TX Southwestern Med Ctr, Dallas, TX USA. [Nelson, Colin] Informed Med Decis Fdn, Boston, MA USA. [Cosenza, Carol] Univ Massachusetts, Boston, MA 02125 USA. [Sepucha, Karen R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S60 EP S61 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300142 ER PT J AU Hebert, P Liu, CF Wong, E Hernandez, S Batten, A Lo, S Lemon, J AF Hebert, Paul Liu, Chuan-Fen Wong, Edwin Hernandez, Susan Batten, Adam Lo, Sophie Lemon, Jackie TI NATIONAL EVALUATION OF THE EFFECTS ON HEALTHCARE UTILIZATION AND COSTS OF THE VA PATIENT CENTERED MEDICAL HOME INITIATIVE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Hebert, Paul; Liu, Chuan-Fen; Wong, Edwin; Hernandez, Susan; Batten, Adam; Lo, Sophie; Lemon, Jackie] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S124 EP S124 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301057 ER PT J AU Heyworth, L Paquin, AM Clark, J Orlov, VJ Stewart, MD Martin, TL Simon, SR AF Heyworth, Leonie Paquin, Allison M. Clark, Justice Orlov, Victor J. Stewart, Max D. Martin, Tracey L. Simon, Steven R. TI VIRTUAL MEDICATION RECONCILIATION: A PILOT STUDY OF INTERACTIVE MEDICATION RECONCILIATION BY SECURE MESSAGING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Heyworth, Leonie; Paquin, Allison M.; Clark, Justice; Orlov, Victor J.; Stewart, Max D.; Martin, Tracey L.; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S239 EP S239 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301323 ER PT J AU Heyworth, L Bitton, A Lipsitz, SR Schilling, T Schiff, GD Bates, DW Simon, SR AF Heyworth, Leonie Bitton, Asaf Lipsitz, Stuart R. Schilling, Thad Schiff, Gordon D. Bates, David W. Simon, Steven R. TI THE EFFECT OF PATIENT-CENTERED MEDICAL HOME TRANSFORMATION COUPLED WITH PAYMENT REFORM: PATIENT EXPERIENCE OUTCOMES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Heyworth, Leonie; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Heyworth, Leonie; Bitton, Asaf; Lipsitz, Stuart R.; Schiff, Gordon D.; Bates, David W.; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schilling, Thad] Atrius Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S216 EP S216 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301272 ER PT J AU Ho, M Aron, D Sales, AE Au, D Helfrich, C Fagan, K Lambert-Kerzner, A Lowery, J Battaglia, C Pogach, L Graham, GD Ellington, V Kirsh, S AF Ho, Michael Aron, David Sales, Anne E. Au, David Helfrich, Christian Fagan, Katherine Lambert-Kerzner, Anne Lowery, Julie Battaglia, Catherine Pogach, Leonard Graham, Glenn D. Ellington, Vaness Kirsh, Susan TI THE VA'S SPECIALTY CARE TRANSFORMATIONAL INITIATIVES TO IMPROVE ACCESS AND DELIVERY OF SPECIALTY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ho, Michael; Fagan, Katherine; Lambert-Kerzner, Anne; Battaglia, Catherine] Eastern Colorado Hlth Care Syst, Denver, CO USA. [Sales, Anne E.; Lowery, Julie] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Pogach, Leonard; Graham, Glenn D.; Ellington, Vaness] Washington DC VA Med Ctr, Washington, DC USA. [Aron, David; Kirsh, Susan] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Au, David; Helfrich, Christian] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S447 EP S448 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302379 ER PT J AU Hong, CS Grant, RW Chang, YC Ashburner, JM He, W Ferris, T Atlas, SJ AF Hong, Clemens S. Grant, Richard W. Chang, Yuchiao Ashburner, Jeffrey M. He, Wei Ferris, Timothy Atlas, Steven J. TI PRIMARY CARE PHYSICIAN-DEFINED COMPLEXITY AND OUTPATIENT CHARLSON SCORE AS PREDICTORS OF HEALTH CARE UTILIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Hong, Clemens S.; Chang, Yuchiao; Ashburner, Jeffrey M.; He, Wei; Ferris, Timothy; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanent, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S156 EP S157 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301131 ER PT J AU Jarvie, JL Regan, MC Cohen, B AF Jarvie, Jennifer L. Regan, Mathilda C. Cohen, Beth TI PROSPECTIVE ASSOCIATION OF PHYSICAL ACTIVITY AND MARKERS OF INFLAMMATION AND INSULIN RESISTANCE IN OUTPATIENTS WITH CORONARY HEART DISEASE: DATA FROM THE HEART AND SOUL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Jarvie, Jennifer L.; Cohen, Beth] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Regan, Mathilda C.; Cohen, Beth] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S160 EP S161 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301140 ER PT J AU Jubelt, LE Graham, J Maeng, DD Metlay, J Epstein, A AF Jubelt, Lindsay E. Graham, Jove Maeng, Daniel D. Metlay, Joshua Epstein, Andrew TI CASE MANAGEMENT PERFORMANCE IN A MEDICAL HOME AND ASSOCIATIONS WITH PATIENT SATISFACTION AND HEALTHCARE UTILIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Jubelt, Lindsay E.; Metlay, Joshua; Epstein, Andrew] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jubelt, Lindsay E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Graham, Jove] Geisinger Ctr Hlth Res, Danville, PA USA. [Maeng, Daniel D.] Geisinger Hlth Syst, Danville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S40 EP S41 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300096 ER PT J AU Justice, AC Tate, JP Brown, ST Gibert, C Rodriguez-Barradas, M Rimland, D Akgun, KM Bryant, K AF Justice, Amy C. Tate, Janet P. Brown, Sheldon T. Gibert, Cynthia Rodriguez-Barradas, Maria Rimland, David Akguen, Kathleen M. Bryant, Kendall TI CAN THE VETERANS AGING COHORT STUDY INDEX IMPROVE CLINICAL JUDGMENT FOR BOTH HIV INFECTED AND UNINFECTED VETERANS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Justice, Amy C.; Tate, Janet P.; Akguen, Kathleen M.] Yale Univ, West Haven, CT USA. [Justice, Amy C.; Tate, Janet P.; Akguen, Kathleen M.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, New York, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Gibert, Cynthia] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rimland, David] Emory Sch Med, Atlanta, GA USA. [Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S39 EP S39 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300093 ER PT J AU Kaminetzky, CP Keedy, JR Evans, GA Poppe, AP Wipf, JE AF Kaminetzky, Catherine P. Keedy, Jacqueline R. Evans, Ginger A. Poppe, Anne P. Wipf, Joyce E. TI INTERPROFESSIONAL PANEL MANAGEMENT: TEACHING RESIDENTS DATA-DRIVEN LONGITUDINAL AND CONTINUOUS CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kaminetzky, Catherine P.; Keedy, Jacqueline R.; Evans, Ginger A.; Poppe, Anne P.; Wipf, Joyce E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kaminetzky, Catherine P.; Keedy, Jacqueline R.; Evans, Ginger A.; Poppe, Anne P.; Wipf, Joyce E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S469 EP S470 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302429 ER PT J AU Kangovi, S Grande, D Mitra, N Sellman, J White, ML McCollum, S Shannon, R Long, JA AF Kangovi, Shreya Grande, David Mitra, Nandita Sellman, Jeffrey White, Mary L. McCollum, Sharon Shannon, Richard Long, Judith A. TI A RANDOMIZED CONTROLLED TRIAL OF A COMMUNITY HEALTH WORKER POST-HOSPITAL CARE TRANSITIONS INTERVENTION FOR LOW SOCIOECONOMIC STATUS PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kangovi, Shreya; Sellman, Jeffrey; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Grande, David; Shannon, Richard; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grande, David; Mitra, Nandita] Univ Penn, Philadelphia, PA 19104 USA. [Kangovi, Shreya; White, Mary L.; McCollum, Sharon] Spectrum Hlth Serv Inc, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S11 EP S12 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300026 ER PT J AU Kaplan-Lewis, ER Cronin, PR Percac-Lima, S AF Kaplan-Lewis, Emma R. Cronin, Patrick R. Percac-Lima, Sanja TI NO-SHOW TO PRIMARY CARE APPOINTMENTS: WHY PATIENTS DO NOT COME? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kaplan-Lewis, Emma R.; Cronin, Patrick R.; Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S130 EP S130 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301069 ER PT J AU Karwowski, E Cheng, T Orlander, JD AF Karwowski, Elizabeth Cheng, Teresa Orlander, Jay D. TI EXAMINING THE INFLUENCE OF A BEHAVIORAL CHANGE ACTIVITY ON SENIOR MEDICAL STUDENT ATTITUDES ABOUT MOTIVATIONAL INTERVIEWING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Karwowski, Elizabeth; Cheng, Teresa; Orlander, Jay D.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Karwowski, Elizabeth; Orlander, Jay D.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S75 EP S75 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300178 ER PT J AU Kertesz, S Kim, TW Gordon, A Young, AS Pollio, DE Jones, RN Holt, CL Austin, EL Roth, D AF Kertesz, Stefan Kim, Theresa W. Gordon, Adam Young, Alexander S. Pollio, David E. Jones, Richard N. Holt, Cheryl L. Austin, Erika L. Roth, David TI COMPARING HOMELESS PERSONS' CARE EXPERIENCES IN TAILORED VERSUS NON-TAILORED PRIMARY CARE SETTINGS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kertesz, Stefan; Austin, Erika L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, Stefan; Austin, Erika L.] U Alabama Birmingham, Birmingham, AL USA. [Kim, Theresa W.] Boston Univ, Boston, MA 02215 USA. [Gordon, Adam] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Gordon, Adam] U Pittsburgh, Pittsburgh, PA USA. [Pollio, David E.] U Alabama, Tuscaloosa, AL USA. [Young, Alexander S.] VA Greater Los Angeles, Los Angeles, CA USA. [Holt, Cheryl L.] U Maryland, Baltimore, MD USA. [Roth, David] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Jones, Richard N.] Hebrew SeniorLife, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S49 EP S50 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300117 ER PT J AU Kolehmainen, CJ Brennan, M Filut, A Isaac, C Carnes, M AF Kolehmainen, Christine J. Brennan, Meghan Filut, Amarette Isaac, Carol Carnes, Molly TI GENDER AND LEADERSHIP IN CARDIOPULMONARY RESUSCITATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kolehmainen, Christine J.; Brennan, Meghan; Filut, Amarette; Isaac, Carol; Carnes, Molly] Univ Wisconsin, Madison, WI USA. [Kolehmainen, Christine J.; Brennan, Meghan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S81 EP S81 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300191 ER PT J AU Krug, MF Davidson, HL Wander, PL Wipf, JE AF Krug, Michael F. Davidson, Heather L. Wander, P. L. Wipf, Joyce E. TI THE EFFECTS OF A DECADE OF PROGRESSIVE DUTY HOUR LIMITATIONS AT A MULTI-HOSPITAL INTERNAL MEDICINE RESIDENCY PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Krug, Michael F.; Davidson, Heather L.; Wander, P. L.; Wipf, Joyce E.] Univ Washington, Seattle, WA 98195 USA. [Davidson, Heather L.; Wipf, Joyce E.] VA Puget Sound HCS, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S201 EP S202 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301237 ER PT J AU Kruse, GR Khan, SM Zaslavsky, AM Ayanian, JZ Sequist, TD AF Kruse, Gina R. Khan, Sami M. Zaslavsky, Alan M. Ayanian, John Z. Sequist, Thomas D. TI OVERUSE, UNDERUSE, AND MISUSE OF COLORECTAL CANCER SCREENING TESTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kruse, Gina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khan, Sami M.; Ayanian, John Z.; Sequist, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zaslavsky, Alan M.; Ayanian, John Z.] Harvard Univ, Sch Med, Boston, MA USA. [Sequist, Thomas D.] Harvard Vanguard Med Associates, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S133 EP S134 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301076 ER PT J AU Kullgren, JT Troxel, AB Loewenstein, G Norton, L Gatto, D Tao, YY Zhu, JS Schofield, H Shea, JA Asch, DA Pellathy, T Driggers, J Volpp, KG AF Kullgren, Jeffrey T. Troxel, Andrea B. Loewenstein, George Norton, Laurie Gatto, Dana Tao, Yuanyuan Zhu, Jingsan Schofield, Heather Shea, Judy A. Asch, David A. Pellathy, Thomas Driggers, Jay Volpp, Kevin G. TI A MIXED-METHODS RANDOMIZED CONTROLLED TRIAL OF EMPLOYER MATCHING OF DEPOSIT CONTRACTS TO PROMOTE WEIGHT LOSS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kullgren, Jeffrey T.] Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA. [Kullgren, Jeffrey T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Troxel, Andrea B.; Norton, Laurie; Gatto, Dana; Tao, Yuanyuan; Zhu, Jingsan; Shea, Judy A.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Schofield, Heather] Harvard Univ, Cambridge, MA 02138 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Pellathy, Thomas] McKinsey & Co Inc, Pittsburgh, PA USA. [Driggers, Jay] Horizon Healthcare Innovat, Newark, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S5 EP S5 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300011 ER PT J AU Kullgren, JT Duey, KA Werner, RM AF Kullgren, Jeffrey T. Duey, Katia A. Werner, Rachel M. TI A CENSUS OF STATE-BASED CONSUMER HEALTH CARE PRICE WEBSITES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Kullgren, Jeffrey T.] Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA. [Kullgren, Jeffrey T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Duey, Katia A.; Werner, Rachel M.] Univ Penn, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S4 EP S4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300008 ER PT J AU Lee, JS Nsa, W Hausmann, LR Trivedi, AN Bratzler, DW Auden, D Goodrich, K Larbi, FM Fine, MJ AF Lee, Jonathan S. Nsa, Wato Hausmann, Leslie R. Trivedi, Amal N. Bratzler, Dale W. Auden, Dana Goodrich, Kate Larbi, Fiona M. Fine, Michael J. TI NATIONAL TRENDS IN PROCESSES AND OUTCOMES OF CARE FOR ELDERLY PATIENTS HOSPITALIZED FOR PNEUMONIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Lee, Jonathan S.; Hausmann, Leslie R.; Fine, Michael J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Nsa, Wato; Auden, Dana] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Hausmann, Leslie R.