FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Luke, JJ Ott, PA AF Luke, Jason John Ott, Patrick Alexander TI Kinase inhibitors and immune check-point blockade for the treatment of metastatic melanoma and advanced cancer: synergistic or antagonistic? SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE BRAF; CTLA-4; immune checkpoint blockade; immunotherapy; kinase inhibitors; MEK; melanoma ID BRAF INHIBITION; TUMOR MICROENVIRONMENT; ANTITUMOR-ACTIVITY; T-CELLS; DASATINIB; IMMUNOTHERAPY; VEMURAFENIB; ACTIVATION; IPILIMUMAB; EXPRESSION AB In recent years, therapeutic approaches for many tumors have broadened or even shifted entirely from cytotoxic chemotherapy to specific targeting of dysregulated proteins (predominately kinases), and more recently, harnessing of the anti-tumor immune response. The most prominent example of this shift is the management of metastatic melanoma, where BRAF and MEK inhibition and CLTA-4 blockade have established an entirely new standard of care in the last 3 years. Targeted kinase inhibition and immune checkpoint blockade have different strengths and weaknesses. Kinase inhibitors generally have rapid and impressive response rates but modest progression-free survival while immunotherapy can achieve durable tumor control, but is often associated with lower response rates and slower time to clinical benefit. These approaches would seem to be complementary however the results of early combination studies suggest that caution is advised when combining targeted kinase inhibition with immunotherapy. In this context, rigorous biomarker driven clinical trials are needed to further elucidate mechanisms of both benefit and toxicity. Depending on disease specific biology, it seems likely that both combination and sequential approaches of kinase inhibitors with immunotherapy will be required in order to harness the full potential of these approaches. C1 [Luke, Jason John] Harvard Univ, Ctr Immuno Oncol, Early Drug Dev Ctr, Dana Farber Canc Inst,Med Sch,Melanoma Dis Ctr, Boston, MA 02215 USA. [Ott, Patrick Alexander] Harvard Univ, Ctr Immuno Oncol, Sch Med, Dana Farber Canc Inst,Melanoma Dis Ctr, Boston, MA 02215 USA. RP Luke, JJ (reprint author), Harvard Univ, Ctr Immuno Oncol, Early Drug Dev Ctr, Dana Farber Canc Inst,Med Sch,Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Jason_luke@dfci.harvard.edu; Patrick_ott@dfci.harvard.edu NR 24 TC 8 Z9 8 U1 1 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2013 VL 14 IS 18 BP 2457 EP 2462 DI 10.1517/14656566.2013.849244 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255QP UT WOS:000327255200002 PM 24138302 ER PT J AU Morasco, BJ Cavanagh, R Gritzner, S Dobscha, SK AF Morasco, Benjamin J. Cavanagh, Renee Gritzner, Susan Dobscha, Steven K. TI Care management practices for chronic pain in veterans prescribed high doses of opioid medications SO FAMILY PRACTICE LA English DT Article DE Chronic pain; clinical treatment guidelines; high-dose opioids; opioids; primary care ID CHRONIC NONCANCER PAIN; CLINICAL GUIDELINES; BACK-PAIN; THERAPY; ADHERENCE; PATTERNS; OVERDOSE AB Background. There is growing interest in the primary care management of patients with chronic non-cancer pain (CNCP) who are prescribed long-term opioid therapy. Objective. The aim of this study was to examine the care management practices and medical utilization of patients prescribed high doses of opioids relative to patients prescribed traditional doses of opioids. Methods. We conducted a retrospective cohort study of veterans who had CNCP in 2008 and reviewed medical care for the prior 2 years. Patients with CNCP who were prescribed high-dose opioid therapy (>= 180 mg morphine equivalent per day for 90+ consecutive days; n = 60) were compared with patients prescribed traditional dose opioid therapy (5-179 mg morphine equivalent per day for 90+ consecutive days; n = 60). Results. Patients in the high-dose group had several aspects of documented care that differed from patients in the traditional dose group, including more medical visits, attempting an opioid taper, receiving a urine drug screen and developing a pain goal. The majority of variables that were assessed did not differ between groups, including documented assessments of functional status or co-morbid psychopathology, opioid rotation, discussion of treatment side effects, non-pharmacological treatments or collaboration with mental health or pain specialists. Conclusions. Further work is needed to identify mechanisms for optimizing care management for patients with CNCP who are prescribed high doses of opioid medications. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Med & Psychiat, Portland, OR 97239 USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Cavanagh, Renee] Portland Vet Affairs Res Fdn, Portland, OR USA. [Cavanagh, Renee; Gritzner, Susan] Univ Pacific, Sch Profess Psychol, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [K23DA023467]; Portland Veterans Affairs Medical Center FX Funding: National Institute on Drug Abuse (K23DA023467 to BJM); Portland Veterans Affairs Medical Center. NR 20 TC 11 Z9 11 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 EI 1460-2229 J9 FAM PRACT JI Fam. Pr. PD DEC PY 2013 VL 30 IS 6 BP 671 EP 678 DI 10.1093/fampra/cmt038 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 259EW UT WOS:000327511200010 PM 23901065 ER PT J AU Richter, JM AF Richter, James M. TI Colonoscopy quality improvement: practice to public health SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL-CANCER; SCREENING COLONOSCOPY; UNITED-STATES; INDICATORS; EXPERIENCE; NEOPLASIA; PROGRAM; IMPACT; COST; CARE C1 [Richter, James M.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Richter, James M.] Harvard Univ, Sch Med, Boston, MA USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, Blake 4, Boston, MA 02114 USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2013 VL 78 IS 6 BP 919 EP 924 DI 10.1016/j.gie.2013.07.051 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 257OJ UT WOS:000327394000018 PM 24094468 ER PT J AU Frakt, AB Pizer, SD Feldman, R AF Frakt, Austin B. Pizer, Steven D. Feldman, Roger TI Plan-Provider Integration, Premiums, and Quality in the Medicare Advantage Market SO HEALTH SERVICES RESEARCH LA English DT Article DE Medicare; health economics; industrial organization; health care ID COMPETITION; CARE; INFORMATION; CAPITATION; CHOICES AB ObjectiveTo investigate how integration between Medicare Advantage plans and health care providers is related to plan premiums and quality ratings. Data SourceWe used public data from the Centers for Medicare and Medicaid Services (CMS) and the Area Resource File and private data from one large insurer. Premiums and quality ratings are from 2009 CMS administrative files and some control variables are historical. Study DesignWe estimated ordinary least-squares models for premiums and plan quality ratings, with state fixed effects and firm random effects. The key independent variable was an indicator of plan-provider integration. Data CollectionWith the exception of Medigap premium data, all data were publicly available. We ascertained plan-provider integration through examination of plans' websites and governance documents. Principal FindingsWe found that integrated plan-providers charge higher premiums, controlling for quality. Such plans also have higher quality ratings. We found no evidence that integration is associated with more generous benefits. ConclusionsCurrent policy encourages plan-provider integration, although potential effects on health insurance products and markets are uncertain. Policy makers and regulators may want to closely monitor changes in premiums and quality after integration and consider whether quality improvement (if any) justifies premium increases (if they occur). C1 [Frakt, Austin B.; Pizer, Steven D.] VA Boston Healthcare Syst, Hlth Care Financing & Econ, Boston, MA 02176 USA. [Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02176 USA. [Frakt, Austin B.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Boston, MA 02176 USA. [Frakt, Austin B.] Univ Penn, Leonard Davis Inst, Boston, MA 02176 USA. [Pizer, Steven D.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02176 USA. [Feldman, Roger] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, Hlth Care Financing & Econ, 150 S Huntington Ave 152H, Boston, MA 02176 USA. EM frakt@bu.edu FU Attorney General of the Commonwealth of Pennsylvania FX This research was supported by a contract with the Attorney General of the Commonwealth of Pennsylvania. The views expressed in this article are those of the authors and do not necessarily reflect the positions of the Department of Veterans Affairs, Boston University, the University of Minnesota, the University of Pennsylvania, or the Commonwealth of Pennsylvania. NR 35 TC 5 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2013 VL 48 IS 6 BP 1996 EP 2013 DI 10.1111/1475-6773.12076 PN 1 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 257NT UT WOS:000327392300012 PM 23800017 ER PT J AU Zickmund, SL Yang, S Mulvey, EP Bost, JE Shinkunas, LA LaBrecque, DR AF Zickmund, Susan L. Yang, Suzanne Mulvey, Edward P. Bost, James E. Shinkunas, Laura A. LaBrecque, Douglas R. TI Predicting Cancer Mortality: Developing a New Cancer Care Variable Using Mixed Methods and the Quasi-Statistical Approach SO HEALTH SERVICES RESEARCH LA English DT Article DE Cancer; mixed methods; prognosis; quasi-statistical; view of self ID DEPRESSION; SURVIVAL; DESIGNS; IMPACT AB ObjectiveTo demonstrate the value of using a variable derived from qualitative analysis in subsequent quantitative analyses. Data Sources/Study SettingMixed methods data were combined with 10-year mortality outcomes. Participants with cancer were recruited from services at a large teaching hospital, and mortality data were from the Social Security Death Index. Study DesignAn observational concurrent or convergent mixed methods design was used to collect demographics and structured ratings along with qualitative data from 909 cancer patients at baseline. Data Collection/Extraction MethodsCoding rules for qualitative data were defined for open-ended responses from cancer participants speaking about their view of self, and a variable was numerically coded for each case. Mortality outcomes were matched to baseline data, including the view of self variable. Principal FindingsIndividuals with an improved view of self had a significantly lower mortality rate than those for whom it was worse or unchanged, even when adjusting for age, gender, and cancer stage. ConclusionsStatistical analysis of qualitative data is feasible and can identify new predictors with health services' implications associated with cancer mortality. Future studies should consider the value of testing coded qualitative variables in relation with key health care outcomes. C1 [Zickmund, Susan L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Zickmund, Susan L.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15206 USA. [Yang, Suzanne] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mulvey, Edward P.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Bost, James E.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Shinkunas, Laura A.] Univ Iowa, Carver Coll Med, Program Bioeth & Humanities, Iowa City, IA USA. [LaBrecque, Douglas R.] Univ Iowa Healthcare, Dept Internal Med, Iowa City, IA USA. RP Zickmund, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. EM susan.zickmund@va.gov FU Veterans Administration (VA) Health Services Research & Development (HSR&D) Merit Review Award FX This work was supported in part by a Veterans Administration (VA) Health Services Research & Development (HSR&D) Merit Review Award. Douglas LaBrecque is an Advisory Board member for HepQant LLC and has provided Continuing Medical Education presentations for the Chronic Liver Disease Foundation, Simply Speaking HBV, and Prova, Inc. These have not impacted the content of this manuscript. Dr. Susan Zickmund and Dr. Suzanne Yang are both affiliated with the VA Pittsburgh Healthcare System, which requires administrative review of manuscripts for the sole purpose of verifying correct assignment of the author's affiliation with the VA and the presence of a disclaimer stating that contents do not represent the views of the VA or the US Government. Publication is otherwise unconstrained. All remaining authors have no conflicts of interest (i.e., financial and personal relationships between themselves and others that might bias their work). NR 35 TC 3 Z9 3 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2013 VL 48 IS 6 BP 2208 EP 2223 DI 10.1111/1475-6773.12116 PN 2 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 257NP UT WOS:000327391900005 PM 24138682 ER PT J AU Hamilton, AB Cohen, AN Glover, DL Whelan, F Chemerinski, E McNagny, KP Mullins, D Reist, C Schubert, M Young, AS AF Hamilton, Alison B. Cohen, Amy N. Glover, Dawn L. Whelan, Fiona Chemerinski, Eran McNagny, Kirk P. Mullins, Deborah Reist, Christopher Schubert, Max Young, Alexander S. TI Implementation of Evidence-Based Employment Services in Specialty Mental Health SO HEALTH SERVICES RESEARCH LA English DT Article DE Mixed methods; implementation research; schizophrenia; supported employment; health services ID SUPPORTED EMPLOYMENT; ORGANIZATIONAL READINESS; COMPETITIVE EMPLOYMENT; SCHIZOPHRENIA; QUALITY; CARE; MANAGEMENT; ILLNESS; DESIGNS AB ObjectiveStudy a quality improvement approach for implementing evidence-based employment services at specialty mental health clinics. Data Sources/Study SettingSemistructured interviews with clinicians and administrators before, during, and after implementation. Qualitative field notes, structured baseline and follow-up interviews with patients, semistructured interviews with patients after implementation, and administrative data. Study DesignSite-level controlled trial at four implementation and four control sites. Hybrid implementation-effectiveness study with mixed methods intervention evaluation design. Data Collection/Extraction MethodsSite visits, in-person and telephone interviews, patient surveys, patient self-assessment. A total of 801 patients completed baseline surveys and 53 clinicians and other clinical key stakeholders completed longitudinal qualitative interviews. Principal FindingsAt baseline, sites varied in the availability, utilization, and quality of supported employment. Each site needed quality improvement for this service, though for differing reasons, with some needing development of the service itself and others needing increased service capacity. Improvements in knowledge, attitudes, beliefs, and referral behaviors were evident in mid- and postimplementation interviews, though some barriers persisted. Half of patients expressed an interest in working at baseline. Patients at implementation sites were 2.3 times more likely to receive employment services during the study year. Those who had a service visit were more likely to be employed at follow-up than those who did not. ConclusionsStudies of implementation and effectiveness require mixed methods to both enhance implementation in real time and provide context for interpretation of complex results. In this study, a quality improvement approach resulted in superior patient-level outcomes and improved clinician knowledge, attitudes, and behaviors, in the context of substantial variation among sites. C1 [Hamilton, Alison B.; Cohen, Amy N.; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Hamilton, Alison B.; Cohen, Amy N.; Glover, Dawn L.; Young, Alexander S.] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. [Whelan, Fiona] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Biostat Core SIStat, Los Angeles, CA 90073 USA. [Chemerinski, Eran] James J Peters VA Med Ctr, Bronx, NY USA. [McNagny, Kirk P.; Reist, Christopher] Long Beach VA Healthcare Syst, Long Beach, CA USA. [Mullins, Deborah] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Schubert, Max] Cent Texas Vet Healthcare Syst, Waco, TX USA. RP Hamilton, AB (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. EM alisonh@ucla.edu FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service Quality Enhancement Research Initiative (QUERI) [MNT 03-213]; Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); UCLA-RAND NIMH Partnered Research Center for Quality Care [P30 MH082760]; National Institute of Mental Health [R25 MH080916-01A2]; VA HSRD QUERI FX The research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative (QUERI; MNT 03-213), and Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); and by the UCLA-RAND NIMH Partnered Research Center for Quality Care (P30 MH082760). At the time of manuscript preparation, Dr. Hamilton was an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University, St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and VA HSR&D QUERI. The views expressed in this article are those of the authors and do not necessarily represent the views of affiliated institutions. NR 37 TC 4 Z9 4 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2013 VL 48 IS 6 BP 2224 EP 2244 DI 10.1111/1475-6773.12115 PN 2 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 257NP UT WOS:000327391900006 PM 24138608 ER PT J AU Sweeney, CJ AF Sweeney, Christopher J. TI Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Sweeney, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02215 USA. EM christopher_sweeney@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2013 VL 27 IS 6 BP XI EP XII DI 10.1016/j.hoc.2013.10.006 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 261QV UT WOS:000327680600001 PM 24188263 ER PT J AU Puchner, SB Ferencik, M Karolyi, M Do, S Maurovich-Horvat, P Kauczor, HU Hoffmann, U Schlett, CL AF Puchner, Stefan B. Ferencik, Maros Karolyi, Mihaly Do, Synho Maurovich-Horvat, Pal Kauczor, Hans-Ulrich Hoffmann, Udo Schlett, Christopher L. TI The effect of iterative image reconstruction algorithms on the feasibility of automated plaque assessment in coronary CT angiography SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Coronary; CT angiography; Iterative reconstruction algorithm; Automated; Plaque assessment ID 64-SLICE COMPUTED-TOMOGRAPHY; ACUTE CHEST-PAIN; X-RAY CT; INTRAVASCULAR ULTRASOUND; ARTERY PLAQUES; CARDIAC CT; QUALITY; METAANALYSIS; LESION; QUANTIFICATION AB To evaluate the effect of adaptive statistical (ASIR) and model based (MBIR) iterative reconstruction algorithms on the feasibility of automated plaque assessment in coronary computed tomography angiography (CCTA) compared to filtered back projection reconstruction (FBPR) algorithm. Three ex vivo human donor hearts were imaged by CCTA and reconstructed with FBPR, ASIR and MBIR. Commercial plaque assessment software was applied for the automated delineation of the outer and inner vessel-wall boundaries. Manually corrections were performed where necessary and the percentages were compared between the reconstruction algorithms. In total 2,295 CCTA cross-sections with 0.5 mm increments were assessed (765 co-registered FBPR/ASIR/MBIR triplets). Any boundary corrections were performed in 31.0 % of all cross-sections (N = 712). The percentage of corrected crosssections was lower for MBIR (24.1 %) as compared to ASIR (32.4 %, p = 0.0003) and FBPR (36.6 %, p < 0.0001), and marginal between ASIR/FBPR (p = 0.09). The benefit of MBIR over FBPR was associated with the presence of moderate and severe calcification (OR 2.9 and 5.7, p < 0.0001; respectively). Using MBIR significantly reduced the need for vessel-wall boundary corrections compared to other reconstruction algorithms, particular at the site of calcifications. Thus, MBIR may improve the feasibility of automated plaque assessment in CCTA and potentially its clinical applicability. C1 [Puchner, Stefan B.; Ferencik, Maros; Karolyi, Mihaly; Do, Synho; Maurovich-Horvat, Pal; Hoffmann, Udo; Schlett, Christopher L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02114 USA. [Puchner, Stefan B.] Med Univ Vienna, Div Cardiovasc & Intervent Radiol, Dept Radiol, Vienna, Austria. [Ferencik, Maros] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Karolyi, Mihaly; Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, MTA SE Lendulet Cardiovasc Imaging Res Grp, H-1085 Budapest, Hungary. [Kauczor, Hans-Ulrich; Schlett, Christopher L.] Heidelberg Univ, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. RP Puchner, SB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Dept Radiol, 165 Cambridge St, Boston, MA 02114 USA. EM sbpuchner@partners.org; christopher.schlett@post.harvard.edu OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU GE Healthcare, Milwaukee WI FX This work was supported by an unrestricted grant from GE Healthcare, Milwaukee WI. In addition, the authors had access to pre-commercial reconstruction algorithms as developed by GE Healthcare. Further, the commercially available software for the (semi-)automated plaque assessment was provided free of charge by Vital Images, Minnetonka, MN. NR 33 TC 7 Z9 7 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD DEC PY 2013 VL 29 IS 8 BP 1879 EP 1888 DI 10.1007/s10554-013-0281-z PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 257RH UT WOS:000327403100026 PM 23990390 ER PT J AU Paganetti, H AF Paganetti, Harald TI Advancing (Proton) Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID RANGE UNCERTAINTIES C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM hpaganetti@partners.org NR 10 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2013 VL 87 IS 5 BP 871 EP 873 DI 10.1016/j.ijrobp.2013.08.030 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 258ZG UT WOS:000327496600013 PM 24267966 ER PT J AU Kraan, AC van de Water, S Teguh, DN Al-Mamgani, A Madden, T Kooy, HM Heijmen, BJM Hoogeman, MS AF Kraan, Aafke C. van de Water, Steven Teguh, David N. Al-Mamgani, Abrahim Madden, Tom Kooy, Hanne M. Heijmen, Ben J. M. Hoogeman, Mischa S. TI Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Range, and Setup Errors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MODULATED PROTON THERAPY; WORST-CASE OPTIMIZATION; NECK-CANCER; ADAPTIVE RADIOTHERAPY; BEAM ANGLE; HEAD; SENSITIVITY; PLANS; ALGORITHM; COPLANAR AB Purpose: Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions. Methods and Materials: We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation. Results: For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% > 95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust. Conclusions: For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery. (C) 2013 Elsevier Inc. C1 [Kraan, Aafke C.; van de Water, Steven; Teguh, David N.; Al-Mamgani, Abrahim; Heijmen, Ben J. M.; Hoogeman, Mischa S.] Erasmus MC Daniel den Hoed Canc Ctr, NL-3075 EA Rotterdam, Netherlands. [Madden, Tom; Kooy, Hanne M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kraan, AC (reprint author), Erasmus MC Daniel den Hoed Canc Ctr, Dept Radiat Oncol, Groene Hilledijk 301, NL-3075 EA Rotterdam, Netherlands. EM aafke.kraan@pi.infn.it NR 30 TC 22 Z9 22 U1 1 U2 9 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 DEC 1 PY 2013 VL 87 IS 5 BP 888 EP 896 DI 10.1016/j.ijrobp.2013.09.014 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 258ZG UT WOS:000327496600016 PM 24351409 ER PT J AU Vichare, A Washington, R Patton, C Arnone, A Olsen, C Fung, CY Hopkins, S Pohar, S AF Vichare, Anushree Washington, Raynard Patton, Caroline Arnone, Anna Olsen, Christine Fung, Claire Y. Hopkins, Shane Pohar, Surjeet TI An Assessment of the Current US Radiation Oncology Workforce: Methodology and Global Results of the American Society for Radiation Oncology 2012 Workforce Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID UNITED-STATES; PHYSICIAN WORKFORCE AB Purpose: To determine the characteristics, needs, and concerns of the current radiation oncology workforce, evaluate best practices and opportunities for improving quality and safety, and assess what we can predict about the future workforce. Methods and Materials: An online survey was distributed to 35,204 respondents from all segments of the radiation oncology workforce, including radiation oncologists, residents, medical dosimetrists, radiation therapists, medical physicists, nurse practitioners, nurses, physician assistants, and practice managers/administrators. The survey was disseminated by the American Society for Radiation Oncology (ASTRO) together with specialty societies representing other workforce segments. An overview of the methods and global results is presented in this paper. Results: A total of 6765 completed surveys were received, a response rate of 19%, and the final analysis included 5257 respondents. Three-quarters of the radiation oncologists, residents, and physicists who responded were male, in contrast to the other segments in which two-thirds or more were female. The majority of respondents (58%) indicated they were hospital-based, whereas 40% practiced in a free-standing/satellite clinic and 2% in another setting. Among the practices represented in the survey, 21.5% were academic, 25.2% were hospital, and 53.3% were private. A perceived oversupply of professionals relative to demand was reported by the physicist, dosimetrist, and radiation therapist segments. An undersupply was perceived by physician's assistants, nurse practitioners, and nurses. The supply of radiation oncologists and residents was considered balanced. Conclusions: This survey was unique as it attempted to comprehensively assess the radiation oncology workforce by directly surveying each segment. The results suggest there is potential to improve the diversity of the workforce and optimize the supply of the workforce segments. The survey also provides a benchmark for future studies, as many changes in the healthcare field exert pressure on the workforce. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Vichare, Anushree; Washington, Raynard; Patton, Caroline; Arnone, Anna] ASTRO, Fairfax, VA USA. [Olsen, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fung, Claire Y.] Commonwealth Newburyport Canc Ctr, Newburyport, MA USA. [Hopkins, Shane] William R Bliss Canc Ctr, Ames, IA USA. [Pohar, Surjeet] Indiana Univ, Hlth Canc Ctr East, Indianapolis, IN 46204 USA. RP Pohar, S (reprint author), Indiana Univ Hlth, Dept Radiat Oncol, IU Hlth Canc Ctr E, 6845 Rama Dr, Indianapolis, IN 46219 USA. EM spohar@netzero.net OI Patton, Caroline/0000-0001-9439-9777; Pohar, Surjeet/0000-0002-8206-6462 NR 16 TC 7 Z9 7 U1 0 U2 3 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 DEC 1 PY 2013 VL 87 IS 5 BP 1129 EP 1134 DI 10.1016/j.ijrobp.2013.08.050 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 258ZG UT WOS:000327496600049 PM 24210081 ER PT J AU Pohar, S Fung, CY Hopkins, S Miller, R Azawi, S Arnone, A Patton, C Olsen, C AF Pohar, Surjeet Fung, Claire Y. Hopkins, Shane Miller, Robert Azawi, Samar Arnone, Anna Patton, Caroline Olsen, Christine TI American Society for Radiation Oncology (ASTRO) 2012 Workforce Study: The Radiation Oncologists' and Residents' Perspectives SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article AB Purpose: The American Society for Radiation Oncology (ASTRO) conducted the 2012 Radiation Oncology Workforce Survey to obtain an up-to-date picture of the workforce, assess its needs and concerns, and identify quality and safety improvement opportunities. The results pertaining to radiation oncologists (ROs) and residents (RORs) are presented here. Methods: The ASTRO Workforce Subcommittee, in collaboration with allied radiation oncology professional societies, conducted a survey study in early 2012. An online survey questionnaire was sent to all segments of the radiation oncology workforce. Respondents who were actively working were included in the analysis. This manuscript describes the data for ROs and RORs. Results: A total of 3618 ROs and 568 RORs were surveyed. The response rate for both groups was 29%, with 1047 RO and 165 ROR responses. Among ROs, the 2 most common racial groups were white (80%) and Asian (15%), and the male-to-female ratio was 2.85 (74% male). The median age of ROs was 51. ROs averaged 253.4 new patient consults in a year and 22.9 on-treatment patients. More than 86% of ROs reported being satisfied or very satisfied overall with their career. Close to half of ROs reported having burnout feelings. There was a trend toward more frequent burnout feelings with increasing numbers of new patient consults. ROs' top concerns were related to documentation, reimbursement, and patients' health insurance coverage. Ninety-five percent of ROs felt confident when implementing new technology. Fifty-one percent of ROs thought that the supply of ROs was balanced with demand, and 33% perceived an oversupply. Conclusions: This study provides a current snapshot of the 2012 radiation oncology physician workforce. There was a predominance of whites and men. Job satisfaction level was high. However a substantial fraction of ROs reported burnout feelings. Perceptions about supply and demand balance were mixed. ROs top concerns reflect areas of attention for the healthcare sector as a whole. (C) 2013 Elsevier Inc. C1 [Pohar, Surjeet] Indiana Univ Hlth East, Indianapolis, IN 46219 USA. [Fung, Claire Y.] Commonwealth Newburyport Canc Ctr, Newburyport, MA USA. [Hopkins, Shane] William R Bliss Canc Ctr, Ames, IA USA. [Miller, Robert] Mayo Clin, Rochester, MN USA. [Azawi, Samar] Univ Calif Irvine, VA Veteran Hosp, Newport Beach, CA USA. [Arnone, Anna; Patton, Caroline] ASTRO, Fairfax, VA USA. [Olsen, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pohar, S (reprint author), Indiana Univ Hlth East, 6845 Rama Dr, Indianapolis, IN 46219 USA. EM spohar@iuhealth.org OI Patton, Caroline/0000-0001-9439-9777; Pohar, Surjeet/0000-0002-8206-6462 NR 16 TC 9 Z9 9 U1 0 U2 1 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 DEC 1 PY 2013 VL 87 IS 5 BP 1135 EP 1140 DI 10.1016/j.ijrobp.2013.08.038 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 258ZG UT WOS:000327496600050 PM 24161423 ER PT J AU Tickle, TL Segata, N Waldron, L Weingart, U Huttenhower, C AF Tickle, Timothy L. Segata, Nicola Waldron, Levi Weingart, Uri Huttenhower, Curtis TI Two-stage microbial community experimental design SO ISME JOURNAL LA English DT Article DE 16S; microbial; microbiome; sampling; sequencing; two-stage ID INFLAMMATORY-BOWEL-DISEASE; PAIRED-END; POPULATIONS; SEQUENCE; TOOLS; AGE AB Microbial community samples can be efficiently surveyed in high throughput by sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of samples is then selected for subsequent metagenomic, metabolomic or other follow-up. Two-stage study design has long been used in ecology but has not yet been studied in-depth for high-throughput microbial community investigations. To avoid ad hoc sample selection, we developed and validated several purposive sample selection methods for two-stage studies (that is, biological criteria) targeting differing types of microbial communities. These methods select follow-up samples from large community surveys, with criteria including samples typical of the initially surveyed population, targeting specific microbial clades or rare species, maximizing diversity, representing extreme or deviant communities, or identifying communities distinct or discriminating among environment or host phenotypes. The accuracies of each sampling technique and their influences on the characteristics of the resulting selected microbial community were evaluated using both simulated and experimental data. Specifically, all criteria were able to identify samples whose properties were accurately retained in 318 paired 16S amplicon and whole-community metagenomic (follow-up) samples from the Human Microbiome Project. Some selection criteria resulted in follow-up samples that were strongly non-representative of the original survey population; diversity maximization particularly undersampled community configurations. Only selection of intentionally representative samples minimized differences in the selected sample set from the original microbial survey. An implementation is provided as the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for two-stage study design of microbial communities. C1 [Tickle, Timothy L.; Segata, Nicola; Waldron, Levi; Weingart, Uri; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tickle, Timothy L.; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA USA. [Waldron, Levi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu OI Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU Army Research Office [W911NF-11-1-0429]; National Science Foundation [CAREER DBI-1053486]; Danone grant [PLF-5972-GD]; Juvenile Diabetes Research Foundation FX We thank Daniela Boernigen, Xochitl Morgan, Vagheesh Narasimhan and Joshua Reyes for their input on methodology. This work was supported by the Army Research Office grant W911NF-11-1-0429, the National Science Foundation grant CAREER DBI-1053486, by Danone grant PLF-5972-GD and the Juvenile Diabetes Research Foundation. NR 31 TC 5 Z9 5 U1 3 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 EI 1751-7370 J9 ISME J JI ISME J. PD DEC PY 2013 VL 7 IS 12 BP 2330 EP 2339 DI 10.1038/ismej.2013.139 PG 10 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 258ID UT WOS:000327451800008 PM 23949665 ER PT J AU Gelman, A Miller, E Schwarz, EB Akers, AY Jeong, K Borrero, S AF Gelman, Amanda Miller, Elizabeth Schwarz, Eleanor Bimla Akers, Aletha Y. Jeong, Kwonho Borrero, Sonya TI Racial Disparities in Human Papillomavirus Vaccination: Does Access Matter? SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Race/ethnicity; Human papillomavirus; National Survey of Family Growth; Disparities; Vaccination ID NATIONAL IMMUNIZATION SURVEY; YOUNG-ADULT WOMEN; CARE PROVIDER RECOMMENDATION; HEALTH INTERVIEW SURVEY; UNITED-STATES; ADOLESCENT FEMALES; HPV VACCINE; SERIES INITIATION; GIRLS; COMPLETION AB Purpose: To examine the association between race/ethnicity and human papillomavirus (HPV) vaccine initiation and to determine how access to health care influences this relationship. Methods: We used nationally representative data from the National Survey of Family Growth to assess HPV vaccine initiation in 2,168 females aged 15-24 years. A series of regression analyses were performed to determine the independent effect of race/ethnicity on HPV vaccine initiation after controlling for sociodemographic variables and health care access measures. Age-stratified regression analyses were also performed to assess whether the relationship between race/ethnicity and HPV vaccine initiation differed among females aged 15-18 and 19-24 years. Results: There were significant racial/ethnic disparities in HPV vaccination; United States (US)-born Hispanics, foreign-born Hispanics, and African-Americans were less likely to have initiated vaccination than were whites (p < .001). Adjusting for sociodemographic characteristics attenuated the disparity for both US-born and foreign-born Hispanics (adjusted odds ratio [AOR], .76; 95% confidence interval [CI], .50-1.16; and AOR, .67; 95% CI, .37-1.19) but not for African-Americans (AOR, .47, 95% CI, .33-.66). Adding health care access measures further attenuated the disparity for US-born and foreign-born Hispanics (AOR, .85, 95% CI, .54-1.34; and AOR, .84, 95% CI, .45-1.55). However, African-Americans remained less likely than whites to have initiated vaccination (AOR, .49, 95% CI, .36-.68). These racial/ethnic trends were similar for females aged 15-18 and 19-24 years. Conclusions: Lower rates of HPV vaccination among African-American females do not appear to be explained by differential access to health care. More research is necessary to elucidate factors contributing to HPV vaccination in this population. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Gelman, Amanda] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Miller, Elizabeth] Univ Pittsburgh, Med Ctr, Div Adolescent Med, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor Bimla; Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor Bimla; Akers, Aletha Y.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Jeong, Kwonho] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Borrero, S (reprint author), Univ Pittsburgh, Div Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu RI Miller, Elizabeth/E-7939-2012; OI Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU University of Pittsburgh's Clinical and Translational Sciences Institute (National Institutes of Health) [UL1 RR024153, UL1TR000005] FX The project described was supported by the University of Pittsburgh's Clinical and Translational Sciences Institute (National Institutes of Health through Grants UL1 RR024153 and UL1TR000005). An abstract of this work was submitted to the 2013 Society of General Internal Medicine Meeting. NR 35 TC 12 Z9 12 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 2013 VL 53 IS 6 BP 756 EP 762 DI 10.1016/j.jadohealth.2013.07.002 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 258TJ UT WOS:000327481300014 PM 23992645 ER PT J AU Senecal, EL Heitz, C Beeson, MS AF Senecal, Emily L. Heitz, Corey Beeson, Michael S. TI CREATION AND IMPLEMENTATION OF A NATIONAL EMERGENCY MEDICINE FOURTH-YEAR STUDENT EXAMINATION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency medicine student examination assessment ID TESTING TOOL; CLERKSHIP; CURRICULUM; EXAM AB Background: A National Board of Medical Examiners examination does not exist for Emergency Medicine (EM) students. To fill this void, the Clerkship Directors in Emergency Medicine tasked a committee with development of an examination for 4th-year (M4) EM students, based on a published syllabus, and consisting of questions written according to published question-writing guidelines. Study Objectives: Describe examination development and statistics at 9 months. Methods: The committee reviewed an existing EM student question database at www.saemtests.org for statistical performance, compliance with item-writing guidelines, and topic inclusion within the published EM M4 syllabus. For syllabus topics without existing questions, committee members wrote new items. LXR 6.0 software (Applied Measurement Professionals, Inc., Georgetown, SC) was used for examination administration. Data gathered included numbers of examinations completed, mean scores with SD, and point biserial correlation (rpb). Results: Of the 553 questions assessed, 157 questions met the stated criteria, and 37 were included in the examination. Thirteen new questions were written by committee members to cover all curriculum topics. The National EM M4 Examination was released online August 1, 2011. Nine months later, the examination had been completed 1642 times by students from 27 clerkships. Mean score was 79.69% (SD 3.89). Individual question difficulties ranged from 26% to 99%. Question rpbs ranged from 0.067 to 0.353, mean 0.213 (SD 0.066). Conclusions: A national group of EM educators developed an examination to assess a published clerkship syllabus. The examination contains questions written according to published item-writing guidelines, and exhibits content validity, appropriate difficulty levels, and adequate question discriminatory ability. (C) 2013 Elsevier Inc. C1 [Senecal, Emily L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Heitz, Corey] Virginia Tech Carilion Sch Med, Dept Emergency Med, Carilion Clin, Roanoke, VA USA. [Beeson, Michael S.] Northeast Ohio Med Univ, Akron Gen Med Ctr, Dept Emergency Med, Akron, OH USA. RP Senecal, EL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2013 VL 45 IS 6 BP 924 EP 933 DI 10.1016/j.jemermed.2013.05.051 PG 10 WC Emergency Medicine SC Emergency Medicine GA 259OI UT WOS:000327535800037 PM 23948604 ER PT J AU Lee, TC Raghavan, D Curtin, HD AF Lee, Thomas C. Raghavan, Deepak Curtin, Hugh D. TI Image-Guided Percutaneous Aspiration and Gelfoam Treatment of Petrous Apex Cholesterol Granuloma: A New Theory and Method for Diagnosis and Treatment SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE cholesterol granuloma; petrous apex; Gelfoam; image guided ID SURGICAL-MANAGEMENT; SURGERY; LESIONS AB Although diagnosis of cholesterol granulomas of the skull base can be straightforward with computed tomography (CT) and magnetic resonance imaging (MRI) appearance, treatment is controversial with various skull base approaches described in the literature. This report describes a 35-year-old man who presented with a symptomatic, enlarging cystic lesion in the left petrous apex and clivus that had imaging features of a cholesterol granuloma (cholesterol cyst). Due to a prior history of treated mediastinal germ cell tumor, pathologic confirmation of the lesion was requested. A CT-guided percutaneous aspiration revealed dark used motor oil-like fluid. Continued aspiration yielded a change in the character of the fluid to marrow red. Injection of contrast revealed no communication with cerebrospinal fluid. Gelfoam (Pfizer, New York, New York, USA) was subsequently injected percutaneously into the residual cavity. Histopathology showed no evidence of malignancy and follow-up MRI at 1month, 3 months, 6 months, and 1year demonstrated continued decrease in size and signal of the lesion. C1 [Lee, Thomas C.; Raghavan, Deepak; Curtin, Hugh D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Curtin, Hugh D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Lee, TC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Dept Neuroradiol, 75 Francis St,PBB3,Room 339, Boston, MA 02115 USA. EM tclee@post.