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Trivedi, Amal N.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Goodrich, Kate; Larbi, Fiona M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S126 EP S127 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301062 ER PT J AU Lee, JS Nsa, W Hausmann, LR Trivedi, AN Bratzler, DW Auden, D Goodrich, K Larbi, FM Fine, MJ AF Lee, Jonathan S. Nsa, Wato Hausmann, Leslie R. Trivedi, Amal N. Bratzler, Dale W. Auden, Dana Goodrich, Kate Larbi, Fiona M. Fine, Michael J. TI ASSOCIATIONS BETWEEN PROCESSES OF CARE AND MORTALITY IN A NATIONAL COHORT OF ELDERLY PATIENTS HOSPITALIZED FOR PNEUMONIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Lee, Jonathan S.; Hausmann, Leslie R.; Fine, Michael J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Nsa, Wato; Auden, Dana] Univ Pittsburgh, Med Ctr, Oklahoma City, OK USA. [Hausmann, Leslie R.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Trivedi, Amal N.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Goodrich, Kate; Larbi, Fiona M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S28 EP S28 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300067 ER PT J AU Lee, PT Cunningham, E Munson, D Joyner, J Wakeman, S Tipirneni, R Dunkle, A Paterniti, D Stone, VE AF Lee, Patrick T. Cunningham, Elizabeth Munson, David Joyner, Joseph Wakeman, Sarah Tipirneni, Renuka Dunkle, Ashley Paterniti, Debora Stone, Valerie E. TI MIXED-METHODS EVALUATION OF THE MGH GLOBAL PRIMARY CARE CURRICULUM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Lee, Patrick T.; Cunningham, Elizabeth; Munson, David; Joyner, Joseph; Wakeman, Sarah; Tipirneni, Renuka; Dunkle, Ashley; Stone, Valerie E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Patrick T.] Cambridge Hlth Alliance, Cambridge, MA USA. [Paterniti, Debora] Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S472 EP S473 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302437 ER PT J AU Levy, D Munshi, V Ashburner, JM Zai, A Grant, RW Atlas, SJ AF Levy, Douglas Munshi, Vidit Ashburner, Jeffrey M. Zai, Adrian Grant, Richard W. Atlas, Steven J. TI THE EFFECTIVENESS AND COSTS OF TWO POPULATION-BASED CANCER SCREENING PROGRAMS: THE VALUE OF PCP INPUT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Levy, Douglas; Munshi, Vidit; Ashburner, Jeffrey M.; Grant, Richard W.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S216 EP S217 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301273 ER PT J AU Linsky, A Simon, SR Bokhour, BG AF Linsky, Amy Simon, Steven R. Bokhour, Barbara G. TI PROVIDER PERCEPTIONS OF INTENTIONAL MEDICATION DISCONTINUATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ Sch Med, Boston, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bokhour, Barbara G.] ENRM VA Med Ctr, Bedford, MA USA. [Bokhour, Barbara G.] Boston Univ Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S161 EP S161 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301141 ER PT J AU Linsky, A Maniam, N Volk, LA Simon, SR AF Linsky, Amy Maniam, Nivethietha Volk, Lynn A. Simon, Steven R. TI EFFECT OF COMPUTERIZED CLINICAL DECISION SUPPORT ON APPROPRIATE LABORATORY MONITORING OF MEDICATIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Maniam, Nivethietha; Volk, Lynn A.] Partners Healthcare Syst, Wellesley, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S67 EP S68 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300159 ER PT J AU Liu, MPH Landrum, MB Weeks, JC Huskamp, HA Kahn, KL He, YL Mack, JW Keating, NL AF Liu, Michael Pang-Hsiang Landrum, Mary Beth Weeks, Jane C. Huskamp, Haiden A. Kahn, Katherine L. He, Yulei Mack, Jennifer W. Keating, Nancy L. TI PHYSICIANS' PROPENSITY TO DISCUSS PROGNOSIS ON PATIENTS' PROGNOSIS AWARENESS FOR METASTATIC LUNG OR COLORECTAL CANCER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Liu, Michael Pang-Hsiang; Landrum, Mary Beth; Huskamp, Haiden A.; He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Weeks, Jane C.; Mack, Jennifer W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kahn, Katherine L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Liu, Michael Pang-Hsiang/B-9903-2015 OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S147 EP S148 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301110 ER PT J AU Liu, MPH Chinn, GM Keating, NL AF Liu, Michael Pang-Hsiang Chinn, Garrett M. Keating, Nancy L. TI HOSPICE ENROLLMENT PREFERENCES AMONG PHYSICIANS AND THE TIMING OF THEIR END-OF-LIFE CARE DISCUSSIONS WITH TERMINALLY-ILL CANCER PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Chinn, Garrett M.] VA Boston Healthcare Syst, Boston, MA USA. [Liu, Michael Pang-Hsiang; Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Chinn, Garrett M.; Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Liu, Michael Pang-Hsiang/B-9903-2015 OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S90 EP S90 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300214 ER PT J AU Makam, AN Boscardin, WJ Miao, YH Steinman, M AF Makam, Anil N. Boscardin, W. John Miao, Yinghui Steinman, Michael TI THE RISK OF THIAZIDE-INDUCED ADVERSE EFFECTS IN OLDER ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Makam, Anil N.; Boscardin, W. John; Miao, Yinghui; Steinman, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boscardin, W. John; Miao, Yinghui; Steinman, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S209 EP S209 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301257 ER PT J AU Maniam, N Chinn, GM Volk, LA Williams, DH Bates, DW Simon, SR AF Maniam, Nive Chinn, Garrett M. Volk, Lynn A. Williams, Deborah H. Bates, David W. Simon, Steven R. TI IMPLEMENTATION OF A WEB-BASED PATIENT PORTAL TO IMPROVE TEST RESULT NOTIFICATION IN A COMMUNITY-BASED PEDIATRIC PRIMARY CARE PRACTICE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Maniam, Nive; Volk, Lynn A.; Williams, Deborah H.; Bates, David W.] Partners HealthCare, Wellesley, MA USA. [Maniam, Nive; Chinn, Garrett M.; Volk, Lynn A.; Bates, David W.; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chinn, Garrett M.; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S438 EP S438 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302360 ER PT J AU Mann, EA Kinsosian, B Miller, RK Mary-Ann, H Hammond, J Feinberg, A AF Mann, Elizabeth A. Kinsosian, Bruce Miller, Rachel K. Mary-Ann, Haggerty Hammond, James Feinberg, Ariel TI HOSPITAL AT HOME AS AN INTERAGENCY COLLABORATIVE AT THE PHILADELPHIA VA MEDICAL CENTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Mann, Elizabeth A.; Kinsosian, Bruce; Miller, Rachel K.] Univ Penn, Philadelphia, PA 19104 USA. [Kinsosian, Bruce; Miller, Rachel K.; Mary-Ann, Haggerty; Hammond, James; Feinberg, Ariel] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S437 EP S437 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302357 ER PT J AU McCormick, D Hanchate, AD Lasser, KE Lin, MY D'Amore, M Kressin, NR AF McCormick, Danny Hanchate, Amresh D. Lasser, Karen E. Lin, Mengyun D'Amore, Meredith Kressin, Nancy R. TI IMPACT OF MASSACHUSETTS HEALTH CARE REFORM ON INSURANCE COVERAGE, ACCESS TO AND RECEIPT OF CARE AND HEALTH STATUS AMONG PATIENTS WITH CARDIOVASCULAR DISEASE OR RISK FACTORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [McCormick, Danny] Cambridge Hlth Alliance, Cambridge, MA USA. [McCormick, Danny] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Lasser, Karen E.; Lin, Mengyun; D'Amore, Meredith; Kressin, Nancy R.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S98 EP S98 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300234 ER PT J AU Nall, R Vanka, A Ford, K Libman, H AF Nall, Ryan Vanka, Anita Ford, Kelly Libman, Howard TI OUTPATIENT INTENSIVE ORIENTATION PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Nall, Ryan; Vanka, Anita; Ford, Kelly; Libman, Howard] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S474 EP S475 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302441 ER PT J AU Nall, R Comstock, P AF Nall, Ryan Comstock, Paige TI FATIGUE AND SECOND DEGREE AV BLOCK IN A YOUNG HEALTHY MALE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Nall, Ryan; Comstock, Paige] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S326 EP S326 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302075 ER PT J AU Nasir, S Bates, JT AF Nasir, Saifullah Bates, Jeffrey T. TI CLOPIDOGREL HYPERSENSITIVITY REACTION AFTER PLACEMENT OF A DRUG-ELUTING STENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Nasir, Saifullah; Bates, Jeffrey T.] Baylor Coll Med, Houston, TX 77030 USA. [Nasir, Saifullah; Bates, Jeffrey T.] Houston VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S309 EP S309 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302030 ER PT J AU Neugarten, C Saha, S Roter, D Korthuis, PT Cohn, JA Sharp, VL Moore, RD Beach, MC AF Neugarten, Carter Saha, Somnath Roter, Deborah Korthuis, Philip T. Cohn, Jonathan A. Sharp, Victoria L. Moore, Richard D. Beach, Mary Catherine TI AT EASE AND DIS-EASE: PATIENT REQUESTS FOR REASSURANCE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Neugarten, Carter; Roter, Deborah; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Saha, Somnath; Korthuis, Philip T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sharp, Victoria L.] St Lukes Roosevelt, New York, NY USA. [Cohn, Jonathan A.] Wayne State Univ, Detroit, MI USA. RI Roter, Debra/N-8830-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S30 EP S30 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300071 ER PT J AU Ong, M Wells, KB Jones, L Chung, B Dixon, E Tang, LQ Gilmore, J Sherbourne, C Ngo, VK Stockdale, SE Ramos, E Belin, TR Miranda, J AF Ong, Michael Wells, Kenneth B. Jones, Loretta Chung, Bowen Dixon, Elizabeth Tang, Lingqi Gilmore, James Sherbourne, Cathy Ngo, Victoria K. Stockdale, Susan E. Ramos, Esmeralda Belin, Thomas R. Miranda, Jeanne TI COMMUNITY-PARTNERED CLUSTER-RANDOMIZED COMPARATIVE EFFECTIVENESS TRIAL OF COMMUNITY ENGAGEMENT AND PLANNING OR PROGRAM TECHNICAL ASSISTANCE TO ADDRESS DEPRESSION DISPARITIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wells, Kenneth B.; Chung, Bowen; Sherbourne, Cathy; Ngo, Victoria K.] RAND Corp, Santa Monica, CA USA. [Ong, Michael; Wells, Kenneth B.; Tang, Lingqi; Stockdale, Susan E.; Ramos, Esmeralda; Belin, Thomas R.; Miranda, Jeanne] Univ Calif Los Angeles, Los Angeles, CA USA. [Jones, Loretta] Hlth African Amer Families II, Los Angeles, CA USA. [Jones, Loretta] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. [Chung, Bowen] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Dixon, Elizabeth] QueensCare Hlth & Faith Partnership, Los Angeles, CA USA. [Gilmore, James] Behav Hlth Serv, Gardena, CA USA. [Stockdale, Susan E.] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S47 EP S47 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300112 ER PT J AU Ong, M Miranda, J Jones, L Chung, B Dixon, E Tang, LQ Gilmore, J Sherbourne, C Ngo, VK Stockdale, SE Ramos, E Belin, TR Wells, KB AF Ong, Michael Miranda, Jeanne Jones, Loretta Chung, Bowen Dixon, Elizabeth Tang, Lingqi Gilmore, James Sherbourne, Cathy Ngo, Victoria K. Stockdale, Susan E. Ramos, Esmeralda Belin, Thomas R. Wells, Kenneth B. TI COMMUNITY-PARTNERED EVALUATION OF DEPRESSION SERVICES FOR CLIENTS OF COMMUNITY-BASED AGENCIES IN UNDER-RESOURCED COMMUNITIES IN LOS ANGELES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ong, Michael; Miranda, Jeanne; Tang, Lingqi; Ramos, Esmeralda; Belin, Thomas R.] Univ Calif Los Angeles, Los Angeles, CA USA. [Jones, Loretta] Hlth African Amer Families II, Los Angeles, CA USA. [Jones, Loretta] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. [Chung, Bowen; Sherbourne, Cathy; Ngo, Victoria K.; Wells, Kenneth B.] RAND Corp, Santa Monica, CA USA. [Chung, Bowen] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Dixon, Elizabeth] QueensCare Hlth & Faith Partnership, Los Angeles, CA USA. [Gilmore, James] Behav Hlth Serv, Gardena, CA USA. [Stockdale, Susan E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S48 EP S48 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300113 ER PT J AU Percac-Lima, S Bond, B Saadi, A AF Percac-Lima, Sanja Bond, Barbara Saadi, Altaf TI BOSNIAN, IRAQI, AND SOMALI REFUGEE WOMEN SPEAK: A COMPARATIVE STUDY OF REFUGEE HEALTH BELIEFS ON PREVENTIVE HEALTH AND BREAST CANCER SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Percac-Lima, Sanja] Massachussetts Gen Hosp, Chelsea, MA USA. [Bond, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Percac-Lima, Sanja; Saadi, Altaf] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S35 EP S35 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300083 ER PT J AU Reddy, SM Dick, AM Gerber, MR Mitchell, KS AF Reddy, Shivani M. Dick, Alexandra M. Gerber, Megan R. Mitchell, Karen S. TI TREATMENT SEEKING CHARACTERISTICS OF WOMEN PARTICIPATING IN A YOGA INTERVENTION FOR PTSD SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Reddy, Shivani M.; Gerber, Megan R.; Mitchell, Karen S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reddy, Shivani M.; Dick, Alexandra M.; Gerber, Megan R.; Mitchell, Karen S.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S225 EP S226 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301292 ER PT J AU Reddy, SM Gerber, MR Mitchell, KS AF Reddy, Shivani M. Gerber, Megan R. Mitchell, Karen S. TI THE EFFECT OF A YOGA INTERVENTION ON ALCOHOL AND DRUG ABUSE RISK IN VETERAN AND CIVILIAN WOMEN WITH PTSD SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Reddy, Shivani M.; Gerber, Megan R.; Mitchell, Karen S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reddy, Shivani M.; Gerber, Megan R.; Mitchell, Karen S.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S200 EP S200 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301234 ER PT J AU Redmond, N Litaker, MS Conner, M Kertesz, S AF Redmond, Nicole Litaker, Mark S. Conner, Michael Kertesz, Stefan TI DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF VETERANS WITH A HISTORY OF INCARCERATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Redmond, Nicole; Litaker, Mark S.; Kertesz, Stefan] Univ Alabama Birmingham, Birmingham, AL USA. [Litaker, Mark S.; Conner, Michael; Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S58 EP S59 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300137 ER PT J AU Rigotti, NA Japuntich, S Regan, S Kelley, JH Chang, YC Reyen, M Viana, JC Park, ER Levy, D Korotkin, M Streck, J Singer, DE AF Rigotti, Nancy A. Japuntich, Sandra Regan, Susan Kelley, Jennifer H. Chang, Yuchiao Reyen, Michele Viana, Joseph C. Park, Elyse R. Levy, Douglas Korotkin, Molly Streck, Joanna Singer, Daniel E. TI PROMOTING SMOKING CESSATION AFTER HOSPITAL DISCHARGE: THE HELPING HAND RANDOMIZED CONTROLLED COMPARATIVE EFFECTIVENESS TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Rigotti, Nancy A.; Regan, Susan; Kelley, Jennifer H.; Chang, Yuchiao; Reyen, Michele; Viana, Joseph C.; Park, Elyse R.; Levy, Douglas; Korotkin, Molly; Streck, Joanna; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Japuntich, Sandra] Boston VA Hlth Care Syst, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S160 EP S160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301139 ER PT J AU Ripp, J Fallar, R Katz, JT Bazari, H Bellini, L Korenstein, D AF Ripp, Jonathan Fallar, Robert Katz, Joel T. Bazari, Hasan Bellini, Lisa Korenstein, Deborah TI THE IMPACT OF DUTY HOUR RESTRICTIONS ON JOB BURNOUT IN INTERNAL MEDICINE RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ripp, Jonathan; Fallar, Robert; Korenstein, Deborah] Mt Sinai Sch Med, New York, NY USA. [Katz, Joel T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bellini, Lisa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S204 EP S204 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301243 ER PT J AU Seal, KH Samuelson, K McCamish, N Koenig, CJ Bertenthal, D Tarasovsky, G Choucroun, G AF Seal, Karen H. Samuelson, Kristin McCamish, Nicole Koenig, Christopher J. Bertenthal, Daniel Tarasovsky, Gary Choucroun, Gerard TI OUTCOMES OF A NEW WEB-BASED PTSD TRAINING FOR PRIMARY CARE PROVIDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Seal, Karen H.; Samuelson, Kristin; McCamish, Nicole; Koenig, Christopher J.; Bertenthal, Daniel; Tarasovsky, Gary; Choucroun, Gerard] San Francisco VA Med Ctr, San Francisco, CA USA. [Seal, Karen H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Samuelson, Kristin] Alliant Int Univ, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S473 EP S474 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302439 ER PT J AU Silverman, JB Compton, N AF Silverman, Julie B. Compton, Nicholas TI AN UNCOMMON CAUSE OF DYSASTHESIA AND PRURITUS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Silverman, Julie B.; Compton, Nicholas] VA Puget Sound, Seattle, WA USA. [Silverman, Julie B.; Compton, Nicholas] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S286 EP S286 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301443 ER PT J AU Simmons, LH Sepucha, KR Leavitt, L AF Simmons, Leigh H. Sepucha, Karen R. Leavitt, Lauren TI LETTING PATIENTS DECIDE: A NOVEL STRATEGY FOR INCREASING USE OF PATIENT DECISION AIDS IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Simmons, Leigh H.; Sepucha, Karen R.; Leavitt, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S441 EP S442 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302367 ER PT J AU Simmons, LH Welch, LC Pober, DM Trachtenberg, FL McKinlay, JB AF Simmons, Leigh H. Welch, Lisa C. Pober, David M. Trachtenberg, Felicia L. McKinlay, John B. TI IN THE PRESENCE OF A MENTAL HEALTH COMORBIDITY, WHAT PREDICTS GUIDELINE ADHERENCE FOR A CHRONIC CONDITION (TYPE 2 DIABETES)? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Welch, Lisa C.; Pober, David M.; Trachtenberg, Felicia L.; McKinlay, John B.] New England Res Inst, Watertown, MA 02172 USA. [Simmons, Leigh H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S107 EP S107 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301016 ER PT J AU Simon, SR Checchi, K McNair, SS Rubin, A Marcello, T Bickmore, T AF Simon, Steven R. Checchi, Kyle McNair, Sarah S. Rubin, Amy Marcello, Thomas Bickmore, Timothy TI A PILOT STUDY OF A COMPUTER-BASED RELATIONAL AGENT TO SCREEN FOR SUBSTANCE-USE PROBLEMS IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Simon, Steven R.; Checchi, Kyle; McNair, Sarah S.; Marcello, Thomas] VA Boston, Boston, MA USA. [Checchi, Kyle; McNair, Sarah S.] Harvard Univ, Sch Med, Boston, MA USA. [Rubin, Amy] Boston Univ, Boston, MA 02215 USA. [Rubin, Amy] VA Boston Healthcare Syst, Boston, MA USA. [Simon, Steven R.; Marcello, Thomas] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bickmore, Timothy] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S6 EP S7 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300015 ER PT J AU Sudore, RL Knight, SJ Stewart, AL McMahan, RD Feuz, M Miao, YH Barnes, DE AF Sudore, Rebecca L. Knight, Sara J. Stewart, Anita L. McMahan, Ryan D. Feuz, Mariko Miao, Yinghui Barnes, Deborah E. TI A NOVEL WEBSITE TO PREPARE DIVERSE OLDER ADULTS FOR DECISION MAKING AND ADVANCE CARE PLANNING: A PILOT STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Sudore, Rebecca L.; Stewart, Anita L.; McMahan, Ryan D.; Feuz, Mariko; Miao, Yinghui; Barnes, Deborah E.] UCSF, San Francisco, CA USA. [Sudore, Rebecca L.; Knight, Sara J.; McMahan, Ryan D.; Feuz, Mariko; Miao, Yinghui] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Vet Hlth Adm, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S6 EP S6 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300013 ER PT J AU Sugiyama, T Zingmond, D Lorenz, K Diamant, A O'Malley, K Citko, J Gonzalez, V Wenger, N AF Sugiyama, Takehiro Zingmond, David Lorenz, Karl Diamant, Allison O'Malley, Kate Citko, Judy Gonzalez, Victor Wenger, Neil TI IMPLICATIONS OF POVERTY, HOSPITAL TYPE, AND A GRASSROOTS COMMUNITY INTERVENTION ON DISSEMINATION OF PHYSICIAN ORDERS FOR LIFE SUSTAINING TREATMENT IN CALIFORNIA HOSPITALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Sugiyama, Takehiro; Zingmond, David; Diamant, Allison; Gonzalez, Victor; Wenger, Neil] Univ Calif Los Angeles, Los Angeles, CA USA. [Sugiyama, Takehiro] Univ Tokyo, Tokyo, Japan. [Lorenz, Karl] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [O'Malley, Kate] Calif HealthCare Fdn, Oakland, CA USA. [Citko, Judy] Coalit Compassionate Care Calif, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S104 EP S104 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301009 ER PT J AU Takahashi, TA Berger, DB Wipf, JE Shannon, SE Zierler, BK AF Takahashi, Traci A. Berger, Douglas B. Wipf, Joyce E. Shannon, Sarah E. Zierler, Brenda K. TI "MEET YOUR COLLEAGUES": ENHANCING THE APPEAL OF EDUCATION IN COLLABORATIVE CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Takahashi, Traci A.; Berger, Douglas B.; Wipf, Joyce E.] VA Puget Sound, Seattle, WA USA. [Takahashi, Traci A.; Berger, Douglas B.; Wipf, Joyce E.; Shannon, Sarah E.; Zierler, Brenda K.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S488 EP S488 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302473 ER PT J AU Taksler, G Cutler, DM Giovannucci, E Smith, MR Keating, NL AF Taksler, Glen Cutler, David M. Giovannucci, Edward Smith, Matthew R. Keating, Nancy L. TI VITAMIN D AND RACIAL DIFFERENCES IN PROSTATE CANCER INCIDENCE AND MORTALITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Taksler, Glen] NYU, Sch Med, New York, NY USA. [Cutler, David M.] Harvard Univ, Cambridge, MA 02138 USA. [Cutler, David M.] Natl Bur Econ Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Giovannucci, Edward; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Smith, Matthew R.; Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S239 EP S240 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301325 ER PT J AU Talamantes, E Moreno, G Guerrero, LR Mangione, C Morales, L AF Talamantes, Efrain Moreno, Gerardo Guerrero, Lourdes R. Mangione, Carol Morales, Leo TI HABLAMOS JUNTOS (TOGETHER WE SPEAK): A BRIEF PATIENT-REPORTED MEASURE OF THE QUALITY OF INTERPRETERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Talamantes, Efrain; Moreno, Gerardo; Guerrero, Lourdes R.; Mangione, Carol] Univ Calif Los Angeles, Los Angeles, CA USA. [Talamantes, Efrain] US Dept Vet Affairs, Los Angeles, CA USA. [Morales, Leo] Univ Washington, Seattle, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S83 EP S83 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300197 ER PT J AU Thorndike, AN Mills, S Sonnenberg, L Palakshappa, D Gao, T Pau, CT Regan, S AF Thorndike, Anne N. Mills, Sarah Sonnenberg, Lillian Palakshappa, Deepak Gao, Tian Pau, Cindy T. Regan, Susan TI RANDOMIZED INTERVENTION TO PROMOTE PHYSICAL ACTIVITY OF INTERNAL MEDICINE RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Thorndike, Anne N.; Mills, Sarah; Sonnenberg, Lillian; Palakshappa, Deepak; Gao, Tian; Pau, Cindy T.; Regan, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S165 EP S165 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301151 ER PT J AU Trivedi, AN Nsa, W Hausmann, LR Lee, JS Ma, A Bratzler, DW Goodrich, K Larbi, FM Fine, MJ AF Trivedi, Amal N. Nsa, Wato Hausmann, Leslie R. Lee, Jonathan S. Ma, Allen Bratzler, Dale W. Goodrich, Kate Larbi, Fiona M. Fine, Michael J. TI TRENDS IN THE QUALITY OF CARE AND RACIAL/ETHNIC DISPARITIES IN US HOSPITALS, 2005-2010 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Trivedi, Amal N.] Providence VA Med Ctr, Providence, RI USA. [Trivedi, Amal N.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Nsa, Wato; Ma, Allen; Bratzler, Dale W.] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hausmann, Leslie R.; Lee, Jonathan S.; Goodrich, Kate; Larbi, Fiona M.] Ctr Medicare Serv, Baltimore, MD USA. [Hausmann, Leslie R.; Lee, Jonathan S.; Goodrich, Kate; Larbi, Fiona M.] Ctr Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S228 EP S228 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301298 ER PT J AU Trivedi, R Kivlahan, D McCarthy, J Post, EP Saxon, AJ Pomerantz, A Sun, H Piette, JD Fihn, SD Nelson, KM AF Trivedi, Ranak Kivlahan, Dan McCarthy, John Post, Edward P. Saxon, Andrew J. Pomerantz, Andrew Sun, Haili Piette, John D. Fihn, Stephan D. Nelson, Karin M. TI BURDEN OF MENTAL ILLNESS AMONG VA PRIMARY CARE PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Trivedi, Ranak; Saxon, Andrew J.; Sun, Haili; Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Trivedi, Ranak; Saxon, Andrew J.; Fihn, Stephan D.; Nelson, Karin M.] Univ Washington, Seattle, WA 98195 USA. [McCarthy, John; Post, Edward P.; Piette, John D.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [McCarthy, John; Post, Edward P.; Piette, John D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kivlahan, Dan; Pomerantz, Andrew] VA Off Mental Hlth Serv, White River, VT USA. [Pomerantz, Andrew] Dartmouth Coll, Hanover, NH 03755 USA. [Fihn, Stephan D.] VA Off Analyt & Business Intelligence, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S37 EP S38 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300089 ER PT J AU Turner, BJ Finley, E Garza, DR Vale, S Simmonds, MJ Pugh, MJ AF Turner, Barbara J. Finley, Erin Garza, Diandrea R. Vale, Shruthi Simmonds, Maureen J. Pugh, Mary Jo TI THEMES FROM FOCUS GROUPS OF VETERANS WITH CHRONIC NON-CANCER PAIN ON HIGH DOSE OPIOID ANALGESICS: LOVE/HATE OF OPIOIDS AND CHALLENGES WITH ALTERNATIVE PAIN CARE STRATEGIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Turner, Barbara J.; Finley, Erin; Garza, Diandrea R.; Vale, Shruthi; Simmonds, Maureen J.; Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Finley, Erin; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S221 EP S222 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301284 ER PT J AU Varkey, AB Manwell, LB Ibrahim, SA Brown, R Laiteerapong, N Schwartz, MD Williams, E Burgess, D Wiltshire, J Montague, E Poplau, S Linzer, M AF Varkey, Anita B. Manwell, Linda Baier Ibrahim, Said A. Brown, Roger Laiteerapong, Neda Schwartz, Mark D. Williams, Eric Burgess, Diana Wiltshire, Jacqueline Montague, Enid Poplau, Sara Linzer, Mark TI IMPACT OF WORK CONDITIONS ON ERRORS AND QUALITY: A COMPARISON OF PRIMARY CARE CLINICS SERVING LARGE PROPORTIONS OF MINORITY PATIENTS TO THOSE THAT DO NOT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Varkey, Anita B.