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD DEC PY 2013 VL 74 IS 6 BP 342 EP 346 DI 10.1055/s-0033-1345107 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 255ES UT WOS:000327222800003 PM 24436935 ER PT J AU Vestal, ML Wong, EB Milner, DA Gormley, WB Dunn, IF AF Vestal, Matthew L. Wong, Emily B. Milner, Dan A., Jr. Gormley, William B. Dunn, Ian F. TI Cerebral melioidosis for the first time in the western hemisphere Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE melioidosis; cerebral melioidosis; Burkholderia pseudomallei; neurological melioidosis; neurosurgery; infection ID CEFTAZIDIME PLUS COTRIMOXAZOLE; PSEUDOMONAS-PSEUDOMALLEI; BURKHOLDERIA-PSEUDOMALLEI; NEUROLOGICAL MELIOIDOSIS; CHLORAMPHENICOL; DOXYCYCLINE; THERAPY; TRANSMISSION; ABSCESSES; AUSTRALIA AB This report is the first published case of cerebral melioidosis in the western hemisphere. In this paper the authors review the literature on neurological melioidosis and its presentation and treatment in endemic areas, describe the clinical course of this unique case of a presentation of the disease with cranial abscess in the US, review the pathological and radiological findings associated with this seminal case, and put forth recommendations for recognizing and treating possible future instances of the disease within the western hemisphere. C1 [Vestal, Matthew L.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Vestal, Matthew L.; Gormley, William B.; Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Wong, Emily B.] Brigham & Womens Hosp, Dept Infect Dis, Boston, MA 02115 USA. [Milner, Dan A., Jr.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Vestal, Matthew L.; Milner, Dan A., Jr.; Gormley, William B.; Dunn, Ian F.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Emily B.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. RP Vestal, ML (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM Matthew.Vestal@partners.org FU NIAID NIH HHS [T32 AI007387] NR 39 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2013 VL 119 IS 6 BP 1591 EP 1595 DI 10.3171/2013.5.JNS12555 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 257EU UT WOS:000327367200033 PM 23767895 ER PT J AU Duhaime, AC AF Duhaime, Ann-Christine TI The challenge of matching across ages SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD DEC PY 2013 VL 12 IS 6 BP 535 EP 536 DI 10.3171/2013.4.PEDS1396 PG 2 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 257EV UT WOS:000327367300001 PM 24063586 ER PT J AU Taylor, SR Smith, C Harris, BT Costine, BA Duhaime, AC AF Taylor, Sabrina R. Smith, Colin Harris, Brent T. Costine, Beth A. Duhaime, Ann-Christine TI Maturation-dependent response of neurogenesis after traumatic brain injury in children SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE traumatic brain injury; neurogenesis; subventricular zone; hippocampus; subgranular zone; development; trauma ID CONTROLLED CORTICAL IMPACT; SUBVENTRICULAR ZONE CELLS; ADULT HUMAN BRAIN; DENTATE GYRUS; ENHANCED NEUROGENESIS; NEURONAL MIGRATION; CEREBRAL-CORTEX; HEAD-INJURY; HIPPOCAMPAL NEUROGENESIS; DOUBLECORTIN EXPRESSION AB Object. Traumatic brain injury (TBI) is the leading cause of acquired disability in children, yet innate repair mechanisms are incompletely understood. Given data from animal studies documenting neurogenesis in response to trauma and other insults, the authors investigated whether similar responses could be found in children of different ages after TBI. Methods. Immunohistochemistry was used to label doublecortin (DCX), a protein expressed by immature migrating neuroblasts (newborn neurons), in specimens from patients ranging in age from 3 weeks to 10 years who had died either after TBI or from other causes. Doublecortin-positive (DCX+) cells were examined in the subventricular zone (SVZ) and periventricular white matter (PWM) and were quantified within the granule cell layer (GCL) and subgranular zone (SGZ) of the dentate gyms to determine if age and/or injury affect the number of DCX+ cells in these regions. Results. The DCX+ cells decreased in the SVZ as patient age increased and were found in abundance around a focal subacute infarct in a 1-month-old non-TBI patient, but were scarce in all other patients regardless of age or history of trauma. The DCX+ cells in the PWM and dentate gyrus demonstrated a migratory morphology and did not co-localize with markers for astrocytes, microglia, or macrophages. In addition, there were significantly more DCX+ cells in the GCL and SGZ of the dentate gyms in children younger than 1 year old than in older children. The density of immature migrating neuroblasts in infants (under 1 year of age) was significantly greater than in young children (2-6 years of age, p = 0.006) and older children (7-10 years of age, p = 0.007). Conclusions. The main variable influencing the number of migrating neuroblasts observed in the SVZ, PWM, and hippocampus was patient age. Trauma had no discernible effect on the number of migrating neuroblasts in this cohort of patients in whom death typically occurred within hours to days after TBI. C1 [Taylor, Sabrina R.] Dartmouth Coll, Program Expt & Mol Med, Hanover, NH 03755 USA. [Taylor, Sabrina R.; Costine, Beth A.; Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Taylor, Sabrina R.; Costine, Beth A.; Duhaime, Ann-Christine] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Colin] Univ Edinburgh, Dept Neuropathol, Edinburgh EH8 9YL, Midlothian, Scotland. [Harris, Brent T.] Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. [Harris, Brent T.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. RP Taylor, SR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 149 13th St,3-328, Charlestown, MA 02129 USA. EM srtaylor@partners.org FU NIH [P30 NS 045776] FX We thank Igor Bageyev for his expertise and assistance in obtaining images, and Dr. Christian Waeber (Center for Neuroscience, Massachusetts General Hospital) for access to microscopy facilities, which are funded through NIH Grant No. P30 NS 045776. NR 77 TC 5 Z9 5 U1 0 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD DEC PY 2013 VL 12 IS 6 BP 545 EP 554 DI 10.3171/2013.8.PEDS13154 PG 10 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 257EV UT WOS:000327367300004 PM 24053630 ER PT J AU Petrossian, MT Paul, LR Multhaupt-Buell, TJ Eckhardt, C Hayes, MT Duhaime, AC Eskandar, EN Sharma, N AF Petrossian, Melita T. Paul, Lisa R. Multhaupt-Buell, Trisha J. Eckhardt, Christine Hayes, Michael T. Duhaime, Ann-Christine Eskandar, Emad N. Sharma, Nutan TI Pallidal deep brain stimulation for dystonia: a case series Clinical article SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE early-onset dystonia; deep brain stimulation; functional neurosurgery ID PRIMARY GENERALIZED DYSTONIA; TERM-FOLLOW-UP; PRIMARY CERVICAL DYSTONIA; MOVEMENT-DISORDERS; EXPERIENCE; SEIZURES; SURGERY; RISK AB Object. Pallidal deep brain stimulation (DBS) is a treatment option for those with early-onset dystonia. However, there are limited data on long-term outcome and treatment complications. The authors report on the short- and long-term effects of pallidal DBS in a cohort of patients with early-onset dystonia. Methods. Fourteen consecutive pediatric patients with early-onset dystonia were systematically evaluated and treated. The duration of follow-up ranged from 16 to 84 months. Results. There were no immediate postoperative complications. At last follow-up, 12 of the 14 patients displayed a significant decline in the Burke-Fahn-Marsden Dystonia Rating Scale motor subscale score, with an average decrease of 62% +/- 8.4%. The most common hardware complication was lead fracture (14.3%). Conclusions. These data provide further evidence that DBS is a safe and effective treatment for those with early-onset dystonia. C1 [Petrossian, Melita T.; Paul, Lisa R.; Hayes, Michael T.; Sharma, Nutan] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Petrossian, Melita T.; Paul, Lisa R.; Multhaupt-Buell, Trisha J.; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eckhardt, Christine; Duhaime, Ann-Christine; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Sharma, N (reprint author), 149 13th St,Rm 6407, Charlestown, MA 02129 USA. EM nsharma@partners.org FU National Institute of Neurological Disorders and Stroke, NIH [P50NS037409] FX This study was funded by a grant (no. P50NS037409) to Dr. Sharma from the National Institute of Neurological Disorders and Stroke, NIH. NR 21 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD DEC PY 2013 VL 12 IS 6 BP 582 EP 587 DI 10.3171/2013.8.PEDS13134 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 257EV UT WOS:000327367300008 PM 24093589 ER PT J AU Baca, CB Vickrey, BG Vassar, SD Cook, A Berg, AT AF Baca, Christine B. Vickrey, Barbara G. Vassar, Stefanie D. Cook, Aaron Berg, Anne T. TI Injuries in Adolescents with Childhood-Onset Epilepsy Compared with Sibling Controls SO JOURNAL OF PEDIATRICS LA English DT Article ID SEIZURE-RELATED INJURIES; EUROPEAN COHORT; CHILDREN; RISK; ACCIDENTS; PEOPLE; CIRCUMSTANCES AB Objective To compare the occurrence of injuries in adolescents with childhood-onset epilepsy and matched sibling controls. Study design Retrospective case-control lifetime injury assessments were obtained from a community-based cohort of adolescents with childhood-onset epilepsy diagnosed 9 years earlier and their siblings. The children with epilepsy (n = 501; mean age, 15.3 years) included those with complicated (abnormal neurologic examination or IQ <80; n = 133) and uncomplicated (normal neurologic examination and IQ >= 80; n = 368) epilepsy. Children with uncomplicated epilepsy were matched to sibling controls (n = 210 pairs). The children reported whether or not they had ever (before and after epilepsy diagnosis) experienced injuries "serious enough to require medical attention" and if so, the type of treatment required. Results Almost one-half (49.1%) of the children with epilepsy experienced injury, of whom 8.9% required surgery/hospitalization and 17.1% had injury related to a seizure. Fewer children with uncomplicated epilepsy had seizure-related injuries versus those with complicated epilepsy (13.6% vs 27.4%; P <= .01). The proportion of children with epilepsy with any injury by type (not mutually exclusive) were: 25.2% with fractures (n=126); 24.4% with head injuries (n = 122); 10.2% with other injuries (n = 51); 8.4% with dental injuries (n = 42); and 8% with burns/scalds (n = 40). A similar proportion of children with uncomplicated epilepsy experienced any injury (overall and by type) compared to matched sibling controls, with the exception that more children with uncomplicated epilepsy had head injuries (30.0% vs 19.5%; P < .02). Conclusion With the exception of head injuries, we found no evidence of an increased risk of injury in a representative cohort of children with epilepsy compared with matched sibling controls. This finding may reflect the fact that the sample was not biased to more severe cases, or that safety precautions to prevent injury were widely used. C1 [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.; Cook, Aaron] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Chicago, IL USA. [Berg, Anne T.] Northwestern Mem Feinberg Sch Med, Dept Pediat, Chicago, IL USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Box 951769,C-247 RNRC, Los Angeles, CA 90095 USA. EM cbower@mednet.ucla.edu FU National Institutes of Health (National Institute of Neurological Disorders and Stroke [NINDS] [R37-NS31146]; NINDS [R37-NS31146] FX Funded by the National Institutes of Health (National Institute of Neurological Disorders and Stroke [NINDS] R37-NS31146 [PI: A.B.]). All authors funded by NINDS (R37-NS31146). The study sponsor did not have a role in study design, collection, analysis, interpretation of data, writing of the report, or decision to submit the manuscript. NR 30 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2013 VL 163 IS 6 BP 1684 EP U232 DI 10.1016/j.jpeds.2013.07.046 PG 12 WC Pediatrics SC Pediatrics GA 259RE UT WOS:000327543200034 PM 24054432 ER PT J AU Whitaker, RM Wills, LP Stallons, LJ Schnellmann, RG AF Whitaker, Ryan M. Wills, Lauren P. Stallons, L. Jay Schnellmann, Rick G. TI cGMP-Selective Phosphodiesterase Inhibitors Stimulate Mitochondrial Biogenesis and Promote Recovery from Acute Kidney Injury SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; PGC-1-ALPHA MESSENGER-RNA; RECEPTOR ACTIVATION; ENERGY-METABOLISM; OXIDANT INJURY; HEART-FAILURE; BRAIN-INJURY; COACTIVATOR; DYSFUNCTION; EXERCISE AB Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors, cilostamide and trequinsin, for 24 hours increased peroxisome proliferator-activated receptor gamma coactivator-1 alpha, and multiple mitochondrial electron transport chain genes. Cilostamide and trequinsin also increased mRNA expression of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex. Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal cortex. Treatment of mice with sildenafil after folic acid-induced AKI promoted restoration of MB and renal recovery. These data provide strong evidence that specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in vivo, and suggest their potential efficacy in AKI and other diseases characterized by mitochondrial dysfunction and suppressed MB. C1 [Schnellmann, Rick G.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, 280 Calhoun St, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM084147, P20-GM103542-02]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [F30-DK096964, F32-DK098053]; National Institutes of Health National Heart, Lung, and Blood Institute [T32-HL007260]; National Institutes of Health National Center for Research Resources [C06-RR015455, UL1-RR029882]; Department of Veterans Affairs Biomedical Laboratory Research and Development Program [BX000851]; South Carolina Clinical and Translational Research Institute; academic home at the Medical University of South Carolina FX This study was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants R01-GM084147 (to R. G. S.) and P20-GM103542-02 (to SC COBRE in Oxidants, Redox Balance, and Stress Signaling)]; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants F30-DK096964 (to R. M. W.) and F32-DK098053 (to L.J.S.)]; the National Institutes of Health National Heart, Lung, and Blood Institute [Grant T32-HL007260]; the National Institutes of Health National Center for Research Resources [Grant C06-RR015455]; and the Department of Veterans Affairs Biomedical Laboratory Research and Development Program [Grant BX000851]. This publication was supported, in part, by the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina, and funded by the National Institutes of Health National Center for Research Resources [Grant UL1-RR029882]. NR 51 TC 24 Z9 25 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2013 VL 347 IS 3 BP 626 EP 634 DI 10.1124/jpet.113.208017 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258IQ UT WOS:000327453200011 PM 24042162 ER PT J AU Kelz, RR Sellers, MM Reinke, CE Medbery, RL Morris, J Ko, C AF Kelz, Rachel R. Sellers, Morgan M. Reinke, Caroline E. Medbery, Rachel L. Morris, Jon Ko, Clifford TI Quality In-Training Initiatived-A Solution to the Need for Education in Quality Improvement: Results from a Survey of Program Directors SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL OUTCOMES; AMERICAN-COLLEGE; HOSPITALS; NSQIP AB BACKGROUND: The Next Accreditation System and the Clinical Learning Environment Review Program will emphasize practice-based learning and improvement and systems-based practice. We present the results of a survey of general surgery program directors to characterize the current state of quality improvement in graduate surgical education and introduce the Quality In-Training Initiative (QITI). STUDY DESIGN: In 2012, a 20-item survey was distributed to 118 surgical residency program directors from ACS NSQIP-affiliated hospitals. The survey content was developed in collaboration with the QITI to identify program director opinions regarding education in practice-based learning and improvement and systems-based practice, to investigate the status of quality improvement education in their respective programs, and to quantify the extent of resident participation in quality improvement. RESULTS: There was a 57% response rate. Eighty-five percent of program directors (n = 57) reported that education in quality improvement is essential to future professional work in the field of surgery. Only 28% (n = 18) of programs reported that at least 50% of their residents track and analyze their patient outcomes, compare them with norms/benchmarks/published standards, and identify opportunities to make practice improvements. CONCLUSIONS: Program directors recognize the importance of quality improvement efforts in surgical practice. Subpar participation in basic practice-based learning and improvement activities at the resident level reflects the need for support of these educational goals. The QITI will facilitate programmatic compliance with goals for quality improvement education. ((C) 2013 by the American College of Surgeons) C1 [Kelz, Rachel R.; Sellers, Morgan M.; Reinke, Caroline E.; Morris, Jon] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Kelz, Rachel R.; Reinke, Caroline E.] Univ Penn, Leonard Davis Inst Healthcare Econ, Wharton Sch, Philadelphia, PA 19104 USA. [Sellers, Morgan M.; Ko, Clifford] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Medbery, Rachel L.] Emory Univ, Sch Med, Atlanta, GA USA. RP Kelz, RR (reprint author), Univ Penn, Perelman Sch Med, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. EM Rachel.Kelz@uphs.upenn.edu NR 15 TC 8 Z9 8 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2013 VL 217 IS 6 BP 1126 EP + DI 10.1016/j.jamcollsurg.2013.07.395 PG 12 WC Surgery SC Surgery GA 258DT UT WOS:000327440100021 PM 24246623 ER PT J AU Clerte, M Baron, DM Brouckaert, P Ernande, L Raher, MJ Flynn, AW Picard, MH Bloch, KD Buys, ES Scherrer-Crosbie, M AF Clerte, Maeva Baron, David M. Brouckaert, Peter Ernande, Laura Raher, Michael J. Flynn, Aidan W. Picard, Michael H. Bloch, Kenneth D. Buys, Emmanuel S. Scherrer-Crosbie, Marielle TI Brown Adipose Tissue Blood Flow and Mass in Obesity: A Contrast Ultrasound Study in Mice SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Brown adipose tissue; Imaging; Obesity; Contrast ultrasound; db/db mice ID DIET-INDUCED THERMOGENESIS; LEFT-VENTRICULAR MASS; COLD-ACCLIMATED RATS; ECHOCARDIOGRAPHIC-ASSESSMENT; NONSHIVERING THERMOGENESIS; MYOCARDIAL-INFARCTION; CAFETERIA DIET; ENERGY-BALANCE; MOUSE; NORADRENALINE AB Background: When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice. Methods: Contrast ultrasound of BAT (Definity 2 mu L/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve's plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mmintervals after stimulation with NE and used to assess BAT volume and mass. Results: BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound-derived BAT mass was correlated with BAT mass obtained at necropsy (R-2 = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet. Conclusions: Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass. C1 [Clerte, Maeva; Ernande, Laura; Flynn, Aidan W.; Picard, Michael H.; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Cardiol Div,Dept Med, Boston, MA USA. [Baron, David M.; Brouckaert, Peter; Raher, Michael J.; Bloch, Kenneth D.; Buys, Emmanuel S.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res,Sch Med, Boston, MA USA. [Brouckaert, Peter] Univ Ghent, VIB Dept Mol Biomed Res, B-9000 Ghent, Belgium. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 254,55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU National Institutes of Health (Bethesda, MD) [R21-DK092909]; American Heart Association (Dallas, TX) [10SDG2610313]; Fondation LeDucq; Lantheus Medical Imaging, Inc. (North Billerica, MA) FX This work was supported by grant R21-DK092909 from the National Institutes of Health (Bethesda, MD; to M. S.-C.), by Scientist Development Grant 10SDG2610313 from the American Heart Association (Dallas, TX; to E. S. B.), and by a grant from Fondation LeDucq (to K. D. B). Definity was generously provided by Lantheus Medical Imaging, Inc. (North Billerica, MA). NR 45 TC 11 Z9 12 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2013 VL 26 IS 12 BP 1465 EP 1473 DI 10.1016/j.echo.2013.07.015 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259OS UT WOS:000327536800015 PM 23993691 ER PT J AU Kimball, AB Papp, KA Wasfi, Y Chan, D Bissonnette, R Sofen, H Yeilding, N Li, S Szapary, P Gordon, KB AF Kimball, A. B. Papp, K. A. Wasfi, Y. Chan, D. Bissonnette, R. Sofen, H. Yeilding, N. Li, S. Szapary, P. Gordon, K. B. CA PHOENIX 1 Investigators TI Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; CHRONIC PLAQUE PSORIASIS; DOUBLE-BLIND; PHASE-III; SAFETY; METAANALYSIS; THERAPY; ADALIMUMAB; OUTCOMES AB Background Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use. Objective To evaluate long-term efficacy and safety of ustekinumab through 5years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45mg or 90mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving 1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re-randomized at Week 40 to continue every-12-week maintenance) and Partial Responders (i.e. = 24 months, respectively; biphasic: median, 2.7 and 15.9 months for a time to recurrence of <10 and >= 10 months, respectively). Conclusions: Chest wall resection is a safe and effective therapeutic option in the management of localized chest wall recurrence of malignant pleural mesothelioma. The time to recurrence appears to be predictive of the expected survival benefit in both epithelial and biphasic malignant pleural mesothelioma. C1 [Burt, Bryan M.] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Stanford, CA 94305 USA. [Ali, Syed O.] Altru Hlth Syst, Dept Cardiothorac Surg, Grand Forks, ND USA. [DaSilva, Marcelo C.; Richards, William G.; Baldini, Elizabeth H.; Sugarbaker, David J.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [DaSilva, Marcelo C.; Yeap, Beow Y.; Richards, William G.; Baldini, Elizabeth H.; Sugarbaker, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dsugarbaker@partners.org NR 20 TC 4 Z9 4 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2013 VL 146 IS 6 BP 1373 EP 1380 DI 10.1016/j.jtcvs.2013.07.012 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 254BL UT WOS:000327135800016 PM 24113019 ER PT J AU Hamann, HA Lee, JW Schiller, JH Horn, L Wagner, LI Chang, VTS Fisch, MJ AF Hamann, Heidi A. Lee, Ju-Whei Schiller, Joan H. Horn, Leora Wagner, Lynne I. Chang, Victor Tsu-Shih Fisch, Michael J. TI Clinician Perceptions of Care Difficulty, Quality of Life, and Symptom Reports for Lung Cancer Patients An Analysis from the Symptom Outcomes and Practice Patterns (SOAPP) Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Nihilism; Quality of life; Care difficulty; Symptom reports ID CELL; CHEMOTHERAPY; BREAST; TRIAL; CRIZOTINIB; PHYSICIANS; GEFITINIB; ONCOLOGY; SURVIVAL; NIHILISM AB Introduction: Despite recent therapeutic advances, lung cancer is a difficult disease to manage. This study assessed clinicians' perceptions of care difficulty, quality of life (QOL), and symptom reports for their lung cancer patients compared with their patients with breast, prostate, and colon cancer. Methods: This report focused on secondary analyses from the Eastern Cooperative Oncology Group (ECOG) Symptom Outcomes and Practice Patterns (SOAPP) study (E2Z02); outcome measures included clinician ratings of 3106 solid tumor patients. Univariate analyses focused on patterns of disease-specific perceptions; multivariable analyses examined whether disease-specific differences persisted after covariate inclusion. Results: In univariate comparisons, clinicians rated lung cancer patients as more difficult to treat than other solid tumor patients, with poorer QOL and higher symptom reports. After covariates were adjusted, the odds of clinicians perceiving lower QOL for their lung cancer patients were 3.6 times larger than for patients with other solid tumors (odds ratio = 3.6 [95% confidence interval, 2.0-6.6]; p < 0.0001). In addition, the odds of clinicians perceiving weight difficulties for their lung cancer patients were 3.2 times larger (odds ratio = 3.2 [95% confidence interval, 1.7-6.0]; p = 0.0004). No other outcome showed significant differences between lung versus other cancers in multivariable models. Conclusion: Clinicians were more pessimistic about the well-being of their lung cancer patients compared with patients with other solid tumors. Differences remained for clinician perceptions of patient QOL and weight difficulty, even after controlling for such variables as stage, performance status, and patient-reported outcomes. These continuing disparities suggest possible perception bias. More research is needed to confirm this disparity and explore the underpinnings. C1 [Hamann, Heidi A.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Dept Psychiat, Dallas, TX 75390 USA. [Hamann, Heidi A.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Dept Clin Sci, Dallas, TX 75390 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Dept Internal Med, Dallas, TX 75390 USA. [Horn, Leora] Vanderbilt Univ, Dept Med Oncol, Nashville, TN 37235 USA. [Wagner, Lynne I.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Chang, Victor Tsu-Shih] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Chang, Victor Tsu-Shih] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. RP Hamann, HA (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Heidi.hamann@utsouthwestern.edu FU Public Health Service Grants [CA37403, CA21076, CA49957, CA17145, CA15488]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services; National Lung Cancer Partnership and its North Carolina chapter FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D.) and supported in part by Public Health Service Grants CA37403, CA21076, CA49957, CA17145, CA15488, and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. The contents of this article do not necessarily represent the official views of the National Cancer Institute. Dr. Hamann was supported by a grant from the National Lung Cancer Partnership and its North Carolina chapter. NR 28 TC 11 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2013 VL 8 IS 12 BP 1474 EP 1483 DI 10.1097/01.JTO.0000437501.83763.5d PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 257XG UT WOS:000327420500014 PM 24189514 ER PT J AU Gainor, JF Ou, SHI Logan, J Borges, LF Shaw, AT AF Gainor, Justin F. Ou, Sai-Hong Ignatius Logan, Jennifer Borges, Lawrence F. Shaw, Alice T. TI The Central Nervous System as a Sanctuary Site in ALK-Positive Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Anaplastic lymphoma kinase; ALK; Intramedullary spinal cord metastasis; Leptomeningeal carcinomatosis ID LEPTOMENINGEAL CARCINOMATOSIS; INHIBITOR CRIZOTINIB; BRAIN METASTASES; ADENOCARCINOMA; THERAPY AB Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small-cell lung cancer that is highly responsive to treatment with the ALK inhibitor crizotinib. Recently, it has been recognized that the brain is a frequent site of relapse among ALK-positive patients treated with crizotinib. In this report, we expand on these observations and present a series of ALK-positive patients with two distinct forms of metastatic, central nervous system involvement: intramedullary spinal cord metastasis and leptomeningeal carcinomatosis. C1 [Gainor, Justin F.; Logan, Jennifer; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Borges, Lawrence F.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurosurg, Boston, MA 02114 USA. [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org FU U.S. National Institutes of Health [5R01CA164273-02]; V Foundation Translational Research Grant FX Supported by a grant from the U.S. National Institutes of Health 5R01CA164273-02 and by a V Foundation Translational Research Grant. NR 19 TC 41 Z9 42 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2013 VL 8 IS 12 BP 1570 EP 1573 DI 10.1097/JTO.0000000000000029 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 257XG UT WOS:000327420500026 PM 24389440 ER PT J AU Eswara, JR McDougal, WS AF Eswara, Jairam R. McDougal, W. Scott TI Long-Term Outcomes of Surgical Management for Nonmalignant Perineal Disease SO JOURNAL OF UROLOGY LA English DT Article DE perineum; surgical flaps; Fournier gangrene; lymphatic diseases; wound closure techniques ID GENITAL LYMPHEDEMA; RECONSTRUCTION; FLAPS AB Purpose: A number of nonmalignant perineal diseases (focal and systemic) require surgery. The long-term outcome of various types of wound coverage for these diseases is not well described. We report the outcomes of perineal reconstruction for these diseases. Materials and Methods: We identified 32 patients who underwent surgery from July 1995 to December 2012 for a nonmalignant conditions, including local disease (perineal gangrene and focal granulomatous/idiopathic lymphangitis) and regional/systemic disease (post-radiation lymphedema, lymphedema praecox and hidradenitis suppurativa), who had greater than 1-year followup. Wound closure was achieved by split-thickness skin graft, primary closure, musculocutaneous flap or healing by secondary intention. Long-term cosmetic/functional outcomes were measured semiquantitatively. Results: Median patient age was 57 years (range 41 to 86) and median followup was 60 months (range 12 to 99). Of the patients 23 (72%) received a split-thickness skin graft, 2 (6%) underwent primary closure, 2 (6%) received a pedicled flap and 5 (16%) healed by secondary intention. Patients with perineal gangrene (21), focal granulomatous lymphangitis (4) and focal idiopathic lymphangitis (1) had favorable cosmetic/functional results regardless of closure type. All 4 patients with perineal gangrene who received a penile split-thickness skin graft and had erectile function before illness regained function after closure. Grafting for systemic lymphatic disease, such as post-radiation lymphedema in 3 cases, lymphedema praecox in 2 and hidradenitis suppurativa in 1, had mostly unfavorable cosmetic/functional long-term results. Conclusions: Wound closure, including grafts/flaps, for local cutaneous and lymphatic diseases affecting the perineum have excellent cosmetic and functional results. In contrast, grafts for regional/systemic diseases have suboptimal results and may assume the characteristics of the original disease. C1 [Eswara, Jairam R.; McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM jeswara@gmail.com NR 14 TC 0 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD DEC PY 2013 VL 190 IS 6 BP 2139 EP 2143 DI 10.1016/j.juro.2013.05.113 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 258EC UT WOS:000327441000057 PM 23764084 ER PT J AU Kantarjian, H Steensma, D Light, D AF Kantarjian, Hagop Steensma, David Light, Donald TI Should oncologists support the Affordable Care Act? SO LANCET ONCOLOGY LA English DT Editorial Material C1 [Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA. [Steensma, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Light, Donald] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. RP Kantarjian, H (reprint author), Univ Texas MD Anderson Canc Ctr, Leukemia Dept, 1400 Holcombe, Houston, TX 77030 USA. EM hkantarj@mdanderson.org OI Steensma, David/0000-0001-5130-9284 FU NCI NIH HHS [P30 CA016672] NR 6 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2013 VL 14 IS 13 BP 1258 EP 1259 PG 3 WC Oncology SC Oncology GA 259PU UT WOS:000327539600030 PM 24275127 ER PT J AU Araujo, JC Trudel, GC Saad, F Armstrong, AJ Yu, EY Bellmunt, J Wilding, G McCaffrey, J Serrano, SV Matveev, VB Efstathiou, E Oudard, S Morris, MJ Sizer, B Goebell, PJ Heidenreich, A de Bono, JS Begbie, S Hong, JH Richardet, E Gallardo, E Paliwal, P Durham, S Cheng, S Logothetis, CJ AF Araujo, John C. Trudel, Geralyn C. Saad, Fred Armstrong, Andrew J. Yu, Evan Y. Bellmunt, Joaquim Wilding, George McCaffrey, John Serrano, Sergio V. Matveev, Vsevolod B. Efstathiou, Eleni Oudard, Stephane Morris, Michael J. Sizer, Bruce Goebell, Peter J. Heidenreich, Axel de Bono, Johann S. Begbie, Stephen Hong, Jun H. Richardet, Eduardo Gallardo, Enrique Paliwal, Prashni Durham, Susan Cheng, Shinta Logothetis, Christopher J. TI Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID KINASE INHIBITOR; SRC-KINASE; INCREASED SURVIVAL; BONE; PREDNISONE; MITOXANTRONE; ABIRATERONE; CHEMOTHERAPY; GROWTH; PAIN AB Background Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. Methods In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 mu mol/mol creatinine vs >= 60 mu mol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. Findings Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19.0 months (IQR 11.2-25.1) and 914 patients had died. Median overall survival was 21.5 months (95% CI 20.3-22.8) in the dasatinib group and 21.2 months (20.0-23.4) in the placebo group (stratified hazard ratio [HR] 0.99, 95.5% CI 0.87-1.13; p=0.90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). Interpretation The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. C1 [Araujo, John C.; Logothetis, Christopher J.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Trudel, Geralyn C.] Bristol Myers Squibb Co, Montreal, PQ, Canada. [Saad, Fred] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Armstrong, Andrew J.] Duke Canc Inst, Durham, NC USA. [Armstrong, Andrew J.] Duke Univ, Duke Prostate Ctr, Durham, NC USA. [Yu, Evan Y.] Univ Washington, Seattle, WA 98195 USA. [Yu, Evan Y.] Seattle Canc Care Alliance, Seattle, WA USA. [Bellmunt, Joaquim] Univ Hosp del Mar, IMIM, Barcelona, Spain. [Bellmunt, Joaquim] Dana Farber Canc Ctr, Boston, MA USA. [Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [McCaffrey, John] ICORG, Dublin, Ireland. [Serrano, Sergio V.] Hosp Canc Barretos, Sao Paulo, Brazil. [Matveev, Vsevolod B.] NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [Efstathiou, Eleni] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Oudard, Stephane] Hosp European Georges Pompidou, Paris, France. [Morris, Michael J.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. [Sizer, Bruce] Essex Cty Hosp, Colchester, Essex, England. [Goebell, Peter J.] Univ Erlangen Nurnberg, Dept Urol, D-91054 Erlangen, Germany. [Goebell, Peter J.] Univ Erlangen Nurnberg, Dept Hematol & Oncol AURONTE, D-91054 Erlangen, Germany. [Heidenreich, Axel] Univ Hosp Aachen, Dept Urol, Aachen, Germany. [de Bono, Johann S.] Inst Canc Res, Sutton, Surrey, England. [de Bono, Johann S.] Royal Marsden Hosp, Sutton, Surrey, England. [Begbie, Stephen] Port Macquarie Base Hosp, Port Macquarie, NSW, Australia. [Hong, Jun H.] Univ Ulsan, Dept Urol, Asan Med Ctr, Seoul, South Korea. [Richardet, Eduardo] Univ Catolico Cordoba, Inst Oncol Cordoba, Cordoba, Argentina. [Gallardo, Enrique] Parc Tauli Sabadell Hosp Univ, Sabadell, Spain. [Paliwal, Prashni; Durham, Susan] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Cheng, Shinta] Bristol Myers Squibb Co, Lawrenceville, NJ USA. RP Araujo, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. EM johna@mdanderson.org OI Morris, Michael J./0000-0002-9454-0096 FU Bristol-Myers Squibb FX Bristol-Myers Squibb. NR 35 TC 67 Z9 73 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2013 VL 14 IS 13 BP 1307 EP 1316 DI 10.1016/S1470-2045(13)70479-0 PG 10 WC Oncology SC Oncology GA 259PU UT WOS:000327539600043 PM 24211163 ER PT J AU Dedhia, RC Shwaish, K Snyderman, CH Monte, R Eibling, DE AF Dedhia, Raj C. Shwaish, Kawa Snyderman, Carl H. Monte, Robert Eibling, David E. TI Perioperative Process Errors and Delays in Otolaryngology at a Veterans Hospital: Prospective Study SO LARYNGOSCOPE LA English DT Article DE Veterans Affairs; quality improvement; patient safety; otolaryngology; surgical workflow ID OPERATING-ROOM; SAFETY CLIMATE; COMMUNICATION; OUTCOMES; BRIEFINGS; THEATER; PROGRAM; IMPROVE; FLOW; CARE AB Objectives/HypothesisTo understand the leading causes for process errors and delays in the otolaryngology operating room and recognize the impact of process errors and delays on patient safety, operating room resources and hospital costs. Study DesignProspective, observational study. MethodsA 4-week study was conducted during 1 calendar month in 2012, evaluating 23 elective otolaryngology cases. A standardized data collection tool was developed and refined based on prestudy pilot observations. Two trained observers recorded relevant times and actions from patient check-in time in the preoperative holding area to the wheels out time. ResultsThe mean case observation time was 220.0167.8 minutes, with mean duration of operation length being 107.0146.2 minutes. The perioperative period was divided into six stages: patient holding, room preparation, preintubation, postintubation, intraoperative, and postextubation. One hundred process errors were recorded (average of 4.3 per case), 34% of which were due to communication failures. Forty delays were observed, resulting in 336 minutes of standstill delay. Again, communication failures represented the most common etiology, with 17 communication failures resulting in 146 minutes of standstill delay. The preintubation stage was most affected by delay, with 1 in 6 minutes comprising standstill delay. ConclusionProcess errors and significant delays were common in cases performed at our institution; communication errors were the most common etiology. There is opportunity for preoperative team discussion and the use of technology to minimize communication-related process errors and standstill delays. Further work is currently being undertaken to study this critical issue across specialties. Level of Evidence2c. Laryngoscope, 123:3010-3015, 2013 C1 [Dedhia, Raj C.; Snyderman, Carl H.; Eibling, David E.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. [Shwaish, Kawa; Monte, Robert] Vet Affairs Pittsburgh Healthcare Syst, Vet Engn Resources Ctr, Pittsburgh, PA USA. RP Eibling, DE (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. EM david.eibling@va.gov NR 23 TC 0 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3010 EP 3015 DI 10.1002/lary.24191 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500038 PM 23649943 ER PT J AU Lim, CM Mehta, V Chai, R Pinheiro, CND Rath, T Snyderman, C Duvvuri, U AF Lim, Chwee Ming Mehta, Vikas Chai, Raymond Pinheiro, Carlos-Neto D. Rath, Tanya Snyderman, Carl Duvvuri, Umamaheswar TI Transoral Anatomy of the Tonsillar Fossa and Lateral Pharyngeal Wall: Anatomic Dissection With Radiographic and Clinical Correlation SO LARYNGOSCOPE LA English DT Article DE Transoral robotic surgery; tonsillar fossa; lateral pharyngeal wall; anatomic dissection ID ROBOTIC SURGERY; ASSISTED SURGERY; NECK-CANCER; RECONSTRUCTION; CARCINOMA; TORS; HEAD AB Objectives/HypothesisTo evaluate the transoral anatomy of the tonsillar fossa and lateral pharyngeal wall and to correlate these findings with radiographic measurements and transoral robotic surgery (TORS) of patients with early tonsillar tumor. Study DesignPreclinical cadaveric study and patient cohort. MethodsSix complete cadaveric dissections were performed to identify key anatomic landmarks, and these landmarks were validated in two consecutive patients with T1 human papillomavirus-positive squamous cell carcinoma of the tonsil treated by TORS. For radiographic landmark analysis, 25 patients who underwent contrast-enhanced computed tomography (CT) of the neck for a variety of endoscopic skull base procedures were selected. Measurements were taken from the lateral pharyngeal wall at C2-C3 interspace and greater horn of hyoid (C6) to the external carotid artery (ECA). ResultsThe glossopharyngeal (IX) nerve was consistently identified deep to the superior constrictor musculature and at the intersection of the posterior tonsillar pillar with the base of tongue. The styloglossus muscle forms the deep plane medial to the ECA. The mean measurements for left C2-C3 interspace to the ECA and right C2-C3 interspace to ECA were 17.6 0.8 mm and 18.4 0.8 mm, respectively. Similarly, the mean measurements for left hyoid to ECA and right hyoid to ECA were 3.4 +/- 0.8 mm and 4.3 +/- 0.6 mm, respectively. ConclusionsA systematic approach to dissect the tonsillar fossa and lateral pharyngeal wall can be performed using key anatomic landmarks. CT measurements taken at the C2-C3 interspace and greater horn of hyoid bone (C6 level) to the ECA are consistently and reliably achieved. Level of EvidenceNA. Laryngoscope, 123:3021-3025, 2013 C1 [Lim, Chwee Ming; Mehta, Vikas; Chai, Raymond; Pinheiro, Carlos-Neto D.; Snyderman, Carl; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Otolaryngol Head & Neck Surg,Vet Affaris Pit, Pittsburgh, PA 15213 USA. [Rath, Tanya] Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Radiol, Pittsburgh, PA 15213 USA. [Lim, Chwee Ming] Natl Univ Singapore, Dept Otolaryngol, Singapore 117548, Singapore. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Vet Affairs Pittsburgh HealthCare Syst, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM duvuriu@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Biomedical Laboratory Research and Development; PNC Foundation FX This material is based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Biomedical Laboratory Research and Development. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States government. We acknowledge support from the PNC Foundation. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 9 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3021 EP 3025 DI 10.1002/lary.23927 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500040 PM 24105605 ER PT J AU Caragacianu, D Kamani, D Randolph, GW AF Caragacianu, Diana Kamani, Dipti Randolph, Gregory W. TI Intraoperative Monitoring: Normative Range Associated With Normal Postoperative Glottic Function SO LARYNGOSCOPE LA English DT Article DE Intraoperative nerve monitoring; recurrent laryngeal nerve; normal parameters; postoperative glottis and/or recurrent laryngeal nerve function; bilateral vocal cord palsy; complications of thyroid surgery ID RECURRENT LARYNGEAL NERVE; VESTIBULAR SCHWANNOMA SURGERY; THYROID-SURGERY; QUANTITATIVE PARAMETERS; NEUROMONITORING IONM; PARATHYROID SURGERY; ENDOCRINE SURGEONS; INJURY; PALSY; RISK AB Objectives/HypothesisDespite increasing use of intraoperative nerve monitoring (IONM), there is limited information on normative electrophysiologic electromyographic (EMG) parameters. The objective of this study was to define normative parameters of recurrent laryngeal nerve (RLN) intraoperative neuromonitoring during thyroid surgery associated with normal postoperative vocal cord function. Study DesignProspective data collection in a tertiary care center. MethodsQuantitative analysis of evoked waveform amplitude and threshold was performed on 125 patients with 167 nerves at risk. Values were displayed as a mean with 5th percentile and 95th percentiles (5th-95th). Postoperative vocal cord function in all patients was documented. ResultsAll patients had normal postoperative laryngeal function (group I-normal) except for two patients who had postoperative transient vocal cord paralysis (group II-abnormal/outlier). The final amplitude between 247 and 3607 V at the end of dissection/end of surgery was associated in all group I patients with a normal postoperative neural function. Final intraoperative amplitude measures for group II averaged just 97.5 V, significantly different than our normative ranges obtained for group I, and fell outside of the group I 5% to 95% percentile range (P=.016). Final amplitude adequately predicted postoperative RLN impaired function immediately after surgery. ConclusionsWe propose IONM EMG data criteria that predict normal postoperative vocal cord function monitoring and provide information about nerve functioning at the end of the operation, thereby allowing adaptation of the surgical strategy when a bilateral procedure is indicated to avoid bilateral nerve paralysis. Level of Evidence4 Laryngoscope, 123:3026-3031, 2013 C1 [Caragacianu, Diana; Kamani, Dipti; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Div Surg Oncol Endocrine Surg Serv, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu NR 35 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3026 EP 3031 DI 10.1002/lary.24195 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500041 PM 23686787 ER PT J AU Chapuy, CI Annino, DJ Tishler, RB Haddad, RI Snavely, A Goguen, LA AF Chapuy, Claudia I. Annino, Donald J. Tishler, Roy B. Haddad, Robert I. Snavely, Anna Goguen, Laura A. TI Success of Endoscopic Pharyngoesophageal Dilation After Head and Neck Cancer Treatment SO LARYNGOSCOPE LA English DT Article DE Esophageal stenosis; pharyngoesophageal stenosis; dysphagia; esophageal dilation; head and neck cancer; combined antegrade and retrograde endoscopic dilation ID RETROGRADE ESOPHAGEAL DILATION; SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; CHEMOTHERAPY; MANAGEMENT; STRICTURE; STENOSIS; RADIOTHERAPY; CHEMORADIATION; DYSPHAGIA AB Objectives/HypothesisTo assess clinical success and safety of endoscopic pharyngoesophageal dilation after chemoradiation or radiation for head and neck cancer and to identify variables associated with dilation failure. Study DesignCase series with chart review. MethodsBetween 2000 and 2008, a total of 111 patients treated with chemoradiation or radiation for head and neck cancer with subsequent pharyngoesophageal stenosis requiring endoscopic dilation were identified. Patients were evaluated for endoscopic dilation technique, severity of stenosis, technical and clinical success, and intra- and postoperative complications. The Diet/GT score (range, 1-5) was utilized to measure swallow success. Variables associated with dilation failure were analyzed by univariate and multivariate logistic regression. ResultsThere were 271 dilations analyzed, with 42 combined antegrade retrograde dilations, 208 dilations over a guidewire, and 21 dilations without guidewire. Intraoperative patency and successful dilation of the stenotic segment was achieved in 95% of patients. A Diet/GT score of 5 (gastrostomy tube removed and soft/regular diet) was attained in 84 of 111 (76%) patients. Safety analysis showed complications occurred in 9% of all dilations. Perforations were noted in 4% of all procedures, with only two esophageal perforations requiring significant intervention. Multiple dilations were associated with an increased risk for perforations. Further logistic regression analyses revealed that the number of dilations was indicating a poor outcome and low Diet/GT score. ConclusionsPharyngoesophageal stenosis, occurring after chemoradiation and radiation treatment, can be successfully and safely treated with endoscopic dilation techniques. Patients with restenosis, requiring multiple dilations, have a higher risk of persistent dysphagia. Level of Evidence4 Laryngoscope, 123:3066-3073, 2013 C1 [Chapuy, Claudia I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Annino, Donald J.; Goguen, Laura A.] Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. [Tishler, Roy B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Snavely, Anna] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Goguen, LA (reprint author), Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, 75 Francis St, Boston, MA 02115 USA. EM lgoguen@partners.org FU NIH [2 T32 CA 9337-31] FX Salary for Anna Snavely, PhD, was supported by NIH grant (2 T32 CA 9337-31). The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 33 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3066 EP 3073 DI 10.1002/lary.24268 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500048 PM 23775806 ER PT J AU Fink, DS Achkar, J Franco, RA Song, PC AF Fink, Daniel S. Achkar, Jihad Franco, Ramon A. Song, Phillip C. TI Interarytenoid Botulinum Toxin Injection for Recalcitrant Vocal Process Granuloma SO LARYNGOSCOPE LA English DT Article DE Botulinum; botox; granuloma; vocal process ID LARYNGEAL GRANULOMA; FOLD GRANULOMA; THERAPY AB Objectives/HypothesisThis study evaluated the efficacy of botulinum toxin type A injected into the interarytenoid muscle to treat recalcitrant vocal process granulomas. Study DesignRetrospective clinical review at a tertiary care center. MethodsEight patients with vocal process granulomas refractory to a variety of prior treatments including surgical resection, proton pump inhibitor therapy, and voice therapy underwent percutaneous injection of botulinum toxin type A into the interarytenoid muscle, performed in an office setting. Doses ranged from 5 U to 25 U in one to two injections. ResultsOne patient demonstrated no improvement, two patients demonstrated partial resolution, and five patients demonstrated complete resolution of their granulomas. Four patients noted transient breathiness. There were no other side effects. All patients tolerated the injections without difficulty. ConclusionBotulinum toxin injection into the interarytenoid muscle appears to be a safe and effective modality for treating recalcitrant vocal process granuloma. Laryngoscope, 123:3084-3087, 2013 C1 [Fink, Daniel S.; Achkar, Jihad; Franco, Ramon A.; Song, Phillip C.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Song, PC (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Phillip_Song@MEEI.Harvard.edu NR 19 TC 1 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3084 EP 3087 DI 10.1002/lary.23915 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500051 PM 24115127 ER PT J AU Chambers, KJ Bhattacharyya, N AF Chambers, Kyle J. Bhattacharyya, Neil TI The Increasing Role of Otolaryngology in the Management of Surgical Thyroid Disorders SO LARYNGOSCOPE LA English DT Article DE Thyroid disorders; specialty; thyroidectomy; epidemiology; otolaryngology; thyroid nodule ID UNITED-STATES; ENDOCRINE SURGERY; OPERATIVE EXPERIENCE; CANCER; TRENDS; OUTCOMES; RESIDENTS; DISEASE; VOLUME AB Objectives/HypothesisTo determine trends in office visits and medical specialty seen for surgical diagnoses of the thyroid gland. Study DesignA cross-sectional analysis of a national healthcare database. MethodsFrom the National Ambulatory Medical Care Survey (NAMCS), all cases of surgical thyroid disorders (e.g., benign neoplasm of thyroid gland, malignant neoplasm of thyroid gland, multinodular goiter) were extracted for 2 calendar year cohorts: 1995 to 1999 and 2005 to 2009. In addition to demographic information, the medical specialty of the health care provider seen was extracted. Comparisons were conducted for the proportion of surgical thyroid cases seen between general surgeons and otolaryngologists for the respective cohorts. ResultsIn the 1995 to 1999 cohort, there were a total of 10713 thousand outpatient visits annually to either general surgery or otolaryngology for surgical thyroid conditions. Among these, 62.78.4 thousand visits (58.3 +/- 5.6%) were seen by general surgery versus 44.8 +/- 9.1 thousand (41.7 +/- 5.6%) seen by otolaryngology. In comparison, in the 2005 to 2009 cohort, there were 218 +/- 29 thousand visits annually for surgical thyroid conditions. Among these, 88.4 +/- 17 thousand (40.5 +/- 5.4%) were seen by general surgery versus 130 +/- 21 thousand (59.5 +/- 5.4%) seen by otolaryngology. The increase in proportion of surgical thyroid patients seen by otolaryngology in the second 5 year cohort was statistically significant (P=0.032, chi-square). ConclusionsThere is a national trend in the United States toward otolaryngologists seeing an increasing majority proportion of increasingly prevalent surgical thyroid conditions. These data objectively confirm the perceived increasing role of otolaryngologists in the management of surgical thyroid disorders on a national level. Level of Evidence2a. Laryngoscope, 123:3239-3242, 2013 C1 [Chambers, Kyle J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. [Chambers, Kyle J.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 31 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP 3239 EP 3242 DI 10.1002/lary.24065 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500078 PM 23553532 ER PT J AU Oyer, SL Mulligan, JK Psaltis, AJ Henriquez, OA Schlosser, RJ AF Oyer, Samuel L. Mulligan, Jennifer K. Psaltis, Alkis J. Henriquez, Oswaldo A. Schlosser, Rodney J. TI Cytokine Correlation Between Sinus Tissue and Nasal Secretions Among Chronic Rhinosinusitis and Controls SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; cytokine; nasal secretion ID COLLECTION METHOD; POLYPS; CELLS; EOSINOPHILS; EXPRESSION; PROFILES; MARKERS; DISEASE; ASTHMA AB Objectives/HypothesisCompare cytokine levels in sinus tissue to sinus secretions from controls and chronic rhinosinusitis patients. Study DesignIn vitro. MethodsPolyurethane foam sponges were placed into middle meati of patients with chronic rhinosinusitis without nasal polyps (CRSsNP), with polyps (CRSwNP), and controls. Sinus biopsies were then taken from the same location. Protein levels of tumor necrosis factor-alpha (TNF-), interferon- (IFN-), and interleukins (IL) 2, 4, 6, 8, 10, and 17A were measured via cytometric bead assay for each sample. Protein values from sinus tissue and secretions were compared with Pearson's correlation between samples as well as one-way ANOVA with posthoc t test between groups. ResultsSamples from 43 patients in total were examined. Mucus was measured from 10 controls, 11 CRSsNP and 10 CRSwNP, and sinus tissue was measured from 10 controls, 15 CRSsNP and 10 CRSwNP. IL-8 and IFN- levels were outside of the detectable range of the assay. Levels of secreted IL-2, 4, 6, 10, and 17A correlated with tissue levels (P<0.05 for all, r>0.49) while TNF- did not (P=0.71). CRSsNP had elevated mucus levels of IL-2, 4, 6, 10, and 17A compared to controls. CRSwNP had elevated mucus levels of IL-4, 6, 10, 17A, and TNF- compared to controls. ConclusionsCytokine levels in sinus secretions correlate with levels in sinus tissue and are elevated in CRS versus control based on Th1/Th2 skewing. Level of EvidenceN/A (in vitro). Laryngoscope, 123:E72-E78, 2013 C1 [Oyer, Samuel L.; Mulligan, Jennifer K.; Henriquez, Oswaldo A.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Psaltis, Alkis J.] Stanford Med Ctr, Rhinol Div, Dept Otolaryngol Head & Neck Surg, Stanford, CA USA. RP Schlosser, RJ (reprint author), MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM schlossr@musc.edu FU Flight Attendants Medical Research Institute [113039, 092401]; Department of Veterans Affairs; Medtronic; Arthrocare; NeilMed FX Funded in part by grants to R.J.S. (grant 113039) and J.K.M. (grant 092401) from the Flight Attendants Medical Research Institute, and to R.J.S. from the Department of Veterans Affairs. R.J.S. is a consultant for BrainLAB, Olympus, and Sunovion and received previous grant support from Medtronic, Arthrocare, NeilMed, and the speaker's bureau for NeilMed. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 32 TC 25 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2013 VL 123 IS 12 BP E72 EP E78 DI 10.1002/lary.24305 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 256LA UT WOS:000327310500001 PM 23852962 ER PT J AU Tsoukas, MA Farr, OM Mantzoros, CS AF Tsoukas, Michael A. Farr, Olivia M. Mantzoros, Christos S. TI Advances in metabolism SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID TYPE-2 DIABETES-MELLITUS; DENSITY-LIPOPROTEIN CHOLESTEROL; IMPROVES INSULIN-RESISTANCE; IMPAIRED FASTING GLUCOSE; C-REACTIVE PROTEIN; SERUM ADIPONECTIN; CARDIOVASCULAR-DISEASE; PROSTATE-CANCER; SKELETAL-MUSCLE; TISSUE EXPRESSION C1 [Tsoukas, Michael A.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Tsoukas, MA (reprint author), Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA. EM mtsouka1@bidmc.harvard.edu OI Farr, Olivia/0000-0002-5182-3432 NR 84 TC 7 Z9 7 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2013 VL 62 IS 12 BP 1700 EP 1713 DI 10.1016/j.metabol.2013.09.003 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257WO UT WOS:000327418700002 PM 24112391 ER PT J AU Walford, GA Davis, J Warner, AS Ackerman, RJ Billings, LK Chamarthi, B Fanelli, RR Hernandez, AM Huang, CM Khan, SQ Littleton, KR Lo, J McCarthy, RM Rhee, EP Deik, A Stolerman, E Taylor, A Hudson, MS Wang, TJ Altshuler, D Grant, RW Clish, CB Gerszten, RE Florez, JC AF Walford, Geoffrey A. Davis, Jaclyn Warner, A. Sofia Ackerman, Rachel J. Billings, Liana K. Chamarthi, Bindu Fanelli, Rebecca R. Hernandez, Alicia M. Huang, Chunmei Khan, Sabina Q. Littleton, Katherine R. Lo, Janet McCarthy, Rita M. Rhee, Eugene P. Deik, Amy Stolerman, Elliot Taylor, Andrew Hudson, Margo S. Wang, Thomas J. Altshuler, David Grant, Richard W. Clish, Clary B. Gerszten, Robert E. Florez, Jose C. TI Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE branched chain amino acids; aromatic amino acids ID INSULIN-RESISTANCE; METABOLITE PROFILES; GLUCOSE CHALLENGE; MEN; HYPERGLYCEMIA; OBESITY AB Objective. Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. Materials and Methods. A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention. Results. Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P < 0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P = 0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P < 0.05). Conclusions. BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. (C) 2013 Elsevier Inc. All rights reserved. C1 [Walford, Geoffrey A.; Davis, Jaclyn; Warner, A. Sofia; Ackerman, Rachel J.; Billings, Liana K.; Fanelli, Rebecca R.; Hernandez, Alicia M.; Huang, Chunmei; Khan, Sabina Q.; Littleton, Katherine R.; Stolerman, Elliot; Taylor, Andrew; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Walford, Geoffrey A.; Huang, Chunmei; Lo, Janet; Rhee, Eugene P.; Altshuler, David; Gerszten, Robert E.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Walford, Geoffrey A.; Billings, Liana K.; Chamarthi, Bindu; Huang, Chunmei; Lo, Janet; McCarthy, Rita M.; Rhee, Eugene P.; Hudson, Margo S.; Altshuler, David; Gerszten, Robert E.; Florez, Jose C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chamarthi, Bindu; McCarthy, Rita M.; Hudson, Margo S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rhee, Eugene P.; Deik, Amy; Clish, Clary B.; Gerszten, Robert E.] Broad Inst, Cambridge, MA 02142 USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Simches Res Bldg CPZN 5-250,185 Cambridge St, Boston, MA 02114 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Grant, Richard/0000-0002-6164-8025 FU NIH [DK007028]; Scholars in Clinical Science program of Harvard Catalyst-The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University; American Diabetes Association; Doris Duke Charitable Foundation; NIDDK [R01 DK088214.A1] FX GAW, Massachusetts General Hospital, receives support from NIH training grant DK007028, from the Scholars in Clinical Science program of Harvard Catalyst-The Harvard Clinical and Translational Science Center (Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers), and the American Diabetes Association Merck Clinical and Translational Postdoctoral Fellowship. Metabolite profiling was partially funded by a Doris Duke Charitable Foundation Award (to DA). JCF, Massachusetts General Hospital, is supported by R01 DK088214.A1 from NIDDK. NR 15 TC 19 Z9 19 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2013 VL 62 IS 12 BP 1772 EP 1778 DI 10.1016/j.metabol.2013.07.003 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257WO UT WOS:000327418700009 PM 23953891 ER PT J AU Dalamaga, M Karmaniolas, K Chamberland, J Nikolaidou, A Lekka, A Dionyssiou-Asteriou, A Mantzoros, CS AF Dalamaga, Maria Karmaniolas, Konstantinos Chamberland, John Nikolaidou, Athina Lekka, Antigoni Dionyssiou-Asteriou, Amalia Mantzoros, Christos S. TI Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Obesity; Insulin resistance; Cancer; Leukemia; Insulin ID DIABETES-MELLITUS; BONE-MARROW; CANCER; OBESITY; HUMANS; EXPRESSION; LEUKEMIA; GROWTH; MECHANISMS; PROGNOSIS AB Objective. Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. Materials & Methods. In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. Results. Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. Conclusion. Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dalamaga, Maria; Nikolaidou, Athina; Dionyssiou-Asteriou, Amalia] Univ Athens, Sch Med, Attikon Gen Univ Hosp, Dept Clin Biochem, Athens 12462, Greece. [Karmaniolas, Konstantinos] NIMTS Gen Hosp, Dept Internal Med, Hematol Sect, Athens 11528, Greece. [Chamberland, John; Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Lekka, Antigoni] NIMTS Gen Hosp, Hematol Lab, Athens 11528, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Dalamaga, M (reprint author), Univ Athens, Sch Med, Attikon Gen Univ Hosp, Rimini 1, Athens 12462, Greece. EM madalamaga@med.uoa.gr OI Chamberland, John/0000-0002-7862-1371; Dalamaga, Maria/0000-0002-7008-388X FU Beth Israel Deaconess Medical Center FX This study was supported by a discretionary grant from Beth Israel Deaconess Medical Center. NR 51 TC 9 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2013 VL 62 IS 12 BP 1830 EP 1839 DI 10.1016/j.metabol.2013.09.007 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257WO UT WOS:000327418700016 PM 24140093 ER PT J AU Lu, YT Zhao, LB Shen, QL Garcia, MA Wu, DX Hou, S Song, M Xu, XC OuYang, WH OuYang, WWL Lichterman, J Luo, Z Xuan, X Huang, JT Chung, LWK Rettig, M Tseng, HR Shao, C Posadas, EM AF Lu, Yi-Tsung Zhao, Libo Shen, Qinglin Garcia, Mitch A. Wu, Dongxia Hou, Shuang Song, Min Xu, Xiaochun OuYang, Wei-Han OuYang, William W. -L. Lichterman, Jake Luo, Zheng Xuan, Xuan Huang, Jiaoti Chung, Leland W. K. Rettig, Matthew Tseng, Hsian-Rong Shao, Chen Posadas, Edwin M. TI NanoVelcro Chip for CTC enumeration in prostate cancer patients SO METHODS LA English DT Article DE Nanomaterials; Microfluidics; Circulating tumor cell; Prostate cancer; Diagnostics ID CIRCULATING TUMOR-CELLS; METASTATIC BREAST-CANCER; EFFICIENT CAPTURE; BLOOD; PROGRESSION; SURVIVAL; TECHNOLOGY; ENRICHMENT; SYSTEMS AB Circulating tumor cells (CTCs) are one of the most crucial topics in rare cell biology and have become the focus of a significant and emerging area of cancer research. While CTC enumeration is a valid biomarker in prostate cancer, the current FDA-approved CTC technology is unable to detect CTCs in a large portion of late stage prostate cancer patients. Here we introduce the NanoVelcro CTC Chip, a device composed of a patterned silicon nanowire substrate (SiNW) and an overlaid polydimethylsiloxane (PDMS) chaotic mixer. Validated by two institutions participating in the study, the NanoVelcro Chip assay exhibits very consistent efficiency in CTC-capture from patient samples. The utilized protocol can be easily replicated at different facilities. We demonstrate the clinical utility of the NanoVelcro Chip by performing serial enumerations of CTCs in prostate cancer patients after undergoing systemic therapy. Changes in CTC numbers after 4-10 weeks of therapy were compared with their clinical responses. We observed a statistically significant reduction in CTCs counts in the clinical responders. We performed long-term follow up with serial CTC collection and enumeration in one patient observing variations in counts correlating with treatment response. This study demonstrates the consistency of the NanoVelcro Chip assay over time for CTC enumeration and also shows that continuous monitoring of CTC numbers can be employed to follow responses to different treatments and monitor disease progression. Published by Elsevier Inc. C1 [Lu, Yi-Tsung; Lichterman, Jake; Chung, Leland W. K.; Shao, Chen; Posadas, Edwin M.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Lu, Yi-Tsung; Lichterman, Jake; Chung, Leland W. K.; Shao, Chen; Posadas, Edwin M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Lu, Yi-Tsung; Lichterman, Jake; Chung, Leland W. K.; Shao, Chen; Posadas, Edwin M.] Cedars Sinai Med Ctr, Urol Oncol Program, Los Angeles, CA 90048 USA. [Lu, Yi-Tsung; Lichterman, Jake; Chung, Leland W. K.; Shao, Chen; Posadas, Edwin M.] Cedars Sinai Med Ctr, Urooncol Res Program, Los Angeles, CA 90048 USA. [Zhao, Libo; Shen, Qinglin; Garcia, Mitch A.; Wu, Dongxia; Hou, Shuang; Song, Min; Xu, Xiaochun; OuYang, Wei-Han; OuYang, William W. -L.; Luo, Zheng; Xuan, Xuan; Tseng, Hsian-Rong] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Zhao, Libo; Shen, Qinglin; Garcia, Mitch A.; Wu, Dongxia; Hou, Shuang; Song, Min; Xu, Xiaochun; OuYang, Wei-Han; OuYang, William W. -L.; Luo, Zheng; Xuan, Xuan; Tseng, Hsian-Rong] Univ Calif Los Angeles, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA. [Zhao, Libo; Shen, Qinglin; Garcia, Mitch A.; Wu, Dongxia; Hou, Shuang; Song, Min; Xu, Xiaochun; OuYang, Wei-Han; OuYang, William W. -L.; Luo, Zheng; Xuan, Xuan; Tseng, Hsian-Rong] Univ Calif Los Angeles, Calif NanoSyst Inst CNSI, Los Angeles, CA 90095 USA. [Huang, Jiaoti] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Rettig, Matthew] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA 90073 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. [Shao, Chen] Fourth Mil Med Univ, Xijing Hosp, Dept Urol, Xian 710032, Peoples R China. RP Chung, LWK (reprint author), Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. EM HRTseng@mednet.ucla.edu; Edwin.Posadas@csmc.edu RI Zhao, Libo/G-2421-2010; Tseng, Hsian-Rong/G-2222-2010 FU Creativity Award from Prostate Cancer Foundation (PCF); UCLA Prostate Cancer SPORE Program; NIH/NCI Innovative Molecular Analysis Technologies (IMAT) Program [R21 CA151159, R33 CA157396]; DoD Idea Award [W81XWH-11-1-0422]; PCF Young Investigator Award FX The research endeavors at UCLA were supported by a Creativity Award from Prostate Cancer Foundation (PCF), UCLA Prostate Cancer SPORE Program, 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 31 TC 25 Z9 27 U1 6 U2 49 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD DEC 1 PY 2013 VL 64 IS 2 BP 144 EP 152 DI 10.1016/j.ymeth.2013.06.019 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 260AM UT WOS:000327567400008 PM 23816790 ER PT J AU El Fakhri, G Trott, CM Sitek, A Bonab, A Alpert, NM AF El Fakhri, Georges Trott, Cathryn M. Sitek, Arkadiusz Bonab, Ali Alpert, Nathaniel M. TI Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Dynamic PET; Quantitation; Brain imaging ID KINETIC-ANALYSIS; BLOOD-FLOW; QUANTIFICATION; VALIDATION; SIMULATION; RECEPTORS; SPECT; MODEL; SCAN AB With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions. To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (brain metabolism) and C-11-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously. The theoretical development shows that GFADS can decompose the studies at several levels: (1) It decomposes the FDG and raclopride study so that they can be analyzed as though they were obtained separately. (2) If additional physiologic/anatomic constraints can be imposed, further decomposition is possible. (3) For the example of raclopride, specific and nonspecific binding can be determined on a pixel-by-pixel basis. We found good agreement between the estimated GFADS factors and the simulated ground truth time activity curves (TACs), and between the GFADS factor images and the corresponding ground truth activity distributions with errors less than 7.3 +/- 1.3 %. Biases in estimation of specific D2 binding and relative metabolism activity were within 5.9 +/- 3.6 % compared to the ground truth values. We also evaluated our approach in simultaneous dual-isotope brain PET studies in a rhesus monkey and obtained accuracy of better than 6 % in a mid-striatal volume, for striatal activity estimation. Dynamic image sequences acquired following near-simultaneous injection of two PET radiopharmaceuticals can be separated into components based on the differences in the kinetics, provided their kinetic behaviors are distinct. C1 [El Fakhri, Georges; Trott, Cathryn M.; Sitek, Arkadiusz; Bonab, Ali; Alpert, Nathaniel M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Med Imaging Sci NMMI,Radiol Dept, Boston, MA 02115 USA. RP El Fakhri, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Med Imaging Sci NMMI,Radiol Dept, Boston, MA 02115 USA. EM elfakhri@pet.mgh.harvard.edu RI Trott, Cathryn/B-5325-2013; OI Trott, Cathryn/0000-0001-6324-1766; Sitek, Arkadiusz/0000-0002-0677-4002 FU NIH [R01-HL110241, R01CA165221] FX This work was supported by NIH grants R01-HL110241 and R01CA165221. Drs. El Fakhri, Trott, Sitek Alpert, and Bonab are with the Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. NR 29 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD DEC PY 2013 VL 15 IS 6 BP 666 EP 674 DI 10.1007/s11307-013-0631-1 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 255CH UT WOS:000327216300004 PM 23636489 ER PT J AU Pak, E Segal, RA Stiles, CD AF Pak, Ekaterina Segal, Rosalind A. Stiles, Charles D. TI New progenitors NESTIN(g) in the EGL SO NATURE NEUROSCIENCE LA English DT Editorial Material ID MEDULLOBLASTOMA; MATH1; MICE C1 [Pak, Ekaterina; Segal, Rosalind A.; Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pak, Ekaterina; Segal, Rosalind A.; Stiles, Charles D.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Pak, E (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM charles_stiles@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2013 VL 16 IS 12 BP 1710 EP 1712 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 257VV UT WOS:000327416800002 PM 24270268 ER PT J AU Hickman, SE Kingery, ND Ohsumi, TK Borowsky, ML Wang, LC Means, TK El Khoury, J AF Hickman, Suzanne E. Kingery, Nathan D. Ohsumi, Toshiro K. Borowsky, Mark L. Wang, Li-chong Means, Terry K. El Khoury, Joseph TI The microglial sensome revealed by direct RNA sequencing SO NATURE NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; ALZHEIMERS-DISEASE; ALTERNATIVE ACTIVATION; BRAIN; BETA; MACROPHAGES; MICE; NEURODEGENERATION; NEUROTOXICITY AB Microglia, the principal neuroimmune sentinels of the brain, continuously sense changes in their environment and respond to invading pathogens, toxins and cellular debris. Microglia exhibit plasticity and can assume neurotoxic or neuroprotective priming states that determine their responses to danger. We used direct RNA sequencing, without amplification or cDNA synthesis, to determine the quantitative transcriptomes of microglia of healthy adult and aged mice. We validated our findings using fluorescence dual in situ hybridization, unbiased proteomic analysis and quantitative PCR. We found that microglia have a distinct transcriptomic signature and express a unique cluster of transcripts encoding proteins for sensing endogenous ligands and microbes that we refer to as the sensome. With aging, sensome transcripts for endogenous ligand recognition were downregulated, whereas those involved in microbe recognition and host defense were upregulated. In addition, aging was associated with an overall increase in the expression of microglial genes involved in neuroprotection. C1 [Hickman, Suzanne E.; Kingery, Nathan D.; Means, Terry K.; El Khoury, Joseph] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Charlestown, MA USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Wang, Li-chong] Adv Cell Diagnost, Hayward, CA USA. [El Khoury, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA USA. RP Hickman, SE (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM shickman@partners.org; jelkhoury@partners.org FU National Institute of Neurological Disorders and Stroke [NS059005]; National Institute of Aging [AG032349] FX We thank F. Ozsolak (Helicos) for supervising the sequencing experiments, R. Mylvaganam for performing cell sorting and J. Liao (Applied Biomics) for analysis of the proteomic data. This work was supported by grants from the National Institute of Neurological Disorders and Stroke (NS059005) and the National Institute of Aging (AG032349) to J.E.K. NR 50 TC 200 Z9 202 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2013 VL 16 IS 12 BP 1896 EP 1905 DI 10.1038/nn.3554 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 257VV UT WOS:000327416800029 PM 24162652 ER PT J AU Matsumoto, AM AF Matsumoto, Alvin M. TI Reproductive Endocrinology Estrogens-not just female hormones SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID MEN; ESTRADIOL AB In a carefully conducted, outstanding example of clinical research, Finkelstein et al. clearly demonstrate the physiological underpinnings for the action of testosterone and the relative roles of its androgenic and estrogenic effects on body composition and sexual function. This study has important clinical implications for testosterone replacement therapy of male hypogonadism. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Matsumoto, AM (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 South Columbian Way,S-182-GRECC, Seattle, WA 98108 USA. EM alvin.matsumoto@va.gov NR 7 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD DEC PY 2013 VL 9 IS 12 BP 693 EP 694 DI 10.1038/nrendo.2013.211 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257DO UT WOS:000327364000001 PM 24146027 ER PT J AU Edlow, BL Giacino, JT Hirschberg, RE Gerrard, J Wu, O Hochberg, LR AF Edlow, Brian L. Giacino, Joseph T. Hirschberg, Ronald E. Gerrard, Jason Wu, Ona Hochberg, Leigh R. TI Unexpected Recovery of Function After Severe Traumatic Brain Injury: The Limits of Early Neuroimaging-Based Outcome Prediction SO NEUROCRITICAL CARE LA English DT Article DE Traumatic brain injury; Coma; Magnetic resonance imaging; Traumatic axonal injury; Diffusion-weighted imaging; Apparent diffusion coefficient; Diffusion tensor imaging ID DIFFUSE AXONAL INJURY; MINIMALLY CONSCIOUS STATE; DISABILITY RATING-SCALE; SEVERE HEAD-INJURY; PERSISTENT VEGETATIVE STATE; WHITE-MATTER INJURY; PROGNOSTIC VALUE; WEIGHTED MR; CORPUS-CALLOSUM; CARDIAC-ARREST AB Prognostication in the early stage of traumatic coma is a common challenge in the neuro-intensive care unit. We report the unexpected recovery of functional milestones (i.e., consciousness, communication, and community reintegration) in a 19-year-old man who sustained a severe traumatic brain injury. The early magnetic resonance imaging (MRI) findings, at the time, suggested a poor prognosis. During the first year of the patient's recovery, MRI with diffusion tensor imaging and T2*-weighted imaging was performed on day 8 (coma), day 44 (minimally conscious state), day 198 (post-traumatic confusional state), and day 366 (community reintegration). Mean apparent diffusion coefficient (ADC) and fractional anisotropy values in the corpus callosum, cerebral hemispheric white matter, and thalamus were compared with clinical assessments using the Disability Rating Scale (DRS). Extensive diffusion restriction in the corpus callosum and bihemispheric white matter was observed on day 8, with ADC values in a range typically associated with neurotoxic injury (230-400 x 10(-6) mm(2)/s). T2*-weighted MRI revealed widespread hemorrhagic axonal injury in the cerebral hemispheres, corpus callosum, and brainstem. Despite the presence of severe axonal injury on early MRI, the patient regained the ability to communicate and perform activities of daily living independently at 1 year post-injury (DRS = 8). MRI data should be interpreted with caution when prognosticating for patients in traumatic coma. Recovery of consciousness and community reintegration are possible even when extensive traumatic axonal injury is demonstrated by early MRI. C1 [Edlow, Brian L.; Hochberg, Leigh R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Edlow, Brian L.; Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Giacino, Joseph T.; Hirschberg, Ronald E.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Giacino, Joseph T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hirschberg, Ronald E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Gerrard, Jason] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Wu, Ona] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Ctr Neurorestorat & Neurotechnol, Dept Vet Affairs Med Ctr, Providence, RI USA. RP Edlow, BL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM bedlow@partners.org OI Hochberg, Leigh/0000-0003-0261-2273 FU National Institutes of Health [R25NS065743, P41EB015896]; National Institute on Disability and Rehabilitation Research [H133A120085]; Center for Integration of Medicine and Innovative Technology (Boston, MA) FX This study was supported in part by grants from the National Institutes of Health (R25NS065743 and P41EB015896), the National Institute on Disability and Rehabilitation Research (H133A120085), and the Center for Integration of Medicine and Innovative Technology (Boston, MA). The views in this article represent those of the authors alone, and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. Government. NR 76 TC 5 Z9 5 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2013 VL 19 IS 3 BP 364 EP 375 DI 10.1007/s12028-013-9870-x PG 12 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 257OB UT WOS:000327393200015 PM 23860665 ER PT J AU Silva, PS Cavallerano, JD Sun, JK Soliman, AZ Aiello, LM Aiello, LP AF Silva, Paolo S. Cavallerano, Jerry D. Sun, Jennifer K. Soliman, Ahmed Z. Aiello, Lloyd M. Aiello, Lloyd Paul TI Peripheral Lesions Identified by Mydriatic Ultrawide Field Imaging: Distribution and Potential Impact on Diabetic Retinopathy Severity SO OPHTHALMOLOGY LA English DT Article ID INTENSIVE TREATMENT; MACULAR EDEMA; COMPLICATIONS; PHOTOGRAPHY; MELLITUS; FILM; INTERVENTIONS; PROGRESSION; RETINA; TRIAL AB Objective: To assess diabetic retinopathy (DR) as determined by lesions identified using mydriatic ultrawide field imaging (DiSLO200; Optos plc, Scotland, UK) compared with Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field film photography. Design: Prospective comparative study of DiSLO200, ETDRS 7-standard field film photographs, and dilated fundus examination (DFE). Participants: A total of 206 eyes of 103 diabetic patients selected to represent all levels of DR. Methods: Subjects had DiSLO200, ETDRS 7-standard field film photographs, and DFE. Images were graded for severity and distribution of DR lesions. Discrepancies were adjudicated, and images were compared side by side. Main Outcome Measures: Distribution of hemorrhage and/or microaneurysm (H/Ma), venous beading (VB), intraretinal microvascular abnormality (IRMA), and new vessels elsewhere (NVE). Kappa (kappa) and weighted kappa statistics for agreement. Results: The distribution of DR severity by ETDRS 7-standard field film photographs was no DR 12.5%; nonproliferative DR mild 22.5%, moderate 30%, and severe/very severe 8%; and proliferative DR 27%. Diabetic retinopathy severity between DiSLO200 and ETDRS film photographs matched in 80% of eyes (weighted kappa = 0.74, kappa = 0.84) and was within 1 level in 94.5% of eyes. DiSLO200 and DFE matched in 58.8% of eyes (weighted kappa = 0.69, kappa = 0.47) and were within 1 level in 91.2% of eyes. Forty eyes (20%) had DR severity discrepancies between DiSLO200 and ETDRS film photographs. The retinal lesions causing discrepancies were H/Ma 52%, IRMA 26%, NVE 17%, and VB 4%. Approximately one-third of H/Ma, IRMA, and NVE were predominantly outside ETDRS fields. Lesions identified on DiSLO200 but not ETDRS film photographs suggested a more severe DR level in 10% of eyes. Distribution in the temporal, superotemporal, inferotemporal, superonasal, and inferonasal fields was 77%, 72%, 61%, 65%, and 59% for H/Ma, respectively (P < 0.0001); 22%, 24%, 21%, 28%, and 22% for VB, respectively (P = 0.009); 52%, 40%, 29%, 47%, and 36% for IRMA, respectively (P< 0.0001), and 8%, 4%, 4%, 8%, and 5% for NVE, respectively (P = 0.03). All lesions were more frequent in the temporal fields compared with the nasal fields (P< 0.0001). Conclusions: DiSLO200 images had substantial agreement with ETDRS film photographs and DFE in determining DR severity. On the basis of DiSLO200 images, significant nonuniform distribution of DR lesions was evident across the retina. The additional peripheral lesions identified by DiSLO200 in this cohort suggested a more severe assessment of DR in 10% of eyes than was suggested by the lesions within the ETDRS fields. However, the implications of peripheral lesions on DR progression within a specific ETDRS severity level over time are unknown and need to be evaluated prospectively. (C) 2013 by the American Academy of Ophthalmology. C1 [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Soliman, Ahmed Z.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Soliman, Ahmed Z.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu FU Optos, plc, (Dunfermline, Fife, Scotland, UK) FX The performance of the study published by Silva et al14 was supported in part by grant funding provided to the Joslin Diabetes Center by Optos, plc, (Dunfermline, Fife, Scotland, UK). Ultrawide field images taken during that study were acquired on an Optos P200MA that was provided by Optos, plc, to the Joslin Diabetes Center on temporary loan. Subsequent studies that reviewed images obtained from the original cohort of patients reported in this article received no external funding. Optos, plc, was the partial sponsor and funding organization of the initial study and had no oversight in the design, conduct, or reports of the past or current research. NR 26 TC 29 Z9 33 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2013 VL 120 IS 12 BP 2587 EP 2595 DI 10.1016/j.ophtha.2013.05.004 PG 9 WC Ophthalmology SC Ophthalmology GA 255OL UT WOS:000327249600044 PM 23778092 ER PT J AU Kirkizlar, E Serban, N Sisson, JA Swann, JL Barnes, CS Williams, MD AF Kirkizlar, Eser Serban, Nicoleta Sisson, Jennifer A. Swann, Julie L. Barnes, Claire S. Williams, Michael D. TI Evaluation of Telemedicine for Screening of Diabetic Retinopathy in the Veterans Health Administration SO OPHTHALMOLOGY LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; DIGITAL FUNDUS PHOTOGRAPHY; COMPLICATIONS TRIAL; UTILITY VALUES; EYE DISEASE; MELLITUS; PROGRAM; CARE; OPHTHALMOSCOPY; SPECIFICITY AB Objective: To explore the cost-effectiveness of telemedicine for the screening of diabetic retinopathy (DR) and identify changes within the demographics of a patient population after telemedicine implementation. Design: A retrospective medical chart review (cohort study) was conducted. Participants: A total of 900 type 1 and type 2 diabetic patients enrolled in a medical system with a telemedicine screening program for DR. Methods: The cost-effectiveness of the DR telemedicine program was determined by using a finite-horizon, discrete time, discounted Markov decision process model populated by parameters and testing frequency obtained from patient records. The model estimated the progression of DR and determined average quality-adjusted life years (QALYs) saved and average additional cost incurred by the telemedicine screening program. Main Outcome Measures: Diabetic retinopathy, macular edema, blindness, and associated QALYs. Results: The results indicate that telemedicine screening is cost-effective for DR under most conditions. On average, it is cost-effective for patient populations of >3500, patients aged <80 years, and all racial groups. Observable trends were identified in the screening population since the implementation of telemedicine screening: the number of known DR cases has increased, the overall age of patients receiving screenings has decreased, the percentage of nonwhites receiving screenings has increased, the average number of miles traveled by a patient to receive a screening has decreased, and the teleretinal screening participation is increasing. Conclusions: The current teleretinal screening program is effective in terms of being cost-effective and increasing population reach. Future screening policies should give consideration to the age of patients receiving screenings and the system's patient pool size because our results indicate it is not cost-effective to screen patients aged older than 80 years or in populations with <3500 patients. (C) 2013 by the American Academy of Ophthalmology. C1 [Kirkizlar, Eser] Natera Inc, San Carlos, CA USA. [Serban, Nicoleta; Sisson, Jennifer A.; Swann, Julie L.] Georgia Inst Technol, Atlanta, GA 30332 USA. [Barnes, Claire S.] US Dept Vet Affairs, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Williams, Michael D.] US Dept Vet Affairs, Atlanta VA Med Ctr, Rehabil Res & Dev Ctr Excellence, Atlanta, GA USA. RP Swann, JL (reprint author), Georgia Inst Technol, Sch ISyE, Groseclose 0205,Room 411, Atlanta, GA 30332 USA. EM jswann@isye.gatech.edu OI Swann, Julie/0000-0003-2151-4396 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Rehabilitation Research and Development Service [C4758W]; Health Systems Institute; Georgia Institute of Technology; Zalesky Family FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Rehabilitation Research and Development Service, including Career Development Award C4758W. This material was supported by a seed grant from the Health Systems Institute, Georgia Institute of Technology. This material received student funding through the Georgia Institute of Technology President Undergraduate Research Award. J.L.S. was partially supported as the Harold R. and Mary Anne Nash professor, by the Zalesky Family, and by Andrea Laliberte through gifts to the Georgia Institute of Technology. NR 41 TC 20 Z9 20 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2013 VL 120 IS 12 BP 2604 EP 2610 DI 10.1016/j.ophtha.2013.06.029 PG 7 WC Ophthalmology SC Ophthalmology GA 255OL UT WOS:000327249600046 PM 24084501 ER PT J AU Hill-Burns, EM Singh, N Ganguly, P Hamza, TH Montimurro, J Kay, DM Yearout, D Sheehan, P Frodey, K Mclear, JA Feany, MB Hanes, SD Wolfgang, WJ Zabetian, CP Factor, SA Payami, H AF Hill-Burns, E. M. Singh, N. Ganguly, P. Hamza, T. H. Montimurro, J. Kay, D. M. Yearout, D. Sheehan, P. Frodey, K. Mclear, J. A. Feany, M. B. Hanes, S. D. Wolfgang, W. J. Zabetian, C. P. Factor, S. A. Payami, H. TI A genetic basis for the variable effect of smoking/nicotine on Parkinson's disease SO PHARMACOGENOMICS JOURNAL LA English DT Article DE SV2C; nicotine; Parkinson's disease ID DOSE TRANSDERMAL NICOTINE; SYNAPTIC VESICLE PROTEIN; SMOKING; MODEL; ASSOCIATION; TRANSPORTER; CAFFEINE; THERAPY; COFFEE; RISK AB Prior studies have established an inverse association between cigarette smoking and the risk of developing Parkinson's disease (PD), and currently, the disease-modifying potential of the nicotine patch is being tested in clinical trials. To identify genes that interact with the effect of smoking/nicotine, we conducted genome-wide interaction studies in humans and in Drosophila. We identified SV2C, which encodes a synaptic-vesicle protein in PD-vulnerable substantia nigra (P = 1 x 10(-7) for gene-smoking interaction on PD risk), and CG14691, which is predicted to encode a synaptic-vesicle protein in Drosophila (P = 2 x 10(-11) for nicotine-paraquat interaction on gene expression). SV2C is biologically plausible because nicotine enhances the release of dopamine through synaptic vesicles, and PD is caused by the depletion of dopamine. Effect of smoking on PD varied by SV2C genotype from protective to neutral to harmful (P = 5 x 10(-10)). Taken together, cross-validating evidence from humans and Drosophila suggests SV2C is involved in PD pathogenesis and it might be a useful marker for pharmacogenomics studies involving nicotine. C1 [Hill-Burns, E. M.; Singh, N.; Ganguly, P.; Hamza, T. H.; Montimurro, J.; Kay, D. M.; Sheehan, P.; Frodey, K.; Mclear, J. A.; Hanes, S. D.; Payami, H.] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12208 USA. [Yearout, D.; Zabetian, C. P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Yearout, D.; Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Feany, M. B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Feany, M. B.] Harvard Univ, Sch Med, Boston, MA USA. [Hanes, S. D.; Wolfgang, W. J.] New York State Dept Hlth, Wadsworth Ctr, Div Infect Dis, Albany, NY 12208 USA. [Hanes, S. D.; Wolfgang, W. J.; Payami, H.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA. [Hanes, S. D.] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA. [Factor, S. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, 150 New Scotland Ave, Albany, NY 12208 USA. EM hpayami@wadsworth.org OI Kay, Denise/0000-0002-9928-2698; Wolfgang, William/0000-0003-1769-0215; Zabetian, Cyrus/0000-0002-7739-4306 FU National Institute of Neurological Disorders and Stroke [R01NS36960, R01NS067469]; Department of Veterans Affairs [1I01BX000531]; National Institute of Aging [P30AG08017]; Office of Research & Development, Clinical Sciences Research & Development Service, Department of Veteran Affairs; Close to the Cure Foundation; National Institutes of Health [HHSN268200782096C] FX We thank the persons with Parkinson's disease and volunteers who participated in the study. We also thank Dr John Nutt for his continued support for this project and Dr Sridar Chittur (Center for Functional Genomics at State University of New York at Albany) for processing the expression arrays. The project was funded by grants from the National Institute of Neurological Disorders and Stroke (R01NS36960 and R01NS067469). Additional support was provided by a Merit Review Award from the Department of Veterans Affairs (1I01BX000531), National Institute of Aging (P30AG08017), Office of Research & Development, Clinical Sciences Research & Development Service, Department of Veteran Affairs, and the Close to the Cure Foundation. Genotyping services were provided by the Center for Inherited Disease Research, which is funded by the National Institutes of Health (HHSN268200782096C). NR 35 TC 12 Z9 13 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD DEC PY 2013 VL 13 IS 6 BP 530 EP 537 DI 10.1038/tpj.2012.38 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 258HJ UT WOS:000327449700008 PM 23032990 ER PT J AU Romero, JM Pizzolato, R Atkinson, W Meader, A Jaimes, C Lamuraglia, G Jaff, MR Buonanno, F Almandoz, JD Gonzalez, RG AF Romero, Javier M. Pizzolato, Raffaella Atkinson, Wendy Meader, Anna Jaimes, Camilo Lamuraglia, Glenn Jaff, Michael R. Buonanno, Ferdinando Almandoz, Josser Delgado Gonzalez, Ramon G. TI Vasa Vasorum Enhancement on Computerized Tomographic Angiography Correlates With Symptomatic Patients With 50% to 70% Carotid Artery Stenosis SO STROKE LA English DT Article DE atherosclerosis; carotid artery diseases ID ATHEROSCLEROTIC PLAQUE; INTRAPLAQUE HEMORRHAGE; GLOBAL BURDEN; NEOVASCULARIZATION; ENDARTERECTOMY; STROKE; RUPTURE; TRIAL; INFLAMMATION; PROGRESSION AB Background and Purpose Significant stenosis of the internal carotid artery (ICA) is an established stroke risk factor. Recent evidence suggests that features within the atherosclerotic plaque also have prognostic value. The purpose of this study was to correlate the enhancement of the vasa vasorum (VV) overlying the carotid artery plaque with acute neurological symptoms in patients with 50% to 70% ICA stenosis. Methods We conducted a 4-year retrospective computerized tomographic angiographic review to identify patients with 50% to 70% stenosis of the ICA. Three types of plaques were identified: enhancing VV, calcified, and nonenhancing-noncalcified. Medical records were reviewed for cardiovascular risk factors and neurological status, and imaging was reviewed for signs of a recent stroke. Results We identified a total of 428 patients with 50% to 70% ICA stenosis: 103 (24.1%) had enhancing VV, 202 (47.2%) calcified, and 123 (28.7%) nonenhancing-noncalcified arteries; 97 were symptomatic and 331 asymptomatic. Thirty-three (34%) symptomatic subjects demonstrated enhancing VV, 42 (20%) had calcified arterial plaques, and 22 (17%) had nonenhancing-noncalcified arterial plaques. Fisher exact tests revealed that the proportion of symptomatic individuals with enhancing VV plaque was double that of the other groups combined (P=0.015; odds ratio, 1.92; 95% confidence interval, 1.17-3.16). Regression analyses confirmed this association as independent from other known cardiovascular risk factors. Conclusions In patients with 50% to 70% ICA stenosis, VV enhancement recognized on computed tomographic angiography is strongly associated with acute neurological symptoms compared with calcified and nonenhancing-noncalcified arterial plaques. This finding may aid in the identification of patients at increased risk for ischemic stroke within populations with the same degree of stenosis. C1 [Romero, Javier M.; Pizzolato, Raffaella; Atkinson, Wendy; Meader, Anna; Jaimes, Camilo; Gonzalez, Ramon G.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lamuraglia, Glenn] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Dept Cardiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buonanno, Ferdinando] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Almandoz, Josser Delgado] Abbott NW Hosp, Dept Intervent Neuroradiol, Neurosci Inst, Minneapolis, MN 55407 USA. RP Romero, JM (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, GRB, 55 Fruit St,Off 279, Boston, MA 02114 USA. EM Jmromero@partners.org NR 34 TC 4 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP 3344 EP 3349 DI 10.1161/STROKEAHA.113.002400 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300303 PM 24172578 ER PT J AU Li, PY Mao, LL Zhou, GQ Leak, RK Sun, BL Chen, J Hu, XM AF Li, Peiying Mao, Leilei Zhou, Guoqing Leak, Rehana K. Sun, Bao-Liang Chen, Jun Hu, Xiaoming TI Adoptive Regulatory T-Cell Therapy Preserves Systemic Immune Homeostasis After Cerebral Ischemia SO STROKE LA English DT Article DE immunosuppression; inflammation; stroke; T-lymphocytes; regulatory ID EXPERIMENTAL STROKE; INJURY; INFECTIONS; ACTIVATION; PROMOTES; SURVIVAL; MICE AB Background and Purpose Cerebral ischemia has been shown to result in peripheral inflammatory responses followed by long-lasting immunosuppression. Our recent study demonstrated that intravenous delivery of regulatory T cells (Tregs) markedly protected against transient cerebral ischemia by suppressing neutrophil-derived matrix metallopeptidase 9 production in the periphery. However, the effect of Tregs on systemic inflammatory responses and immune status has not been fully characterized. Methods Cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were isolated from donor animals by CD4 and CD25 double selection and transferred intravenously to ischemic recipients at 2 hours after middle cerebral artery occlusion. Animals were euthanized on different days after reperfusion. The effects of Tregs on systemic inflammation and immune status were evaluated using flow cytometry, ELISAs, and immunohistochemistry. Results Systemic administration of purified Tregs raises functional Tregs in the blood and peripheral organs, including spleen and lymph nodes. These exogenous Tregs remain in the blood and peripheral organs for 12 days. Functionally, Treg adoptive transfer markedly inhibits middle cerebral artery occlusion-induced elevation of inflammatory cytokines (interleukin-6 and tumor necrosis factor ) in the blood. Furthermore, Treg treatment corrects long-term lymphopenia and improves cellular immune functions after ischemic brain injury. As a result, Treg-treated animals exhibit decreased bacterial loads in the blood during recovery from cerebral ischemic attack. Conclusions Treg treatment did not exacerbate poststroke immunosuppression. On the contrary, Treg-treated animals displayed improved immune status after focal cerebral ischemia. C1 [Li, Peiying; Mao, Leilei; Chen, Jun; Hu, Xiaoming] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Li, Peiying; Mao, Leilei; Chen, Jun; Hu, Xiaoming] Fudan Univ, Dept Anesthesiol, Huashan Hosp, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Li, Peiying; Mao, Leilei; Chen, Jun; Hu, Xiaoming] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Zhou, Guoqing; Sun, Bao-Liang] Shandong Univ, Dept Neurol, Tai An, Shandong, Peoples R China. [Zhou, Guoqing; Sun, Bao-Liang] Shandong Univ, Key Lab Cerebral Microcirculat, Tai An, Shandong, Peoples R China. [Zhou, Guoqing; Sun, Bao-Liang] Taishan Med Coll, Affiliated Hosp, Tai An, Shandong, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15219 USA. [Chen, Jun; Hu, Xiaoming] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Hu, XM (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu; hux2@upmc.edu OI Leak, Rehana/0000-0003-2817-7417 FU American Heart Association [13SDG14570025]; National Institutes of Health [NS36736, NS43802, NS45048]; Veterans Affairs Pittsburgh Health Care System (Pittsburgh, PA); Chinese Natural Science Foundation [81070947, 81271275]; Shandong Natural Science Foundation [ZR2012HZ006] FX Dr Hu is supported by a Scientist Development Grant (13SDG14570025) from the American Heart Association. Dr Chen is supported by National Institutes of Health grants NS36736, NS43802, and NS45048 and Veterans Affairs Pittsburgh Health Care System (Pittsburgh, PA). Dr Sun is supported by Chinese Natural Science Foundation grants (81070947, 81271275) and Shandong Natural Science Foundation (ZR2012HZ006). NR 18 TC 18 Z9 18 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP 3509 EP 3515 DI 10.1161/STROKEAHA.113.002637 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300325 PM 24092548 ER PT J AU Miyamoto, N Maki, T Pham, LDD Hayakawa, K Seo, JH Mandeville, ET Mandeville, JB Kim, KW Lo, EH Arai, K AF Miyamoto, Nobukazu Maki, Takakuni Pham, Loc-Duyen D. Hayakawa, Kazuhide Seo, Ji Hae Mandeville, Emiri T. Mandeville, Joseph B. Kim, Kyu-Won Lo, Eng H. Arai, Ken TI Oxidative Stress Interferes With White Matter Renewal After Prolonged Cerebral Hypoperfusion in Mice SO STROKE LA English DT Article DE mice; oligodendrocyte; reactive oxygen species; white matter diseases ID FREE-RADICAL SCAVENGER; OLIGODENDROCYTE PRECURSOR CELLS; ELEMENT-BINDING PROTEIN; ISCHEMIC BRAIN-DAMAGE; IN-VIVO; NEUROVASCULAR NICHE; REACTIVE OXYGEN; EDARAVONE; INJURY; REPAIR AB Background and Purpose White matter injury caused by cerebral hypoperfusion may contribute to the pathophysiology of vascular dementia and stroke, but the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that oxidative stress interferes with endogenous white matter repair by disrupting renewal processes mediated by oligodendrocyte precursor cells (OPCs). Methods In vitro, primary rat OPCs were exposed to sublethal CoCl2 for 7 days to induce prolonged chemical hypoxic stress. Then, OPC proliferation/differentiation was assessed. In vivo, prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in mice. Then, reactive oxygen species production, myelin density, oligodendrocyte versus OPC counts, and cognitive function were evaluated. To block oxidative stress, OPCs and mice were treated with the radical scavenger edaravone. Results Prolonged chemical hypoxic stress suppressed OPC differentiation in vitro. Radical scavenging with edaravone ameliorated these effects. After 28 days of cerebral hypoperfusion in vivo, reactive oxygen species levels were increased in damaged white matter, along with the suppression of OPC-to-oligodendrocyte differentiation and loss of myelin staining. Concomitantly, mice showed functional deficits in working memory. Radical scavenging with edaravone rescued OPC differentiation, ameliorated myelin loss, and restored working memory function. Conclusions Our proof-of-concept study demonstrates that after prolonged cerebral hypoperfusion, oxidative stress interferes with white matter repair by disrupting OPC renewal mechanisms. Radical scavengers may provide a potential therapeutic approach for white matter injury in vascular dementia and stroke. C1 [Miyamoto, Nobukazu; Maki, Takakuni; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Seo, Ji Hae; Mandeville, Emiri T.; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Miyamoto, Nobukazu; Maki, Takakuni; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Seo, Ji Hae; Mandeville, Emiri T.; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mandeville, Joseph B.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, NeuroVasc Coordinat Res Ctr, Coll Pharm, Seoul, South Korea. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea. RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, E 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation; Executive Committee on Research Fund for Medical Discovery of Massachusetts General Hospital; American Heart Association; National Institutes of Health, Research Abroad from the Uehara Memorial Foundation; National Research Foundation of Korea through the World Class University Program [R31-2008-000-10103-0]; Global Research Laboratory Program [2011-0021874] FX This work was supported, in part, by the Deane Foundation, the Executive Committee on Research Fund for Medical Discovery of Massachusetts General Hospital, American Heart Association, National Institutes of Health, Research Abroad from the Uehara Memorial Foundation, National Research Foundation of Korea through the World Class University Program (R31-2008-000-10103-0), and the Global Research Laboratory Program (2011-0021874). NR 43 TC 21 Z9 21 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP 3516 EP 3521 DI 10.1161/STROKEAHA.113.002813 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300326 PM 24072001 ER PT J AU Kamalian, S Morais, LT Pomerantz, SR Aceves, M Sit, SP Bose, A Hirsch, JA Lev, MH Yoo, AJ AF Kamalian, Shervin Morais, Livia T. Pomerantz, Stuart R. Aceves, Mario Sit, Siu Po Bose, Arani Hirsch, Joshua A. Lev, Michael H. Yoo, Albert J. TI Clot Length Distribution and Predictors in Anterior Circulation Stroke Implications for Intra-Arterial Therapy SO STROKE LA English DT Article DE clot-length; hyperdense MCA; intra-arterial therapy; IV-tPA; stroke ID ISCHEMIC-STROKE; THROMBUS; RECONSTRUCTIONS; RECANALIZATION AB Background and Purpose Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots 8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation <8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (14.2) and 16.1 (7.6-25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was 8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions The majority of anterior circulation proximal occlusions are 8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length 8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths. C1 [Kamalian, Shervin; Morais, Livia T.; Pomerantz, Stuart R.; Hirsch, Joshua A.; Lev, Michael H.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kamalian, Shervin; Morais, Livia T.; Pomerantz, Stuart R.; Hirsch, Joshua A.; Lev, Michael H.; Yoo, Albert J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Aceves, Mario; Sit, Siu Po; Bose, Arani] Penumbra Inc, Alameda, CA USA. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St GRB-241, Boston, MA 02114 USA. EM ajyoo@partners.org RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 FU National Institutes of Health [8UL1TR000170-05] FX Dr Kamalian received training support from Harvard Catalyst by the National Institutes of Health (8UL1TR000170-05) award. The content is solely the authors' responsibility and does not necessarily represent the official views of NIH, Harvard University/Catalyst and its affiliated healthcare centers. NR 8 TC 12 Z9 12 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP 3553 EP 3556 DI 10.1161/STROKEAHA.113.003079 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300334 PM 24105699 ER PT J AU Dowlatshahi, D Brouwers, B Demchuk, A Hill, M Aviv, R Ufholz, L Wintermark, M Hemphil, J Murai, Y Wang, Y Zhao, X Wang, Y Li, N Greenberg, S Romero, J Rosand, J Goldstein, J Sharma, M AF Dowlatshahi, D. Brouwers, B. Demchuk, A. Hill, M. Aviv, R. Ufholz, L. Wintermark, M. Hemphil, I. I. I. J. Murai, Y. Wang, Y. Zhao, X. Wang, Y. Li, N. Greenberg, S. Romero, J. Rosand, J. Goldstein, J. Sharma, M. TI The Predictive Ability of the CTA Spot for Hematoma Enlargement is Dependent on Time Since ICH Onset: a Systematic Review and Patient-Level Meta-Analysis SO STROKE LA English DT Meeting Abstract CT Canadian Stroke Congress CY OCT 17-20, 2013 CL Montreal, CANADA C1 [Dowlatshahi, D.; Ufholz, L.] Univ Ottawa, Ottawa, ON, Canada. [Dowlatshahi, D.; Ufholz, L.] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Brouwers, B.; Greenberg, S.; Romero, J.; Rosand, J.; Goldstein, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Demchuk, A.; Hill, M.] Univ Calgary, Calgary, AB, Canada. [Aviv, R.] Univ Toronto, Toronto, ON, Canada. [Wintermark, M.] Univ Virginia, Charlottesville, VA 22903 USA. [Hemphil, I. I. I. J.] UCSF, San Francisco, CA USA. [Murai, Y.] Nippon Med Sch, Tokyo 113, Japan. [Wang, Y.; Zhao, X.; Wang, Y.; Li, N.] Capital Med Univ, Beijing, Peoples R China. [Sharma, M.] Populat Hlth Res Inst, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP E206 EP E206 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300172 ER PT J AU Greenberg, SM AF Greenberg, Steven M. TI C. Miller Fisher: An Appreciation SO STROKE LA English DT Editorial Material DE history; ischemic attack; transient; stroke C1 [Greenberg, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program,Dept Neurol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Harvard Univ, Sch Med, MGH Stroke Res Ctr, Hemorrhag Stroke Res Program,Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP E171 EP E172 DI 10.1161/STROKEAHA.113.001554 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300004 ER PT J AU Lanthier, S Calabrese, LH Ferro, JM Putaala, J Strbian, D Letourneau-Guillon, L Raymond, J Guilbert, F Frosch, M Chagnon, M Singhal, AB Poppe, AY AF Lanthier, S. Calabrese, L. H. Ferro, J. M. Putaala, J. Strbian, D. Letourneau-Guillon, L. Raymond, J. Guilbert, F. Frosch, M. Chagnon, M. Singhal, A. B. Poppe, A. Y. TI The INTERnational Study on Primary Angiitis of the CEntral nervous system (INTERSPACE): A Call to the World SO STROKE LA English DT Meeting Abstract CT Canadian Stroke Congress CY OCT 17-20, 2013 CL Montreal, CANADA C1 [Lanthier, S.; Raymond, J.; Guilbert, F.; Poppe, A. Y.] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Calabrese, L. H.] Cleveland Clin, Cleveland, OH 44106 USA. [Ferro, J. M.] Hosp Santa Maria, Lisbon, Portugal. [Putaala, J.; Strbian, D.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Letourneau-Guillon, L.] Univ Montreal, Dept Radiol, Montreal, PQ, Canada. [Frosch, M.; Singhal, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chagnon, M.] Univ Montreal, Dept Math & Stat, Montreal, PQ H3C 3J7, Canada. [Singhal, A. B.] Harvard Univ, Sch Med, Boston, MA USA. EM sylanthier@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2013 VL 44 IS 12 BP E227 EP E227 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 257LR UT WOS:000327386300276 ER PT J AU Pal, J Gold, JS Munshi, NC Shammas, MA AF Pal, Jagannath Gold, Jason S. Munshi, Nikhil C. Shammas, Masood A. TI Biology of telomeres: importance in etiology of esophageal cancer and as therapeutic target SO TRANSLATIONAL RESEARCH LA English DT Article ID BARRETTS ADENOCARCINOMA CELLS; DNA-DAMAGE; MULTIPLE-MYELOMA; GROWTH ARREST; HOMOLOGOUS RECOMBINATION; CHROMOSOMAL INSTABILITY; MYOCARDIAL-INFARCTION; MAMMALIAN TELOMERES; GENOME INSTABILITY; CIGARETTE-SMOKING AB The purpose of this review is to highlight the importance of telomeres, the mechanisms implicated in their maintenance, and their role in the etiology as well as the treatment of human esophageal cancer. We will also discuss the role of telomeres in the maintenance and preservation of genomic integrity, the consequences of telomere dysfunction, and the various factors that may affect telomere health in esophageal tissue predisposing it to oncogenesis. There has been growing evidence that telomeres, which can be affected by various intrinsic and extrinsic factors, contribute to genomic instability, oncogenesis, as well as proliferation of cancer cells. Telomeres are the protective DNA-protein complexes at chromosome ends. Telomeric DNA undergoes progressive shortening with age leading to cellular senescence and/or apoptosis. If senescence/apoptosis is prevented as a consequence of specific genomic changes, continued proliferation leads to very short (le, dysfunctional) telomeres that can potentially cause genomic instability, thus, increasing the risk for activation of telomere maintenance mechanisms and oncogenesis. Like many other cancers, esophageal cancer cells have short telomeres and elevated telomerase, the enzyme that maintains telomeres in most cancer cells. Homologous recombination, which is implicated in the alternate pathway of telomere elongation, is also elevated in Barrett's-associated esophageal adenocarcinoma. Evidence from our laboratory indicates that both telomerase and homologous recombination contribute to telomere maintenance, DNA repair, and the ongoing survival of esophageal cancer cells. This indicates that telomere maintenance mechanisms may potentially be targeted to make esophageal cancer cells static. The rate at which telomeres in healthy cells shorten is determined by a number of intrinsic and extrinsic factors, including those associated with lifestyle. Avoidance of factors that may directly or indirectly injure esophageal tissue including its telomeric and other genomic DNA can not only reduce the risk of development of esophageal cancer but may also have positive impact on overall health and lifespan. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Shammas, MA (reprint author), Harvard Univ, Sch Med, VAMC, 1400 VFW Pkwy,Bldg 3,Room 2A111, West Roxbury, MA 02132 USA. EM Masood_shammas@dfci.harvard.edu RI Gold, Jason/O-5112-2014 OI Gold, Jason/0000-0002-2925-4755 FU National Cancer Institute [R01CA125711]; Department of Veterans Affairs [I01- BX001584]; National Institutes of Health [RO1-124929, PO1-155258, P50-100007, PO1-78378] FX Research work conducted in our laboratory and some of the work discussed here is supported in part by grants from National Cancer Institute R01CA125711 to M.A.S., from the Department of Veterans Affairs Merit Review Awards I01- BX001584 (to N.C.M.) and from the National Institutes of Health Grants RO1-124929, PO1-155258, P50-100007 and PO1-78378 to N.C.M. J.S.G. is supported by a Career Development Award from the Department of Veterans Affairs. NR 76 TC 6 Z9 8 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 EI 1878-1810 J9 TRANSL RES JI Transl. Res. PD DEC PY 2013 VL 162 IS 6 BP 364 EP 370 DI 10.1016/j.trsl.2013.09.003 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 257VT UT WOS:000327416600004 PM 24090770 ER PT J AU Reinke, LF Uman, J Udris, EM Moss, BR Au, DH AF Reinke, Lynn F. Uman, Jane Udris, Edmunds M. Moss, Brianna R. Au, David H. TI Preferences for Death and Dying Among Veterans With Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE patient preferences; death and dying; end-of-life communication; chronic obstructive pulmonary disease ID OF-LIFE CARE; END; COMMUNICATION; CLINICIAN; FAMILIES; QUALITY AB Rationale: Studies identify common factors important for a good death. However, it is important for clinicians to individualize end-of-life care by eliciting patients' preferences. We sought to determine preferences for death and dying among veterans with chronic obstructive pulmonary disease (COPD) by performing a cross-sectional study. Participants (n = 376) completed a preferences about death and dying questionnaire. Results: Common themes ranked as most important by veterans include health care costs (86.6%) and avoiding strain on loved ones (78.8%). Unique items include being unafraid of dying (67.1%) and having discussed your treatment preferences with your clinician (59.3%). Conclusion: Preferences for death and dying are consistent among individuals with life-limiting illness, thus should be incorporated as core components in all end-of-life care planning. We identified unique preferences important to patients with COPD. This study suggests that clinicians need to engage in end-of-life discussions to learn about individual preferences to improve the patients' dying experience. C1 [Reinke, Lynn F.; Uman, Jane; Udris, Edmunds M.; Moss, Brianna R.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv R&D Seattle, Seattle, WA 98108 USA. [Reinke, Lynn F.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Au, David H.] Univ Washington, Sch Med, Div Pulm & Crit Care, Seattle, WA 98195 USA. RP Reinke, LF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM reinkl@uw.edu FU Health Services Research and Development, Department of Veterans Affairs [11R 02-292, TPP-61-021]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This study was funded by Health Services Research and Development, Department of Veterans Affairs 11R 02-292 and TPP-61-021. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 20 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD DEC PY 2013 VL 30 IS 8 BP 768 EP 772 DI 10.1177/1049909112471579 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 255NJ UT WOS:000327246400005 PM 23298873 ER PT J AU Farless, LB Steil, N Williams, BR Bailey, FA AF Farless, Laura B. Steil, Neal Williams, Beverly Rosa Bailey, F. Amos TI Intermittent Subcutaneous Furosemide: Parenteral Diuretic Rescue for Hospice Patients With Congestive Heart Failure Resistant to Oral Diuretic SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE congestive heart failure; hospice; subcutaneous therapy; home infusion; diuretic resistance; dyspnea AB Patients with congestive heart failure (CHF) account for up to 12% of the hospice population and often experience significant symptoms related to volume overload. Diuretic therapy is the cornerstone of treatment but administration (PO) often becomes ineffective and (IV, IM) routes cause discomfort or may not be feasible to ameliorate symptoms. Subcutaneous dosing of furosemide has been explored as a potential alternative for management of CHF symptoms. We report 2 cases of CHF resistant to oral diuretic and examine the clinical utility of subcutaneous furosemide in an inpatient palliative care unit and a home hospice setting. Our case series supports the use of subcutaneous therapy as a potential alternative in palliative care and hospice patients. C1 [Farless, Laura B.; Steil, Neal; Williams, Beverly Rosa; Bailey, F. Amos] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Bailey, FA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham VAMC 11G,700 South 19th St, Birmingham, AL 35233 USA. EM amos.bailey@va.gov NR 5 TC 3 Z9 3 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD DEC PY 2013 VL 30 IS 8 BP 791 EP 792 DI 10.1177/1049909112465795 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 255NJ UT WOS:000327246400009 PM 23136114 ER PT J AU Thanarajasingam, G Kim, HT Cutler, C Ho, VT Koreth, J Alyea, EP Antin, JH Soiffer, RJ Armand, P AF Thanarajasingam, Gita Kim, Haesook T. Cutler, Corey Ho, Vincent T. Koreth, John Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. Armand, Philippe TI Outcome and Prognostic Factors for Patients Who Relapse after Allogeneic Hematopoietic. Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic stem cell transplantation; Relapse; Prognostic factors; Donor lymphocyte infusion ID 1ST INTERNATIONAL WORKSHOP; ACUTE MYELOID-LEUKEMIA; PREVENTION; COMORBIDITY; STRATEGIES; COMMITTEE; BIOLOGY; MARROW; ADULTS; INDEX AB Disease relapse remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT), yet little is known about the relevant prognostic factors after relapse. We studied 1080 patients transplanted between 2004 and 2008, among whom 351 relapsed. The 3-year postrelapse overall survival (prOS) rate was 19%. Risk factors for mortality after relapse included shorter time to relapse, higher disease risk index at HSCT, myeloablative conditioning, high pretransplantation comorbidity index, and graft-versus-host disease (GVHD) occurring before relapse. Important prognostic factors did not vary by disease type. Based on this, we could stratify patients into 3 groups, with 3-year prOS rates of 36%, 14%, and 3% (P < .0001). This score was validated in an historical cohort of 276 patients. Postrelapse donor lymphocyte infusion or repeat HSCT was associated with improved prOS, as was the development of GVHD after relapse. These differences remained significant in models that accounted. for other prognostic factors and in landmark analyses of patients who survived at least 2 months from relapse. The results of this study may aid with prognostication and management of patients who relapse after HSCT and motivate the design of clinical trials aimed at relapse prevention or treatment in higher-risk patients. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Thanarajasingam, Gita] Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org FU NIH [P01 CA142106]; Jock and Bunny Adams Research Endowment; Conquer Cancer/ASCO Foundation FX Financial disclosure: Supported by NIH grant P01 CA142106 and the Jock and Bunny Adams Research Endowment. P.A. is supported by a career development award from the Conquer Cancer/ASCO Foundation. NR 19 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2013 VL 19 IS 12 BP 1713 EP 1718 DI 10.1016/j.bbmt.2013.09.011 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 257CL UT WOS:000327361100011 PM 24076323 ER PT J AU Prabhakarpandian, B Pant, K Scott, RC Pattillo, CB Irimia, D Kiani, MF Sundaram, S AF Prabhakarpandian, Balabhaskar Pant, Kapil Scott, Robert C. Pattillo, Christopher B. Irimia, Daniel Kiani, Mohammad F. Sundaram, Shivshankar TI Synthetic microvascular networks for quantitative analysis of particle adhesion (vol 10, pg 585, 2008) SO BIOMEDICAL MICRODEVICES LA English DT Correction C1 [Prabhakarpandian, Balabhaskar; Pant, Kapil; Sundaram, Shivshankar] CFD Res Corp, Biomed Technol, Huntsville, AL 35805 USA. [Scott, Robert C.; Pattillo, Christopher B.; Kiani, Mohammad F.] Temple Univ, Dept Mech Engn, Philadelphia, PA 19122 USA. [Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Kiani, Mohammad F.] Temple Univ, Dept Radiat Oncol, Philadelphia, PA 19122 USA. RP Sundaram, S (reprint author), CFD Res Corp, Biomed Technol, 215 Wynn Dr, Huntsville, AL 35805 USA. EM sxs@cfdrc.com NR 1 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 EI 1572-8781 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD DEC PY 2013 VL 15 IS 6 BP 1087 EP 1087 DI 10.1007/s10544-013-9823-3 PG 1 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 253JM UT WOS:000327081100018 ER PT J AU Regan, MM Pagani, O Fleming, GF Walley, BA Price, KN Rabaglio, M Maibach, R Ruepp, B Coates, AS Goldhirsch, A Colleoni, M Gelber, RD Francis, PA AF Regan, Meredith M. Pagani, Olivia Fleming, Gini F. Walley, Barbara A. Price, Karen N. Rabaglio, Manuela Maibach, Rudolf Ruepp, Barbara Coates, Alan S. Goldhirsch, Aron Colleoni, Marco Gelber, Richard D. Francis, Prudence A. CA IBCSG Investigator SOFT Investigator Text Investigator TI Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: Design of the TEXT and SOFT trials SO BREAST LA English DT Article DE Premenopausal; Endocrine-responsive; Early breast cancer; Adjuvant therapy; Trial design ID PLUS ZOLEDRONIC ACID; RANDOMIZED-TRIALS; CHEMOTHERAPY; THERAPY; TAMOXIFEN AB Objectives: In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? Methods: TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. Results: TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid-and late-2014. Conclusions: We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer. Trial Registration TEXT: Clinicaltrials.gov NCT00066703 SOFT: Clinicaltrials.gov NCT00066690 (C) 2013 Elsevier Ltd. All rights reserved. C1 [Regan, Meredith M.; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Colleoni, Marco; Francis, Prudence A.] Int Breast Canc Study Grp, Bern, Switzerland. [Pagani, Olivia] Osped Italiano, Inst Oncol So Switzerland IOSI, Lugano, Switzerland. [Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Fleming, Gini F.] Alliance Clin Trials Oncol, Chicago, IL USA. [Fleming, Gini F.] Univ Chicago Hosp, Chicago, IL 60637 USA. [Walley, Barbara A.] Natl Canc Inst Canada, Clin Trial Grp, Calgary, AB, Canada. [Walley, Barbara A.] Tom Baker Canc Clin, Calgary, AB, Canada. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Rabaglio, Manuela; Maibach, Rudolf; Ruepp, Barbara] Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. [Rabaglio, Manuela] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron; Colleoni, Marco] European Inst Oncol, Milan, Italy. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Francis, Prudence A.] St Vincents Hosp, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence A.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Francis, Prudence A.] ANZBCTG, Newcastle, NSW, Australia. RP Regan, MM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu; olivia.pagani@ibcsg.org; gfleming@medicine.bsd.uchicago.edu; barbara.walley@albertahealthservices.ca; price@jimmy.harvard.edu; manuela.rabaglio@ibcsg.org; rudolf.maibach@ibcsg.org; barbara.ruepp@ibcsg.org; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org; marco.colleoni@ieo.it; gelber@jimmy.harvard.edu; prue.francis@petermac.org FU Pfizer; International Breast Cancer Study Group; US National Cancer Institute; NHMRC [351161, 510788]; Swedish Cancer Society; Cancer Council Australia; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); US National Cancer Institute [CA75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX TEXT and SOFT receive financial support for trial conduct from Pfizer, the International Breast Cancer Study Group and the US National Cancer Institute. Pfizer and Ipsen provide drug supply. Support for the coordinating group, IBCSG: Swedish Cancer Society, The Cancer Council Australia, Australia & New Zealand Breast Cancer Trials Group (NHMRC Project Grants 351161 and 510788), Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), US National Cancer Institute (CA75362), Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). The pharmaceutical companies have no role in the reporting or interpretation of the trials, other than a minority representation on the Steering Committee. NR 23 TC 22 Z9 22 U1 1 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD DEC PY 2013 VL 22 IS 6 BP 1094 EP 1100 DI 10.1016/j.breast.2013.08.009 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 248EU UT WOS:000326677500014 PM 24095609 ER PT J AU Yiu, G Marra, KV Arroyo, JG AF Yiu, Glenn Marra, Kyle V. Arroyo, Jorge G. TI Authors response: surgical outcomes after epiretinal membrane peeling combined with cataract surgery SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter DE Retina; Treatment Surgery; Wound healing C1 [Yiu, Glenn] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Marra, Kyle V.; Arroyo, Jorge G.] Harvard Univ, Div Ophthalmol, Beth Israel Med Ctr, Boston, MA 02114 USA. [Yiu, Glenn; Arroyo, Jorge G.] Harvard Univ, Harvard Med Sch, Dept Ophthalmol, Boston, MA 02114 USA. RP Yiu, G (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD DEC PY 2013 VL 97 IS 12 BP 1609 EP 1609 DI 10.1136/bjophthalmol-2013-304142 PG 1 WC Ophthalmology SC Ophthalmology GA 250UJ UT WOS:000326881000026 PM 24092885 ER PT J AU Nash, WP Litz, BT AF Nash, William P. Litz, Brett T. TI Moral Injury: A Mechanism for War-Related Psychological Trauma in Military Family Members SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Review DE Post-traumatic stress disorder; Military families; Deployment; Belief systems; Theoretical models ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH-SERVICES; SECONDARY TRAUMATIZATION; VIETNAM VETERANS; COMBAT; DEPLOYMENT; CHILDREN; PTSD; PARTNERS; IMPACT AB Recent research has provided compelling evidence of mental health problems in military spouses and children, including post-traumatic stress disorder (PTSD), related to the war-zone deployments, combat exposures, and post-deployment mental health symptoms experienced by military service members in the family. One obstacle to further research and federal programs targeting the psychological health of military family members has been the lack of a clear, compelling, and testable model to explain how war-zone events can result in psychological trauma in military spouses and children. In this article, we propose a possible mechanism for deployment-related psychological trauma in military spouses and children based on the concept of moral injury, a model that has been developed to better understand how service members and veterans may develop PTSD and other serious mental and behavioral problems in the wake of war-zone events that inflict damage to moral belief systems rather by threatening personal life and safety. After describing means of adapting the moral injury model to family systems, we discuss the clinical implications of moral injury, and describe a model for its psychological treatment. C1 [Nash, William P.] Boston VA Res Inst, Boston, MA 02130 USA. [Nash, William P.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Nash, WP (reprint author), 408 Adahi RD SE, Vienna, VA 22180 USA. EM william.nash@opstress.net NR 74 TC 7 Z9 7 U1 3 U2 35 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1096-4037 EI 1573-2827 J9 CLIN CHILD FAM PSYCH JI Clin. Child Fam. Psychol. Rev. PD DEC PY 2013 VL 16 IS 4 BP 365 EP 375 DI 10.1007/s10567-013-0146-y PG 11 WC Psychology, Clinical SC Psychology GA 250ZG UT WOS:000326895300003 PM 23852334 ER PT J AU Jeon, J Sato, K Niedzwiecki, D Ye, X Saltz, LB Mayer, RJ Mowat, RB Whittom, R Hantel, A Benson, A Wigler, DS Atienza, D Messino, M Kindler, H Venook, A Fuchs, CS Meyerhardt, JA AF Jeon, Justin Sato, Kaori Niedzwiecki, Donna Ye, Xing Saltz, Leonard B. Mayer, Robert J. Mowat, Rex B. Whittom, Renaud Hantel, Alexander Benson, Al Wigler, Devin S. Atienza, Daniel Messino, Michael Kindler, Hedy Venook, Alan Fuchs, Charles S. Meyerhardt, Jeffrey A. TI Impact of Physical Activity After Cancer Diagnosis on Survival in Patients With Recurrent Colon Cancer: Findings From CALGB 89803/Alliance SO CLINICAL COLORECTAL CANCER LA English DT Article DE Cancer recurrence; Exercise; Physical activity; Recurrent colon cancer; Survival ID ACCENT DATA SET; COLORECTAL-CANCER AB Physical activity after diagnosis in patients with colorectal cancer reduced the risk of recurrence and all-cause mortality. However, the association between physical activity and the risk of mortality after recurrence has not been studied. The current study observed a trend toward statistical significance in the association between physical activity after diagnosis and survival after cancer recurrence in colon cancer survivors. Background: The impact of physical activity on survival outcomes in patients with recurrent colon cancer has not been studied. We tested the association between the level of postdiagnosis physical activity and survival outcomes of patients with recurrent colon cancer. Patients and Methods: We conducted a prospective observational study of 237 patients with stage III colon cancer who had recurrence of disease. Physical activity was measured approximately 6 months after the completion of therapy (14 months after surgical resection) but before detection of recurrent disease. The primary end point of the study was survival time after recurrence. Results: The hazard ratio comparing patients who reported at least 18 metabolic equivalent task (MET) hours per week of physical activity with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval, 0.46-1.11). Increasing total MET hours of physical activity per week was associated with a borderline statistical significance trend for improved survival after recurrence (P = .052). The benefit of physical activity on survival was not significantly modified by sex, body mass index (BMI), number of positive lymph nodes, age, baseline performance status, adjuvant chemotherapy regimen, or recurrence-free survival period. Conclusion: To our knowledge, this is the first study investigating the association of physical activity with survival outcome of patients with recurrent colon cancer. Although the association exceeded our pre-defined P trend <.05 for statistical significance, these findings warrant further studies of physical activity in patients with recurrent colorectal cancer. C1 [Jeon, Justin; Sato, Kaori; Mayer, Robert J.; Wigler, Devin S.