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Manwell, Linda Baier; Brown, Roger] Univ Wisconsin, Madison, WI USA. [Ibrahim, Said A.] VA Philadelphia Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Perelman Univ Penn, Sch Med, Philadelphia, PA USA. [Laiteerapong, Neda] Univ Chicago, Chicago, IL 60637 USA. [Schwartz, Mark D.] NYU, Sch Med, New York, NY USA. [Schwartz, Mark D.] VA New York Harbor Hlth Care Syst, New York, NY USA. [Williams, Eric] Univ Alabama, Tuscaloosa, AL USA. [Burgess, Diana] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Burgess, Diana] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Wiltshire, Jacqueline] Univ S Florida, Tampa, FL USA. [Montague, Enid] Northwestern Univ, Chicago, IL 60611 USA. [Poplau, Sara; Linzer, Mark] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RI Burgess, Diana/A-1946-2016 NR 0 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S100 EP S100 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300238 ER PT J AU Wachterman, MW Simon, SR Lipsitz, SR Keating, NL AF Wachterman, Melissa W. Simon, Steven R. Lipsitz, Stuart R. Keating, Nancy L. TI PATTERNS OF HOSPICE CARE AMONG VETERANS AND NON-VETERANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wachterman, Melissa W.; Simon, Steven R.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Wachterman, Melissa W.; Simon, Steven R.; Lipsitz, Stuart R.; Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S142 EP S143 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301098 ER PT J AU Wakeman, S Baggett, M Campbell, E Pham-Kanter, G AF Wakeman, Sarah Baggett, Meridale Campbell, Eric Pham-Kanter, Genevieve TI INTERNAL MEDICINE RESIDENTS' TRAINING IN SUBSTANCE USE DISORDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wakeman, Sarah; Baggett, Meridale] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wakeman, Sarah; Campbell, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Campbell, Eric; Pham-Kanter, Genevieve] Mongan Inst Hlth Policy, Boston, MA USA. [Pham-Kanter, Genevieve] Univ Colorado Anschutz Med Campus, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S109 EP S110 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301022 ER PT J AU Wang, EA McGinnis, KA Akgun, KM Edelman, J Justice, AC Rimland, D Wang, KR Fiellin, DA AF Wang, Emily A. McGinnis, Kathleen A. Akguen, Kathleen M. Edelman, Jennifer Justice, Amy C. Rimland, David Wang, Karen Fiellin, David A. TI INCARCERATION IS ASSOCIATED WITH WORSE HEALTH OUTCOMES AND ANTIRETROVIRAL ADHERENCE AMONG HIV-INFECTED PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wang, Emily A.; Akguen, Kathleen M.; Edelman, Jennifer; Justice, Amy C.; Fiellin, David A.] Yale Univ, New Haven, CT USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Justice, Amy C.; Wang, Karen] VA CT Healthcare Syst, West Haven, CT USA. [Rimland, David] Atlanta VAMC, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S107 EP S108 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301017 ER PT J AU Wang, ES Conde, M Simon, B Leykum, L AF Wang, Emily S. Conde, Michelle Simon, Bret Leykum, Luci TI KNOWLEDGE AND PERCEPTIONS OF NON-PHYSICIAN PRIMARY CARE TEAM MEMBERS REGARDING END OF YEAR PCP TRANSITIONS IN A RESIDENT CONTINUITY CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wang, Emily S.; Conde, Michelle; Leykum, Luci] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Wang, Emily S.; Conde, Michelle; Simon, Bret; Leykum, Luci] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S112 EP S112 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301028 ER PT J AU Ward, CE He, W Ashburner, JM Atlas, SJ AF Ward, Charlotte E. He, Wei Ashburner, Jeffrey M. Atlas, Steven J. TI DEVELOPMENT OF AN INTERACTIVE, WEB-BASED COMPREHENSIVE PERFORMANCE DASHBOARD FOR USE IN PRIMARY CARE PRACTICE NETWORKS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ward, Charlotte E.; He, Wei; Ashburner, Jeffrey M.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S434 EP S434 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302352 ER PT J AU Ward, CE Edgman-Levitan, S Cohen, MJ Berman, R AF Ward, Charlotte E. Edgman-Levitan, Susan Cohen, Marya J. Berman, Rebecca TI THE ASSOCIATION BETWEEN MEDICAL STUDENT CAREER INTERESTS AND ATTITUDES TOWARD PRIMARY CARE, FACULTY MENTORSHIP, AND INSTITUTIONAL SUPPORT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ward, Charlotte E.; Edgman-Levitan, Susan; Cohen, Marya J.; Berman, Rebecca] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S195 EP S196 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301223 ER PT J AU Ward, CE Ashburner, JM He, W Atlas, SJ AF Ward, Charlotte E. Ashburner, Jeffrey M. He, Wei Atlas, Steven J. TI THE ASSOCIATION BETWEEN PATIENT EXPERIENCE OF CARE AND SUBSEQUENT CANCER PREVENTION AND CHRONIC DISEASE OUTCOMES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ward, Charlotte E.; Ashburner, Jeffrey M.; He, Wei; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S196 EP S197 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301225 ER PT J AU Ward, CE Ashburner, J He, W Atlas, SJ AF Ward, Charlotte E. Ashburner, JeffreyM. He, Wei Atlas, Steven J. TI THE ASSOCIATION BETWEEN OUTPATIENT EXPERIENCE OF CARE AND SUBSEQUENT RESOURCE UTILIZATION IN A PRIMARY CARE NETWORK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Ward, Charlotte E.; Ashburner, JeffreyM.; He, Wei; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S196 EP S196 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301224 ER PT J AU Warde, CM Pearson, M AF Warde, Carole M. Pearson, Marjorie TI A CURRICULUM TO IMPROVE AND TEACH PRIMARY CARE TEAM FUNCTION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Warde, Carole M.] Greater Los Angeles VA Hlth Syst, North Hills, CA USA. [Pearson, Marjorie] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S450 EP S451 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302385 ER PT J AU Wu, CA Mulder, AL Costa, MV Zai, A Tishler, L Saltzman, JR Bitton, A Ellner, AL AF Wu, Charlotte A. Mulder, Amara L. Costa, Manuela V. Zai, Adrian Tishler, Lori Saltzman, John R. Bitton, Asaf Ellner, Andrew L. TI A POPULATION MANAGEMENT SYSTEM FOR IMPROVING COLORECTAL SCREENING RATES IN A PRIMARY CARE SETTING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Wu, Charlotte A.; Mulder, Amara L.; Costa, Manuela V.; Tishler, Lori; Saltzman, John R.; Bitton, Asaf; Ellner, Andrew L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wu, Charlotte A.; Bitton, Asaf; Ellner, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA. [Zai, Adrian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S428 EP S429 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939302340 ER PT J AU Young, EA Stratton, KA Brin, M AF Young, Eric A. Stratton, Kristin A. Brin, Michael TI DECLINE IN INTERNAL MEDICINE RESIDENTS' ACLS EXPERIENCE IN THE MODERN TRAINING ERA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Young, Eric A.; Stratton, Kristin A.; Brin, Michael] Denver VA Med Ctr, Denver, CO USA. [Young, Eric A.; Stratton, Kristin A.] Univ Colorado Denver, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S57 EP S58 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939300135 ER PT J AU Zulman, D Yoon, J Cohen, DM Wagner, TH Ritchie, C Asch, S AF Zulman, Donna Yoon, Jean Cohen, Danielle M. Wagner, Todd H. Ritchie, Christine Asch, Steven TI MULTIMORBIDITY AND HEALTH CARE UTILIZATION AMONG HIGH-COST PATIENTS: IMPLICATIONS FOR CARE COORDINATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 24-27, 2013 CL Denver, CO SP Soc Gen Internal Med C1 [Zulman, Donna; Yoon, Jean; Cohen, Danielle M.; Wagner, Todd H.; Asch, Steven] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Zulman, Donna; Cohen, Danielle M.; Wagner, Todd H.; Asch, Steven] Stanford Univ, Stanford, CA 94305 USA. [Ritchie, Christine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ritchie, Christine] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 SU 1 BP S123 EP S124 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB6ZP UT WOS:000331939301055 ER PT J AU Maguire, CA Bovenberg, MS Crommentuijn, MHW Niers, JM Kerami, M Teng, J Sena-Esteves, M Badr, CE Tannous, BA AF Maguire, Casey A. Bovenberg, M. Sarah Crommentuijn, Matheus H. W. Niers, Johanna M. Kerami, Mariam Teng, Jian Sena-Esteves, Miguel Badr, Christian E. Tannous, Bakhos A. TI Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes SO MOLECULAR THERAPY-NUCLEIC ACIDS LA English DT Article DE bioluminescence imaging; firefly luciferase; Gaussia luciferase; Vargula luciferase ID VARGULA-HILGENDORFII LUCIFERASE; FIREFLY LUCIFERASE; GENE-EXPRESSION; REPORTER APPLICATIONS; SECRETED LUCIFERASE; RENILLA LUCIFERASE; MOUSE-BRAIN; STEM-CELLS; T-CELLS; APOPTOSIS AB Bioluminescence imaging (BLI) has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc) and Renilla or Gaussia (Gluc) luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc) as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) delivered using an adeno-associated viral vector (AAV) on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-kappa B (NF-kappa B) activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience. C1 [Maguire, Casey A.; Bovenberg, M. Sarah; Crommentuijn, Matheus H. W.; Niers, Johanna M.; Kerami, Mariam; Teng, Jian; Badr, Christian E.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Maguire, Casey A.; Bovenberg, M. Sarah; Crommentuijn, Matheus H. W.; Niers, Johanna M.; Kerami, Mariam; Teng, Jian; Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, M. Sarah] Leiden Univ, Dept Neurosurg, Med Ctr, Leiden, Netherlands. [Crommentuijn, Matheus H. W.; Niers, Johanna M.; Kerami, Mariam] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Tannous, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu OI Crommentuijn, Matheus/0000-0001-8217-5370 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke (NINDS) [P30NS045776, 1R01NS064983]; American Brain Tumor Association; Fulbright scholarship; Huygens Scholarship Program; VSB fonds; Saal van Zwanenberg Foundation; NINDS [P30NS045776] FX This work was supported by grant from National Institutes of Health/National Institute of Neurological Disorders and Stroke (NINDS) P30NS045776 and 1R01NS064983 (B. A. T.) and by a Fellowship from the American Brain Tumor Association (C. A. M.). M. S. B. was supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB fonds, and the Saal van Zwanenberg Foundation. We thank Hiroaki Wakimoto for the GBM8 cells. We acknowledge the Neuroscience Center Nucleic Acid Quantitation Core and Image Analysis Core (supported by NINDS P30NS045776). The authors declared no conflict of interest. NR 38 TC 22 Z9 23 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2162-2531 J9 MOL THER-NUCL ACIDS JI Mol. Ther.-Nucl. Acids PD JUN PY 2013 VL 2 AR e99 DI 10.1038/mtna.2013.25 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC4BV UT WOS:000332466500004 PM 23778500 ER PT J AU Singh, JA Wells, G Christensen, R Ghogomu, E Macdonald, J Maxwell, L Tarp, S Buchbinder, R Tugwell, P AF Singh, J. A. Wells, G. Christensen, R. Ghogomu, E. Macdonald, J. Maxwell, L. Tarp, S. Buchbinder, R. Tugwell, P. CA Cochrane Biol Study Grp TI RISK OF CANCER, SERIOUS LUNG INFECTIONS AND DEATH WITH BIOLOGICS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (RCTS) SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Wells, G.; Ghogomu, E.; Maxwell, L.; Tugwell, P.] Univ Ottawa, Ottawa, ON, Canada. [Christensen, R.] Copenhagen Univ Hosp, Frederiksberg, Denmark. [Macdonald, J.] Robarts Res Inst, London, ON N6A 5C1, Canada. [Tarp, S.] Copenhagen Univ Hosp, Frederiksberg, Denmark. [Buchbinder, R.] Monash Univ, Malvern, Australia. RI Buchbinder, Rachelle/G-2952-2011 NR 1 TC 0 Z9 1 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 74 EP 74 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587901274 ER PT J AU Singh, JA Lewallen, D AF Singh, J. A. Lewallen, D. TI INCOME AND PATIENT-REPORTED OUTCOMES (PROS) AFTER PRIMARY TOTAL KNEE ARTHROPLASTY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Lewallen, D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 81 EP 82 PG 2 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587901296 ER PT J AU Khanna, D Gladue, H Fitzgerald, J Channick, R Chung, L Distler, O Furst, D Hachulla, E Humbert, M Langelben, D Mathai, S Saggar, R Visovatti, S McLaughlin, V AF Khanna, D. Gladue, H. Fitzgerald, J. Channick, R. Chung, L. Distler, O. Furst, D. Hachulla, E. Humbert, M. Langelben, D. Mathai, S. Saggar, R. Visovatti, S. McLaughlin, V. TI RECOMMENDATIONS FOR SCREENING AND DETECTION OF CONNECTIVE-TISSUE DISEASE ASSOCIATED PULMONARY ARTERIAL HYPERTENSION SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Khanna, D.; Gladue, H.; Visovatti, S.; McLaughlin, V.] Univ Michigan, Ann Arbor, MI 48109 USA. [Fitzgerald, J.; Furst, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Channick, R.] Mass Gen Hosp, Boston, MA USA. [Chung, L.] Stanford Univ, Stanford, CA 94305 USA. [Distler, O.] Univ Zurich, Zurich, Switzerland. [Hachulla, E.] Univ Hosp Lille, Lille, France. [Humbert, M.] Univ S Paris, Paris, France. [Langelben, D.] McGill Univ, Montreal, PQ, Canada. [Mathai, S.] Johns Hopkins Univ, Baltimore, MD USA. [Saggar, R.] St Joseph Hosp, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 146 EP 146 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587901477 ER PT J AU Hirsh, JM Quinzanos, I Keniston, A Caplan, L AF Hirsh, J. M. Quinzanos, I. Keniston, A. Caplan, L. TI VERBALLY ADMINISTERED PATIENT GLOBAL ASSESSMENTS AND ASSESSMENTS OF DISEASE ACTIVITY DEMONSTRATE GOOD CORRELATION WITH TRADITIONAL WRITTEN VERSIONS: THE TALK-THE-LINE OBSERVATIONAL STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Hirsh, J. M.; Keniston, A.] Denver Hlth, Denver, CO USA. [Quinzanos, I.; Caplan, L.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 149 EP 149 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587901485 ER PT J AU O'Dell, JR Mikuls, TR Taylor, T Ahluwalia, V Brophy, M Warren, S Lew, R Phibbs, C Anis, AH Cannella, AC Kunkel, GA Keystone, E AF O'Dell, J. R. Mikuls, T. R. Taylor, T. Ahluwalia, V. Brophy, M. Warren, S. Lew, R. Phibbs, C. Anis, A. H. Cannella, A. C. Kunkel, G. A. Keystone, E. CA CSP551 RACAT Res Grp TI RANDOMIZED DOUBLE-BLIND COMPARATIVE EFFECTIVENESS IN RA PATIENTS WITH ACTIVE DISEASE DESPITE METHOTREXATE (MTX): A COMPARISON OF CONVENTIONAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS WITH A BIOLOGICAL SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [O'Dell, J. R.; Mikuls, T. R.; Cannella, A. C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Taylor, T.] VA Med Ctr, White River Jct, VT USA. [Ahluwalia, V.] Osler Hlth Ctr, Mississauga, ON, Canada. [Brophy, M.; Lew, R.] VA Boston Healthcare Syst, Boston, MA USA. [Warren, S.] VA CSP Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. [Phibbs, C.] Palo Alto VA Hlth Care Syst, Hearth Econ Resource Ctr 152, Palo Alto, CA USA. [Anis, A. H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kunkel, G. A.] George Wahlen Vet Affairs Med Ctr, Div Rheumatol, Salt Lake City, UT USA. [Keystone, E.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 1 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 240 EP 240 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587902143 ER PT J AU Singh, JA Lewallen, D AF Singh, J. A. Lewallen, D. TI PATIENTS WITH OSTEOARTHRITIS HAVE BETTER FUNCTIONAL OUTCOMES COMPARED TO RHEUMATOID ARTHRITIS AFTER PRIMARY HIP ARTHROPLASTY: A COHORT STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Lewallen, D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 351 EP 351 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587902471 ER PT J AU Caplan, L Luong, PT Richards, JS Majithia, V Bobba, S Qaiyumi, S Davis, LA AF Caplan, L. Luong, P. T. Richards, J. S. Majithia, V. Bobba, S. Qaiyumi, S. Davis, L. A. TI VALIDATION OF MODIFIED DISEASE ACTIVITY AND FUNCTIONAL STATUS QUESTIONNAIRES IN SPONDYLOARTHRITIS SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Caplan, L.; Luong, P. T.; Bobba, S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Richards, J. S.; Qaiyumi, S.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Majithia, V.] Montgomery Vet Affairs Med Ctr, Jackson, MS USA. [Davis, L. A.] Denver Hlth, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 534 EP 534 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587903361 ER PT J AU Singh, JA Lewallen, D AF Singh, J. A. Lewallen, D. TI IPSILATERAL LOWER EXTREMITY JOINT INVOLVEMENT INCREASES THE RISK OF POOR PAIN AND FUNCTION OUTCOMES AFTER HIP OR KNEE ARTHROPLASTY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Lewallen, D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 552 EP 553 PG 2 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587903418 ER PT J AU Singh, JA Lewallen, D AF Singh, J. A. Lewallen, D. TI UNDERLYING DIAGNOSIS PREDICTS PATIENT-REPORTED OUTCOMES AFTER REVISION TOTAL HIP ARTHROPLASTY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Lewallen, D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 553 EP 553 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587903419 ER PT J AU Singh, JA Lewallen, D AF Singh, J. A. Lewallen, D. TI MEDICAL COMORBIDITY IS ASSOCIATED WITH PERSISTENT INDEX HIP PAIN AFTER PRIMARY THA SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Lewallen, D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2013 VL 72 SU 3 BP 696 EP 696 PG 1 WC Rheumatology SC Rheumatology GA AB1XT UT WOS:000331587904154 ER PT J AU Brown, RT Steinman, MA AF Brown, Rebecca T. Steinman, Michael A. TI Characteristics of Emergency Department Visits by Older Versus Younger Homeless Adults in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH-CARE; SUBSTANCE USE; GERIATRIC SYNDROMES; ALCOHOL-PROBLEMS; FREQUENT USERS; SAN-FRANCISCO; POPULATION; EPIDEMIOLOGY; PEOPLE; URBAN AB Objectives. We compared the characteristics of emergency department (ED) visits of older versus younger homeless adults. Methods. We analyzed 2005-2009 data from the National Hospital Ambulatory Medical Care Survey, a nationally representative survey of visits to hospitals and EDs, and used sampling weights, strata, and clustering variables to obtain nationally representative estimates. Results. The ED visits of homeless adults aged 50 years and older accounted for 36% of annual visits by homeless patients. Although demographic characteristics of ED visits were similar in older and younger homeless adults, clinical and health services characteristics differed. Older homeless adults had fewer discharge diagnoses related to psychiatric conditions (10% vs 20%; P = .002) and drug abuse (7% vs 15%; P = .003) but more diagnoses related to alcohol abuse (31% vs 23%; P = .03) and were more likely to arrive by ambulance (48% vs 36%; P = .02) and to be admitted to the hospital (20% vs 11%; P = .003). Conclusions. Older homeless adults' patterns of ED care differ from those of younger homeless adults. Health care systems need to account for these differences to meet the needs of the aging homeless population. C1 [Brown, Rebecca T.; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.; Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94112 USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,UCSF Box VA-181G, San Francisco, CA 94112 USA. EM rebecca.brown@ucsf.edu FU National Institute on Aging [T32 AG000212]; American Federation for Aging Research [1K23 AG030999] FX R.T. Brown was supported by the National Institute on Aging (grant T32 AG000212). M. A. Steinman was supported by the National Institute on Aging, and the American Federation for Aging Research (grant 1K23 AG030999). NR 44 TC 8 Z9 9 U1 1 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2013 VL 103 IS 6 BP 1046 EP 1051 DI 10.2105/AJPH.2012.301006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA3FI UT WOS:000330977900036 PM 23597348 ER PT J AU Tsai, AC AF Tsai, Alexander C. TI ACHIEVING CONSENSUS ON TERMINOLOGY DESCRIBING MULTIVARIABLE ANALYSES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. RP Tsai, AC (reprint author), 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org FU NIMH NIH HHS [MH-096620, K23 MH096620] NR 4 TC 1 Z9 1 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2013 VL 103 IS 6 BP E1 EP E1 DI 10.2105/AJPH.2013.301234 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA3FI UT WOS:000330977900001 PM 23597350 ER PT J AU Wang, EA Hong, CS Shavat, S Kessell, ER Sanders, R Kushel, MB AF Wang, Emily A. Hong, Clemens S. Shavat, Shira Kessell, Eric R. Sanders, Ronald Kushel, Margot B. TI EXCLUSION OF NON-ENGLISH-SPEAKING, RECENTLY RELEASED PRISONERS RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Wang, Emily A.] Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. [Hong, Clemens S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Shavat, Shira; Sanders, Ronald] San Francisco Dept Publ Hlth, Transit Clin, Southeast Hlth Ctr, San Francisco, CA USA. [Shavat, Shira] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Kessell, Eric R.] Univ Calif San Francisco, Div Hosp Med, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Kushel, Margot B.] Univ Calif San Francisco, Dept Internal Med, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, 367 Cedar St,Harkness Bldg A,Suite 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2013 VL 103 IS 6 BP E6 EP E7 DI 10.2105/AJPH.2013.301363 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA3FI UT WOS:000330977900007 PM 23597355 ER PT J AU Duggan, M Rago, A Sharma, U Zugates, G Freyman, T Busold, R Caulkins, J Pham, Q Chang, YC Mejaddam, A Beagle, J Velmahos, G deMoya, M Zukerberg, L Ng, TF King, LTCDR AF Duggan, Michael Rago, Adam Sharma, Upma Zugates, Greg Freyman, Toby Busold, Rany Caulkins, John Quynh Pham Chang, Yuchaio Mejaddam, Ali Beagle, John Velmahos, George deMoya, Marc Zukerberg, Lawrence Tat Fong Ng King, L. T. C. David R. TI Self-expanding polyurethane polymer improves survival in a model of noncompressible massive abdominal hemorrhage SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Combat; battlefield; noncompressible; hemorrhage; prehospital ID OPERATION-IRAQI-FREEDOM; FIBRIN SEALANT FOAM; HEMOSTATIC AGENT; LIVER-INJURIES; BLOOD-LOSS; DRESSINGS; TRAUMA; SWINE; BANDAGE; CARE AB BACKGROUND: Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield. Two dynamically mixed and percutaneously injected liquids were engineered to create an in situ self-expanding polymer foam to facilitate hemostasis in massive bleeding. We hypothesized that intraperitoneal injection of the polymer could achieve conformal contact with sites of injury and improve survival in swine with lethal hepatoportal injury. METHODS: High grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncoagulopathic, noncompressible hemorrhage. Animals received either standard battlefield fluid resuscitation (control, n = 12) or fluid resuscitation plus intraperitoneal injection of hemostatic foam(polymer, n = 15) and were monitored for 3 hours. Blood loss was quantified, and all hepatoportal injuries were inspected for consistency. RESULTS: Before intervention, all animals initially experienced severe, profound hypotension and near-arrest (mean arterial pressure at 10 minutes, 21 [5.3] mm Hg). Overall survival at 3 hours was 73% in the polymer group and 8% in the control group (p = 0.001). Median survival time was more than 150 minutes in the polymer group versus 23 minutes (19-41.5 minutes) in the control group (p < 0.001), and normalized blood loss in the polymer group was 0.47 (0.30) g/kg per minute versus 3.0 (1.3) g/kg per minute in the controls (p = < 0.001). All hepatoportal injuries were anatomically similar, and the polymer had conformal contact with injured tissues. CONCLUSION: Intraperitoneal polymer injection during massive noncompressible hemorrhage reduces blood loss and improves survival in a lethal, closed-cavity, hepatoportal injury model. Chronic safety and additional efficacy studies in other models are needed. (Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Duggan, Michael; Chang, Yuchaio; Mejaddam, Ali; Beagle, John; Velmahos, George; deMoya, Marc; Zukerberg, Lawrence; King, L. T. C. David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rago, Adam; Sharma, Upma; Zugates, Greg; Freyman, Toby; Busold, Rany; Caulkins, John; Quynh Pham; Tat Fong Ng] Arsenal Med Inc, Watertown, MA USA. RP King, LTCDR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 FU DARPA; ARO [W911NF-10-C-0089] FX This work was supported by DARPA and ARO contract W911NF-10-C-0089. NR 22 TC 17 Z9 19 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JUN PY 2013 VL 74 IS 6 BP 1462 EP 1467 DI 10.1097/TA.0b013e31828da937 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AB4DO UT WOS:000331739800012 PM 23694873 ER PT J AU Borczuk, P Penn, J Peak, D Chang, YC AF Borczuk, Pierre Penn, Joshua Peak, David Chang, Yuchiao TI Patients with traumatic subarachnoid hemorrhage are at low risk for deterioration or neurosurgical intervention SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Mild head trauma; subarachnoid hemorrhage; neurosurgical consultation ID MINOR HEAD-INJURY; BRAIN-INJURY; COMPUTED-TOMOGRAPHY; UTILITY; CONSULTATION; MANAGEMENT; RULE AB BACKGROUND: Current standard of care for patients with traumatic intracranial hemorrhage (TIH) includes neurosurgical consultation and/or transfer to a trauma center with neurosurgical backup. We hypothesize that a set of low-risk criteria can be applied to such patients to identify those who may not require neurosurgical evaluation. METHODS: This is a cross-sectional study of consecutive emergency department patients in 2009 and 2010 with TIH on computerized tomographic scan owing to blunt head trauma. Patients presented to an urban academic Level I trauma center (volume, 92,000) were older than 15 years and had a Glasgow Coma Scale (GCS) score of 13 or greater. Charts were abstracted using a standardized data form by two emergency physicians. Our principal outcome was deterioration represented by a composite of neurosurgical intervention, clinical deterioration, or worsening computerized tomographic scan result. RESULTS: During the study period, 404 patients were seen with TIH and met our inclusion criteria, and 48 of those patients (11.8%) deteriorated. Patients with isolated subarachnoid hemorrhage, were less likely to deteriorate (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.011-0.58). Characteristics associated with deterioration were subdural hematomas (OR, 2.63; 95% CI, 1.198-5.81) or presenting GCS of less than 15 (OR, 2.12; 95% CI, 1.01-4.43). The use of anticoagulant medications or antiplatelet agents were not associated with deterioration for warfarin, aspirin, or clopidogrel; however bleeding diatheses were corrected with vitamin K, fresh frozen plasma, and platelets as necessary. CONCLUSION: Patients with isolated traumatic subarachnoid hemorrhage are at low risk for deterioration. These individuals may not need neurosurgical consultation or transfer to a trauma center where neurosurgical backup is available. Those patients with subdural hematoma or a GCS of less than 15 have a higher risk of deterioration and require neurosurgical