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Jeon, Justin] Yonsei Univ, Coll Sci Educ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Niedzwiecki, Donna; Ye, Xing] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mowat, Rex B.] Toledo Community Hosp, Oncol Program, Toledo, OH USA. [Whittom, Renaud] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Hantel, Alexander] Edward Canc Ctr, Naperville, IL USA. [Benson, Al] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Atienza, Daniel] Virginia Oncol Associates, Norfolk, VA USA. [Messino, Michael] Mission Hosp Inc, Southeast Canc Control Consortium, Asheville, NC USA. [Kindler, Hedy] Univ Chicago, Chicago, IL 60637 USA. [Venook, Alan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jmeyerhardt@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute [CA31946, CA33601]; Pfizer Oncology; National Research Foundation of Korea (NRF); Ministry of Education [2011-0004892]; National R & D program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [1120230]; [CA32291]; [CA77651]; [CA35415]; [CO15]; [CA047577]; [CA037447]; [CA041287]; [CA47559]; [CA60138] FX The research for CALGB 89803 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Monica M. Bertagnolli, MD, Chairman) and to the CALGB Statistical Center (Daniel J. Sargent, PhD, CA33601). Support was also received from Pharmacia & Upjohn Company, now Pfizer Oncology. Justin Jeon was supported by the National Research Foundation of Korea (NRF), Ministry of Education, (No.2011-0004892) and the National R & D program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1120230) and also in part by CA32291. Xing Ye was supported in part by CA33601. Leonard B. Saltz was supported in part by CA77651. Rex B. Mowat was supported in part by CA35415. Renaud Whittom was supported in part by Grant CO15. Daniel Atienza was supported in part by CA047577. Alan Vinook was supported in part by CA037447. Hedy Kindler was supported in part by CA041287. Al Benson was supported in part by CA47559. Michael Messino was supported in part by CA60138. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 16 TC 7 Z9 7 U1 1 U2 12 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD DEC PY 2013 VL 12 IS 4 BP 233 EP 238 DI 10.1016/j.clcc.2013.06.005 PG 6 WC Oncology SC Oncology GA 253AC UT WOS:000327053000002 PM 24035029 ER PT J AU Caliendo, AM Gilbert, DN Ginocchio, CC Hanson, KE May, L Quinn, TC Tenover, FC Alland, D Blaschke, AJ Bonomo, RA Carroll, KC Ferraro, MJ Hirschhorn, LR Joseph, WP Karchmer, T MacIntyre, AT Reller, LB Jackson, AF AF Caliendo, Angela M. Gilbert, David N. Ginocchio, Christine C. Hanson, Kimberly E. May, Larissa Quinn, Thomas C. Tenover, Fred C. Alland, David Blaschke, Anne J. Bonomo, Robert A. Carroll, Karen C. Ferraro, Mary Jane Hirschhorn, Lisa R. Joseph, W. Patrick Karchmer, Tobi MacIntyre, Ann T. Reller, L. Barth Jackson, Audrey F. CA IDSA TI Better Tests, Better Care: Improved Diagnostics for Infectious Diseases SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE diagnostics; rapid diagnostics; point-of-care testing; molecular diagnostics; clinical microbiology; infectious diseases ID DESORPTION IONIZATION-TIME; POLYMERASE-CHAIN-REACTION; FLIGHT MASS-SPECTROMETRY; VENTILATOR-ASSOCIATED PNEUMONIA; BLOOD-STREAM INFECTIONS; PEDIATRIC EMERGENCY-DEPARTMENT; RESPIRATORY-TRACT INFECTIONS; HUMAN SEPTIC SHOCK; CHLAMYDIA-TRACHOMATIS; PATIENT-MANAGEMENT AB In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians. C1 [Caliendo, Angela M.] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Gilbert, David N.] Providence Portland Med Ctr, Div Infect Dis, Portland, OR USA. [Gilbert, David N.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Ginocchio, Christine C.] North Shore LIJ Labs, Div Infect Dis Diagnost, Lake Success, NY USA. [Ginocchio, Christine C.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. [Ginocchio, Christine C.] Hofstra North Shore LIJ Sch Med, Dept Mol Med, Hempstead, NY USA. [Hanson, Kimberly E.] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. [Hanson, Kimberly E.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [May, Larissa] George Washington Univ, Dept Emergency Med, Washington, DC USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Quinn, Thomas C.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Tenover, Fred C.] Cepheid, Sunnyvale, CA USA. [Alland, David] Rutgers State Univ, Rutgers New Jersey Med Sch, Dept Med, Ctr Emerging Pathogens, Newark, NJ USA. [Blaschke, Anne J.] Univ Utah, Sch Med, Dept Pediat, Div Pediat Infect Dis, Salt Lake City, UT USA. [Bonomo, Robert A.] Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Res Serv, Cleveland, OH USA. [Bonomo, Robert A.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Carroll, Karen C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Med Microbiol, Baltimore, MD 21205 USA. [Carroll, Karen C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Ferraro, Mary Jane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ferraro, Mary Jane] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirschhorn, Lisa R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Hirschhorn, Lisa R.] JSI Res & Training Inst, Boston, MA USA. [Joseph, W. Patrick] Siemens Clin Lab, Berkeley, CA USA. [Joseph, W. Patrick] Genom Hlth, Redwood City, CA USA. [Joseph, W. Patrick] XDx Lab, San Francisco, CA USA. [Joseph, W. Patrick] Tethys Biosci, Emeryville, CA USA. [Karchmer, Tobi] Becton Dickinson & Co, Sparks, MD USA. [MacIntyre, Ann T.] Nova SE Univ, Dept Internal Med, Ft Lauderdale, FL 33314 USA. [Reller, L. Barth] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Reller, L. Barth] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Jackson, Audrey F.] Infect Dis Soc Amer, Arlington, VA 22209 USA. RP Jackson, AF (reprint author), Infect Dis Soc Amer, 1300 Wilson Blvd,Ste 300, Arlington, VA 22209 USA. EM ajackson@idsociety.org FU IDSA FX This supplement is sponsored by IDSA. The policy paper was developed by IDSA's Diagnostics Task Force through discussion and deliberation over several months, and the authors thank all who provided input and interesting discussion during that time. The authors extend special thanks to Drs Johan S. Bakken and Janet Nicholson for careful review of the manuscript. NR 82 TC 103 Z9 104 U1 2 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2013 VL 57 SU 3 BP S139 EP S170 DI 10.1093/cid/cit578 PG 32 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251XB UT WOS:000326965600001 PM 24200831 ER PT J AU Becker, SJE Briet, JP Hageman, MGJS Ring, D AF Becker, Stephanie J. E. Briet, Jan Paul Hageman, Michiel G. J. S. Ring, David TI Death, Taxes, and Trapeziometacarpal Arthrosis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CARPOMETACARPAL JOINT; OSTEOARTHRITIS; PREVALENCE; THUMB; ASSOCIATIONS; DISABILITY; HAND; PAIN AB Hand surgeons treat trapeziometacarpal arthrosis as if everyone with the disease presents for treatment despite evidence that suggests that trapeziometacarpal arthrosis is a normal part of human aging for which-it seems safe to assume-most people never seek medical attention. The aims of our study were (1) to confirm the prevalence of radiographic trapeziometacarpal arthrosis in a very large sample and to determine if age and sex are associated with (2) any radiographic evidence of trapeziometacarpal arthrosis; and (3) radiographic evidence of severe trapeziometacarpal arthrosis. A total of 2321 patients 31 years or older with radiographs obtained during treatment of a distal radius fracture at a tertiary care medical center emergency department between 2002 and 2012 were analyzed. Trapeziometacarpal arthrosis was graded using the 3-point scale of Sodha et al. (none, definite, destroyed trapeziometacarpal joint); we used regression analyses to determine the association of age (in 10-year age groups) and sex with the presence of trapeziometacarpal arthrosis. The prevalence of trapeziometacarpal arthrosis steadily increased to 85% between the ages of 71 and 80 years and reached 100% in women (with 50% of them being classified as severe) aged 91 years or older and 93% in men of 81 years or older. Severe arthrosis was more prevalent at earlier ages among women and reached 35% in women and 34% in men who were 81 years or older. Logistic regression identified higher age as the strongest factor associated with trapeziometacarpal arthrosis, but sex was also a factor. Radiographic trapeziometacarpal arthrosis is an expected part of human aging. Given that only three patients in this large cohort had evidence of prior surgery, it seems that most people adapt to trapeziometacarpal arthrosis. Treatments that optimize adaptation in patients who present with trapeziometacarpal arthrosis-related symptoms and disability merit additional study. Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Becker, Stephanie J. E.; Briet, Jan Paul; Hageman, Michiel G. J. S.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 FU Anna Foundation\NOREF; Marti-Keunig Eckhart Stichting, The Netherlands; Skeletal Dynamics LLC (Miami, FL, USA); Wright Medical Technology, Inc (Arlington, TN, USA) FX One of the authors (SJEB) certifies that she has or may receive payments or benefits, during the study period, greater than USD 10,000 from Anna Foundation vertical bar NOREF, Genootschap Noorthey and Stichting Vreedefonds, The Netherlands, for Scientific Research. One of the authors (MGJSH) certifies that he has or may receive payments or benefits, during the study period, greater than USD 10,000 from Anna Foundation vertical bar NOREF, and Marti-Keunig Eckhart Stichting, The Netherlands, for Scientific Research. One of the authors (DR) certifies that he has or may receive payments or benefits, during the study period, less than USD 10,000 from Skeletal Dynamics LLC (Miami, FL, USA) and Wright Medical Technology, Inc (Arlington, TN, USA). NR 9 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2013 VL 471 IS 12 BP 3738 EP 3744 DI 10.1007/s11999-013-3243-9 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253KI UT WOS:000327083800004 PM 23959907 ER PT J AU McCarthy, JC Glassner, PJ AF McCarthy, Joseph C. Glassner, Philip J. TI Correlation of Magnetic Resonance Arthrography with Revision Hip Arthroscopy SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ACETABULAR LABRAL TEARS; MR ARTHROGRAPHY; FOLLOW-UP; DIAGNOSIS; PATHOLOGY; ACCURACY; SHOULDER; LESIONS; KNEE AB Arthroscopic approaches for the diagnosis and treatment of hip disorders are well established; however, there are limited data regarding revision hip arthroscopy. There have been several studies evaluating the findings of MR arthrography with primary hip arthroscopy, but to our knowledge, no study has evaluated the diagnostic value of MR arthrography before revision hip arthroscopy. We obtained sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MR arthrography to detect labral lesions, chondral lesions and loose bodies before revision hip arthroscopy. We performed a single-surgeon, retrospective review of 70 revision hip arthroscopies (62 patients) and assessed the association between MR arthrography findings and intraoperative findings. There were 43 females and 19 males with a mean age of 36 years (range, 17-59 years). Radiographic interpretation was performed by one of four fellowship-trained musculoskeletal radiologists at three institutions, who had at least 5 years of experience. Radiographic findings were compared with surgical findings by one of the authors for calculation of sensitivity, specificity, PPV, and NPV. The sensitivity, specificity, PPV, and NPV of MR arthrography for detecting labral tears were 82%, 70%, 94%, and 39%, respectively. The sensitivity, specificity, PPV, and NPV of MR arthrography for detecting chondral damage were 65%, 90%, 94%, and 50%, respectively. The sensitivity, specificity, PPV, and NPV of MR arthrography for detecting loose bodies were 33%, 100%, 100%, and 88%, respectively. Our study showed the utility of MR arthrography to assist in the diagnosis and treatment of patients with ongoing or recurrent symptoms who have had prior hip arthroscopy. Our data show that MR arthrography is superior at ruling in, rather than ruling out, labral lesions, chondral lesions, and loose bodies, as there were studies interpreted as normal which in fact showed disorders. Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [McCarthy, Joseph C.] Newton Wellesley Hosp, Dept Orthoped Surg, Newton, MA 02462 USA. [Glassner, Philip J.] Hunterdon Orthopaed Inst, Flemington, NJ USA. RP McCarthy, JC (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM Jcmccarthy1@partners.org FU Innomed Inc (Savannah, GA, USA); Arthrex (Naples, FL, USA); Zimmer (Warsaw, IN, USA) FX One of the authors certifies that he (JCM) has received or may receive payments or benefits, during the study period, an amount less than USD 10,000 from Innomed Inc (Savannah, GA, USA), and an amount less than USD 10,000 from Arthrex (Naples, FL, USA). One of the authors certifies that he (PJG) has received or may receive payments or benefits, during the study period, an amount less than USD 10,000 from Zimmer (Warsaw, IN, USA). NR 31 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2013 VL 471 IS 12 BP 4006 EP 4011 DI 10.1007/s11999-013-3202-5 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253KI UT WOS:000327083800041 PM 23904247 ER PT J AU Bot, AGJ Becker, SJE van Dijk, CN Ring, D Vranceanu, AM AF Bot, Arjan G. J. Becker, Stephanie J. E. van Dijk, C. Niek Ring, David Vranceanu, Ana-Maria TI Abbreviated Psychologic Questionnaires Are Valid in Patients With Hand Conditions SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID IDIOPATHIC ARM PAIN; MISSING DATA; MULTIPLE IMPUTATION; HEALTH-STATUS; DEPRESSION; DISABILITY; SHOULDER; OUTCOMES; QUICKDASH; DISTRESS AB The Pain Catastrophizing Scale (PCS) and Short Health Anxiety Inventory (SHAI) can help hand surgeons identify opportunities for psychologic support, but they are time consuming. If easier-to-use tools were available and valid, they might be widely adopted. We tested the validity of shorter versions of the PCS and SHAI, the PCS-4 and the SHAI-5, by assessing: (1) the difference in mean scaled scores of the short and long questionnaires; (2) floor and ceiling effects between the short and long questionnaires; (3) correlation between the short questionnaires and the outcome measures (an indication of construct validity); and (4) variability in disability and pain, between the short and long questionnaires. One hundred sixty-four new or followup adult patients in one hand surgery clinic completed the SHAI-18, SHAI-5, PCS-13, PCS-4, Patient Health Questionnaire (PHQ)-9, PHQ-2, DASH, and QuickDASH questionnaires, and an ordinal pain scale, as part of a prospective cross-sectional study. Mean scores for the short and long questionnaires were compared with paired t-tests. Floor and ceiling effects were calculated. Pearson's correlation was used to assess the correlation between the short and long questionnaires and with outcome measures. Regression analyses were performed to find predictors of pain and disability. There were small, but significant differences between the mean scores for the DASH and QuickDASH (QuickDASH higher), SHAI-18 and SHAI-5 (SHAI-18 higher), and PCS-13 and PCS-4 (PCS-4 higher), but not the PHQ-9 and PHQ-2. Floor effects ranged between 0% and 65% and ceiling effects between 0% and 3%. There were greater floor effects for the PHQ-2 than for the PHQ-9, but floor and ceiling effects were otherwise comparable for the other short and long questionnaires. All questionnaires showed convergent and divergent validity and criterion validity was shown in multivariable analyses. Content validity, construct convergent validity, and criterion validity were established for the short versions of the PCS and SHAI. Using shorter forms creates small differences in mean values that we believe are unlikely to affect study results and are more efficient and advantageous because of the decreased responder burden. Level III, diagnostic study. See Instructions for Authors for a complete description of levels of evidence. C1 [Bot, Arjan G. J.; Becker, Stephanie J. E.; Ring, David] Harvard Univ, Dept Orthopaed Surg, Sch Med, Boston, MA 02115 USA. [Bot, Arjan G. J.; Becker, Stephanie J. E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. [Vranceanu, Ana-Maria] Harvard Univ, Dept Psychol, Sch Med, Boston, MA USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Benson Henry Mind Body Inst, Dept Behav Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Dept Orthopaed Surg, Sch Med, Boston, MA 02115 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 FU Boehringer Ingelheim (Alkmaar, the Netherlands); Biomet (Dordrecht, the Netherlands); Stryker (Waardenburg, the Netherlands); Amgen BV (Breda, the Netherlands); Smith & Nephew BV (Hoofddorp, the Netherlands); Skeletal Dynamics; Wright Medical Technology, Inc (Arlington, TN, USA); Biomet, Inc (Warsaw, IN, USA); AO North America (Paoli, PA, USA); AO International (Dubendorf, Switzerland); Prins Bernhard Cultuurfonds/Banning-de Jong Fonds (Amsterdam, the Netherlands); VSBfonds (Utrecht, the Netherlands); Anna Fonds (Oegstgeest, the Netherlands); Anna Fonds, Genootschap Noorthey (Bussum, the Netherlands); Vreedefonds (Voorburg, the Netherlands) FX The institution of one of the authors (CND) has received, during the study period, funding from Boehringer Ingelheim (Alkmaar, the Netherlands), Biomet (Dordrecht, the Netherlands), Stryker (Waardenburg, the Netherlands), and Amgen BV (Breda, the Netherlands).; One of the authors (CND) certifies that he or she, or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000, from Smith & Nephew BV (Hoofddorp, the Netherlands). One of the authors (DR) certifies that he or she, or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000, from Skeletal Dynamics; less than USD 10,000 from Wright Medical Technology, Inc (Arlington, TN, USA) and Biomet, Inc (Warsaw, IN, USA); and less than USD 10,000 from AO North America (Paoli, PA, USA) and AO International (Dubendorf, Switzerland). One of the authors (AGJB) certifies that he has received, during the study period, funding from Prins Bernhard Cultuurfonds/Banning-de Jong Fonds (Amsterdam, the Netherlands), VSBfonds (Utrecht, the Netherlands), and Anna Fonds (Oegstgeest, the Netherlands). One of the authors (SJEB) certifies that he has received, during the study period, funding from Anna Fonds, Genootschap Noorthey (Bussum, the Netherlands), and Vreedefonds (Voorburg, the Netherlands). NR 31 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2013 VL 471 IS 12 BP 4037 EP 4044 DI 10.1007/s11999-013-3213-2 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253KI UT WOS:000327083800046 PM 23913341 ER PT J AU Ungi, T Moult, E Schwab, JH Fichtinger, G AF Ungi, Tamas Moult, Eric Schwab, Joseph H. Fichtinger, Gabor TI Tracked Ultrasound Snapshots in Percutaneous Pedicle Screw Placement Navigation: A Feasibility Study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID INTRAOPERATIVE COMPUTED-TOMOGRAPHY; CT REGISTRATION; LUMBAR SPINE; SYSTEM; INSERTION; DEFORMITY; ACCURACY; FIXATION; GUIDANCE; GUIDE AB Computerized navigation improves the accuracy of minimally invasive pedicle screw placement during spine surgery. Such navigation, however, exposes both the patient and the staff to radiation during surgery. To avoid intraoperative exposure to radiation, tracked ultrasound snapshots-ultrasound image frames coupled with corresponding spatial positions-could be used to map preoperatively defined screw plans into the intraoperative coordinate frame. The feasibility of such an approach, however, has not yet been investigated. Are there vertebral landmarks that can be identified using tracked ultrasound snapshots? Can tracked ultrasound snapshots allow preoperative pedicle screw plans to be accurately mapped-compared with CT-derived pedicle screw plans-into the intraoperative coordinate frame in a simulated setting? Ultrasound visibility of registration landmarks was checked on volunteers and phantoms. An ultrasound machine with integrated electromagnetic tracking was used for tracked ultrasound acquisition. Registration was performed using 3D Slicer open-source software (www.slicer.org). Two artificial lumbar spine phantoms were used to evaluate registration accuracy of pedicle screw plans using tracked ultrasound snapshots. Registration accuracy was determined by comparing the ultrasound-derived plans with the CT-derived plans. The four articular processes proved to be identifiable using tracked ultrasound snapshots. Pedicle screw plans were registered to the intraoperative coordinate system using landmarks. The registrations were sufficiently accurate in that none of the registered screw plans intersected the pedicle walls. Registered screw plan positions had an error less than 1.28 +/- A 1.37 mm (average +/- A SD) in each direction and an angle difference less than 1.92A degrees A A +/- A 1.95A degrees around each axis relative to the CT-derived positions. Registration landmarks could be located using tracked ultrasound snapshots and permitted accurate mapping of pedicle screw plans to the intraoperative coordinate frame in a simulated setting. Tracked ultrasound may allow accurate computer-navigated pedicle screw placement while avoiding ionizing radiation in the operating room; however, further studies that compare this approach with other navigation techniques are needed to confirm the practical use of this new approach. C1 [Ungi, Tamas; Moult, Eric; Fichtinger, Gabor] Queens Univ, Lab Percutaneous Surg, Sch Comp, Kingston, ON K7M2N8, Canada. [Schwab, Joseph H.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Ungi, T (reprint author), Queens Univ, Lab Percutaneous Surg, Sch Comp, 557 Goodwin Hall, Kingston, ON K7M2N8, Canada. EM ungi@cs.queensu.ca NR 22 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2013 VL 471 IS 12 BP 4047 EP 4055 DI 10.1007/s11999-013-3239-5 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253KI UT WOS:000327083800048 PM 23955194 ER PT J AU Harris, WH AF Harris, William H. TI Editor's Spotlight/Take 5: CT Pulmonary Angiography After Total Joint Arthroplasty: Overdiagnosis and Iatrogenic Harm? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM wharrishm@hotmail.com NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2013 VL 471 IS 12 BP 4089 EP 4090 DI 10.1007/s11999-013-3301-3 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253KI UT WOS:000327083800054 PM 24072628 ER PT J AU Mayer, F Stahrenberg, R Groschel, K Mostardt, S Biermann, J Edelmann, F Liman, J Wasem, J Goehler, A Wachter, R Neumann, A AF Mayer, Felix Stahrenberg, Raoul Groeschel, Klaus Mostardt, Sarah Biermann, Janine Edelmann, Frank Liman, Jan Wasem, Jurgen Goehler, Alexander Wachter, Rolf Neumann, Anja TI Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Atrial fibrillation; Stroke; Holter monitoring; Cost-effectiveness; Markov model ID NONVALVULAR ATRIAL-FIBRILLATION; QUALITY-OF-LIFE; INTRACEREBRAL HEMORRHAGE; ORAL ANTICOAGULATION; RISK-FACTORS; ACUTE STROKE; METAANALYSIS; MANAGEMENT; WARFARIN; ASPIRIN AB Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Predicted lifelong discounted costs were 33,837 a,not sign for patients diagnosed by the 7-d-Holter and 33,852 a,not sign by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 a,not sign/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness. C1 [Mayer, Felix; Mostardt, Sarah; Biermann, Janine; Wasem, Jurgen; Goehler, Alexander; Neumann, Anja] Univ Duisburg Essen, Inst Hlth Care Management & Res, D-45127 Essen, Germany. [Stahrenberg, Raoul; Edelmann, Frank; Wachter, Rolf] Univ Gottingen, Dept Cardiol & Pneumol, D-37073 Gottingen, Germany. [Groeschel, Klaus; Liman, Jan] Univ Gottingen, Dept Neurol, Gottingen, Germany. [Groeschel, Klaus] Johannes Gutenberg Univ Mainz, Dept Neurol, D-55122 Mainz, Germany. [Edelmann, Frank; Wachter, Rolf] German Cardiovasc Res Ctr, Gottingen, Germany. [Goehler, Alexander] Univ Hlth Sci, Hall In Tirol, Austria. [Goehler, Alexander] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Goehler, Alexander] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment,Dept Radiol, Boston, MA USA. RP Neumann, A (reprint author), Univ Duisburg Essen, Inst Hlth Care Management & Res, Campus Essen,Schutzenbahn 70, D-45127 Essen, Germany. EM fel_mayer@web.de; anja.neumann@medman.uni-due.de OI Wasem, Juergen/0000-0001-9653-168X; Wachter, Rolf/0000-0003-2231-2200; Groschel, Klaus/0000-0002-0244-6116 FU Medtronic FX Research Grant: Rolf Wachter is a principal investigator (local) of the CRYSTAL-AF study, sponsored by Medtronic (>$10 k). Speakers' Bureau: Rolf Wachter has received payment for speakers' bureau appointments by Medtronic (<$10 k). Research Grant: for the Ex-DHF study (>$10 k). Speakers' Bureau: Novartis, Pfizer, Servier, BG Medicine, Berlin Chemie AG (<$ 10k). The remaining all other authors have no conflicts of interest. NR 43 TC 3 Z9 3 U1 0 U2 13 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 EI 1861-0692 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD DEC PY 2013 VL 102 IS 12 BP 875 EP 884 DI 10.1007/s00392-013-0601-2 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 254ZL UT WOS:000327208800003 PM 23904073 ER PT J AU Richter, S Sercia, L Branda, J Burnham, CA Bythrow, M Ferraro, M Garner, O Ginocchio, C Jennemann, R Lewinski, M Manji, R Mochon, A Rychert, J Westblade, L Procop, G AF Richter, S. S. Sercia, L. Branda, J. A. Burnham, C. -A. D. Bythrow, M. Ferraro, M. J. Garner, O. B. Ginocchio, C. C. Jennemann, R. Lewinski, M. A. Manji, R. Mochon, A. B. Rychert, J. A. Westblade, L. F. Procop, G. W. TI Identification of Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the VITEK MS system SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID DESORPTION IONIZATION-TIME; BACTERIAL IDENTIFICATION; ROUTINE IDENTIFICATION; CLINICAL MICROBIOLOGY; COST-EFFECTIVENESS; ESCHERICHIA-COLI; SHIGELLA; IMPACT AB This multicenter study evaluated the accuracy of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry identifications from the VITEK MS system (bioM,rieux, Marcy l'Etoile, France) for Enterobacteriaceae typically encountered in the clinical laboratory. Enterobacteriaceae isolates (n = 965) representing 17 genera and 40 species were analyzed on the VITEK MS system (database v2.0), in accordance with the manufacturer's instructions. Colony growth (a parts per thousand currency sign72 h) was applied directly to the target slide. Matrix solution (alpha-cyano-4-hydroxycinnamic acid) was added and allowed to dry before mass spectrometry analysis. On the basis of the confidence level, the VITEK MS system provided a species, genus only, or no identification for each isolate. The accuracy of the mass spectrometric identification was compared to 16S rRNA gene sequencing performed at MIDI Labs (Newark, DE). Supplemental phenotypic testing was performed at bioM,rieux when necessary. The VITEK MS result agreed with the reference method identification for 96.7 % of the 965 isolates tested, with 83.8 % correct to the species level and 12.8 % limited to a genus-level identification. There was no identification for 1.7 % of the isolates. The VITEK MS system misidentified 7 isolates (0.7 %) as different genera. Three Pantoea agglomerans isolates were misidentified as Enterobacter spp. and single isolates of Enterobacter cancerogenus, Escherichia hermannii, Hafnia alvei, and Raoultella ornithinolytica were misidentified as Klebsiella oxytoca, Citrobacter koseri, Obesumbacterium proteus, and Enterobacter aerogenes, respectively. Eight isolates (0.8 %) were misidentified as a different species in the correct genus. The VITEK MS system provides reliable mass spectrometric identifications for Enterobacteriaceae. C1 [Richter, S. S.; Sercia, L.; Procop, G. W.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44195 USA. [Branda, J. A.; Ferraro, M. J.; Rychert, J. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, J. A.; Ferraro, M. J.; Rychert, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Burnham, C. -A. D.; Westblade, L. F.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Jennemann, R.] Barnes Jewish Hosp, St Louis, MO USA. [Bythrow, M.; Ginocchio, C. C.; Manji, R.] North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, Lake Success, NY USA. [Garner, O. B.; Lewinski, M. A.; Mochon, A. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Ginocchio, C. C.; Westblade, L. F.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. RP Richter, S (reprint author), Cleveland Clin, Dept Clin Pathol, 9500 Euclid Ave LL1-2, Cleveland, OH 44195 USA. EM richtes@ccf.org OI Burnham, Carey-Ann/0000-0002-1137-840X FU bioMerieux FX Financial support for this project was provided by bioMerieux. NR 30 TC 26 Z9 27 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 EI 1435-4373 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD DEC PY 2013 VL 32 IS 12 BP 1571 EP 1578 DI 10.1007/s10096-013-1912-y PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 250ZT UT WOS:000326896700011 PM 23818163 ER PT J AU Lonial, S Kaufman, J Laubach, J Richardson, P AF Lonial, Sagar Kaufman, Jonathan Laubach, Jacob Richardson, Paul TI Elotuzumab: a novel anti-CS1 monoclonal antibody for the treatment of multiple myeloma SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE CS1; elotuzumab; monoclonal IgG1 antibody; multiple myeloma ID LENALIDOMIDE PLUS DEXAMETHASONE; DOSE DEXAMETHASONE; BORTEZOMIB; MULTICENTER; THALIDOMIDE; COMBINATION; GUIDELINES; SURVIVAL; THERAPY; CS1 AB Introduction: While conventional therapies are associated with high response rates in patients with newly diagnosed multiple myeloma, the development of drug resistance remains an issue, and effective therapy for relapsed and refractory patients represents a major clinical unmet need. Areas covered: We reviewed the published data regarding the development and clinical investigation of a CS1-targeted monoclonal antibody, elotuzumab, for the potential treatment of multiple myeloma. Preclinical pharmacological data, along with clinical efficacy, safety, and tolerability of elotuzumab alone and in combination, are summarized. Expert opinion: Elotuzumab, in combination with lenalidomide, demonstrated a remarkably high overall response rate in Phase I and II studies. Additionally, the improvements observed in progression-free survival suggested important superiority over lenalidomide/dexamethasone alone, with a similar tolerability profile. While elotuzumab is associated with a higher incidence of infusion reactions, these can be effectively mitigated with appropriate premedication. The high activity of the elotuzumab/lenalidomide combination is now being further investigated in randomized Phase III trials. Elotuzumab represents an exciting future potential treatment option for patients with multiple myeloma, including those with relapsed and refractory disease, as well as in the induction and post-transplant maintenance settings, and possibly even for early therapy in patients with high-risk smoldering myeloma. C1 [Lonial, Sagar; Kaufman, Jonathan] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Laubach, Jacob] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Richardson, Paul] Harvard Univ, Sch Med, Jerome Lipper Ctr Multiple Myeloma, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Jerome Lipper Ctr Multiple Myeloma, Dana Farber Canc Inst, 450 Brookline Ave,Mayer 232, Boston, MA 02215 USA. EM Paul_Richardson@dfci.harvard.edu FU Merck; Celgene; Novartis FX S Lonial has acted as a consultant for Millennium, Celgene, Novartis, BMS, Onyx, and Sanofi. J Kaufman received research support from Merck, Celgene, and Novartis, and has acted as a consultant for Onyx, Celgene, Janssen, and Aeterna Zentaris. P Richardson has served on advisory committees for Celgene, Millennium, Johnson & Johnson, and Bristol-Myers Squibb. The remaining author has nothing to disclose. Professional medical writing and editorial assistance was provided by Adam McGechan of Caudex Medical and was funded by Bristol-Myers Squibb. NR 36 TC 15 Z9 16 U1 2 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD DEC PY 2013 VL 13 IS 12 BP 1731 EP 1740 DI 10.1517/14712598.2013.847919 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 251UZ UT WOS:000326957600011 PM 24151843 ER PT J AU Michaud, DS Izard, J Wilhelm-Benartzi, CS You, DH Grote, VA Tjonneland, A Dahm, CC Overvad, K Jenab, M Fedirko, V Boutron-Ruault, MC Clavel-Chapelon, F Racine, A Kaaks, R Boeing, H Foerster, J Trichopoulou, A Lagiou, P Trichopoulos, D Sacerdote, C Sieri, S Palli, D Tumino, R Panico, S Siersema, PD Peeters, PHM Lund, E Barricarte, A Huerta, JM Molina-Montes, E Dorronsoro, M Quiros, JR Duell, EJ Ye, WM Sund, M Lindkvist, B Johansen, D Khaw, KT Wareham, N Travis, RC Vineis, P Bueno-de-Mesquita, HB Riboli, E AF Michaud, Dominique S. Izard, Jacques Wilhelm-Benartzi, Charlotte S. You, Doo-Ho Grote, Verena A. Tjonneland, Anne Dahm, Christina C. Overvad, Kim Jenab, Mazda Fedirko, Veronika Boutron-Ruault, Marie Christine Clavel-Chapelon, Franoise Racine, Antoine Kaaks, Rudolf Boeing, Heiner Foerster, Jana Trichopoulou, Antonia Lagiou, Pagona Trichopoulos, Dimitrios Sacerdote, Carlotta Sieri, Sabina Palli, Domenico Tumino, Rosario Panico, Salvatore Siersema, Peter D. Peeters, Petra H. M. Lund, Eiliv Barricarte, Aurelio Huerta, Jose-Maria Molina-Montes, Esther Dorronsoro, Miren Ramon Quiros, J. Duell, Eric J. Ye, Weimin Sund, Malin Lindkvist, Bjorn Johansen, Dorthe Khaw, Kay-Tee Wareham, Nick Travis, Ruth C. Vineis, Paolo Bueno-de-Mesquita, H. Bas Riboli, Elio TI Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study SO GUT LA English DT Article DE Pancreatic Cancer; Epidemiology; Bacterial Pathogenesis ID LINKED-IMMUNOSORBENT-ASSAY; PERIODONTAL HEALTH-STATUS; PORPHYROMONAS-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; LARGE-SCALE; DISEASE; MICROBIOTA; RESPONSES; VIRULENCE; ABO AB Objective Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. Design We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. Results Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200ng/ml vs 200ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). Conclusions Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response. C1 [Michaud, Dominique S.] Brown Univ, Div Biol & Med, Dept Epidemiol, Providence, RI 02912 USA. [Michaud, Dominique S.; Wilhelm-Benartzi, Charlotte S.; Vineis, Paolo; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Izard, Jacques; You, Doo-Ho] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Wilhelm-Benartzi, Charlotte S.] Univ London Imperial Coll Sci Technol & Med, London, England. [Grote, Verena A.; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Dahm, Christina C.; Overvad, Kim] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, Aarhus, Denmark. [Dahm, Christina C.] Aarhus Univ Hosp, Dept Cardiol, DK-8000 Aarhus, Denmark. [Jenab, Mazda; Fedirko, Veronika] Int Agcy Res Canc IARC WHO, Lyon, France. [Boutron-Ruault, Marie Christine; Clavel-Chapelon, Franoise; Racine, Antoine] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, F-94805 Villejuif, France. [Boutron-Ruault, Marie Christine; Clavel-Chapelon, Franoise; Racine, Antoine] Paris South Univ, UMRS 1018, Villejuif, France. [Boeing, Heiner; Foerster, Jana] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Trichopoulou, Antonia; Lagiou, Pagona] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece. [Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece. [Lagiou, Pagona; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lagiou, Pagona; Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy. [Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy. [Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, Dept Prevent & Predict Med, Milan, Italy. [Palli, Domenico] ISPO Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy. [Panico, Salvatore] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy. [Siersema, Peter D.; Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway. [Barricarte, Aurelio] Publ Hlth Inst Navarra, Pamplona, Spain. [Barricarte, Aurelio; Huerta, Jose-Maria; Molina-Montes, Esther] CIBER Epidemiol & Salud Publ CIBERESP, Pamplona, Spain. [Huerta, Jose-Maria] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain. [Molina-Montes, Esther] Andalusian Sch Publ Hlth, Granada, Spain. [Dorronsoro, Miren] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain. [Ramon Quiros, J.] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Asturias, Spain. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr Environm & Canc, Barcelona, Spain. [Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ye, Weimin] Umea Univ, Med Biobank, Umea, Sweden. [Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden. [Sund, Malin] Umea Univ, Dept Surg, Umea, Sweden. [Sund, Malin] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Lindkvist, Bjorn] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden. [Johansen, Dorthe] Skane Univ Hosp, SUS, Dept Surg, Malmo, Sweden. [Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Cambridge, England. [Wareham, Nick] MRC, Epidemiol Unit, Cambridge, England. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. RP Michaud, DS (reprint author), Brown Univ, Dept Epidemiol, Box G-S121-2, Providence, RI 02912 USA. EM Dominique_Michaud@brown.edu RI Clavel-Chapelon, Francoise/G-6733-2014; Panico, Salvatore/K-6506-2016; Dahm, Christina/G-9787-2014; Michaud, Dominique/I-5231-2014; Boutron-Ruault, Marie-Christine/H-3936-2014; Huerta, Jose Maria/N-8654-2015; Sieri, Sabina/K-4667-2016; OI Panico, Salvatore/0000-0002-5498-8312; Izard, Jacques/0000-0002-5904-5436; Dahm, Christina/0000-0003-0481-2893; Sund, Malin/0000-0002-7516-9543; Huerta, Jose Maria/0000-0002-9637-3869; Sieri, Sabina/0000-0001-5201-172X; Foerster, Jana/0000-0003-4589-2682; Duell, Eric J/0000-0001-5256-0163; Sacerdote, Carlotta/0000-0002-8008-5096; PALLI, Domenico/0000-0002-5558-2437; Wilhelm-Benartzi, Charlotte/0000-0003-4927-6158 FU NIH/NCI R21 [CA139193]; Cancer Research UK [A11692, C864/A8257]; MRC [G0401527, D74922]; European Commission (DG-SANCO); International Agency for Research on Cancer; Danish Cancer Society (Denmark); Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; Federal Ministry of Education and Research (Germany); Hellenic Health Foundation; Stavros Niarchos Foundation; Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports; Netherlands Cancer Registry; LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Health Research Fund (FIS); Regional Government of Andalucia; Regional Government of Asturias; Regional Government of Basque Country; Regional Government of Murcia [6236]; Regional Government of Navarra; ISCIII RETIC (Spain) [RD06/0020]; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; Wellcome Trust (UK) FX Primary: NIH/NCI R21 CA139193 MPI: Dominique Michaud and Jacques Izard. Cancer Research UK A11692 PI Dame Beral. valerie.beral@ndm.ox.ac.uk. Cancer Research UK Grant number C864/A8257 PI Kay-Tee Khaw kk101@medschl.cam.ac.uk. MRC Grant reference G0401527 Grant D74922 PI Kay-Tee Khaw kk101@medschl.cam.ac.uk. The sponsors were not involved in the design, data collection, analysis, or interpretation of the study nor were they involved in writing the manuscript. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). We thank Emily McDonald for her technical support for the immunoassay and Melissa Elliot for her support in R programming. NR 56 TC 30 Z9 31 U1 0 U2 13 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 DEC PY 2013 VL 62 IS 12 BP 1764 EP 1770 DI 10.1136/gutjnl-2012-303006 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 250TH UT WOS:000326877200014 PM 22990306 ER PT J AU Hart, PA Kamisawa, T Brugge, WR Chung, JB Culver, EL Czako, L Frulloni, L Go, VLW Gress, TM Kim, MH Kawa, S Lee, KT Lerch, MM Liao, WC Lohr, M Okazaki, K Ryu, JK Schleinitz, N Shimizu, K Shimosegawa, T Soetikno, R Webster, G Yadav, D Zen, Y Chari, ST AF Hart, Phil A. Kamisawa, Terumi Brugge, William R. Chung, Jae Bock Culver, Emma L. Czako, Laszlo Frulloni, Luca Go, Vay Liang W. Gress, Thomas M. Kim, Myung-Hwan Kawa, Shigeyuki Lee, Kyu Taek Lerch, Markus M. Liao, Wei-Chih Lohr, Matthias Okazaki, Kazuichi Ryu, Ji Kon Schleinitz, Nicolas Shimizu, Kyoko Shimosegawa, Tooru Soetikno, Roy Webster, George Yadav, Dhiraj Zen, Yoh Chari, Suresh T. TI Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis SO GUT LA English DT Article DE Autoimmune Disease; Pancreatic Cancer; Pancreato-Biliary Disorders ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; CLINICAL PROFILE; FEATURES; THERAPY AB Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed. C1 [Hart, Phil A.; Chari, Suresh T.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Kamisawa, Terumi] Tokyo Metropolitan Komagome Hosp, Dept Internal Med, Tokyo 1138677, Japan. [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Dept Internal Med, Boston, MA 02114 USA. [Chung, Jae Bock] Yonsei Univ, Coll Med, Dept Internal Med, Inst Gastroenterol,Severance Hosp, Seoul, South Korea. [Culver, Emma L.] John Radcliffe Hosp, Translat Gastroenterol Unit, Oxford OX3 9DU, England. [Czako, Laszlo] Univ Szeged, Dept Internal Med 1, Szeged, Hungary. [Frulloni, Luca] Univ Verona, Dept Med Biomed & Surg Sci, I-37100 Verona, Italy. [Go, Vay Liang W.