evaluation. (Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Borczuk, Pierre; Peak, David] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Borczuk, Pierre; Penn, Joshua; Peak, David] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Penn, Joshua] Winchester Hosp, Dept Emergency Med, Boston, MA USA. RP Borczuk, P (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM pborczuk@partners.org NR 19 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JUN PY 2013 VL 74 IS 6 BP 1504 EP 1509 DI 10.1097/TA.0b013e31829215cf PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AB4DO UT WOS:000331739800018 PM 23694879 ER PT J AU Varshney, N Jain, A Chan, V Yu, L Sarraf, D AF Varshney, Neeta Jain, Atul Chan, Vicki Yu, Le Sarraf, David TI Anti-VEGF response in macular hemorrhage and incidence of retinal pigment epithelial tears SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; INTRAVITREAL BEVACIZUMAB INJECTION; CARDIOVASCULAR RISK-FACTORS; SUBMACULAR HEMORRHAGE; CHOROIDAL NEOVASCULARIZATION; PNEUMATIC DISPLACEMENT; RANIBIZUMAB INJECTION; DEGENERATION; MANAGEMENT; DISEASE AB Objective: To study the visual and anatomic outcomes of serial anti-vascular endothelial growth factor (anti-VEGF) therapy for severe macular hemorrhage in eyes with exudative age-related macular degeneration (AMD). Design: Consecutive retrospective analysis. Participants: Twenty eyes from 20 patients with severe macular hemorrhage (greater than 50% blockage with formal fluorescein angiography [FA]) secondary to wet AMD were studied. Methods: We performed a chart review of patients at a single centre from May 2006 to September 2009. Presenting visual acuity and diameter of hemorrhage were recorded as well as number of injections, time by which no hemorrhage was remaining, and final anatomic outcome. Cardiovascular risk factors and use of antiplatelet medication or anticoagulation were noted. Results: Average presenting visual acuity was 1.55 (20/710), and number of injections needed for resolution of hemorrhage was 4. Visual acuity significantly improved from 1.55 (20/710) to 0.70 (20/100) after injections. Thirty-five percent of eyes were found to have an associated retinal pigment epithelial (RPE) tear, and these eyes were found to have received more injections. Final visual acuity was not significantly different in eyes with RPE tears compared with nontear eyes. Eighty-one percent of patients had associated cardiovascular risk factors; antiplatelet therapy and anticoagulation were not found to play a role in hemorrhage size. Conclusions: RPE tears are found in a significant number of individuals with large macular hemorrhages secondary to exudative macular degeneration, but with continued treatment with anti-VEGF therapy, visual acuity can significantly improve even in the presence of these tears. Eyes with severe macular hemorrhage thus should be considered candidates for anti-VEGF therapy. C1 [Varshney, Neeta; Chan, Vicki; Yu, Le; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Jain, Atul] San Diego Retina Associates, San Diego, CA USA. [Sarraf, David] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Sarraf, David] Kaiser Permanente, Woodland Hills, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Karl Kirchgessner Foundation FX This work was supported by grants from Karl Kirchgessner Foundation (D.S.). NR 39 TC 1 Z9 1 U1 1 U2 2 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD JUN PY 2013 VL 48 IS 3 BP 210 EP 215 DI 10.1016/j.jcjo.2013.01.023 PG 6 WC Ophthalmology SC Ophthalmology GA AA5OD UT WOS:000331148400025 PM 23769784 ER PT J AU Yonekawa, Y AF Yonekawa, Yoshihiro TI Aflibercept for the treatment of refractory polypoidal choroidal vasculopathy SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Letter ID RANIBIZUMAB; BEVACIZUMAB; EFFICACY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Yonekawa, Y (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM yoshihiro_yonekawa@meei.harvard.edu NR 8 TC 6 Z9 6 U1 0 U2 3 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD JUN PY 2013 VL 48 IS 3 BP E59 EP E60 DI 10.1016/j.jcjo.2012.12.015 PG 2 WC Ophthalmology SC Ophthalmology GA AA5OD UT WOS:000331148400011 PM 23769799 ER PT J AU Kane, JM Perlis, RH DiCarlo, LA Au-Yeung, K Duong, J Petrides, G AF Kane, John M. Perlis, Roy H. DiCarlo, Lorenzo A. Au-Yeung, Kityee Duong, Jessie Petrides, Georgios TI First Experience With a Wireless System Incorporating Physiologic Assessments and Direct Confirmation of Digital Tablet Ingestions in Ambulatory Patients With Schizophrenia or Bipolar Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RATING-SCALE; ADHERENCE; RELIABILITY; MEDICATION AB Objective: To characterize the feasibility and safety of a wireless networked system incorporating physiologic assessments and direct confirmation of digital tablet ingestions in ambulatory patients with schizophrenia or bipolar disorder. Method: In this 4-week observational study conducted between May 2010 and May 2011 at 2 US academic clinical study sites, 12 adults with bipolar disorder and 16 adults with schizophrenia (all diagnosed according to DSM-IV criteria) utilized a digital health feedback system (DHFS). All subjects were on a stable regimen of oral medication. The DHFS utilized a digital tablet, consisting of an ingestion sensor that was embedded in a tablet containing nonpharmacologic excipients, which subjects coingested with their regularly prescribed medication. The formulation of this digital tablet allowed ingestion sensor separation and activation by stomach fluids after ingestion, followed by communication of a unique identifying signal from the ingestion sensor to an adhesive sensor worn on the torso, which automatically logged the date and time of each digital tablet ingestion. The wearable sensor also collected physiologic measures including activity and heart rate. The primary study objective was to compare the accuracy of DHFS in confirming digital tablet ingestion versus a method of directly observed ingestion; secondary aims included characterization of adherence and physiologic measures longitudinally in these cohorts. Results: 27 of 28 subjects (96%) completed the study. The mean adherence rate was 74% (95% CI, 64%-86%), and 67% (95% CI, 55%-79%) of doses were taken within 2 hours of the prescribed dosing time. Activity consisted of 847 to 15,930 steps daily, and sleep duration ranged from 3.2 to 15.2 hours daily. For individual subjects, mean sleep disruption, defined as the amount of brief arousals and postural changes during sleep events (eg, subject sitting up during the night), was as low as 5% and as high as 43% for the entire study period. The most common adverse event was minor skin irritation that occurred at the site of the wearable sensor in 5 subjects (18%), which did not lead to early discontinuation. No adverse events occurred due to the ingestion sensor. No subjects developed worsening of psychosis attributable to use of the DHFS. Of the 27 subjects who completed the study, 19 (70%) found the DHFS concept easy to understand, 21 (78%) said they would like to receive reminders on their cell phone if they forgot to take their medications, and 24 (89%) thought the DHFS could be useful to them. Conclusions: The DHFS provided a novel means of confirming medication ingestion and tracking selected physiologic parameters, and it was generally well tolerated by patients. C1 [Kane, John M.; Petrides, Georgios] Zucker Hillside Hosp, Glen Oaks, NY USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [DiCarlo, Lorenzo A.; Au-Yeung, Kityee; Duong, Jessie] Proteus Digital Hlth Inc, Redwood City, CA USA. RP DiCarlo, LA (reprint author), 2600 Bridge Pkwy,Ste 101, Redwood City, CA 94065 USA. EM ldicarlo@proteusdh.com FU Proteus Digital Health, Inc, Redwood City, California FX This study was funded by Proteus Digital Health, Inc, Redwood City, California. NR 17 TC 16 Z9 16 U1 1 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2013 VL 74 IS 6 BP E533 EP E540 DI 10.4088/JCP.12m08222 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA5DE UT WOS:000331115200003 PM 23842023 ER PT J AU Purohit, MP Wells, RE Zafonte, R Davis, RB Yeh, GY Phillips, RS AF Purohit, Maulik P. Wells, Rebecca Erwin Zafonte, Ross Davis, Roger B. Yeh, Gloria Y. Phillips, Russell S. TI Neuropsychiatric Symptoms and the Use of Mind-Body Therapies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMMON NEUROLOGICAL CONDITIONS; ALTERNATIVE MEDICINE USE; TRAUMATIC BRAIN-INJURY; STRESS REDUCTION; COMPLEMENTARY; ADULTS; METAANALYSIS; ASSOCIATION; DEPRESSION; DISORDERS AB Objective: Neuropsychiatric symptoms affect 37% of US adults and present in many important diagnoses including posttraumatic stress disorder, traumatic brain injury, and chronic pain. However, these symptoms are difficult to treat with standard treatments, and patients may seek alternative options. In this study, we examined the use of mind-body therapies by adults with neuropsychiatric symptoms. Method: We compared mind-body therapy use (biofeedback, energy healing, meditation, guided imagery, yoga, deep-breathing exercises, hypnosis, progressive relaxation therapy, qigong, and tai chi) between adults with and without neuropsychiatric symptoms (anxiety, depression, insomnia, headaches, memory deficits, attention deficits, and excessive daytime sleepiness) in the 2007 National Health Interview Survey (N = 23,393). Use of >= 1 of these therapies in the prior 12 months was the primary outcome of interest. We also examined prevalence and reasons for mind-body therapy use in adults with neuropsychiatric symptoms. We performed logistic regression to examine the association between neuropsychiatric symptoms and mind-body therapy use to adjust for sociodemographic and clinical factors. Results: Adults with >= 1 neuropsychiatric symptom used mind-body therapies more than adults without symptoms (25.3% vs 15.0%, P<.001). Prevalence increased with increasing number of symptoms (21.5% for 1 symptom, 32.4% for >= 3 symptoms, P<.001); differences persisted after adjustment for potential confounders (odds ratios, 1.39 [95% CI, 1.26-1.53] and 2.48 [95% CI, 2.18-2.82]). Reasons for mind-body therapy use among adults with >= 1 symptom included the ineffectiveness or expense of conventional medicine (30.2%). Most adults (nearly 70%) with >= 1 symptom did not discuss their mind-body therapy use with a conventional provider. Conclusions: Adults with >= 1 neuropsychiatric symptom use mind-body therapies frequently; more symptoms are associated with increased use. Future research is needed to understand the efficacy of these therapies. C1 [Purohit, Maulik P.; Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Purohit, Maulik P.; Zafonte, Ross] Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA USA. [Purohit, Maulik P.; Davis, Roger B.; Yeh, Gloria Y.; Phillips, Russell S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Wells, Rebecca Erwin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wells, Rebecca Erwin] Harvard Univ, Faulkner Hosp, Sch Med, Boston, MA USA. [Phillips, Russell S.] Harvard Univ, Ctr Primary Care, Sch Med, Boston, MA USA. RP Purohit, MP (reprint author), Spaulding Rehabil Hosp Network, 125 Nashua St,720, Boston, MA 02114 USA. EM mpurohit1@partners.org FU institutional National Research Service Award from the National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health [T32AT000051]; American Headache Society; National Institute of Child Health and Human Development Investigator Award [5R24HD065688-02]; Spaulding-Harvard Spinal Cord Injury Model System, US Department of Education, National Institute on Disability and Rehabilitation Research, Traumatic Brain Injury Model Systems grant [H133N110010]; Department of Defense Insight; Harvard Clinical Consortium PTSD/TBI study site (INTRuST), Department of Defense, US Army Medical Research and Materiel Command grant [W81XWH-08-2-0159]; Mid-Career Investigator Award from NCCAM, National Institutes of Health [K24AT000589] FX Drs Purohit and Wells were supported by an institutional National Research Service Award Number T32AT000051 from the National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health. Dr Wells was supported by a headache fellowship from the American Headache Society. Dr Zafonte was supported by National Institute of Child Health and Human Development Investigator Award 5R24HD065688-02; Spaulding-Harvard Spinal Cord Injury Model System, US Department of Education, National Institute on Disability and Rehabilitation Research, Traumatic Brain Injury Model Systems grant H133N110010; Department of Defense Insight; and Harvard Clinical Consortium PTSD/TBI study site (INTRuST), Department of Defense, US Army Medical Research and Materiel Command grant W81XWH-08-2-0159. Drs Phillips and Davis were supported by Mid-Career Investigator Award K24AT000589 from NCCAM, National Institutes of Health. NR 26 TC 8 Z9 8 U1 2 U2 24 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2013 VL 74 IS 6 BP E520 EP + DI 10.4088/JCP.12m08246 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA5DE UT WOS:000331115200001 PM 23842021 ER PT J AU Storch, EA Goddard, AW Grant, JE Nadai, AS Goodman, WK Mutch, PJ Medlock, C Odlaug, B McDougle, CJ Murphy, TK AF Storch, Eric A. Goddard, Andrew W. Grant, Jon E. De Nadai, Alessandro S. Goodman, Wayne K. Mutch, P. Jane Medlock, Carla Odlaug, Brian McDougle, Christopher J. Murphy, Tanya K. TI Double-Blind, Placebo-Controlled, Pilot