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA. [Gress, Thomas M.] Univ Marburg, Dept Gastroenterol Endocrinol Metab & Infectiol, Marburg, Germany. [Kim, Myung-Hwan] Univ Ulsan, Coll Med, Dept Internal Med, Asan Med Ctr, Seoul, South Korea. [Kawa, Shigeyuki] Shinshu Univ, Ctr Hlth Safety & Environm Management, Matsumoto, Nagano 390, Japan. [Lee, Kyu Taek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Lerch, Markus M.] Univ Med Greifswald, Dept Med A, Greifswald, Germany. [Liao, Wei-Chih] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Lohr, Matthias] Karolinska Inst, Dept Surg Gastroenterol, Stockholm, Sweden. [Lohr, Matthias] Karolinska Univ Hosp, Stockholm, Sweden. [Okazaki, Kazuichi] Kansai Med Univ, Dept Gastroenterol & Hepatol, Osaka, Japan. [Ryu, Ji Kon] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Schleinitz, Nicolas] Aix Marseille Univ, Dept Internal Med, Marseille, France. [Shimizu, Kyoko] Tokyo Womens Med Univ, Sch Med, Dept Gastroenterol, Tokyo, Japan. [Shimosegawa, Tooru] Tohoku Univ, Div Gastroenterol, Grad Sch Med, Sendai, Miyagi 980, Japan. [Soetikno, Roy] Affiliated Stanford Univ, Dept Internal Med, Palo Alto, CA USA. [Webster, George] Univ Coll London Hosp, Dept Gastroenterol, London, England. [Yadav, Dhiraj] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. [Zen, Yoh] Kings Coll Hosp London, Inst Liver Studies, London, England. RP Kamisawa, T (reprint author), Tokyo Metropolitan Komagome Hosp, Dept Internal Med, Bunkyo Ku, 3-18-22 Honkomagome, Tokyo 1138677, Japan. EM kamisawa@cick.jp RI Lerch, Markus M./E-2206-2016; Hart, Phil/A-9842-2016; OI Lerch, Markus M./0000-0002-9643-8263; Hart, Phil/0000-0003-4346-6196; LIAO, WEI-CHIH/0000-0001-5362-6953; Culver, Emma/0000-0001-9644-8392; Lohr, Matthias/0000-0002-7647-198X; Frulloni, Luca/0000-0001-7417-2655 NR 19 TC 124 Z9 136 U1 1 U2 21 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 DEC PY 2013 VL 62 IS 12 BP 1771 EP 1776 DI 10.1136/gutjnl-2012-303617 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 250TH UT WOS:000326877200015 PM 23232048 ER PT J AU Revencu, N Boon, LM Mendola, A Cordisco, MR Dubois, J Clapuyt, P Hammer, F Amor, DJ Irvine, AD Baselga, E Dompmartin, A Syed, S Martin-Santiago, A Ades, L Collins, F Smith, J Sandaradura, S Barrio, VR Burrows, PE Blei, F Cozzolino, M Brunetti-Pierri, N Vicente, A Abramowicz, M Desir, J Vilain, C Chung, WK Wilson, A Gardiner, CA Dwight, Y Lord, DJE Fishman, L Cytrynbaum, C Chamlin, S Ghali, F Gilaberte, Y Joss, S Boente, MDC Leaute-Labreze, C Delrue, MA Bayliss, S Martorell, L Gonzalez-Ensenat, MA Mazereeuw-Hautier, J O'Donnell, B Bessis, D Pyeritz, RE Salhi, A Tan, OT Wargon, O Mulliken, JB Vikkula, M AF Revencu, Nicole Boon, Laurence M. Mendola, Antonella Cordisco, Maria Rosa Dubois, Josee Clapuyt, Philippe Hammer, Frank Amor, David J. Irvine, Alan D. Baselga, Eulalia Dompmartin, Anne Syed, Samira Martin-Santiago, Ana Ades, Lesley Collins, Felicity Smith, Janine Sandaradura, Sarah Barrio, Victoria R. Burrows, Patricia E. Blei, Francine Cozzolino, Mariarosaria Brunetti-Pierri, Nicola Vicente, Asuncion Abramowicz, Marc Desir, Julie Vilain, Catheline Chung, Wendy K. Wilson, Ashley Gardiner, Carol A. Dwight, Yim Lord, David J. E. Fishman, Leona Cytrynbaum, Cheryl Chamlin, Sarah Ghali, Fred Gilaberte, Yolanda Joss, Shelagh Boente, Maria Del C. Leaute-Labreze, Christine Delrue, Marie-Ange Bayliss, Susan Martorell, Loreto Gonzalez-Ensenat, Maria-Antonia Mazereeuw-Hautier, Juliette O'Donnell, Brid Bessis, Didier Pyeritz, Reed E. Salhi, Aicha Tan, Oon T. Wargon, Orli Mulliken, John B. Vikkula, Miikka TI RASA1 Mutations and Associated Phenotypes in 68 Families with Capillary Malformation-Arteriovenous Malformation SO HUMAN MUTATION LA English DT Article DE RASA1; capillary malformation; arteriovenous malformation; Sturge-Weber syndrome ID HEREDITARY BENIGN TELANGIECTASIA; GTPASE-ACTIVATING PROTEIN; SEVERE MENTAL-RETARDATION; GLOMUVENOUS MALFORMATIONS; ENDOTHELIAL-CELLS; SOMATIC MUTATIONS; 2-HIT MECHANISM; ANOMALIES; MEF2C; GENE AB Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n=100), common CM(s) (port-wine stain; n=100), Sturge-Weber syndrome (n=37), or isolated AVM(s) (n=24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the second-hit hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. (C) 2013 Wiley Periodicals, Inc. C1 [Revencu, Nicole; Boon, Laurence M.; Mendola, Antonella; Vikkula, Miikka] Catholic Univ Louvain, Lab Human Mol Genet, de Duve Inst, B-1200 Brussels, Belgium. [Revencu, Nicole; Vikkula, Miikka] Catholic Univ Louvain, Clin Univ St Luc, Ctr Human Genet, B-1200 Brussels, Belgium. [Boon, Laurence M.] Clin Univ St Luc, Div Plast Surg, Vasc Anomalies Ctr, B-1200 Brussels, Belgium. [Cordisco, Maria Rosa] Hosp Pediat Prof Dr JP Garrahan, Dept Dermatol, Buenos Aires, DF, Argentina. [Dubois, Josee] St Justine Mother Child Univ Hosp, Dept Med Imaging, Montreal, PQ, Canada. [Clapuyt, Philippe; Hammer, Frank] Catholic Univ Louvain, Clin Univ St Luc, Dept Med Imaging, B-1200 Brussels, Belgium. [Amor, David J.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Parkville, Vic 3052, Australia. [Irvine, Alan D.] Our Ladys Childrens Hosp Crumlin, Dermatol Clin, Dublin, Ireland. [Baselga, Eulalia] Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain. [Dompmartin, Anne] Univ Caen Basse Normandie, CHU Caen, Dept Dermatol, Caen, France. [Syed, Samira] Great Ormond St Hosp Sick Children, Dept Pediat Dermatol, London WC1N 3JH, England. [Martin-Santiago, Ana] Son Espases Univ Hosp, Dept Dermatol, Palma De Mallorca, Spain. [Ades, Lesley; Collins, Felicity; Smith, Janine; Sandaradura, Sarah] Childrens Hosp Westmead, Dept Clin Genet, Sydney, NSW 2145, Australia. [Barrio, Victoria R.] Univ Calif San Diego, Dept Pediat & Dermatol, San Diego, CA 92103 USA. [Barrio, Victoria R.] Rady Childrens Hosp, San Diego, CA USA. [Burrows, Patricia E.] Roosevelt Hosp, Dept Radiol, New York, NY USA. [Blei, Francine] Roosevelt Hosp, Vasc Birthmark Inst New York, New York, NY USA. [Cozzolino, Mariarosaria; Brunetti-Pierri, Nicola] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Vicente, Asuncion] Hosp St Joan de Deu, Dept Dermatol, Barcelona, Spain. [Abramowicz, Marc; Desir, Julie; Vilain, Catheline] Univ Libre Brussels, Hop Erasme, Dept Med Genet, Brussels, Belgium. [Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY USA. [Wilson, Ashley] Morgan Stanley Childrens Hosp New York, New York, NY USA. [Gardiner, Carol A.] Univ Nottingham Hosp, Clin Genet Serv, Nottingham NG7 2UH, England. [Dwight, Yim] Kaiser Permanente Med Ctr, Honolulu, HI USA. [Lord, David J. E.] Childrens Hosp Westmead, Vasc Birthmarks Program, Westmead, NSW 2145, Australia. [Fishman, Leona; Cytrynbaum, Cheryl] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chamlin, Sarah] Childrens Mem Hosp, Div Pediat Dermatol, Chicago, IL 60614 USA. [Ghali, Fred] Pediat Dermatol North Texas, Grapevine, TX USA. [Gilaberte, Yolanda] Hosp San Jorge, Unit Dermatol, Huesca, Spain. [Joss, Shelagh] So Gen Hosp, West Scotland Clin Genet Serv, Glasgow G51 4TF, Lanark, Scotland. [Boente, Maria Del C.] Hosp Nino Jesus, Unit Dermatol, San Miguel De Tucuman, Argentina. [Leaute-Labreze, Christine] CHU Bordeaux, Ctr Reference Malad Rares Peau, Bordeaux, France. [Delrue, Marie-Ange] CHU Bordeaux, Dept Med Genet, Bordeaux, France. [Bayliss, Susan] St Louis Childrens Hosp, St Louis, MO 63178 USA. [Martorell, Loreto] Hosp St Joan de Deu, Barcelona, Spain. [Gonzalez-Ensenat, Maria-Antonia] Hosp St Joan de Deu, Dept Dermatol, Barcelona, Spain. [Mazereeuw-Hautier, Juliette] Hop Larrey, Ctr Reference Malad Rares Peau, Serv Dermatol, Toulouse, France. [O'Donnell, Brid] Childrens Univ Hosp, Dept Dermatol, Dublin 1, Ireland. [Bessis, Didier] CHRU Montpellier, Hop St Eloi, Dept Dermatol, Montpellier, France. [Pyeritz, Reed E.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Salhi, Aicha] Fac Med Alger, Algiers, Algeria. [Tan, Oon T.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Wargon, Orli] Univ New S Wales, Sch Womens & Childrens Hlth, Sydney Childrens Hosp, Dept Paediat Dermatol, Sydney, NSW, Australia. [Mulliken, John B.] Harvard Univ, Childrens Hosp, Sch Med, Dept Plast & Oral Surg, Boston, MA 02115 USA. RP Vikkula, M (reprint author), Catholic Univ Louvain, Lab Human Mol Genet, de Duve Inst, SSS DDUV, Ave Hippocrate 74 5,Bte B1-74-06, B-1200 Brussels, Belgium. EM miikka.vikkula@uclouvain.be RI wargon, orli/D-6204-2015; OI wargon, orli/0000-0002-4466-6985; Vikkula, Miikka/0000-0002-6236-338X; Brunetti-Pierri, Nicola/0000-0002-6895-8819; Irvine, Alan/0000-0002-9048-2044 FU Cliniques universitaires Saint-Luc, Universite catholique de Louvain; Fonds de la Recherche Scientifique Medicale (FRSM); Interuniversity Attraction Poles; Belgian Federal Science Policy, network P7/43, F.R.S.-FNRS (Fonds de la Recherche Scientifique); Communaute francaise de Wallonie-Bruxelles; la Lotterie nationale FX Contract grant sponsors: Cliniques universitaires Saint-Luc, Universite catholique de Louvain; Fonds de la Recherche Scientifique Medicale (FRSM); Interuniversity Attraction Poles initiated by the Belgian Federal Science Policy, network P7/43, F.R.S.-FNRS (Fonds de la Recherche Scientifique); Communaute francaise de Wallonie-Bruxelles; la Lotterie nationale. NR 36 TC 42 Z9 43 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD DEC PY 2013 VL 34 IS 12 BP 1632 EP 1641 DI 10.1002/humu.22431 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 250PC UT WOS:000326864200009 PM 24038909 ER PT J AU Magill, SS Klompas, M Balk, R Burns, SM Deutschman, CS Diekema, D Fridkin, S Greene, L Guh, A Gutterman, D Hammer, B Henderson, D Hess, DR Hill, NS Horan, T Kollef, M Levy, M Septimus, E VanAntwerpen, C Wright, D Lipsett, P AF Magill, Shelley S. Klompas, Michael Balk, Robert Burns, Suzanne M. Deutschman, Clifford S. Diekema, Daniel Fridkin, Scott Greene, Linda Guh, Alice Gutterman, David Hammer, Beth Henderson, David Hess, Dean R. Hill, Nicholas S. Horan, Teresa Kollef, Marin Levy, Mitchell Septimus, Edward VanAntwerpen, Carole Wright, Don Lipsett, Pamela TI Developing a New, National Approach to Surveillance for Ventilator-Associated Events: Executive Summary SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article C1 [Magill, Shelley S.; Fridkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA. [Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Klompas, Michael] Harvard Univ, Pilgrim Hlth Care Inst, Boston, MA USA. [Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA. [Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA. [Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA. [Balk, Robert; Burns, Suzanne M.; Deutschman, Clifford S.; Gutterman, David; Hammer, Beth; Hill, Nicholas S.; Kollef, Marin; Levy, Mitchell; Lipsett, Pamela] Amer Thorac Soc, Soc Crit Care Med, Amer Coll Chest Phys, Crit Care Soc Collaborat Amer Assoc Crit Care Nur, Philadelphia, PA USA. [Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA. [Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Diekema, Daniel] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA USA. [Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Surveillance Working Grp, Atlanta, GA USA. [Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA. [Greene, Linda] Assoc Profess Infect Control & Epidemiol, Washington, DC USA. [Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Hammer, Beth] Zablocki VA Med Ctr, Dept Cardiol, Milwaukee, WI USA. [Henderson, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Hess, Dean R.] Amer Assoc Resp Care, Irving, TX USA. [Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA. [Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA. [Levy, Mitchell] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Div Pulm Crit Care & Sleep, Providence, RI 02912 USA. [Septimus, Edward] Texas A&M Hlth Sci Ctr, Dept Internal Med, College Stn, TX USA. [Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA. [VanAntwerpen, Carole] New York State Dept Hlth, Bur Healthcare Assoc Infect, Albany, NY USA. [VanAntwerpen, Carole] Council State & Terr Epidemiologists, Atlanta, GA USA. [Wright, Don] US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA. [Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg Anesthesiol & Crit Care Med, Baltimore, MD USA. RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-24, Atlanta, GA 30329 USA. EM smagill@cdc.gov FU Centers for Disease Control and Prevention (CDC) FX Financial support. The work described herein was supported by the Centers for Disease Control and Prevention (CDC). NR 2 TC 4 Z9 5 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC 1 PY 2013 VL 34 IS 12 BP 1239 EP 1243 DI 10.1086/673463 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 252AJ UT WOS:000326976300001 PM 24225607 ER PT J AU Chopra, V Safdar, N AF Chopra, Vineet Safdar, Nasia TI Development of a Core Team for the Management of Peripherally Inserted Central Catheters Reply SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID BLOOD-STREAM INFECTION; CENTRAL VENOUS CATHETERS; RISK C1 [Chopra, Vineet] Ann Arbor Vet Affairs Med Ctr, Patient Safety Enhancement Program, Ann Arbor, MI USA. [Chopra, Vineet] Ann Arbor Vet Affairs Med Ctr, Hosp Outcomes Program Excellence, Ann Arbor, MI USA. [Chopra, Vineet] Ann Arbor Vet Affairs Med Ctr, Ctr Clin Management Res, Ann Arbor, MI USA. [Chopra, Vineet] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Safdar, Nasia] Univ Wisconsin, William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Div Infect Dis, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Infect Control Dept, Madison, WI USA. RP Chopra, V (reprint author), 2800 Plymouth Rd,Bldg 16,Room 432W, Ann Arbor, MI 48109 USA. EM vineetc@umich.edu NR 9 TC 0 Z9 0 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC 1 PY 2013 VL 34 IS 12 BP 1329 EP 1330 DI 10.1086/673997 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 252AJ UT WOS:000326976300018 PM 24225624 ER PT J AU Menschikowski, M Hagelgans, A Fuessel, S Mareninova, OA Asatryan, L Wirth, MP Siegert, G AF Menschikowski, Mario Hagelgans, Albert Fuessel, Susanne Mareninova, Olga A. Asatryan, Liana Wirth, Manfred P. Siegert, Gabriele TI Serum amyloid A, phospholipase A(2)-IIA and C-reactive protein as inflammatory biomarkers for prostate diseases SO INFLAMMATION RESEARCH LA English DT Article DE Prostate cancer; Benign prostatic hyperplasia; Serum amyloid A; Secreted phospholipase A(2); C-reactive protein; Inflammation ID NF-KAPPA-B; GROUP-II PHOSPHOLIPASE-A2; LUNG-CANCER; PROGNOSTIC MARKER; GASTRIC-CANCER; TARGET GENE; EXPRESSION; CELLS; HYPERPLASIA; RECEPTOR AB Serum amyloid A (SAA), secreted group IIA phospholipase A(2) (sPLA(2)-IIA), and C-reactive protein (CRP) are acute-phase proteins whose serum concentrations increase not only during inflammatory disorders, but also in the course of malignant diseases. In this study we analyzed serum levels of these inflammatory markers along with prostate-specific antigens (PSA) in patients with benign prostatic hyperplasia (BPH, n = 55), localized prostate cancers (PCa, n = 55), and metastatic prostate cancers (mPCa, n = 27) using immunological assays. We found that in comparison to healthy individuals (n = 55), patients with BPH, PCa and mPCa have elevated serum levels of SAA, sPLA(2)-IIA, and CRP, in addition to elevated levels of PSA. Significant differences with respect to inflammatory biomarkers were found between localized and metastatic PCa (p < 0.001), suggesting a prognostic value of these parameters. In addition, serum concentrations of SAA and sPLA(2)-IIA positively correlate with CRP in BPH patients (p < 0.05) and in patients with PCa and mPCa (p < 0.001), but not with PSA levels, Gleason score, or tumor stage, emphasizing a role of SAA and sPLA(2)-IIA as circulating biomarkers of inflammation rather than of neoplastic transformation. In contrast to PSA, which differed significantly between BPH and localized PCa patients (p < 0.01), such a difference was not found for SAA, sPLA(2)-IIA, and CRP. In order to elucidate whether the elevated levels of SAA and sPLA(2)-IIA can be caused by cancer cell-associated synthesis, in vitro studies were performed. These analyses demonstrated the expression of SAA and sPLA(2)-IIA in LNCaP and PC-3 prostate cell lines, which can be further upregulated by pro-inflammatory cytokines in a cell type-dependent manner. This might suggest that, in addition to the hepatic origin, SAA and sPLA(2)-IIA can also be synthesized and secreted by prostatic cancer tissue itself. The results of the present study emphasize the utility of SAA, sPLA(2)-IIA, and CRP as circulating biomarkers of inflammation during BPH development and PCa progression. C1 [Menschikowski, Mario; Hagelgans, Albert; Siegert, Gabriele] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Fuessel, Susanne; Wirth, Manfred P.] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Urol, D-01307 Dresden, Germany. [Mareninova, Olga A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asatryan, Liana] USC Sch Pharm, Titus Family Dept Clin Pharm & Pharmaceut Econ &, Los Angeles, CA USA. RP Menschikowski, M (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Mario.Menschikowski@uniklinikum-dresden.de NR 53 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1023-3830 EI 1420-908X J9 INFLAMM RES JI Inflamm. Res. PD DEC PY 2013 VL 62 IS 12 BP 1063 EP 1072 DI 10.1007/s00011-013-0665-5 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 253IE UT WOS:000327077100007 PM 24061501 ER PT J AU Alizai, PH Schulze-Hagen, M Klink, CD Ulmer, F Roeth, AA Neumann, UP Jansen, M Rosch, R AF Alizai, P. H. Schulze-Hagen, M. Klink, C. D. Ulmer, F. Roeth, A. A. Neumann, U. P. Jansen, M. Rosch, R. TI Primary anastomosis with a defunctioning stoma versus Hartmann's procedure for perforated diverticulitis-a comparison of stoma reversal rates SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Perforated diverticulitis; Hartmann's procedure; Primary anastomosis; Stoma reversal ID ACUTE SIGMOID DIVERTICULITIS; ACUTE COLONIC DIVERTICULITIS; PRIMARY RESECTION; SURGICAL-MANAGEMENT; COMPLICATED DIVERTICULITIS; GENERALIZED PERITONITIS; SECONDARY ANASTOMOSIS; DISEASE; SURGERY; COLOSTOMY AB The ideal treatment of patients with perforated diverticulitis is still controversial. Hartmann's procedure has been the treatment of choice for decades, but primary anastomosis with a defunctioning stoma has become an accepted alternative. The aim of this study was to evaluate the stoma reversal rates after these two surgical strategies. A retrospective review of the data from patients with perforated sigmoid diverticulitis between 2002 and 2011 undergoing a Hartmann's procedure (HP) versus a primary anastomosis with a defunctioning stoma (PA) was performed. Additionally, patients were contacted by mail or telephone in March 2012 using a standardized questionnaire. A total of 98 patients were identified: 72 undergoing HP and 26 patients receiving PA. The median follow-up time was 63 months (range 4-118). Whilst 85 % of patients with PA have had their stoma reversed, only 58 % of patients with an HP had a stoma reversal (p = 0.046). The median period until stoma reversal was significantly longer for HP (19 weeks) than for PA (12 weeks; p = 0.03). The 30-day mortality for PA was 12 % as opposed to 25 % for HP (p = 0.167). According to the Clavien-Dindo classification, surgical complications occurred significantly less frequently in patients with PA (p = 0.014). The stoma reversal rates for PA are significantly higher than for HP. Thus, depending on the overall clinical situation, primary resection and anastomosis with a proximal defunctioning stoma might be the optimal procedure for selected patients with perforated diverticular disease. C1 [Alizai, P. H.; Schulze-Hagen, M.; Klink, C. D.; Ulmer, F.; Roeth, A. A.; Neumann, U. P.; Rosch, R.] RWTH Aachen Univ Hosp, Dept Gen Visceral & Transplantat Surg, D-52074 Aachen, Germany. [Jansen, M.] HELIOS Klinikum Emil von Behring, Dept Gen Visceral & Minimal Invas Surg, D-14165 Berlin, Germany. [Roeth, A. A.] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Div Genom Stabil & DNA Repair, Boston, MA USA. RP Alizai, PH (reprint author), RWTH Aachen Univ Hosp, Dept Gen Visceral & Transplantat Surg, Pauwelsstr 30, D-52074 Aachen, Germany. EM palizai@ukaachen.de NR 54 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 EI 1432-1262 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD DEC PY 2013 VL 28 IS 12 BP 1681 EP 1688 DI 10.1007/s00384-013-1753-2 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 253ON UT WOS:000327098500011 PM 23913315 ER PT J AU Kwak, YG Truong-Bolduc, QC Bin Kim, H Song, KH Kim, ES Hooper, DC AF Kwak, Yee Gyung Truong-Bolduc, Que Chi Bin Kim, Hong Song, Kyoung-Ho Kim, Eu Suk Hooper, David C. TI Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE efflux pumps; ciprofloxacin; S. aureus ID EFFLUX PUMP GENES; QUINOLONE RESISTANCE; CIPROFLOXACIN RESISTANCE; MOXIFLOXACIN; MUTATIONS; SEQUENCE; GYRB; EPIDEMIOLOGY; BLOOD; MGRA AB Objectives: Although the prevalence of fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) is known to be higher than in methicillin-susceptible S. aureus (MSSA), the reasons have never been identified. Methods: We randomly selected 115 isolates of S. aureus collected from 10 different hospitals in Korea between June 2009 and May 2011. To investigate the difference in fluoroquinolone resistance mechanisms between MRSA and MSSA, we evaluated gyrA and parC mutations and the relative expression of the multidrug efflux pump genes norA, norB and norC. Results: All 62 ciprofloxacin-resistant S. aureus had either gyrA or parC mutations. The S84L mutation of gyrA (59/62, 95.2%) and the S80F mutation of parC (61/62, 98.4%) were the most common. Fifty-eight (93.6%) strains had both the S84L mutation of gyrA and the S80F mutation of parC. Among the 115 isolates, norB overexpression was the most common, occurring in 49 (42.6%) strains. There were only two (1.7%) strains with norA overexpression and none with norC overexpression. Strains overexpressing norB were more common among ciprofloxacin-resistant S. aureus (33/62, 53.2%) than ciprofloxacin-susceptible S. aureus (16/53, 30.2%) (P=0.013). When we analysed 62 ciprofloxacin-resistant S. aureus strains, those overexpressing norB were more common in ciprofloxacin-resistant MRSA (28/46, 60.9%) than in ciprofloxacin-resistant MSSA (5/16, 31.3%) (P=0.041). Conclusions: Increased expression of norB can be a factor that contributes to ciprofloxacin resistance in MRSA strains. C1 [Kwak, Yee Gyung; Truong-Bolduc, Que Chi; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kwak, Yee Gyung; Truong-Bolduc, Que Chi; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Kwak, Yee Gyung] Inje Univ, Coll Med, Dept Internal Med, Pusan, South Korea. [Bin Kim, Hong; Song, Kyoung-Ho; Kim, Eu Suk] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM dhooper@partners.org RI Kim, Hong Bin/J-5452-2012; OI Kim, Hong Bin/0000-0001-6262-372X; Kwak, Yee Gyung/0000-0002-4713-8045; Song, Kyoung-Ho/0000-0002-4517-3840 FU Inje Research and Scholarship Foundation from Inje University College of Medicine; Korea Centers for Disease Control and Prevention; National Institutes of Health, US Public Health Service [R37-AI23988] FX This work was supported by the Inje Research and Scholarship Foundation in 2011 (to Y. G. K.) from Inje University College of Medicine, by a grant (to H. B. K. on behalf of KOISA) from the Korea Centers for Disease Control and Prevention, and by a grant R37-AI23988 (to D. C. H.) from the National Institutes of Health, US Public Health Service. NR 33 TC 10 Z9 11 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2013 VL 68 IS 12 BP 2766 EP 2772 DI 10.1093/jac/dkt286 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 252BS UT WOS:000326980000008 PM 23928023 ER PT J AU Liao, CH Hsueh, PR Jacoby, GA Hooper, DC AF Liao, Chun-Hsing Hsueh, Po-Ren Jacoby, George A. Hooper, David C. TI Risk factors and clinical characteristics of patients with qnr-positive Klebsiella pneumoniae bacteraemia SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE K. pneumoniae; PMQR; resistance ID MEDIATED QUINOLONE RESISTANCE; MULTIDRUG EFFLUX PUMP; ESCHERICHIA-COLI; FLUOROQUINOLONE RESISTANCE; CIPROFLOXACIN RESISTANCE; PLASMID; PREVALENCE; ENTEROBACTERIACEAE; DETERMINANTS; ASSOCIATION AB Objectives: Plasmid-mediated quinolone resistance (PMQR) caused by qnr genes has been known for 15 years. Information about global distribution and prevalence of qnr genes is abundant, but clinical information concerning infections produced by these isolates and risk factors for their acquisition is limited. Methods: Klebsiella pneumoniae blood isolates (n=227) from a 1 year prospective cohort of patients in Taiwan were studied. MICs of quinolones were determined for all isolates, and multiplex PER for the presence of PMQR genes and DNA gyrase mutations was applied to all 24 isolates with ciprofloxacin MICs >= 0.12 mg/L and a control group of 72 isolates with MICs <= 0.06 mg/L. Results: All qnr isolates were in the group with ciprofloxacin MICs >= 0.12 mg/L, constituting 9.4% of tested isolates and 3.9% (qnrB 2.6% and qnrS 1.3%) of total isolates. aac(6')-Ib-cr and gepA were not found. Risk factors for qnr included nosocomial infection, bedridden status, surgery within 3 months, non-K1/K2 serotypes and prior antimicrobial use. Ciprofloxacin MIC >= 0.12 mg/L was associated with prior quinolone use; in contrast, prior cephalosporin use was more closely linked to the presence of qnr. Fourteen-day mortality was similar in patients infected with qnr-positive versus qnr-negative isolates, but there was a trend for increased in-hospital mortality in patients infected with qnr-positive isolates. Conclusions: In K. pneumoniae blood isolates collected at a hospital in Taiwan, the overall prevalence of qnr genes was 3.9%. Prior quinolone use was linked to increased ciprofloxacin MIC, but not with the prevalence of qnr, which was most strongly linked to exposure to other antimicrobials, especially cephalosporins. C1 [Liao, Chun-Hsing] Far Eastern Mem Hosp, Div Infect Dis, New Taipei City, Taiwan. [Hsueh, Po-Ren] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org OI HSUEH, PO-REN/0000-0002-7502-9225 FU US Public Health Service, National Institutes of Health [AT R01-AI057576]; For Eastern Memorial Hospital, Taiwan FX This work was supported in part by a grant from the US Public Health Service, National Institutes of Health, AT R01-AI057576 (to D. C. H. and G. A. J.). Salary support for C.-H. L. was provided by the For Eastern Memorial Hospital, Taiwan. NR 24 TC 7 Z9 7 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2013 VL 68 IS 12 BP 2907 EP 2914 DI 10.1093/jac/dkt295 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 252BS UT WOS:000326980000029 PM 23956373 ER PT J AU Wormser, GP Levin, A Soman, S Adenikinju, O Longo, MV Branda, JA AF Wormser, Gary P. Levin, Andrew Soman, Sandeep Adenikinju, Omosalewa Longo, Michael V. Branda, John A. TI Comparative Cost-Effectiveness of Two-Tiered Testing Strategies for Serodiagnosis of Lyme Disease with Noncutaneous Manifestations SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BORRELIA-BURGDORFERI; ENZYME-IMMUNOASSAY; CLINICAL-PRACTICE; DIAGNOSIS; ASSAY; VLSE AB The mainstay of laboratory diagnosis for Lyme disease is two-tiered serological testing, in which a reactive first-tier enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay is supplemented by separate IgM and IgG immunoblots. Recent data suggest that the C6 ELISA can be substituted for immunoblots without a reduction in either sensitivity or specificity. In this study, the costs of 4 different two-tiered testing strategies for Lyme disease were compared using the median charges for these tests at 6 commercial diagnostic laboratories in 2012. The study found that a whole-cell sonicate ELISA followed by the C6 ELISA was the most cost-effective two-tiered testing strategy for Lyme disease with acute-phase serum samples. We conclude that the C6 ELISA can substitute for immunoblots in the two-tiered testing protocol for Lyme disease without a loss of sensitivity or specificity and is less expensive. C1 [Wormser, Gary P.; Soman, Sandeep; Adenikinju, Omosalewa; Longo, Michael V.] New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. [Levin, Andrew] Immunetics Inc, Boston, MA USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, John A.] Harvard Univ, Sch Med, Boston, MA USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jbranda@partners.org FU Immunetics, Inc.; DiaSorin, Inc.; Alere, Inc.; bioMerieux SA; Becton, Dickinson FX G.P.W. has received research grants from Immunetics, Inc., the manufacturer of the C6 ELISA, and from Bio-Rad, DiaSorin, Inc., and bioMerieux SA. He owns equity in Abbott, has been an expert witness in malpractice cases involving Lyme disease, is an unpaid board member of the American Lyme Disease Foundation, has been an expert witness regarding Lyme disease in a disciplinary action for the Missouri Board of Registration for the Healing Arts, and is a consultant to Baxter on Lyme disease vaccine development. J.A.B. has received research grants from DiaSorin, Inc., Alere, Inc., bioMerieux SA, and Becton, Dickinson to fund separate studies and has submitted a patent application for a point-of-care serodiagnostic test based on the 2-ELISA algorithm described in this paper. A. L. is an employee of and holds equity in Immunetics, Inc., which manufactures the C6 ELISA kit. NR 15 TC 13 Z9 13 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2013 VL 51 IS 12 BP 4045 EP 4049 DI 10.1128/JCM.01853-13 PG 5 WC Microbiology SC Microbiology GA 254EL UT WOS:000327147100023 PM 24068010 ER PT J AU Sullivan, KV Turner, NN Lancaster, DP Shah, AR Chandler, LJ Friedman, DF Blecker-Shelly, DL AF Sullivan, K. V. Turner, N. N. Lancaster, D. P. Shah, A. R. Chandler, L. J. Friedman, D. F. Blecker-Shelly, D. L. TI Superior Sensitivity and Decreased Time to Detection with the Bactec Peds Plus/F System Compared to the BacT/Alert Pediatric FAN Blood Culture System SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; ENTEROCOCCAL BACTEREMIA; STREAM INFECTIONS; BIRTH-WEIGHT; VANCOMYCIN; MEDIA; RATES; RESISTANCE; MORTALITY; CHILDREN AB Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzae in combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system. C1 [Sullivan, K. V.; Turner, N. N.; Lancaster, D. P.; Friedman, D. F.; Blecker-Shelly, D. L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Sullivan, K. V.; Chandler, L. J.; Friedman, D. F.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shah, A. R.; Chandler, L. J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Sullivan, KV (reprint author), Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. EM otak@email.chop.edu NR 24 TC 12 Z9 12 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2013 VL 51 IS 12 BP 4083 EP 4086 DI 10.1128/JCM.02205-13 PG 4 WC Microbiology SC Microbiology GA 254EL UT WOS:000327147100030 PM 24088854 ER PT J AU Seng, EK Lovejoy, TI AF Seng, Elizabeth K. Lovejoy, Travis I. CA Project SAFER Intervention Team TI Reliability and Validity of a Treatment Fidelity Assessment for Motivational Interviewing Targeting Sexual Risk Behaviors in People Living with HIV/AIDS SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Motivational interviewing; Treatment fidelity; Psychometrics; Sexual risk behaviors; HIV/AIDS ID TREATMENT INTEGRITY CODE; RANDOMIZED CLINICAL-TRIAL; INTERRATER RELIABILITY; ASSESSING COMPETENCE; HIV; PREVENTION; ADOLESCENTS; INFECTION; PROGRAM; ADULTS AB This study psychometrically evaluates the Motivational Interviewing Treatment Integrity Code (MITI) to assess fidelity to motivational interviewing to reduce sexual risk behaviors in people living with HIV/AIDS. 74 sessions from a pilot randomized controlled trial of motivational interviewing to reduce sexual risk behaviors in people living with HIV were coded with the MITI. Participants reported sexual behavior at baseline, 3-month, and 6-months. Regarding reliability, excellent inter-rater reliability was achieved for measures of behavior frequency across the 12 sessions coded by both coders; global scales demonstrated poor intraclass correlations, but adequate percent agreement. Regarding validity, principle components analyses indicated that a two-factor model accounted for an adequate amount of variance in the data. These factors were associated with decreases in sexual risk behaviors after treatment. The MITI is a reliable and valid measurement of treatment fidelity for motivational interviewing targeting sexual risk behaviors in people living with HIV/AIDS. C1 [Seng, Elizabeth K.] VA Connecticut Healthcare Syst, Psychol Serv, West Haven, CT 06516 USA. [Seng, Elizabeth K.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Lovejoy, Travis I.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Project SAFER Intervention Team] Ohio Univ, Dept Psychol, Athens, OH 45701 USA. RP Seng, EK (reprint author), VA Connecticut Healthcare Syst, Psychol Serv, 950 Campbell Ave, West Haven, CT 06516 USA. EM seng.elizabeth@gmail.com OI Seng, Elizabeth/0000-0002-8938-4949 NR 35 TC 4 Z9 4 U1 2 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 EI 1573-3572 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD DEC PY 2013 VL 20 IS 4 BP 440 EP 448 DI 10.1007/s10880-012-9343-y PG 9 WC Psychology, Clinical SC Psychology GA 253DS UT WOS:000327062600004 PM 23636311 ER PT J AU Mendu, ML Zager, S Moromizato, T McKane, CK Gibbons, FK Christopher, KB AF Mendu, Mallika L. Zager, Sam Moromizato, Takuhiro McKane, Caitlin K. Gibbons, Fiona K. Christopher, Kenneth B. TI The association between primary language spoken and all-cause mortality in critically ill patients SO JOURNAL OF CRITICAL CARE LA English DT Article DE Language; Language proficiency; Language discordance; Intensive care; Mortality ID LIMITED ENGLISH PROFICIENCY; NEIGHBORHOOD POVERTY RATE; INTENSIVE-CARE-UNIT; EMERGENCY-DEPARTMENT; FOLLOW-UP; RESOURCE UTILIZATION; CANCER INCIDENCE; STATES; SEPSIS; BARRIERS AB Purpose: The study objective was to investigate the association between primary language spoken and all-cause mortality in critically ill patients. Materials and Methods: We performed a cohort study on 48 581 patients 18 years or older who received critical care between 1997 and 2007 in 2 Boston hospitals. The exposure of interest was primary language spoken determined by the patient or family members who interacted with administrative staff during hospital registration. The primary outcome was 30-day mortality. Associations between language and mortality were estimated by bivariable and multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both language and mortality. Adjustment included age, race, sex, Deyo-Charlson index, patient type (medical vs surgical), sepsis, creatinine, hematocrit, white blood count, and number of organs with acute failure. Results: Validation showed that primary language spoken was highly accurate for a statement in the medical record noting the language spoken that matched the assigned language. Patients whose primary language spoken was not English had improved outcomes (odds ratio 30-day mortality, 0.69 [95% confidence interval, 0.60-0.81; P < .001), relative to patients with English as the primary language spoken, fully adjusted. Similar significant associations are seen with death by days 90 and 365 as well as in-hospital mortality. The improved survival in patients with a non-English primary language spoken is not confounded by indicators of severity of disease and is independent of the specific language spoken and neighborhood poverty rate, a proxy for socioeconomic status. There are significant limitations inherent to large database studies that we have acknowledged and addressed with controlling for measured confounding and evaluation of effect modification. Conclusions: In a regional cohort, not speaking English as a primary language is associated with improved outcomes after critical care. Our observations may have clinical relevance and illustrate the intersection of several factors in critical illness outcome including severity of illness, comorbidity, and social and economic factors. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mendu, Mallika L.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Zager, Sam] Maine Med Ctr, Dept Family Med, Portland, ME 04102 USA. [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [McKane, Caitlin K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org NR 59 TC 2 Z9 2 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2013 VL 28 IS 6 BP 928 EP 934 DI 10.1016/j.jcrc.2013.07.057 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 251QN UT WOS:000326945100010 PM 24011755 ER PT J AU Peev, MP Naraghi, L Chang, YC DeMoya, M Fagenholz, P Yeh, D Velmahos, G King, DR AF Peev, Miroslav P. Naraghi, Leily Chang, Yuchiao DeMoya, Marc Fagenholz, Peter Yeh, Daniel Velmahos, George King, David R. TI Real-time sample entropy predicts life-saving interventions after the Boston Marathon bombing SO JOURNAL OF CRITICAL CARE LA English DT Article DE Trauma; Bleeding; Entropy; Bombing ID HEART-RATE-VARIABILITY; DIMINISHED PHYSIOLOGICAL RESERVE; 1,425 TRAUMA PATIENTS; RATE COMPLEXITY; INDICATOR; MORTALITY; INTERVAL AB Purpose: Identifying patients in need of a life-saving intervention (LSI) during a mass casualty event is a priority. We hypothesized that real-time, instantaneous sample entropy (SampEn) could predict the need for LSI in the Boston Marathon bombing victims. Materials and methods: Severely injured Boston Marathon bombing victims (n = 10) had sample entropy (SampEn) recorded upon presentation using a continuous 200-beat rolling average in real time. Treating clinicians were blinded to real-time results. The correlation between SampEn, injury severity, number, and type of LSI was examined. Results: Victims were males (60%) with a mean age of 39.1 years. Injuries involved lower extremities (50.0%), head and neck (24.2%), or upper extremities (9.7%). Sample entropy negatively correlated with Injury Severity Score (r = -0.70; P = .023), number of injuries (r = -0.70; P = .026), and the number and need for LSI (r = -0.82; P = .004). Sample entropy was reduced under a variety of conditions. [GRAPHICS] Conclusions: Sample entropy strongly correlates with injury severity and predicts LSI after blast injuries sustained in the Boston Marathon bombings. Sample entropy may be a useful triage tool after blast injury. (C) 2013 Elsevier Inc. All rights reserved. C1 [King, David R.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 NR 11 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2013 VL 28 IS 6 AR 1109.e1 DI 10.1016/j.jcrc.2013.08.026 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 251QN UT WOS:000326945100047 PM 24120576 ER PT J AU Aboutalebi, A Korman, JB Sohani, AR Hasserjian, RP Louissaint, A Le, L Kraft, S Duncan, LM Nazarian, RM AF Aboutalebi, Amir Korman, John B. Sohani, Aliyah R. Hasserjian, Robert P. Louissaint, Abner, Jr. Le, Long Kraft, Stefan Duncan, Lyn M. Nazarian, Rosalynn M. TI Aleukemic cutaneous myeloid sarcoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE aleukemic cutaneous myeloid sarcoma; histiocytic; molecular; monocytic ID LYMPHOMA STUDY-GROUP; LEUKEMIA-CUTIS; GRANULOCYTIC SARCOMA; MYELOGENOUS LEUKEMIA; ADULT PATIENTS; CELL LYMPHOMA; SKIN; TUMORS; MANIFESTATIONS; INVOLVEMENT AB BackgroundAleukemic cutaneous myeloid sarcoma (CMS) represents an important yet rare entity denoting the presence of a cutaneous myeloid leukemic infiltrate without concurrent peripheral blood or bone marrow disease. The clinicopathologic diagnosis remains elusive due to isolated skin findings and variable immunostaining. Cytogenetic and molecular findings have infrequently been reported. MethodsTwenty-five patients with CMS were identified in the Massachusetts General Hospital pathology database between 2004 and 2012. Patients were excluded if concurrent blood or marrow acute myeloid leukemia (AML), myelodysplastic syndrome or lymphoproliferative disorder were diagnosed. ResultsThree patients were identified: a neonate with recurrent CMS and marrow disease that never met diagnostic criteria for AML and two patients relapsing as CMS without concurrent blood or marrow disease following chemotherapy-induced complete remission. Histology showed atypical mononuclear cell interstitial dermal infiltrates. All cases were CD68+, lysozyme+ and CD117-; one of two were CD34+; two of three were myeloperoxidase negative. 11q23 rearrangement, t(1;14), NPM1 (nucleophosmin I), FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication), and novel FLT3-D835 mutations were identified. ConclusionAn isolated atypical cutaneous infiltrate may represent aleukemic CMS and should prompt a search for other extramedullary sites of involvement. Immunohistochemistry, molecular and cytogenetic studies can help differentiate aleukemic CMS from benign and malignant, monocytic and histiocytic mimickers, and may potentially indicate therapy and prognosis. C1 [Aboutalebi, Amir; Korman, John B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Sohani, Aliyah R.; Hasserjian, Robert P.; Louissaint, Abner, Jr.; Le, Long; Kraft, Stefan; Duncan, Lyn M.; Nazarian, Rosalynn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit,Pathol Serv, 55 Fruit St,WRN 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org RI Xu, Yang/M-1424-2013; OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 53 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD DEC PY 2013 VL 40 IS 12 BP 996 EP 1005 DI 10.1111/cup.12231 PG 10 WC Dermatology; Pathology SC Dermatology; Pathology GA 256QY UT WOS:000327330200004 PM 24274424 ER PT J AU Shalin, SC Rinaldi, C Horn, TD AF Shalin, Sara C. Rinaldi, Carmen Horn, Thomas D. TI Clear cell acanthoma with changes of eccrine syringofibroadenoma: reactive change or clue to etiology? SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE clear cell acanthoma; eccrine syringofibroadenoma; immunohistochemistry ID CYTOKERATIN EXPRESSION; KERATIN EXPRESSION; MASCARO; CLAIRES; VARIANT; PATTERN; ORIGIN AB We observed two patients with solitary lesions showing features of clear cell acanthoma with underlying eccrine syringofibroadenoma-like changes. The pathogenesis of these entities has been debated since their original descriptions, with most recent literature suggesting that both may represent reactive phenomena rather than true neoplasms. Our observation prompted us to perform a retrospective review of clear cell acanthoma cases to determine the frequency of such associated eccrine syringofibroadenoma changes. Of 47 examined cases of clear cell acanthoma, 9 (19%) showed associated changes of eccrine syringofibroadenoma. Immunohistochemical evaluation performed on a subset of cases identified similar but slightly divergent differentiation patterns within the lesions. While epithelial membrane antigen and PAS expression were similar in both components (although slightly different in intensity), the regions resembling eccrine syringofibroadenoma displayed additional immunoreactivities, supporting the presence of two distinct components. We have found that the concurrence of clear cell acanthoma with syringofibroadenomatous changes is more frequent than generally appreciated and suggest that these entities may share derivation from the eccrine apparatus. C1 [Shalin, Sara C.