Trial of Paliperidone Augmentation in Serotonin Reuptake Inhibitor-Resistant Obsessive-Compulsive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RISPERIDONE AUGMENTATION; SCALE AB Objective: This pilot study explored the efficacy and tolerability of paliperidone augmentation of serotonin reuptake inhibitors (SRIs) in adults with treatment-resistant obsessive-compulsive disorder (OCD). Method: Thirty-four patients aged 24-67 years (mean = 43.7 years, SD = 11.4) who met DSM IV criteria for OCD and remained symptomatic following 2 or more past adequate SRI trials (including their current medication) were enrolled from May 2008 to March 2012. Participants were treated for 8 weeks in a double-blind study with either paliperidone (up to 9 mg/d) or matching placebo in addition to their SRI. Blinded raters conducted outcome assessments. The primary outcome, obsessive-compulsive symptom severity, was assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcomes included the Clinical Global Impressions-Severity of Illness and -Improvement scales. Results: Paliperidone administration resulted in significant baseline-to-posttreatment reductions in obsessive-compulsive symptoms as measured by the YBOCS (P<.01, d = 0.66), although placebo administration also resulted in medium-sized, trend-level significant YBOCS changes (P = .05, d = 0.53). In exploratory analyses examining between-group differences, tests for paliperidone superiority relative to placebo were not significant (P = .14, d = 0.34); however, a numerical trend toward significant between-group differences was found, with a reduction of 7.98 points on the YBOCS for the paliperidone group compared to a reduction of 4.02 points for the placebo group. Paliperidone was generally well tolerated and not associated with significant weight gain (mean [SD] weight: paliperidone, pretreatment 84.70 [27.08] kg, posttreatment 84.84 [18.99] kg; vs placebo, pretreatment 77.50 [25.33] kg, posttreatment 77.43 [19.90] kg; P = .21). Conclusions: These results suggest that paliperidone augmentation is well tolerated and has potential efficacy in the short-term treatment of some patients with SRI-resistant OCD. Well-powered, randomized, controlled studies are necessary to more definitively address the efficacy of this treatment strategy. C1 [Storch, Eric A.; De Nadai, Alessandro S.; Mutch, P. Jane; Murphy, Tanya K.] Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA. [Goddard, Andrew W.; Medlock, Carla] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. [Grant, Jon E.; Odlaug, Brian] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Goodman, Wayne K.] Mt Sinai Hosp, Dept Psychiat, New York, NY 10029 USA. [Odlaug, Brian] Univ Copenhagen, Dept Publ Hlth, Fac Hlth & Med Sci, Copenhagen, Denmark. [McDougle, Christopher J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, Rothman Ctr Neuropsychiat, Box 7523,880 6th St South, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu RI Murphy, Tanya/J-7079-2013; OI Odlaug, Brian/0000-0001-5407-0686 FU Janssen Scientific Affairs, LLC FX This work was supported by Janssen Scientific Affairs, LLC, who provided funding and study medication. NR 28 TC 8 Z9 9 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2013 VL 74 IS 6 BP E527 EP E532 DI 10.4088/JCP.12m08278 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA5DE UT WOS:000331115200002 PM 23842022 ER PT J AU Siedner, MJ Lankowski, A Tsai, AC Muzoora, C Martin, JN Hunt, PW Haberer, JE Bangsberg, DR AF Siedner, Mark J. Lankowski, Alexander Tsai, Alexander C. Muzoora, Conrad Martin, Jeffrey N. Hunt, Peter W. Haberer, Jessica E. Bangsberg, David R. TI GPS-measured distance to clinic, but not self-reported transportation factors, are associated with missed HIV clinic visits in rural Uganda SO AIDS LA English DT Article DE distance to clinic; global positioning systems; HIV/AIDS; linkage to care; sub-Saharan Africa; transportation; Uganda ID RECEIVING ANTIRETROVIRAL THERAPY; FOLLOW-UP; INFECTED PATIENTS; WESTERN KENYA; RISK-FACTORS; ADHERENCE; MORTALITY; PROGRAM; AFRICA; ADULTS AB Objective: Studies of the association between transportation barriers and HIV-related health outcomes have shown both positive and negative effects, possibly because a reliable, validated measure of transportation barriers has not been identified. Design: Prospective cohort study of HIV-infected patients in rural Uganda. Methods: Participants were enrolled from the HIV clinic at the regional referral hospital in Mbarara, Uganda as part of the Uganda AIDS Rural Treatment Outcomes (UARTO) Study. We collected the following measures of transportation barriers to HIV clinic: global positioning systems (GPS)-tracked distance measured by driving participants to their homes along their typical route; straight-line GPS distance from clinic to home, calculated with the Great Circle Formula; self-reported travel time; and self-reported travel cost. We assessed inter-measure agreement using linear regression, correlation coefficients and kappa statistics (by measure quartile) and validated measures by fitting linear regression models to estimate associations with days late for clinic visits. Results: One hundred and eighty-eight participants were tracked with GPS. Seventy-six percent were women, with a median age of 40 years and median CD4 cell count of 193 cells/ml. We found a high correlation between GPS-based distance measures (beta = 0.74, P < 0.001, R-2 = 0.92, kappa = 0.73), but little correlation between GPS-based and self-reported measures (all R-2 <= 0.4). GPS-based measures were associated with days late to clinic (P < 0.001); but neither self-reported measure was associated (P > 0.85). Conclusion: GPS-measured distance to clinic is associated with HIV clinic absenteeism and should be prioritized over self-reported measures to optimally risk-stratify patients accessing care in rural, resource-limited settings. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Siedner, Mark J.; Lankowski, Alexander; Tsai, Alexander C.; Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Muzoora, Conrad; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Ragon Inst, Massachusetts Gen Hosp MIT & Harvard, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM msiedner@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health [R01 MH54907, P30 AI27763]; NIH [K23 MH087228, K23 MH096620, K24 MH87227, T32 AI007433]; Harvard Institute for Global Health; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24TW007988]; Doris Duke Charitable Foundation through Harvard Medical School; Mark and Lisa Schwartz Family Foundation; Sullivan Family Foundation; Bacca Foundation FX the Uganda AIDS Rural Treatment Outcomes Study is funded by U.S. National Institutes of Health R01 MH54907 and P30 AI27763. The authors also acknowledge the following additional sources of salary support: NIH K23 MH087228 (Haberer); NIH K23 MH096620 (Tsai); NIH K24 MH87227 (Bangsberg); the Harvard Institute for Global Health, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24TW007988), and NIH T32 AI007433 (M.J.S.); and the Doris Duke Charitable Foundation through Harvard Medical School (A. L.). Additional study funding was provided by the Mark and Lisa Schwartz Family Foundation, the Sullivan Family Foundation, and the Bacca Foundation. NR 35 TC 29 Z9 29 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2013 VL 27 IS 9 BP 1503 EP 1508 DI 10.1097/QAD.0b013e32835fd873 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 301FV UT WOS:000330519100016 PM 23435294 ER PT J AU Parrinello, CM Landay, AL Hodis, HN Gange, SJ Norris, PJ Young, M Anastos, K Tien, PC Xue, XN Lazar, J Benning, L Tracy, RP Kaplan, RC AF Parrinello, Christina M. Landay, Alan L. Hodis, Howard N. Gange, Stephen J. Norris, Philip J. Young, Mary Anastos, Kathryn Tien, Phyllis C. Xue, Xiaonan Lazar, Jason Benning, Lorie Tracy, Russell P. Kaplan, Robert C. TI Treatment-related changes in serum lipids and inflammation: clinical relevance remains unclear. Analyses from the Women's Interagency HIV study SO AIDS LA English DT Article ID INFECTED WOMEN; DISEASE RISK; ATHEROSCLEROSIS AB Among 127 HIV-infected women, the magnitude of high-density lipoprotein cholesterol (HDLc) increases after HAART initiation predicted the magnitude of concurrent decreases in inflammation biomarkers. After HAART initiation, changes in low-density lipoprotein cholesterol (LDLc) and inflammation were unrelated. In the same population, predicted risk of coronary heart disease, based upon levels of standard clinical risk factors, was similar before and after HAART. Thus, it remains unknown whether short-term treatment-related changes in standard risk factors may appreciably change risk of cardiovascular disease (CVD). C1 [Parrinello, Christina M.; Anastos, Kathryn; Xue, Xiaonan; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Landay, Alan L.] Rush Univ, Dept Immunol Microbiol, Med Ctr, Chicago, IL 60612 USA. [Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA. [Gange, Stephen J.; Benning, Lorie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Norris, Philip J.] Univ Calif San Francisco, Dept Lab Med, Blood Syst Res Inst, San Francisco, CA 94143 USA. [Norris, Philip J.] Univ Calif San Francisco, Dept Med, Blood Syst Res Inst, San Francisco, CA USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lazar, Jason] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Kaplan, RC (reprint author), 1300 Morris Pk Ave,Belfer 1306C, Bronx, NY 10461 USA. EM robert.kaplan@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute, the National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Heart, Lung and Blood Institute [1R01HL095140, 1R01HL083760]; University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center [5R01HL095126] FX Data in this manuscript were collected by the WIHS Collaborative Study Group with centres (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, New York (Howard Minkoff); Washington, District of Columbia Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Additional cofunding is provided by the National Heart, Lung and Blood Institute (1R01HL095140, 1R01HL083760 to R. C. K.). Partial funding for laboratory and work as well as assistance with general study coordination was provided by the University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center (5R01HL095126). NR 6 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2013 VL 27 IS 9 BP 1516 EP 1519 DI 10.1097/QAD.0b013e32835fd8a9 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 301FV UT WOS:000330519100019 PM 23435295 ER PT J AU Watkins, JD Sholukh, AM Mukhtar, MM Siddappa, NB Lakhashe, SK Kim, M Reinherz, EL Gupta, S Forthal, DN Sattentau, QJ Villinger, F Corti, D Ruprecht, RM AF Watkins, Jennifer D. Sholukh, Anton M. Mukhtar, Muhammad M. Siddappa, Nagadenahalli B. Lakhashe, Samir K. Kim, Mikyung Reinherz, Ellis L. Gupta, Sandeep Forthal, Donald N. Sattentau, Quentin J. Villinger, Francois Corti, Davide Ruprecht, Ruth M. CA CAVD Project Grp TI Anti-HIV IgA isotypes: differential virion capture and inhibition of transcytosis are linked to prevention of mucosal R5 SHIV transmission SO AIDS LA English DT Article DE HIV neutralization; immunoglobulin A isotypes; mucosal transmission; R5 SHIV; transcytosis; virion capture ID NEUTRALIZING MONOCLONAL-ANTIBODIES; VIRUS; IMMUNIZATION; INDIVIDUALS; PROTECTION; LOAD; AIDS AB Objective: Although passive immunization with anti-HIV-1 Env IgG1 neutralizing monoclonal antibodies (nmAbs) prevented simian-human immunodeficiency virus (SHIV) infection in rhesus monkeys, IgA nmAbs have not been tested. Here, we sought to determine whether human anti-HIV-1 dimeric (d) IgA1, dIgA2, and IgG1 differ in their ability to prevent mucosal R5 SHIV acquisition in rhesus monkeys. Design: DIgA1, dIgA2, and IgG1 versions of nmAb HGN194 were applied intrarectally in three rhesus monkey groups 30 min before intrarectal SHIV challenge. Methods: After a control pharmacokinetic study confirmed that nmAb concentrations in rectal fluids over time were similar for all HGN194 isotypes, control and nmAb-treated animals were challenged intrarectally with an R5 SHIV, and viral loads were monitored. Results: Unexpectedly, dIgA1 provided the best protection in vivo - although all nmAbs showed similar neutralizing activity in vitro. Five out of the six dIgA1-treated rhesus monkeys remained virus-free compared to only one out of six animals given dIgA2 (P = 0.045 by log-rank test) and two out of six rhesus monkeys treated with IgG1 forms of the nmAb (P = 0.12). Protection correlated significantly with virion capture activity by a given nmAb form, as well as inhibition of transcytosis of cell-free virus across an epithelial cell layer in vitro. Conclusions: Our data imply that dIgA1-mediated capturing of virions in mucosal secretions and inhibition of transcytosis can provide significant prevention of lentiviral acquisition - over and above direct virus neutralization. Vaccine strategies that induce mucosal IgA, especially IgA1, should be developed as a first line of defense against HIV-1, a virus predominantly transmitted mucosally. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Watkins, Jennifer D.; Sholukh, Anton M.; Mukhtar, Muhammad M.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Kim, Mikyung; Reinherz, Ellis L.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Watkins, Jennifer D.; Sholukh, Anton M.; Mukhtar, Muhammad M.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Kim, Mikyung; Reinherz, Ellis L.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Sandeep; Forthal, Donald N.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine Sch Med, Irvine, CA 92717 USA. [Sattentau, Quentin J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Villinger, Francois] Emory Univ, Div Pathol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Corti, Davide] Humabs SAGL, Bellinzona, Switzerland. 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 Heeney, Jonathan/0000-0003-2702-1621; Byrareddy, Siddappa /0000-0002-7423-1763 FU Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) [UCL-VDC 38637, CAVD 50314]; NIH [R37 AI34266, R01 DE023049, P01 AI48240]; ORIP [P51 000165]; [R24OD010947] FX This work was supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) UCL-VDC grant 38637 (R. A. W.) and CAVD 50314 (E. L. R.), by NIH grants R37 AI34266 and R01 DE023049 (R. M. R.), P01 AI48240 (R. M. R. and S.-L. H.) and by ORIP P51 000165 awarded to the YNPRC and R24OD010947 (F. V.). NR 22 TC 44 Z9 45 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2013 VL 27 IS 9 BP F13 EP F20 DI 10.1097/QAD.0b013e328360eac6 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 301FV UT WOS:000330519100001 PM 23775002 ER PT J AU Weintraub, D AF Weintraub, Daniel TI Neuropsychiatric Symptoms in Parkinson Disease and Dementia with Lewy Bodies: What Geriatric Psychiatry Can Learn SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID DISORDER C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM Daniel.Weintraub@uphs.upenn.edu FU NINDS NIH HHS [P50 NS053488] NR 8 TC 6 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2013 VL 21 IS 6 BP 497 EP 500 DI 10.1016/j.jagp.2013.02.020 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298XV UT WOS:000330358900001 PM 23668226 ER PT J AU Drye, LT Scherer, RW Lanctot, KL Rosenberg, PB Herrmann, N Bachman, D Mintzer, JE AF Drye, Lea T. Scherer, Roberta W. Lanctot, Krista L. Rosenberg, Paul B. Herrmann, Nathan Bachman, David Mintzer, Jacobo E. CA ADMET Res Grp TI Designing a Trial to Evaluate Potential Treatments for Apathy in Dementia: The Apathy in Dementia Methylphenidate Trial (ADMET) SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer dementia; apathy; methylphenidate; randomized trial ID SEVERE ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; CACHE COUNTY; DOUBLE-BLIND; PSYCHOLOGICAL SYMPTOMS; BEHAVIORAL SYMPTOMS; DIAGNOSTIC-CRITERIA; CLINICAL-PRACTICE; DEPRESSION; PREVALENCE AB Background: Research on efficacious treatments for apathy in Alzheimer disease has been hindered by a lack of consensus diagnosis, difficulties in measurement, and studies with small sample sizes. Methods: In designing the Apathy in Dementia Methylphenidate Trial (ADMET), a trial to evaluate the efficacy and safety of methylphenidate for the treatment of apathy in Alzheimer disease, we encountered the following issues: defining and measuring apathy, distinguishing apathy and depression, determining an appropriate test treatment, selecting relevant secondary outcomes, recruiting participants, and deciding on a suitable method for treatment unmasking. ADMET is a 6-week randomized, double-masked, placebo-controlled multicenter clinical trial with two parallel treatment groups assigned in a 1:1 ratio with randomization stratified by clinical center. The recruitment goal is 60 randomized participants over 2 years. The primary outcomes are change in apathy severity as measured by the Apathy Evaluation Scale and the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change. Conclusion: The design decisions made for ADMET are important elements to be considered in trials assessing the safety and efficacy of medications for clinically significant apathy in Alzheimer disease. C1 [Drye, Lea T.; Scherer, Roberta W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lanctot, Krista L.; Herrmann, Nathan] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Lanctot, Krista L.; Herrmann, Nathan] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Rosenberg, Paul B.] Johns Hopkins Sch Med, Baltimore, MD USA. [Rosenberg, Paul B.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Bachman, David; Mintzer, Jacobo E.] Med Univ S Carolina, Charleston, SC USA. [Bachman, David; Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Drye, LT (reprint author), 615 North Wolfe St,W5010, Baltimore, MD 21205 USA. EM ldrye@jhsph.edu OI Drye, Lea/0000-0002-2964-1878; Lanctot, Krista L./0000-0001-7024-6637 FU National Institute on Aging; National Institute of Mental Health [R01 AG033032-01] FX This study was supported by the National Institute on Aging and National Institute of Mental Health, R01 AG033032-01. NR 70 TC 6 Z9 6 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2013 VL 21 IS 6 BP 549 EP 559 DI 10.1016/j.jagp.2012.12.018 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298XV UT WOS:000330358900007 PM 23567407 ER PT J AU Lawlor, RT Sluss, PM Langer, R Sughayer, MA Igbe, MA Siddiqui, K De Blasio, P Duma, B Mendy, M Chabannon, C Ibrahim, M AF Lawlor, Rita T. Sluss, Patrick M. Langer, Rupert Sughayer, Maher A. Igbe, Michael A. Siddiqui, Khalid De Blasio, Pasquale Duma, Bonginkosi Mendy, Maimuna Chabannon, Christian Ibrahim, Muntaser TI European, Middle Eastern, and African Society for Biopreservation and Biobanking (ESBB). 2012 Conference Session on Biobanking in Emerging Countries SO BIOPRESERVATION AND BIOBANKING LA English DT Article C1 [Lawlor, Rita T.] Univ Verona, ARC Net Appl Res Canc Ctr, I-37100 Verona, Italy. [Sluss, Patrick M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Langer, Rupert] Univ Bern, Inst Pathol, Bern, Switzerland. [Sughayer, Maher A.] King Hussein Canc Ctr, Dept Pathol, Amman, Jordan. [Igbe, Michael A.] Fed Minist Hlth, Dept Publ Hlth, Neglected Trop Dis NTDs Div, Natl Onchocerciasis Control Lymphat Filariasis El, Abuja, Nigeria. [Siddiqui, Khalid] King Saud Univ, Strateg Ctr Diabet Res, Riyadh, Saudi Arabia. [De Blasio, Pasquale] Integrated Syst Engn Srl, R&D Milano, Milan, Italy. [Duma, Bonginkosi] Natl Hlth Lab Serv, Johannesburg, South Africa. [Mendy, Maimuna] Int Agcy Res Canc, Lab Serv & Biobank Grp, F-69372 Lyon, France. [Chabannon, Christian] Inst J Paoli I Calmettes, Dept Canc Biol, Ctr Ressources Biol, Marseille, France. [Chabannon, Christian] Inserm Marseille, Marseille, France. [Ibrahim, Muntaser] Univ Khartoum, Inst Endem Dis, Dept Mol Biol, Khartoum, Sudan. RP Lawlor, RT (reprint author), Univ Verona, Dept Pathol & Diagnost, Policlin GB Rossi, ARC NET Res Ctr, 2 Floor,Piazzale LA Scuro 10, I-37100 Verona, Italy. EM rita.lawlor@arc-net.it RI Siddiqui, Khalid/B-4424-2010; OI Siddiqui, Khalid/0000-0003-4860-1262; Sughayer, Maher/0000-0002-9185-9616; lawlor, Rita/0000-0003-3160-0634 FU EC [FP7-INCO-2011-6, 295010] FX Dr. M. Sughayer's work has been partially supported by the EC within the 7th framework program FP7-INCO-2011-6 under grant agreement no. 295010 (KHCCBIO). NR 11 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD JUN PY 2013 VL 11 IS 3 BP 176 EP 181 DI 10.1089/bio.2013.0017 PG 6 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 300GT UT WOS:000330453100010 PM 24850095 ER PT J AU Khodyakov, D Stockdale, S Jones, A Mango, J Jones, F Lizaola, E AF Khodyakov, Dmitry Stockdale, Susan Jones, Andrea Mango, Joseph Jones, Felica Lizaola, Elizabeth TI On Measuring Community Participation in Research SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE community-academic partnerships; community-based participatory research; community participation in research; evaluation; mixed methods ID HEALTH AB Active participation of community partners in research aspects of community-academic partnered projects is often assumed to have a positive impact on the outcomes of such projects. The value of community engagement in research, however, cannot be empirically determined without good measures of the level of community participation in research activities. Based on our recent evaluation of community-academic partnered projects centered around behavioral health issues, this article uses semistructured interview and survey data to outline two complementary approaches to measuring the level of community participation in research-a "three-model" approach that differentiates between the levels of community participation and a Community Engagement in Research Index (CERI) that offers a multidimensional view of community engagement in the research process. The primary goal of this article is to present and compare these approaches, discuss their strengths and limitations, summarize the lessons learned, and offer directions for future research. We find that whereas the three-model approach is a simple measure of the perception of community participation in research activities, CERI allows for a more nuanced understanding by capturing multiple aspects of such participation. Although additional research is needed to validate these measures, our study makes a significant contribution by illustrating the complexity of measuring community participation in research and the lack of reliability in simple scores offered by the three-model approach. C1 [Khodyakov, Dmitry] RAND Corp, Santa Monica, CA 90401 USA. [Stockdale, Susan] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. [Stockdale, Susan; Mango, Joseph; Lizaola, Elizabeth] Univ Calif Los Angeles, Ctr Hlth Serv & Soc, Semel Inst, Los Angeles, CA USA. [Jones, Andrea; Jones, Felica] Hlth African Amer Families, Los Angeles, CA USA. [Jones, Andrea] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. RP Khodyakov, D (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90401 USA. EM dmitry_khodyakov@rand.org FU NIMH NIH HHS [P30MH082760, P30 MH082760, P30MH068639] NR 13 TC 12 Z9 12 U1 3 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD JUN PY 2013 VL 40 IS 3 BP 346 EP 354 DI 10.1177/1090198112459050 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 298AC UT WOS:000330295200011 PM 23041704 ER PT J AU Swenson, ER AF Swenson, Erik R. TI Hypoxic Pulmonary Vasoconstriction SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article ID RED-BLOOD-CELLS; STRESS DOPPLER-ECHOCARDIOGRAPHY; MICE PARTIALLY DEFICIENT; HIGH-ALTITUDE EXPOSURE; HEALTHY-HUMAN LUNG; VASCULAR-RESPONSE; ARTERY PRESSURE; GAS-EXCHANGE; NITRIC-OXIDE; TIME-COURSE AB Hypoxic pulmonary vasoconstriction (HPV) continues to fascinate cardiopulmonary physiologists and clinicians since its definitive description in 1946. Hypoxic vasoconstriction exists in all vertebrate gas exchanging organs. This fundamental response of the pulmonary vasculature in air breathing animals has relevance to successful fetal transition to air breathing at birth and as a mechanism of ventilation-perfusion matching in health and disease. It is a complex process intrinsic to the vascular smooth muscle, but with in vivo modulation by a host of factors including the vascular endothelium, erythrocytes, pulmonary innervation, circulating hormones and acid-base status to name only a few. This review will provide a broad overview of HPV and its mechansms and discuss the advantages and disadvantages of HPV in normal physiology, disease and high altitude. C1 [Swenson, Erik R.] Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Swenson, Erik R.] Univ Washington, Dept Physiol & Biophys, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 136 TC 29 Z9 31 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD JUN PY 2013 VL 14 IS 2 BP 101 EP 110 DI 10.1089/ham.2013.1010 PG 10 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 302BL UT WOS:000330576200003 PM 23795729 ER PT J AU Counter, SA Buchanan, LH Ortega, F AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando TI Brainstem Auditory Evoked Responses in Children Living at High Altitude in the Andes Mountains SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE altitude; auditory evoked responses; brainstem; hearing; hypoxia ID HYPOBARIC HYPOXIA; DEPRESSION; LATENCY; ABR AB Objectives: This neurophysiological study compared brainstem auditory evoked responses (BAER) in children living at high elevations (2800 to 3000 meters) in the Andes Mountains of Ecuador with a reference group of children living at sea level in the U.S. Methods: BAER absolute latencies of waves I through V; interpeak latencies I-III, III-V, and I-V; amplitudes of waves I and V; and the V/I amplitude ratio were measured by scalp electrodes at acoustic click stimulus rates of 10 and 50 pulses per second (pps). Results: Statistical analysis showed that the high-altitude group had significantly longer absolute and interpeak BAER latencies than the sea-level reference group at both the 10 and 50 pps stimulus rates for most wave peaks. The amplitudes of waves I and V were significantly reduced for the high-altitude group at 10 and 50 pps, suggesting blood O-2 saturation effects. Conclusions: The BAER of children in the high-altitude group suggested physiological anomalies in auditory neural conduction and summation compared with the sea-level group. The results further suggest that small physiological effects of altitude on BAER, especially at elevations near 3000 meters and higher, should be taken into consideration in the evaluation of brainstem auditory function. C1 [Counter, S. Allen] Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurol Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Dept Pediat, Eunice Kenn