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [Rinaldi, Carmen] Dermatol Associates, Portland, ME USA. [Horn, Thomas D.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Horn, Thomas D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Horn, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM THorn@partners.org NR 24 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD DEC PY 2013 VL 40 IS 12 BP 1021 EP 1026 DI 10.1111/cup.12232 PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA 256QY UT WOS:000327330200007 PM 24117902 ER PT J AU Ritzwoller, DP Glasgow, RE Sukhanova, AY Bennett, GG Warner, ET Greaney, ML Askew, S Goldman, J Emmons, KM Colditz, GA AF Ritzwoller, Debra P. Glasgow, Russell E. Sukhanova, Anna Y. Bennett, Gary G. Warner, Erica T. Greaney, Mary L. Askew, Sandy Goldman, Julie Emmons, Karen M. Colditz, Graham A. CA Be Fit Be Well Study Investigators TI Economic Analyses of the Be Fit Be Well Program: A Weight Loss Program for Community Health Centers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE weight loss; RCT; pragmatic trial; cost; cost-effectiveness; health disparities ID UNITED-STATES; CARDIOVASCULAR RISK; ETHNIC DISPARITIES; CLINICAL-TRIALS; OBESE-PATIENTS; PRIMARY-CARE; MANAGEMENT; ADULTS; INTERVENTIONS; PATTERNS AB BACKGROUND: The U.S. Preventive Services Task Force has released new guidelines on obesity, urging primary care physicians to provide obese patients with intensive, multi-component behavioral interventions. However, there are few studies of weight loss in real world nonacademic primary care, and even fewer in largely racial/ethnic minority, low-income samples. To evaluate the recruitment, intervention and replications costs of a 2-year, moderate intensity weight loss and blood pressure control intervention. A comprehensive cost analysis was conducted, associated with a weight loss and hypertension management program delivered in three community health centers as part of a pragmatic randomized trial. Three hundred and sixty-five high risk, low-income, inner city, minority (71 % were Black/African American and 13 % were Hispanic) patients who were both hypertensive and obese. Measures included total recruitment costs and intervention costs, cost per participant, and incremental costs per unit reduction in weight and blood pressure. Recruitment and intervention costs were estimated $2,359 per participant for the 2-year program. Compared to the control intervention, the cost per additional kilogram lost was $2,204 /kg, and for blood pressure, $621 /mmHg. Sensitivity analyses suggest that if the program was offered to a larger sample and minor modifications were made, the cost per participant could be reduced to the levels of many commercially available products. The costs associated with the Be Fit Be Well program were found to be significantly more expensive than many commercially available products, and much higher than the amount that the Centers for Medicare and Medicaid reimburse physicians for obesity counseling. However, given the serious and costly health consequences associated with obesity in high risk, multimorbid and socioeconomically disadvantaged patients, the resources needed to provide interventions like those described here may still prove to be cost-effective with respect to producing long-term behavior change. C1 [Ritzwoller, Debra P.; Sukhanova, Anna Y.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. [Warner, Erica T.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Warner, Erica T.; Greaney, Mary L.; Goldman, Julie; Emmons, Karen M.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci,Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. RP Ritzwoller, DP (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO 80237 USA. EM Debra.Ritzwoller@kp.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Heart Lung Blood Institute [UO1-HL087071]; Foundation for Barnes-Jewish Hospital; National Cancer Institute [5T32CA009001-36]; [K22CA126992]; [K05CA124415-04]; [P30CA091842] FX This work was supported in part by grant funding from the National Heart Lung Blood Institute (UO1-HL087071). G. Bennett was supported by K22CA126992.; K. Emmons was supported by K05CA124415-04. G. Colditz was supported in part by P30CA091842 and the Foundation for Barnes-Jewish Hospital. E. Warner was supported by grant 5T32CA009001-36 from the National Cancer Institute. NR 45 TC 7 Z9 7 U1 0 U2 16 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 DEC PY 2013 VL 28 IS 12 BP 1581 EP 1588 DI 10.1007/s11606-013-2492-3 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253YY UT WOS:000327127700012 PM 23733374 ER PT J AU Weinstock, RS Trief, PM Cibula, D Morin, PC Delahanty, LM AF Weinstock, Ruth S. Trief, Paula M. Cibula, Donald Morin, Philip C. Delahanty, Linda M. TI Weight Loss Success in Metabolic Syndrome by Telephone Interventions: Results from the SHINE Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE obesity; health behavior; prevention ID DIABETES PREVENTION PROGRAM; PRIMARY-CARE PRACTICE; LIFE-STYLE INTERVENTION; OBESITY TREATMENT; RANDOMIZED-TRIAL; TRANSLATION; PHYSICIANS; REDUCTION; METFORMIN; SETTINGS AB BACKGROUND: The Diabetes Prevention Program (DPP) intensive lifestyle intervention resulted in significant weight loss, reducing the development of diabetes, but needs to be adapted to primary care provider (PCP) practices. To compare a DPP-translation using individual (IC) vs. conference (CC) calls delivered by PCP staff for the outcome of percent weight loss over 2 years. Randomized clinical trial. Five PCP sites. Obese patients with metabolic syndrome, without diabetes (IC, n = 129; CC, n = 128). Telephone delivery of the DPP Lifestyle Balance intervention [16-session core curriculum in year 1, 12-session continued telephone contact in year 2 plus telephone coaching sessions (dietitians). Weight (kg), body mass index (BMI), and waist circumference. Baseline data: age = 52 years, BMI = 39 kg/m(2), 75 % female, 85 % non-Hispanic White, 13 % non-Hispanic Black, and 48 % annual incomes <$40,000/year. In the intention-to-treat analyses at year 2, mean percent weight loss was -5.6 % (CC, p < 0.001) and -1.8 % (IC, p = 0.046) and was greater for CC than for IC (p = 0.016). At year 2, mean weight loss was 6.2 kg (CC) and 2.2 kg (IC) (p < 0.001). There was similar weight loss at year 1, but between year 1 and year 2 CC participants continued to lose while IC participants regained. At year 2, 52 % and 43 % (CC) and 29 % and 22 % (IC) of participants lost at least 5 % and 7 % of initial weight. BMI also decreased more for CC than IC (-2.1 kg/m(2) vs. -0.8 kg/m(2) p < 0.001). Waist circumference decreased by 3.1 cm (CC) and 2.4 cm (IC) at year 2. Completers (a parts per thousand yen9 of 16 sessions; mean 13.3 sessions) lost significantly more weight than non-completers (mean 4.3 sessions). PCP staff delivery of the DPP lifestyle intervention by telephone can be effective in achieving weight loss in obese people with metabolic syndrome. Greater weight loss may be attained with a group telephone intervention. C1 [Weinstock, Ruth S.; Trief, Paula M.; Cibula, Donald; Morin, Philip C.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. RP Weinstock, RS (reprint author), SUNY Upstate Med Univ, 750 East Adams St,CWB 353, Syracuse, NY 13210 USA. EM weinstor@upstate.edu FU National Institutes of Health (NIDDK) [R18-DK078553] FX This study was supported by grant R18-DK078553 from the National Institutes of Health (NIDDK; Trief and Weinstock PIs). NR 25 TC 18 Z9 18 U1 1 U2 9 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 DEC PY 2013 VL 28 IS 12 BP 1620 EP 1628 DI 10.1007/s11606-013-2529-7 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253YY UT WOS:000327127700017 PM 23843020 ER PT J AU Maruthur, NM Ma, Y Delahanty, LM Nelson, JA Aroda, V White, NH Marrero, D Brancati, FL Clark, JM AF Maruthur, Nisa M. Ma, Yong Delahanty, Linda M. Nelson, Julie A. Aroda, Vanita White, Neil H. Marrero, David Brancati, Frederick L. Clark, Jeanne M. CA Diabet Prevention Program Res Grp TI Early Response to Preventive Strategies in the Diabetes Prevention Program SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes prevention; diabetes risk; type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; WEIGHT-LOSS; METFORMIN; MELLITUS; THERAPY; TRIAL AB BACKGROUND: Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. 3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program. Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis. After 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15 (0.07-0.30) for 0-< 3 %, 3-< 5 %, 5-< 7 %, 7-< 10 %, and a parts per thousand yen10 % weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted > 60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038). Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes. C1 [Maruthur, Nisa M.; Brancati, Frederick L.; Clark, Jeanne M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Maruthur, Nisa M.; Brancati, Frederick L.; Clark, Jeanne M.] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Ma, Yong] George Washington Univ, Rockville, MD 20852 USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, Julie A.] NIDDK, Southwest Amer Indian Ctr Arizona, Phoenix, AZ USA. [Aroda, Vanita] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [White, Neil H.] Washington Univ, Sch Med, St Louis, MO USA. [Marrero, David] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Marrero, David] Indiana Univ Sch Med, Diabet Translat Res Ctr, Indianapolis, IN 46202 USA. [Brancati, Frederick L.; Clark, Jeanne M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Maruthur, NM (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu FU NIH/NCCR [1KL2RR025006-01] FX Dr. Maruthur was supported by NIH/NCCR grant 1KL2RR025006-01. NR 16 TC 10 Z9 11 U1 0 U2 9 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 DEC PY 2013 VL 28 IS 12 BP 1629 EP 1636 DI 10.1007/s11606-013-2548-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253YY UT WOS:000327127700018 PM 23860722 ER PT J AU Margaretten, ME Katz, P Schmajuk, G Yelin, E AF Margaretten, Mary E. Katz, Patricia Schmajuk, Gabriela Yelin, Edward TI Missed Opportunities for Depression Screening in Patients with Arthritis in the United States SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE arthritis; depression; screening ID RHEUMATOID-ARTHRITIS; PRIMARY-CARE; OLDER-ADULTS; HEALTH-CARE; PSYCHOLOGICAL DISTRESS; PREVENTIVE-SERVICES; RISK-FACTOR; TASK-FORCE; US ADULTS; OSTEOARTHRITIS AB BACKGROUND: Arthritis affects 20 % of the adult US population and is associated with comorbid depression. Depression screening guidelines have been endorsed for high-risk groups, including persons with arthritis, in the hopes that screening will increase recognition and use of appropriate interventions. To examine national rates of depression and depression screening for patients with arthritis between 2006 and 2010. We used nationally representative cross-sections of ambulatory visits in the United States from the National Ambulatory Medical Care Survey from 2006 to 2010, which included 18,507 visits with a diagnosis of arthritis. When weighted to the US population, this total represents approximately 644 million visits. Visits where arthritis was listed among diagnoses. Outcomes were survey-weighted estimates of depression and prevalence of depression screening among patients with arthritis across patient and physician characteristics. Of the 644,419,374 visits with arthritis listed, 83,574,127 (13 %) were associated with a comorbid diagnosis of depression. The odds ratio for comorbid depression with arthritis was 1.42 (95 % CI 1.3, 1.5). Depression screening occurred at 3,835,000 (1 %) visits associated with arthritis. When examining the rates of depression screening between ambulatory visits with and without arthritis listed, there was no difference in depression screening rates; both were approximately 1 %. There was no difference in screening rates by provider type. Compared to visits with other common, chronic conditions, the prevalence of depression at arthritis visits was high (13 per 100 visits), although the prevalence of depression screening at arthritis visits was low (0.68 per 100 visits). Despite the high prevalence of depression with arthritis, screening for depression was performed at few arthritis visits, representing missed opportunities to detect a common, serious comorbidity. Improved depression screening by providers would identify affected patients, and may lead to appropriate interventions such as mental health referrals and/or treatment with anti-depressants. C1 [Margaretten, Mary E.; Katz, Patricia; Schmajuk, Gabriela; Yelin, Edward] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94118 USA. [Schmajuk, Gabriela] San Francisco VA Med Ctr, Div Rheumatol, Dept Med, San Francisco, CA USA. [Margaretten, Mary E.] Arthrit Res Grp UCSF, San Francisco, CA USA. RP Margaretten, ME (reprint author), Univ Calif San Francisco, Div Rheumatol, Calif St,Suite 270, San Francisco, CA 94118 USA. EM Mary.margaretten@ucsf.edu FU National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [KL2TR000143]; Rosalind Russell Medical Research Center for Arthritis Research FX Dr. Margaretten is supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number KL2TR000143. This papers' contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Dr. Margaretten also received support from The Rosalind Russell Medical Research Center for Arthritis Research. The funding sources had no role in the design and conduct of the study, analysis or interpretation of the data, or preparation of final approval of the manuscript prior to publication. NR 46 TC 2 Z9 2 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 DEC PY 2013 VL 28 IS 12 BP 1637 EP 1642 DI 10.1007/s11606-013-2541-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253YY UT WOS:000327127700019 PM 23897128 ER PT J AU Koenig, CJ AF Koenig, Christopher J. TI Capsule Commentary on Betz et al., "I Wish We Could Normalize Driving Health": A Qualitative Study of Clinician Discussions with Older Drivers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. RP Koenig, CJ (reprint author), Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. EM Christopher.koenig@ucsf.edu OI Koenig, Christopher J./0000-0003-0884-4120 NR 4 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 DEC PY 2013 VL 28 IS 12 BP 1644 EP 1644 DI 10.1007/s11606-013-2515-0 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253YY UT WOS:000327127700021 PM 23797919 ER PT J AU Nativ, NI Yarmush, G Chen, A Dong, D Henry, SD Guarrera, JV Klein, KM Maguire, T Schloss, R Berthiaume, F Yarmush, ML AF Nativ, Nir I. Yarmush, Gabriel Chen, Alvin Dong, David Henry, Scot D. Guarrera, James V. Klein, Kenneth M. Maguire, Tim Schloss, Rene Berthiaume, Francois Yarmush, Martin L. TI Rat hepatocyte culture model of macrosteatosis: Effect of macrosteatosis induction and reversal on viability and liver-specific function SO JOURNAL OF HEPATOLOGY LA English DT Article DE Steatosis; Triglyceride; Albumin; Urea; Bile; Liver transplantation; Lipid metabolism ID ISCHEMIA-REPERFUSION INJURY; FATTY LIVER; PRESERVATION INJURY; HEPATIC STEATOSIS; TRANSPLANTATION; INCREASES; MARKERS; CELLS; POOL; TERM AB Background & Aims: A common cause of liver donor ineligibility is macrosteatosis. Recovery of such livers could enhance donor availability. Living donor studies have shown diet-induced reduction of macrosteatosis enables transplantation. However, cadaveric liver macrosteatotic reduction must be performed ex vivo within hours. Towards this goal, we investigated the effect of accelerated macrosteatosis reduction on hepatocyte viability and function using a novel system of macrosteatotic hepatocytes. Methods: Hepatocytes isolated from lean Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty acid-supplemented medium to induce steatosis, and then switched for 2 days to medium supplemented with lipid metabolism promoting agents. Intracellular lipid droplet size distribution and triglyceride, viability, albumin and urea secretion, and bile canalicular function were measured. Results: Fatty acid-supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6 days, the latter evidenced by large lipid droplets dislocating the nucleus to the cell periphery. Macrosteatosis significantly impaired all functions tested. Macrosteatosis decreased upon returning hepatocytes to standard medium, and the rate of decrease was 4-fold faster with supplemented agents, yielding 80% reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar to control lean cells. Accelerated macrosteatotic reduction led to faster recovery of urea secretion and bile canalicular function, but not of albumin secretion. Conclusions: Macrosteatosis reversibly decreases hepatocyte function and supplementary agents accelerate macrosteatosis reduction and some functional restoration with no effect on viability. This in vitro model may be useful to screen agents for macrosteatotic reduction in livers before transplantation. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Nativ, Nir I.; Yarmush, Gabriel; Chen, Alvin; Dong, David; Maguire, Tim; Schloss, Rene; Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Henry, Scot D.; Guarrera, James V.] Columbia Univ Med Ctr, Ctr Liver Dis & Transplantat, Dept Surg, New York, NY USA. [Klein, Kenneth M.] UMDNJ New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM yarmush@rci.rutgers.edu FU NIH [UH2 NS080733, R01DK059766] FX This work was partially supported by NIH grants UH2 NS080733 and R01DK059766. Nir I. Nativ and Gabriel Yarmush were supported by an NIH-funded Biotechnology Training Fellowship. NR 25 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD DEC PY 2013 VL 59 IS 6 BP 1307 EP 1314 DI 10.1016/j.jhep.2013.07.019 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254CV UT WOS:000327141800023 PM 23872604 ER PT J AU Kavishwar, A Moore, A AF Kavishwar, Amol Moore, Anna TI Sphingomyelin Patches on Pancreatic Beta-cells Are Indicative of Insulin Secretory Capacity SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE beta-cells; diabetes; surface markers; sphingomyelin; antibody ID IN-VIVO; IDENTIFICATION; AUTOANTIGEN; MASS; CLONING; MOUSE; MODEL AB The establishment and validation of specific markers on the surfaces of pancreatic beta-cells would have a significant impact on the development of agents that specifically target these cells for imaging and/or image-guided therapy in diabetes patient samples. We have recently described unique, cholesterol-stabilized sphingomyelin (SM) patches on the surfaces of beta-cells using the IC2 antibody. To further investigate the utility of SM patches as a unique beta-cell biomarker, we embarked on the current study to correlate the expression of this antigen with the insulin secretory capacity of beta-cells in tissue samples from patients and animals with type 1 and type 2 diabetes and compared this with samples from normal subjects. We found that the locations of SM patches were consistent with the insulin status of islets in all tissues studied. Using immunohistochemistry and staining with an IC2 antibody, we demonstrated a direct correlation between the reduced expression of SM patches and insulin production in diabetic individuals, indicating that the former could potentially serve as a functional biomarker of beta-cells. We believe that our results have significant implications for the further development of ligands with SM specificity for the non-invasive functional assessment of beta-cells and/or for targeted therapeutic delivery in diabetic patients. C1 [Kavishwar, Amol; Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Bldg 75,13 St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu OI Kavishwar, Amol/0000-0001-8214-6625 FU Juvenile Diabetes Research Foundation [JDRF 37-2009-30] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by the award from Juvenile Diabetes Research Foundation (JDRF 37-2009-30) to AM. NR 23 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 2013 VL 61 IS 12 BP 910 EP 919 DI 10.1369/0022155413502792 PG 10 WC Cell Biology SC Cell Biology GA 256FD UT WOS:000327294200006 PM 23920110 ER PT J AU Zou, L Feng, Y Li, Y Zhang, M Chen, C Cai, JY Gong, Y Wang, L Thurman, JM Wu, XB Atkinson, JP Chao, W AF Zou, Lin Feng, Yan Li, Yan Zhang, Ming Chen, Chan Cai, Jiayan Gong, Yu Wang, Larry Thurman, Joshua M. Wu, Xiaobo Atkinson, John P. Chao, Wei TI Complement Factor B Is the Downstream Effector of TLRs and Plays an Important Role in a Mouse Model of Severe Sepsis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE KIDNEY INJURY; GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; POLYMICROBIAL SEPSIS; UNITED-STATES; TISSUE-INJURY; RECEPTOR 4; PATHWAY; ACTIVATION; MICE AB Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of TLRs mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture in a mouse model, augmented cfB levels in the serum, peritoneal cavity, and major organs including the kidney and heart. Cecal ligation and puncture also led to the alternative pathway activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum alternative pathway via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 upregulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production, and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. C1 [Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Chao, Wei] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Sch Med, Boston, MA 02114 USA. [Wang, Larry] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Thurman, Joshua M.] Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO 80045 USA. [Wu, Xiaobo; Atkinson, John P.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Chao, W (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM wchao@partners.org FU National Institutes of Health [R01-GM080906, R01-GM097259, R01-DK076690, R01-AI041592]; International Anesthesia Research Society FX This work was supported in part by National Institutes of Health Grants R01-GM080906, R01-GM097259, R01-DK076690, and R01-AI041592 and a grant from the International Anesthesia Research Society. NR 61 TC 25 Z9 27 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2013 VL 191 IS 11 BP 5625 EP 5635 DI 10.4049/jimmunol.1301903 PG 11 WC Immunology SC Immunology GA 254QO UT WOS:000327180600029 PM 24154627 ER PT J AU Atai, NA Balaj, L van Veen, H Breakefield, XO Jarzyna, PA Van Noorden, CJF Skog, J Maguire, CA AF Atai, Nadia A. Balaj, Leonora van Veen, Henk Breakefield, Xandra O. Jarzyna, Peter A. Van Noorden, Cornelis J. F. Skog, Johan Maguire, Casey A. TI Heparin blocks transfer of extracellular vesicles between donor and recipient cells SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Extracellular vesicles; Exosomes; Glioblastoma; EGFRvIII; Heparin; Tumor ID CANCER; EXOSOMES; ANTICOAGULANTS; PROGRESSION; BIOGENESIS; SURVIVAL; DELIVERY; SYSTEM; GROWTH; TUMORS AB Extracellular vesicles (EVs) have been implicated in tumorigenesis. Biomolecules which can block EV binding and uptake into recipient cells may be of therapeutic value as well as enhance understanding of EV biology. Here, we show that heparin interacts with uptake of tumor-derived as well as non-tumor-derived EVs into recipient cells. Incubation of glioma cell-derived EVs with heparin resulted in micron-sized structures observed by transmission electron microscopy, with EVs clearly visible within these structures. Inclusion of heparin greatly diminished transfer of labeled EVs from donor to recipient tumor cells. We also show a direct interaction between heparin and EVs using confocal microscopy. We found that the block in EV uptake was at the level of cell binding and not internalization. Finally, incubation of glioma-derived EVs containing EGFRvIII mRNA with heparin reduced transfer of this message to recipient cells. The effect of heparin on EVs uptake may provide a unique tool to study EV function. It may also foster research of heparin or its derivatives as a therapeutic for disease in which EVs play a role. C1 [Atai, Nadia A.; Balaj, Leonora; Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atai, Nadia A.; Balaj, Leonora; Maguire, Casey A.] Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02114 USA. [Atai, Nadia A.; Balaj, Leonora; Breakefield, Xandra O.; Maguire, Casey A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Atai, Nadia A.; van Veen, Henk; Van Noorden, Cornelis J. F.] Univ Amsterdam, Dept Cell Biol & Histol, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. RP Maguire, CA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM cmaguire@partners.org FU NIH/NINDS [1 R21 NS081374-01]; NIH/NCI [CA069246, CA141226, CA156009, CA141150]; American Brain Tumor Association Fellowship; AMC Scholarship, University of Amsterdam; PHS grant [P30NS045776]; NIH [P30NS045776] FX This work was supported by NIH/NINDS 1 R21 NS081374-01 (C. A. M.) NIH/NCI grants CA069246 (X.O.B), CA141226 (X.O.B.); CA156009 (X.O.B.) CA141150 (X.O.B.), an American Brain Tumor Association Fellowship (C. A. M.), and a 2010 AMC Scholarship, University of Amsterdam (N.A.A.). We gratefully acknowledge the Neuroscience Center PCR Core facility, which is funded by PHS grant P30NS045776. We acknowledge the MGH Neuroscience Center Microscopy and Image Analysis Core, which is funded by NIH grant P30NS045776. We thank the van Leeuwenhoek Center for Advanced Microscopy (LCAM) at the Academic Medical Center (University of Amsterdam, the Netherlands) for performing the transmission electron microscopy sample processing and imaging. We thank Lori LoGuidice and Ard Jonker (University of Amsterdam) for technical help. C. A. M. has a financial interest in Exosome Diagnostics, Inc. C.A.M.'s interests were reviewed and are managed by the Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. J.S. is an inventor on the exosome/EVs technology used in this study which has been licensed to Exosome Diagnostics, Inc. He holds equity in, and is now an employee of that company. X.O.B. is on the Scientific Advisory Board of Exosome Diagnostics, Inc. NR 28 TC 39 Z9 39 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2013 VL 115 IS 3 BP 343 EP 351 DI 10.1007/s11060-013-1235-y PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 255CD UT WOS:000327215900004 PM 24002181 ER PT J AU Aizer, AA Ancukiewicz, M Nguyen, PL MacDonald, SM Yock, TI Tarbell, NJ Shih, HA Loeffler, JS Oh, KS AF Aizer, Ayal A. Ancukiewicz, Marek Nguyen, Paul L. MacDonald, Shannon M. Yock, Torunn I. Tarbell, Nancy J. Shih, Helen A. Loeffler, Jay S. Oh, Kevin S. TI Natural history and role of radiation in patients with supratentorial and infratentorial WHO grade II ependymomas: results from a population-based study SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Ependymoma; Gross total resection; Observation; Radiation; Supratentorial ID GROSS-TOTAL RESECTION; INTRACRANIAL EPENDYMOMA; BRAIN-TUMORS; POSTOPERATIVE CHEMOTHERAPY; PROTON RADIOTHERAPY; COMPETING RISK; ADJUVANT CHEMOTHERAPY; LOCALIZED EPENDYMOMA; PEDIATRIC-ONCOLOGY; CLINICAL-OUTCOMES AB Patients with World Health Organization (WHO) grade II supratentorial ependymomas are commonly observed after gross total resection (GTR), although supporting data are limited. We sought to characterize the natural history of such tumors. We used the Surveillance, Epidemiology, and End Results program to identify 112 patients ages 0-77 diagnosed with WHO grade II ependymomas between 1988 and 2007, of whom 63 (56 %) and 49 (44 %) had supratentorial and infratentorial primaries, respectively. Inclusion criteria were strict to ensure patient homogeneity. Of 33 patients with supratentorial tumors after GTR, 18 (55 %) received adjuvant radiation therapy and 15 (45 %) did not. Ependymoma-specific mortality (ESM) was the primary endpoint. With a median follow up of 4.5 years, only 1 of 33 patients with supratentorial ependymoma died of their disease after GTR; the 5-year estimate of ESM in this population was 3.3 % (95 % CI 0.2-14.8 %). Among patients with infratentorial ependymomas after GTR, the 5-year estimate of ESM was 8.7 % (95 % CI 1.4-24.6 %). In patients with subtotally resected tumors, 5-year estimates of ESM in patients with supratentorial and infratentorial primaries were 20.1 % (95 % CI 8.0-36.2 %) and 12.3 % (95 % CI 2.9-28.8 %), respectively. Among the whole cohort, on both univariable and multivariable regression, extent of resection was predictive of ESM, while tumor location and use of radiation were not. After GTR, patients with WHO grade II supratentorial ependymomas have a very favorable natural history with low associated cancer-specific mortality. Observation, with radiation reserved as a salvage option, may be a reasonable postoperative strategy in this population. C1 [Aizer, Ayal A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, Dept Radiat Oncol Biostat, Boston, MA 02114 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [MacDonald, Shannon M.; Yock, Torunn I.; Tarbell, Nancy J.; Shih, Helen A.; Loeffler, Jay S.; Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Aizer, AA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 55 Fruit St,Lunder LL3, Boston, MA 02114 USA. EM aaaizer@partners.org FU Varian FX Author Paul Nguyen MD has received research funding from Varian and consulted for Ferring Inc. NR 42 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2013 VL 115 IS 3 BP 411 EP 419 DI 10.1007/s11060-013-1237-9 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 255CD UT WOS:000327215900011 PM 24057324 ER PT J AU Robinson, JP Bradway, CW Bunting-Perry, L Avi-Itzhak, T Mangino, M Chittams, J Duda, JE AF Robinson, Joanne P. Bradway, Christine W. Bunting-Perry, Lisette Avi-Itzhak, Tamara Mangino, Marie Chittams, Jesse Duda, John E. TI Lower Urinary Tract Symptoms in Men With Parkinson Disease SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article DE lower urinary tract symptoms; men's health; nonmotor symptoms; Parkinson disease ID MICTURITION DISTURBANCE; VOIDING DYSFUNCTION; UNPLEASANT SYMPTOMS; BLADDER FUNCTION; PREVALENCE; QUESTIONNAIRE; MANAGEMENT; NEUROLOGY; DEMENTIA; UPDATE AB Purpose: The aim of this study was to examine the prevalence, presentation, and predictors of lower urinary tract symptoms (LUTS) in men with idiopathic Parkinson disease (PD). Methods: Guided by the Theory of Unpleasant Symptoms, this retrospective exploratory study used data abstracted from admission clinical records of 271 male patients with idiopathic PD enrolled in a movement disorders clinic at a large metropolitan Veterans Affairs Medical Center in the eastern region of the United States. Data from the admission questionnaire, Unified Parkinson's Disease Rating Scale, and Mini Mental State Examination were abstracted by trained research assistants. Interrater reliability for the abstraction process was 0.99 in a randomly selected 10% sample of records. Descriptive statistics were used to determine the prevalence of LUTS. Logistic regression was used to determine LUTS risk factors and predictors. Results: At least one LUTS was reported by 40.2% of participants. Incontinence was the most prevalent symptom, affecting almost 25% of participants, followed by nocturia (14.8%) and frequency (13.7%). Of the 10 identified risk factors for LUTS, four significant predictors were discovered: number of non-PD medications (p < .05), PD duration (p < .05), number of comorbidities (p < .05), and history of a hernia diagnosis (p < .05). Conclusions: Assessment for LUTS should be a component of every evaluation of a patient with PD. Our findings offer a preliminary profile of the male PD patient with LUTS, which is an important step toward effective screening, detection, and access to care and treatment. Next steps in research include further work to identify predictors of LUTS in both male and female PD populations, explore patient perspectives, begin trials of interventions for LUTS in the PD population, and analyze the economic impact. C1 [Robinson, Joanne P.] Rutgers State Univ, Sch Nursing Camden, Camden, NJ 08102 USA. [Bradway, Christine W.; Chittams, Jesse] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Bunting-Perry, Lisette; Duda, John E.] Vet Affairs Med Ctr, Parkinsons Dis Educ & Clin Ctr, Philadelphia, PA USA. [Avi-Itzhak, Tamara] CUNY York Coll, Sch Hlth & Behav Sci, Dept Occupat Therapy, Jamaica, NY 11451 USA. [Mangino, Marie] Vincent Healthcare, Erdenheim, PA USA. [Duda, John E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Robinson, JP (reprint author), Rutgers State Univ, Sch Nursing Camden, Camden, NJ 08102 USA. EM jprobins@camden.rutgers.edu RI mangino, massimo/F-5134-2011 OI mangino, massimo/0000-0002-2167-7470 NR 51 TC 5 Z9 6 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0888-0395 EI 1945-2810 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD DEC PY 2013 VL 45 IS 6 BP 382 EP 392 DI 10.1097/JNN.0b013e3182a3cf67 PG 11 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA 251XF UT WOS:000326966300010 PM 24217149 ER PT J AU Hartwell, KA Miller, PG Mukherjee, S Kahn, AR Stewart, AL Logan, DJ Negri, JM Duvet, M Jaras, M Puram, R Dancik, V Al-Shahrour, F Kindler, T Tothova, Z Chattopadhyay, S Hasaka, T Narayan, R Dai, MJ Huang, C Shterental, S Chu, LP Haydu, JE Shieh, JH Steensma, DP Munoz, B Bittker, JA Shamji, AF Clemons, PA Tolliday, NJ Carpenter, AE Gilliland, DG Stern, AM Moore, MAS Scadden, DT Schreiber, SL Ebert, BL Golub, TR AF Hartwell, Kimberly A. Miller, Peter G. Mukherjee, Siddhartha Kahn, Alissa R. Stewart, Alison L. Logan, David J. Negri, Joseph M. Duvet, Mildred Jaeras, Marcus Puram, Rishi Dancik, Vlado Al-Shahrour, Fatima Kindler, Thomas Tothova, Zuzana Chattopadhyay, Shrikanta Hasaka, Thomas Narayan, Rajiv Dai, Mingji Huang, Christina Shterental, Sebastian Chu, Lisa P. Haydu, J. Erika Shieh, Jae Hung Steensma, David P. Munoz, Benito Bittker, Joshua A. Shamji, Alykhan F. Clemons, Paul A. Tolliday, Nicola J. Carpenter, Anne E. Gilliland, D. Gary Stern, Andrew M. Moore, Malcolm A. S. Scadden, David T. Schreiber, Stuart L. Ebert, Benjamin L. Golub, Todd R. TI Niche-based screening identifies small-molecule inhibitors of leukemia stem cells SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PROGENITOR CELLS; STROMAL CELLS; PROTEIN TRANSFERASE; FREQUENCY-ANALYSIS; INDUCED APOPTOSIS; IN-VIVO; CANCER; GENES; MICE AB Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening. C1 [Hartwell, Kimberly A.; Stewart, Alison L.; Logan, David J.; Negri, Joseph M.; Duvet, Mildred; Dancik, Vlado; Al-Shahrour, Fatima; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Munoz, Benito; Bittker, Joshua A.; Shamji, Alykhan F.; Clemons, Paul A.; Tolliday, Nicola J.; Carpenter, Anne E.; Gilliland, D. Gary; Stern, Andrew M.; Scadden, David T.; Schreiber, Stuart L.; Ebert, Benjamin L.; Golub, Todd R.] Broad Inst, Cambridge, MA 02142 USA. [Hartwell, Kimberly A.; Miller, Peter G.; Jaeras, Marcus; Puram, Rishi; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Shterental, Sebastian; Chu, Lisa P.; Haydu, J. Erika; Gilliland, D. Gary; Ebert, Benjamin L.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Hartwell, Kimberly A.; Miller, Peter G.; Jaeras, Marcus; Puram, Rishi; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Shterental, Sebastian; Chu, Lisa P.; Haydu, J. Erika; Steensma, David P.; Gilliland, D. Gary; Ebert, Benjamin L.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA USA. [Mukherjee, Siddhartha; Duvet, Mildred; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Mukherjee, Siddhartha; Duvet, Mildred; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kahn, Alissa R.; Shieh, Jae Hung] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Chattopadhyay, Shrikanta; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Dai, Mingji; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Steensma, David P.; Gilliland, D. Gary; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gilliland, D. Gary; Schreiber, Stuart L.; Golub, Todd R.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Chevy Chase, MD USA. [Moore, Malcolm A. S.] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Golub, TR (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM m-moore@ski.mskcc.org; dscadden@mgh.harvard.edu; stuart_schreiber@harvard.edu; bebert@partners.org; golub@broadinstitute.org RI Carpenter, Anne/C-4982-2008; Kindler, Thomas/K-5995-2013; OI Carpenter, Anne/0000-0003-1555-8261; Jaras, Marcus/0000-0003-4080-7055; Steensma, David/0000-0001-5130-9284 FU Starr Cancer Consortium (SCC) [l1 A50]; US National Institutes of Health [U54CA112962, U01HL1004402, T32 HL007623, T32 GM007753, N01-CO-12400, R01 GM089652, RL1CA133834, 20XS139, RL1HG004671, RL1GM084437, UL1RR024924]; US National Science Foundation [DBI 1148823] FX We wish to thank L. VerPlank, V. Raksakulthai, A. Liberzon, M. Palmer, G. Cowley, J. Burbank, P. Aspesi Jr., M. Bliss-Moreau, D. Barker, B. Wagner, A. Krivtsov, S. A. Armstrong, R. Karmacharya, J. Perez, R. Onofrio, D. Thomas, R. Busanelli, D. Auclair, K. Masson, J. Du, C. Moore, M. Kharas, Y. Hoshida, D. Bachovchin, A. Mullally, J. Grabarek, A. Fraser, A. Basu, J. Cheah, N. Bodycombe, C. Mulrooney, S. Johnston, G. Walzer, D. Wilpitz, A. Bracha, A. Fabian, C. Hon, J. McGrath, C. Hartland, M. Hickey, T. R. Jones, M. Bray, K. Sokolnicki, R. Okabe, M. Paktinat, M. McConkey, L. Gaffney, L. Solomon, K. Rose and Broad Compound Management. We also thank the Golub, Gilliland and Ebert laboratories for scientific discussions and technical expertise. This work was funded by grants from the Starr Cancer Consortium (SCC Award l1 A50), the US National Institutes of Health (U54CA112962, U01HL1004402, T32 HL007623, T32 GM007753, N01-CO-12400, R01 GM089652, RL1CA133834, 20XS139, RL1HG004671, RL1CA133834, RL1GM084437 and UL1RR024924) and the US National Science Foundation (DBI 1148823). The content of this publication is solely the responsibility of the authors and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. T. R. G., D. G. G. and S. L. S. are investigators at the Howard Hughes Medical Institute. NR 52 TC 41 Z9 41 U1 3 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2013 VL 9 IS 12 BP 840 EP + DI 10.1038/NCHEMBIO.1367 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253ZR UT WOS:000327130000017 PM 24161946 ER PT J AU Chen, JY Calhoun, VD Pearlson, GD Perrone-Bizzozero, N Sui, J Turner, JA Bustillo, JR Ehrlich, S Sponheim, SR Canive, JM Ho, BC Liu, JY AF Chen, Jiayu Calhoun, Vince D. Pearlson, Godfrey D. Perrone-Bizzozero, Nora Sui, Jing Turner, Jessica A. Bustillo, Juan R. Ehrlich, Stefan Sponheim, Scott R. Canive, Jose M. Ho, Beng-Choon Liu, Jingyu TI Guided exploration of genomic risk for gray matter abnormalities in schizophrenia using parallel independent component analysis with reference SO NEUROIMAGE LA English DT Article DE Parallel ICA with reference; sMRI; SNP; Schizophrenia; Multivariate; Semi-blind ID DORSOLATERAL PREFRONTAL CORTEX; CELL-ADHESION MOLECULES; LONG-TERM POTENTIATION; LARGE GENE LISTS; WIDE ASSOCIATION; WORKING-MEMORY; REGRESSION APPROACH; BIPOLAR DISORDER; CEREBRAL-CORTEX; NERVOUS-SYSTEM AB One application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute. The new approach was first evaluated on simulated data for its performance under different configurations of effect size and dimensionality. Then pICA-R was applied to a 300-participant (140 schizophrenia (SZ) patients versus 160 healthy controls) dataset consisting of structural magnetic resonance imaging (sMRI) and single nucleotide polymorphism (SNP) data. Guided by a reference SNP set derived from ANK3, a gene implicated by the Psychiatric Genomic Consortium SZ study, pICA-R identified one pair of SNP and sMRI components with a significant loading correlation of 027 (p = 1.64 x 10(-6)). The sMRI component showed a significant group difference in loading parameters between patients and controls (p = 1.33 x 10(-5)), indicating SZ-related reduction in gray matter concentration in prefrontal and temporal regions. The linked SNP component also showed a group difference (p = 0.04) and was predominantly contributed to by 1030 SNPs. The effect of these top contributing SNPs was verified using association test results of the Psychiatric Genomic Consortium SZ study, where the 1030 SNPs exhibited significant SZ enrichment compared to the whole genome. In addition, pathway analyses indicated the genetic component majorly relating to neurotransmitter and nervous system signaling pathways. Given the simulation and experiment results, pICA-R may prove a promising multivariate approach for use in imaging genomics to discover reliable genetic risk factors under a scenario of relatively high dimensionality and small effect size. (C) 2013 Elsevier Inc. All rights reserved. C1 [Chen, Jiayu; Calhoun, Vince D.; Liu, Jingyu] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Chen, Jiayu; Calhoun, Vince D.; Sui, Jing; Turner, Jessica A.; Liu, Jingyu] Mind Res Network, Albuquerque, NM 87106 USA. [Calhoun, Vince D.; Perrone-Bizzozero, Nora; Bustillo, Juan R.] Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Pearlson, Godfrey D.] Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06106 USA. [Calhoun, Vince D.; Pearlson, Godfrey D.] Yale Univ, Dept Psychiat & Neurobiol, New Haven, CT 06511 USA. [Bustillo, Juan R.; Canive, Jose M.] Univ New Mexico, Dept Psychiat, Sch Med, Albuquerque, NM 87131 USA. [Ehrlich, Stefan] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Ehrlich, Stefan] MIT, Charlestown, MA 02129 USA. [Ehrlich, Stefan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [Sponheim, Scott R.] Minneapolis Vet Affairs Hlth Care Syst, Minneapolis, MN 55417 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55454 USA. [Canive, Jose M.] New Mexico VA Hlth Care Syst, Psychiat Res Program, Albuquerque, NM 87108 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. RP Liu, JY (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM jliu@mrn.org RI Ho, Beng-Choon/D-6959-2011; Turner, Jessica/H-7282-2015; OI Ho, Beng-Choon/0000-0003-3976-1555; Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Liu, Jingyu/0000-0002-1724-7523 FU National Institutes of Health [5P20RR021938, R01EB005846, 1R01MH094524-01A1] FX The authors would like to thank Jill Fries and Marilee Morgan for preprocessing the imaging and genetic data. We also want to thank the University of Iowa Hospital, Massachusetts General Hospital, the University of Minnesota, the University of New Mexico, and the Mind Research Network staff for their efforts in data collection, preprocessing, and analyses. We appreciate the valuable advice given by Rogers Silver at the Mind Research Network. This project was funded by the National Institutes of Health, grant number: 5P20RR021938, R01EB005846, and 1R01MH094524-01A1. NR 98 TC 13 Z9 13 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2013 VL 83 BP 384 EP 396 DI 10.1016/j.neuroimage.2013.05.073 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 251TN UT WOS:000326953700035 PM 23727316 ER PT J AU van Dellen, E Hillebrand, A Douw, L Heimans, JJ Reijneveld, JC Stam, CJ AF van Dellen, E. Hillebrand, A. Douw, L. Heimans, J. J. Reijneveld, J. C. Stam, C. J. TI Local polymorphic delta activity in cortical lesions causes global decreases in functional connectivity SO NEUROIMAGE LA English DT Article DE Functional connectivity; Lesions; Neural mass model; Network analysis; Polymorphic delta activity ID FOCAL BRAIN-LESIONS; SYNCHRONIZATION LIKELIHOOD; OSCILLATORY ACTIVITY; NETWORKS; STROKE; MODEL; GLIOMA; TUMORS; MAGNETOENCEPHALOGRAPHY; ORGANIZATION AB Increasing evidence from neuroimaging and modeling studies suggests that local lesions can give rise to global network changes in the human brain. These changes are often attributed to the disconnection of the lesioned areas. However, damaged brain areas may still be active, although the activity is altered. Here, we hypothesize that empirically observed global decreases in functional connectivity in patients with brain lesions can be explained by specific alterations of local neural activity that are the result of damaged tissue. We simulated local polymorphic delta activity (PDA), which typically characterizes EEG/MEG recordings of patients with cerebral lesions, in a realistic model of human brain activity. 78 neural masses were coupled according to the human structural brain network. Lesions were created by altering the parameters of individual neural masses in order to create PDA (i.e. simulating acute focal brain damage); combining this PDA with weakening of structural connections (i.e. simulating brain tumors), and fully deleting structural connections (i.e. simulating a full resection). Not only structural disconnection but also PDA in itself caused a global decrease in functional connectivity, similar to the observed alterations in MEG recordings of patients with PDA due to brain lesions. Interestingly, connectivity between regions that were not lesioned directly also changed. The impact of FDA depended on the network characteristics of the lesioned region in the structural connectome. This study shows for the first time that locally disturbed neural activity, i.e. PDA, may explain altered functional connectivity between remote areas, even when structural connections are unaffected. We suggest that focal brain lesions and the corresponding altered neural activity should be considered in the framework of the full functionally interacting brain network, implying that the impact of lesions reaches far beyond focal damage. (C) 2013 Elsevier Inc. All rights reserved. C1 [van Dellen, E.; Douw, L.; Heimans, J. J.; Reijneveld, J. C.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Canc Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [Hillebrand, A.; Stam, C. J.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, NL-1007 MB Amsterdam, Netherlands. [Hillebrand, A.; Stam, C. J.] Vrije Univ Amsterdam, Med Ctr, MEG Ctr, NL-1007 MB Amsterdam, Netherlands. [Douw, L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Douw, L.] Harvard Univ, Sch Med, Boston, MA USA. RP van Dellen, E (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Neurol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM E.vanDellen@vumc.nl FU Dutch Epilepsy Foundation (NEF) [09-09]; Rubicon grant of the Netherlands Organisation for Scientific Research (NWO) FX E. van Dellen was supported by the Dutch Epilepsy Foundation (NEF) grant 09-09. L. Douw was supported by the Rubicon grant of the Netherlands Organisation for Scientific Research (NWO). NR 43 TC 11 Z9 12 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 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2013 VL 83 BP 524 EP 532 DI 10.1016/j.neuroimage.2013.06.009 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 251TN UT WOS:000326953700048 PM 23769919 ER PT J AU Nasr, S Devaney, KJ Tootell, RBH AF Nasr, Shahin Devaney, Kathryn J. Tootell, Roger B. H. TI Spatial encoding and underlying circuitry in scene-selective cortex SO NEUROIMAGE LA English DT Article ID PARAHIPPOCAMPAL PLACE AREA; SHORT-TERM-MEMORY; PARIETAL CORTEX; VISUAL-CORTEX; RETROSPLENIAL CORTEX; PERCEPTUAL DECISION; CORTICAL REGIONS; GLOBAL SIGNAL; OBJECT; NAVIGATION AB Three cortical areas (Retro-Splenial Cortex (RSC), Transverse Occipital Sulcus (TOS) and Parahippocampal Place Area (PPA)) respond selectively to scenes. However, their wider role in spatial encoding and their functional connectivity remain unclear. Using fMRI, first we tested the responses of these areas during spatial comparison tasks using dot targets on white noise. Activity increased during task performance in both RSC and TOS, but not in PPA. However, the amplitude of task-driven activity and behavioral measures of task demand were correlated only in RSC. A control experiment showed that none of these areas were activated during a comparable shape comparison task. Secondly, we analyzed functional connectivity of these areas during the resting state. Results revealed a significant connection between RSC and frontal association areas (known to be involved in perceptual decision-making). In contrast, TOS showed functional connections dorsally with the Inferior Parietal Sulcus, and ventrally with the Lateral Occipital Complex - but not with RSC and/or frontal association areas. Moreover, RSC and TOS showed differentiable functional connections with the anterior-medial and posterior-lateral parts of PPA, respectively. These results suggest two parallel pathways for spatial encoding, including RSC and TOS respectively. Only the RSC network was involved in active spatial comparisons. (C) 2013 Elsevier Inc. All rights reserved. C1 [Nasr, Shahin; Devaney, Kathryn J.; Tootell, Roger B. H.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Nasr, S (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM shahin@ranr.mgh.harvard.edu FU National Institutes of Health (NIH) [R01 MH67529, R01 EY017081]; Martinos Center for Biomedical Imaging; NCRR; MIND Institute; NIMH Intramural Research Program FX We thank Drs. A. Afraz, R Rajimehr and M. Vaziri for review and suggestions on the manuscript This study was supported by National Institutes of Health (NIH Grants R01 MH67529 and R01 EY017081 to RBHT), the Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute, and the NIMH Intramural Research Program. NR 61 TC 16 Z9 16 U1 1 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2013 VL 83 BP 892 EP 900 DI 10.1016/j.neuroimage.2013.07.030 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 251TN UT WOS:000326953700082 PM 23872156 ER PT J AU Huang, S Seidman, LJ Rossi, S Ahveninen, J AF Huang, Samantha Seidman, Larry J. Rossi, Stephanie Ahveninen, Jyrki TI Distinct cortical networks activated by auditory attention and working memory load SO NEUROIMAGE LA English DT Article ID SHORT-TERM-MEMORY; VENTROLATERAL PREFRONTAL CORTEX; CONTINUOUS PERFORMANCE-TEST; SPATIAL ATTENTION; SELECTIVE ATTENTION; FUNCTIONAL-ORGANIZATION; PROACTIVE-INTERFERENCE; TEMPORAL DYNAMICS; PARIETAL CORTEX; TASK-DIFFICULTY AB Auditory attention and working memory (WM) allow for selection and maintenance of relevant sound information in our minds, respectively, thus underlying goal-directed functioning in everyday acoustic environments. It is still unclear whether these two closely coupled functions are based on a common neural circuit, or whether they involve genuinely distinct subfunctions with separate neuronal substrates. In a full factorial functional MRI (fMRI) design, we independently manipulated the levels of auditory-verbal WM load and attentional interference using modified Auditory Continuous Performance Tests. Although many frontoparietal regions were jointly activated by increases of WM load and interference, there was a double dissociation between prefrontal cortex (PFC) subareas associated selectively with either auditory attention or WM. Specifically, anterior dorsolateral PFC (DLPFC) and the right anterior insula were selectively activated by increasing WM load, whereas subregions of middle lateral PFC and inferior frontal cortex (IFC) were associated with interference only. Meanwhile, a superadditive interaction between interference and load was detected in left medial superior frontal cortex, suggesting that in this area, activations are not only overlapping, but reflect a common resource pool recruited by increased attentional and WM demands. Indices of WM-specific suppression of anterolateral non-primary auditory cortices (AC) and attention-specific suppression of primary AC were also found, possibly reflecting suppression/interruption of sound-object processing of irrelevant stimuli during continuous task performance. Our results suggest a double dissociation between auditory attention and working memory in subregions of anterior DLPFC vs. middle lateral PFC/IFC in humans, respectively, in the context of substantially overlapping circuits.(C) 2013 Elsevier Inc. All rights reserved. C1 [Huang, Samantha; Rossi, Stephanie; Ahveninen, Jyrki] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Med Sch, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Huang, S (reprint author), MGH MIT HMS Martinos Ctr, Bldg 149 13th St, Boston, MA 02129 USA. EM samhuang@nmr.mgh.harvard.edu FU National Institutes of Health [R01MH083744, R21DC010060, RO1HD040712, R01NS037462, P41RR14075]; Commonwealth Research Center of Massachusetts [SCDMH82101008006]; National Center for Research Resources Shared Instrumentation [S10RR014978, SlORR021110, SlORR019307, S10RR014798, SlORR023401] FX This work was supported by the National Institutes of Health Awards R01MH083744, R21DC010060, RO1HD040712, R01NS037462, and P41RR14075, and Commonwealth Research Center of Massachusetts SCDMH82101008006 (US). The research environment was supported by the National Center for Research Resources Shared Instrumentation Grants S10RR014978, SlORR021110, SlORR019307, S10RR014798, and SlORR023401. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 99 TC 15 Z9 16 U1 5 U2 28 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2013 VL 83 BP 1098 EP 1108 DI 10.1016/Ineuroimage.2013.07.074 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 251TN UT WOS:000326953700102 PM 23921102 ER PT J AU Canterberry, M Hanlon, CA Hartwell, KJ Li, XB Owens, M LeMatty, T Prisciandaro, JJ Borckardt, J Saladin, ME Brady, KT George, MS AF Canterberry, Melanie Hanlon, Colleen A. Hartwell, Karen J. Li, Xingbao Owens, Max LeMatty, Todd Prisciandaro, James J. Borckardt, Jeffrey Saladin, Michael E. Brady, Kathleen T. George, Mark S. TI Sustained Reduction of Nicotine Craving With Real-Time Neurofeedback: Exploring the Role of Severity of Dependence SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CINGULATE CORTEX ACTIVITY; SMOKING-CESSATION; SMOKERS; FMRI; WITHDRAWAL; RELAPSE AB Background: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. Methods: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. Results: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. Conclusions: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods. C1 [Canterberry, Melanie; Hanlon, Colleen A.; Hartwell, Karen J.; Li, Xingbao; Owens, Max; LeMatty, Todd; Prisciandaro, James J.; Borckardt, Jeffrey; Saladin, Michael E.; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. RP Canterberry, M (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,Room 502 North, Charleston, SC 29425 USA. EM canterbe@musc.edu FU National Institute on Drug Abuse at the National Institutes of Health [R33DA026085]; National Institutes of Health [T32DA02788, K01DA0267756] FX This work was supported by the National Institute on Drug Abuse at the National Institutes of Health (R33DA026085 to KTB and MSG). Effort was supported by the National Institutes of Health (T32DA02788 to MC and K01DA0267756 to CAH). NR 24 TC 20 Z9 20 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2013 VL 15 IS 12 BP 2120 EP 2124 DI 10.1093/ntr/ntt122 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 252BD UT WOS:000326978400022 PM 23935182 ER PT J AU Esfahani, SB Yousefzadeh, DK AF Esfahani, Shadi Abdar Yousefzadeh, David K. TI Pericardial Tamponade With a Normal Cardiopericardial Silhouette Due to a Penetrating Metallic Projectile Propelled by a Lawnmower SO PEDIATRIC CARDIOLOGY LA English DT Article DE Lawnmower-related cardiac injury; Pericardial tamponade; Projectile AB This report describes a case of pericardial tamponade in a 6-year-old boy due to a penetrating projectile coat hunger wire propelled by a lawnmower. A dismissible dermal injury at the entry point and a normal initial cardiopericardial silhouette are reported. The report issues a new warning to be added to the warnings already listed in lawnmower manuals. C1 [Esfahani, Shadi Abdar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Yousefzadeh, David K.] Univ Chicago, Comer Childrens Hosp, Dept Radiol, Chicago, IL 60076 USA. [Yousefzadeh, David K.] Univ Chicago, Comer Childrens Hosp, Dept Pediat, Chicago, IL 60076 USA. RP Yousefzadeh, DK (reprint author), Univ Chicago, Comer Childrens Hosp, Dept Radiol, 8900 Little Elm Bend Skokie, Chicago, IL 60076 USA. EM dyousefz@yahoo.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0172-0643 EI 1432-1971 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD DEC PY 2013 VL 34 IS 8 BP 2044 EP 2046 DI 10.1007/s00246-012-0596-x PG 3 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 253EL UT WOS:000327065100067 PM 23184019 ER PT J AU Ramirez-Avila, L Noubary, F Pansegrouw, D Sithole, S Giddy, J Losina, E Walensky, RP Bassett, IV AF Ramirez-Avila, Lynn Noubary, Farzad Pansegrouw, Deirdre Sithole, Siphesihle Giddy, Janet Losina, Elena Walensky, Rochelle P. Bassett, Ingrid V. TI The Acceptability and Feasibility of Routine Pediatric HIV Testing in an Outpatient Clinic in Durban, South Africa SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE routine HIV testing; pediatric; adolescent; South Africa; outpatient clinic ID TO-CHILD TRANSMISSION; CAPE-TOWN; ANTIRETROVIRAL THERAPY; INTEGRATED MANAGEMENT; IMMUNIZATION CLINICS; CARE; PREVALENCE; DIAGNOSIS; PROGRAM; CHALLENGES AB Background: Limited access to HIV testing of children impedes early diagnosis and access to antiretroviral therapy. Our objective was to evaluate the feasibility and acceptability of routine pediatric HIV testing in an urban, fee-for-service, outpatient clinic in Durban, South Africa. Methods: We assessed the number of patients (0-15 years) who underwent HIV testing upon physician referral during a baseline period. We then established a routine, voluntary HIV testing study for pediatric patients, regardless of symptoms. Parents/caretakers were offered free rapid fingerstick HIV testing of their child. For patients <18 months, the biological mother was offered HIV testing and HIV DNA polymerase chain reaction was used to confirm the infant's status. The primary outcome was the HIV testing yield, defined as the average number of positive tests per month during the routine compared with the baseline period. Results: Over a 5-month baseline testing period, 931 pediatric patients registered for outpatient care. Of the 124 (13%) patients who underwent testing on physician referral, 21 (17%, 95% confidence interval: 11-25%) were HIV infected. During a 13-month routine testing period, 2790 patients registered for care and 2106 (75%) were approached for participation. Of these, 1234 were eligible and 771 (62%) enrolled. Among those eligible, 637 (52%, 95% confidence interval: 49-54%) accepted testing of their child or themselves (biological mothers of infants <18 months). There was an increase in the average number of HIV tests during the routine compared with the baseline HIV testing periods (49 versus 25 tests/month, P = 0.001) but no difference in the HIV testing yield during the testing periods (3 versus 4 positive HIV tests/month, P = 0.06). However, during the routine testing period, HIV prevalence remains extraordinarily high with 39 (6%, 95% confidence interval: 4-8%) newly diagnosed HIV-infected children (median 7 years, 56% female). Conclusions: Targeted and symptom-based testing referral identifies an equivalent number of HIV-infected children as routine HIV testing. Routine HIV testing identifies a high burden of HIV and is a feasible and moderately acceptable strategy in an outpatient clinic in a high prevalence area. C1 [Ramirez-Avila, Lynn] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ramirez-Avila, Lynn] Univ Calif Los Angeles, Sch Med, Div Pediat Infect Dis, Los Angeles, CA USA. [Ramirez-Avila, Lynn; Noubary, Farzad; Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Noubary, Farzad; Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Pansegrouw, Deirdre; Sithole, Siphesihle; Giddy, Janet] McCord Hosp, Durban, Kwazulu Natal, South Africa. [Losina, Elena] Boston Univ, Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02215 USA. [Losina, Elena] Boston Univ, Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02215 USA. [Losina, Elena] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Losina, Elena; Walensky, Rochelle P.; Bassett, Ingrid V.] Harvard Univ, Sch Med, Ctr AIDS Res, Cambridge, MA 02138 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ramirez-Avila, L (reprint author), Div Pediat Infect Dis, 10833 Le Conte Ave,22-442 MDCC, Los Angeles, CA 90095 USA. EM lynnramirez@mednet.ucla.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU Boston Children's Hospital Aerosmith Endowment Grant; Harvard Global Health Institute; National Institute of Child Health and Human Development [T32 HD 055148-02]; National Institute of Allergy and Infectious Diseases (NIAID) [T32 AI 007433]; NIAID [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; Harvard University; Massachusetts General Hospital FX Supported by the Boston Children's Hospital Aerosmith Endowment Grant (L.R.A.), the Harvard Global Health Institute (L. R.-A.), National Institute of Child Health and Human Development T32 HD 055148-02 (L. R.-A.), National Institute of Allergy and Infectious Diseases (NIAID) T32 AI 007433 (L.R.A.), NIAID P30 AI060354 (Harvard University Center for AIDS Research) (L. R.-A.), National Institute of Mental Health R01 MH090326 (I. V. B.), R01 MH073445 (R. P. W.), Harvard University Program on AIDS and the Claflin Distinguished Scholar Award of the Massachusetts General Hospital (I. V. B.). NR 40 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2013 VL 32 IS 12 BP 1348 EP 1353 DI 10.1097/INF.0b013e31829ba34b PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 254UH UT WOS:000327192800021 PM 23694834 ER PT J AU Schweizer, MT Lin, J Blackford, A Bardia, A King, S Armstrong, AJ Rudek, MA Yegnasubramanian, S Carducci, MA AF Schweizer, M. T. Lin, J. Blackford, A. Bardia, A. King, S. Armstrong, A. J. Rudek, M. A. Yegnasubramanian, S. Carducci, M. A. TI Pharmacodynamic study of disulfiram in men with non-metastatic recurrent prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE disulfiram; epigenetics; demethylation; hypomethylation ID NF-KAPPA-B; PROTEASOME ACTIVITY; ANTIALCOHOLISM DRUG; DNA METHYLATION; CELL-GROWTH; INHIBITION; APOPTOSIS; COPPER; HYPERMETHYLATION; AGENT AB BACKGROUND: Preclinical drug screens identified disulfiram as a potent in vitro inhibitor of prostate cancer (PCa) cell growth. Although many mechanisms for its anticancer activity have been proposed, tumor suppressor gene re-expression through promoter demethylation emerged as one of the more plausible. METHODS: We conducted an open-label, dose escalation trial of disulfiram in men with non-metastatic recurrent PCa after local therapy. Dose escalation occurred if a demethylating 'response' (that is, >= 10% decrease in peripheral blood mononuclear cell (PBMC) global 5-methyl cytosine (5(me)C) content) was observed in <3 patients in cohort 1. Cohorts 1 and 2 received disulfiram 250 mg and 500 mg daily, respectively. The primary end point was the proportion of subjects with a demethylation response. Secondary end points included the rate of PSA progression at 6 months, changes in PSA doubling time and safety/tolerability. RESULTS: Changes in global 5(me)C content were observed in two of nine patients (22.2%) in cohort 1 and 3 of 10 (30.0%) in cohort 2. Only five subjects were on trial for >= 6 months, all were in cohort 1 and all had PSA progression by 6 months. No changes in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated with six patients experiencing grade 3 adverse events (three per cohort). Three of the responders displayed pretreatment instability in their 5(me)C content. CONCLUSIONS: A minority of patients had transient global PBMC demethylation changes. Instability in 5(me)C may limit the reproducibility of these findings, limiting our ability to confirm our hypothesis. Given the toxicities and no clinical benefits, further development of disulfiram should not be pursued in this population. C1 [Schweizer, M. T.; Blackford, A.; King, S.; Rudek, M. A.; Yegnasubramanian, S.; Carducci, M. A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Lin, J.] Thomas Jefferson Univ, Dept Med Oncol, Philadelphia, PA 19107 USA. [Bardia, A.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Armstrong, A. J.] Duke Univ, Dept Med Oncol, Durham, NC USA. RP Carducci, MA (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1650 Orleans St, Baltimore, MD 21287 USA. EM carducci@jhmi.edu FU NIH/NCI [CA58236]; Commonwealth Foundation; David H Koch Charitable Foundation; DOD [W81XWH-09-1-0149]; Cancer Center Core Grant [P30 CA006973]; Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH) [P30 CA006973, UL1 RR 025005]; Shared Instrument Grant [1S10RR026824-01]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR 025005]; NIH Roadmap for Medical Research FX This study was supported by NIH/NCI CA58236, Commonwealth Foundation; David H Koch Charitable Foundation; DOD no. W81XWH-09-1-0149; DOD; Cancer Center Core Grant P30 CA006973. This research was supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH grants P30 CA006973 and UL1 RR 025005) and the Shared Instrument Grant (1S10RR026824-01). The project described was supported in part by Grant Number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 28 TC 11 Z9 11 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD DEC PY 2013 VL 16 IS 4 BP 357 EP 361 DI 10.1038/pcan.2013.28 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 252OO UT WOS:000327016600012 PM 23958896 ER PT J AU Allott, EH Abern, MR Gerber, L Keto, CJ Aronson, WJ Terris, MK Kane, CJ Amling, CL Cooperberg, MR Moorman, PG Freedland, SJ AF Allott, E. H. Abern, M. R. Gerber, L. Keto, C. J. Aronson, W. J. Terris, M. K. Kane, C. J. Amling, C. L. Cooperberg, M. R. Moorman, P. G. Freedland, S. J. TI Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE metformin; diabetes; biochemical recurrence; outcomes ID CANCER-RISK; DIABETIC-PATIENTS; INCIDENT CANCER; MORTALITY; METAANALYSIS; SURVIVAL; GLUCOSE; PEOPLE; MEN AB BACKGROUND: While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP). METHODS: We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses. RESULTS: Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P < 0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5). CONCLUSIONS: Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up. C1 [Allott, E. H.; Abern, M. R.; Gerber, L.; Keto, C. J.; Freedland, S. J.] Duke Univ, Sch Med, Dept Surg, Div Urol, Durham, NC 27710 USA. [Allott, E. H.] Duke Canc Inst, Canc Prevent Detect & Control Program, Durham, NC USA. [Allott, E. H.; Freedland, S. J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Aronson, W. J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, W. J.] Univ Calif Los Angeles, Sch Med, Div Urol, Los Angeles, CA 90024 USA. [Terris, M. K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, M. K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Kane, C. J.] Univ Calif San Diego, Dept Urol, San Diego, CA 92103 USA. [Amling, C. L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR USA. [Cooperberg, M. R.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA USA. [Moorman, P. G.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Freedland, S. J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI [5R25-CA126938-03]; NIH [1-R01-CA131235-01A1, 1K24CA160653] FX This study was supported by EHA: NCI 5R25-CA126938-03; SJF: NIH Grant 1-R01-CA131235-01A1 and NIH 1K24CA160653. NR 27 TC 32 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD DEC PY 2013 VL 16 IS 4 BP 391 EP 397 DI 10.1038/pcan.2013.48 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 252OO UT WOS:000327016600019 PM 24100644 ER PT J AU van Scheltinga, AFT Bakker, SC van Haren, NEM Derks, EM Buizer-Voskamp, JE Cahn, W Ripke, S Ophoff, RA Kahn, RS AF van Scheltinga, A. F. Terwisscha Bakker, S. C. van Haren, N. E. M. Derks, E. M. Buizer-Voskamp, J. E. Cahn, W. Ripke, S. Ophoff, R. A. Kahn, R. S. CA Psychiat Genome-Wide Assoc Study G TI Schizophrenia genetic variants are not associated with intelligence SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Cognition; deletion; duplication; endophenotype; IQ; polygenic; SNP ID BRAIN VOLUMES; METAANALYSIS; NEUROCOGNITION; CHILDHOOD; PSYCHOSIS; RELATIVES; PATHWAYS; OVERLAP; TWINS AB Background. Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. Method. IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Results. Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p=0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R-2=0.055, p=2.1x10(-7)) and with IQ in the entire sample (R-2=0.018, p=0.0008) but the effect on IQ disappeared after correction for disease status. Conclusions. Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk. C1 [van Scheltinga, A. F. Terwisscha; Bakker, S. C.; van Haren, N. E. M.; Buizer-Voskamp, J. E.; Cahn, W.; Ophoff, R. A.; Kahn, R. S.] Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. [Derks, E. M.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1012 WX Amsterdam, Netherlands. [Ripke, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ophoff, R. A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. RP van Scheltinga, AFT (reprint author), Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Huispostnummer A00-241,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM aterwiss@umcutrecht.nl RI Stroup, Thomas/F-9188-2014; McGrath, John/G-5493-2010; Myin-Germeys, Inez /L-5106-2014; Jablensky, Assen/H-5116-2014; Mortensen, Preben/D-2358-2015; SCHALL, ULRICH/G-7452-2013; Ruderfer, Douglas/M-5795-2016; McQuillin, Andrew/C-1623-2008; Derks, Eske/A-1652-2017; Collier, David/D-1649-2011; Mattheisen, Manuel/B-4949-2012; Catts, Stanley/G-6917-2013; Pantelis, Christos/H-7722-2014; Melle, Ingrid /B-4858-2011; OI Escott-Price, Valentina/0000-0003-1784-5483; lichtenstein, paul/0000-0003-3037-5287; Suvisaari, Jaana/0000-0001-7167-0990; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; Golimbet, Vera/0000-0002-9960-7114; Agartz, Ingrid/0000-0002-9839-5391; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Andreassen, Ole A./0000-0002-4461-3568; Bergen, Sarah/0000-0002-5888-0034; Golimbet, Vera/0000-0002-0114-4300; Stefansson, Hreinn/0000-0002-9331-6666; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Zammit, Stanley/0000-0002-2647-9211; Stroup, Thomas/0000-0002-3123-0672; Morris, Derek/0000-0002-3413-570X; Rethelyi, Janos/0000-0002-3641-012X; Myin-Germeys, Inez/0000-0002-3731-4930; Buccola, Nancy/0000-0003-1378-4636; McGrath, John/0000-0002-4792-6068; Mortensen, Preben/0000-0002-5230-9865; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Derks, Eske/0000-0002-6292-6883; Collier, David/0000-0003-4087-1559; Mattheisen, Manuel/0000-0002-8442-493X; Pantelis, Christos/0000-0002-9565-0238; Melle, Ingrid /0000-0002-9783-548X; Henskens, Frans/0000-0003-2358-5630; Visscher, Peter/0000-0002-2143-8760; McIntosh, Andrew/0000-0002-0198-4588 FU Zorg Onderzoek Nederland, Medische Wetenschappen (ZON-MW, the Netherlands Organization for Health Research and Development) [91686137]; Top Institute Pharma (TI-Pharma) [T5-203]; National Institute of Mental Health [RO1 MG 078075] FX This work was supported by a Veni grant to S. C. B. from Zorg Onderzoek Nederland, Medische Wetenschappen (ZON-MW, the Netherlands Organization for Health Research and Development, project no. 91686137), by Top Institute Pharma (TI-Pharma, project T5-203) and by the National Institute of Mental Health grant RO1 MG 078075 to R.A.O. NR 28 TC 14 Z9 14 U1 0 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD DEC PY 2013 VL 43 IS 12 BP 2563 EP 2570 DI 10.1017/S0033291713000196 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 251QL UT WOS:000326944900009 PM 23410598 ER PT J AU Tofthagen, C Donovan, KA Morgan, MA Shibata, D Yeh, YT AF Tofthagen, Cindy Donovan, Kristine A. Morgan, Mary Ann Shibata, David Yeh, Yating TI Oxaliplatin-induced peripheral neuropathy's effects on health-related quality of life of colorectal cancer survivors SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Oxaliplatin; Oxaliplatin-induced peripheral neuropathy; Colorectal cancer ID COLON-CANCER; CHEMOTHERAPY; NEUROTOXICITY; SEVERITY; COMBINATION; DEPRESSION; SLEEP AB Oxaliplatin is a highly neurotoxic chemotherapeutic agent routinely used for the treatment of colorectal cancer. Recent data suggest that oxaliplatin-induced peripheral neuropathy may be long-lasting; however, the effects of persistent neuropathy on colorectal cancer survivors' physical and emotional well-being are not well understood. This cross sectional, descriptive study included persons who had received oxaliplatin-based chemotherapy for treatment of colorectal cancer at Moffitt Cancer Center between 2003 and 2010. Questionnaires including the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, Center for Epidemiological Studies Depression Scale (CES-D), Insomnia Severity Index, Medical Outcomes Study Short Form 36, and a demographic survey were administered. Pearson's correlations and linear regression analyses were used to examine relationships between neuropathy and depressive symptoms, sleep quality, and health-related quality of life (HRQOL). Eighty-nine percent of participants reported at least one symptom of peripheral neuropathy with a mean of 3.8 (+/- 2.4) neuropathic symptoms. Depressive symptoms on the CES-D were significantly associated with more severe peripheral neuropathy(r = 0.38, p = 0.0001) and interference with activities (r = 0.59, p < 0.0001). Higher degrees of sleep disturbance on the Insomnia Severity Index (ISI) were significantly associated with more severe peripheral neuropathy (r = 0.35, p = 0.0004) and interference with activities(r = 0.52, p < 0.0001). HRQOL was significantly associated with peripheral neuropathy and interference with activities. C1 [Tofthagen, Cindy] Univ S Florida, Coll Nursing, Tampa, FL 33612 USA. [Tofthagen, Cindy] Univ Massachusetts, Boston, MA 02125 USA. [Tofthagen, Cindy; Yeh, Yating] Dana Farber Canc Inst, Boston, MA 02115 USA. [Donovan, Kristine A.; Morgan, Mary Ann; Shibata, David] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Tofthagen, C (reprint author), Univ S Florida, Coll Nursing, 12901 Bruce B Downs Blvd,MDC 22, Tampa, FL 33612 USA. EM ctofthag@health.usf.edu FU University of South Florida Nursing Faculty in Pilot Research Projects Grant; University of Massachusetts Boston-Dana Farber /Harvard Cancer Center U54 Cancer Research Partnership FX This study was supported by a University of South Florida Nursing Faculty in Pilot Research Projects Grant and the University of Massachusetts Boston-Dana Farber /Harvard Cancer Center U54 Cancer Research Partnership. NR 36 TC 29 Z9 29 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD DEC PY 2013 VL 21 IS 12 BP 3307 EP 3313 DI 10.1007/s00520-013-1905-5 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 250YE UT WOS:000326892100010 PM 23903798 ER PT J AU Li, CY Zeliadt, SB Hall, IJ Smith, JL Ekwueme, DU Moinpour, CM Penson, DF Thompson, IM Keane, TE Ramsey, SD AF Li, Chunyu Zeliadt, Steven B. Hall, Ingrid J. Smith, Judith Lee Ekwueme, Donatus U. Moinpour, Carol M. Penson, David F. Thompson, Ian M. Keane, Thomas E. Ramsey, Scott D. TI Burden among partner caregivers of patients diagnosed with localized prostate cancer within 1 year after diagnosis: an economic perspective SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Informal caregiving; Prostate cancer; Local stage; Time cost; Household chores; Productivity ID QUALITY-OF-LIFE; EMPLOYMENT; TIME; MEN; SURVIVORS; CARE; ILLNESS; STATES; BREAST; WORK AB Informal care plays an important role in the overall care for people with cancer. This study estimates lost productivity and informal caregiving and associated costs among partner caregivers of localized prostate cancer patients within 1 year after diagnosis. We applied data from the Family and Cancer Therapy Selection study, a three-wave self-administered survey among patients diagnosed with localized prostate cancer and their partner caregivers in multiple clinics in the USA. Time spent was measured by the sum of working hours lost, informal caregiving hours performed, and hours spent on household chores. The national median income for women 55 years or older was used to calculate costs associated with the time spent using the opportunity cost method. Descriptive and bivariate analyses were conducted. The average working hours decreased from 14.0 h/week (SD = 17.6) to 10.9 h/week (SD = 15.9), without a significant change in responsibility/intensity at work. The mean annual time spent on informal caregiving and household chores was 65.9 h/year (SD = 172.4) and 76.2 h/year (SD = 193.3), respectively. The mean annual economic burden among partner caregivers was US$6,063 (range US$571-US$47,105) in 2009 dollars accounted for by a mean of 276.2 h (range 26-2,146) in the study sample. The time spent on informal caregiving and household chores varied by patient and caregiver characteristics. Pilot estimates on non-medical economic burden among partner caregivers (spouses) during the initial phase of the treatment provide important information for comprehensive estimation of disease burden and can be used in cost-effectiveness analyses of prostate cancer interventions. C1 [Li, Chunyu; Hall, Ingrid J.; Smith, Judith Lee; Ekwueme, Donatus U.] Natl Ctr Chron Dis Prevent & Hlth Promot, Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Zeliadt, Steven B.; Moinpour, Carol M.; Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Serv Div, Seattle, WA 98104 USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Med & Publ Hlth, Nashville, TN USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Keane, Thomas E.] Med Univ S Carolina, Urol Serv, Charleston, SC 29425 USA. RP Li, CY (reprint author), Natl Ctr Chron Dis Prevent & Hlth Promot, Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway NE,MS F-76, Atlanta, GA 30341 USA. EM Cli11@cdc.gov FU Centers for Disease Control and Prevention (CDC), Prevention Research Centers Program, through the University of Washington Health Promotion Research Center [SIP 25-04 1-U48-DP-000050] FX This study was supported by the Cooperative Agreement Number SIP 25-04 1-U48-DP-000050 from the Centers for Disease Control and Prevention (CDC), Prevention Research Centers Program, through the University of Washington Health Promotion Research Center. There is no conflict of interest. The corresponding author has full access to all primary data and agree to allow the journal to review their data if requested. NR 32 TC 4 Z9 5 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD DEC PY 2013 VL 21 IS 12 BP 3461 EP 3469 DI 10.1007/s00520-013-1931-3 PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 250YE UT WOS:000326892100028 PM 23955026 ER PT J AU Jabaji, Z Sears, CM Brinkley, GJ Lei, NY Joshi, VS Wang, JF Lewis, M Stelzner, M Martin, MG Dunn, JCY AF Jabaji, Ziyad Sears, Connie M. Brinkley, Garrett J. Lei, Nan Ye Joshi, Vaidehi S. Wang, Jiafang Lewis, Michael Stelzner, Matthias Martin, Martin G. Dunn, James C. Y. TI Use of Collagen Gel as an Alternative Extracellular Matrix for the In Vitro and In Vivo Growth of Murine Small Intestinal Epithelium SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID STEM-CELL NICHE; SELF-RENEWAL; ORGANOIDS; CULTURE; TRANSPLANTATION; MODEL; COLON; DIFFERENTIATION; IDENTIFICATION; ENGRAFTMENT AB Methods for the in vitro culture of primary small intestinal epithelium have improved greatly in recent years. A critical barrier for the translation of this methodology to the patient's bedside is the ability to grow intestinal stem cells using a well-defined extracellular matrix. Current methods rely on the use of Matrigel, a proprietary basement membrane-enriched extracellular matrix gel produced in mice that is not approved for clinical use. We demonstrate for the first time the capacity to support the long-term in vitro growth of murine intestinal epithelium in monoculture, using type I collagen. We further demonstrate successful in vivo engraftment of enteroids co-cultured with intestinal subepithelial myofibroblasts in collagen gel. Small intestinal crypts were isolated from 6 to 10 week old transgenic enhanced green fluorescent protein (eGFP+) mice and suspended within either Matrigel or collagen gel; cultures were supported using previously reported media and growth factors. After 1 week, cultures were either lysed for DNA or RNA extraction or were implanted subcutaneously in syngeneic host mice. Quantitative real-time polymerase chain reaction (qPCR) was performed to determine expansion of the transgenic eGFP-DNA and to determine the mRNA gene expression profile. Immunohistochemistry was performed on in vitro cultures and recovered in vivo explants. Small intestinal crypts reliably expanded to form enteroids in either Matrigel or collagen in both mono- and co-cultures as confirmed by microscopy and eGFP-DNA qPCR quantification. Collagen-based cultures yielded a distinct morphology with smooth enteroids and epithelial monolayer growth at the gel surface; both enteroid and monolayer cells demonstrated reactivity to Cdx2, E-cadherin, CD10, Periodic Acid-Schiff, and lysozyme. Collagen-based enteroids were successfully subcultured in vitro, whereas pure monolayer epithelial sheets did not survive passaging. Reverse transcriptase-polymerase chain reaction demonstrated evidence of Cdx2, villin 1, mucin 2, chromogranin A, lysozyme 1, and Lgr5 expression, suggesting a fully elaborated intestinal epithelium. Additionally, collagen-based enteroids co-cultured with myofibroblasts were successfully recovered after 5 weeks of in vivo implantation, with a preserved immunophenotype. These results indicate that collagen-based techniques have the capacity to eliminate the need for Matrigel in intestinal stem cell culture. This is a critical step towards producing neo-mucosa using good manufacturing practices for clinical applications in the future. C1 [Jabaji, Ziyad; Sears, Connie M.; Brinkley, Garrett J.; Lei, Nan Ye; Stelzner, Matthias; Dunn, James C. Y.] Univ Calif Los Angeles, David Geffen Sch Med UCLA, Dept Surg, Div Pediat Surg, Los Angeles, CA 90095 USA. [Joshi, Vaidehi S.; Dunn, James C. Y.] Univ Calif Los Angeles, Sch Engn, Dept Bioengn, Los Angeles, CA 90095 USA. [Wang, Jiafang; Martin, Martin G.] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA 90095 USA. [Wang, Jiafang; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med UCLA, Los Angeles, CA 90095 USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Stelzner, Matthias] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Martin, Martin G.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. RP Dunn, JCY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med UCLA, Dept Surg, Div Pediat Surg, 10833 Le Conte Ave,CHS 72-172,MC 709818, Los Angeles, CA 90095 USA. EM jdunn@mednet.ucla.edu FU National Institute of Diabetes and Digestive and Kidney Diseases U01 Intestinal Stem Cell Consortium [DK085535-01, DK085535-02S2, DK083762, DK083319]; National Institute of Allergy and Infectious Diseases FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases U01 Intestinal Stem Cell Consortium (DK085535-01 and DK085535-02S2), DK083762, and DK083319 and the National Institute of Allergy and Infectious Diseases. We sincerely thank Renee Bowers (UCLA) and Nazlin Sharif (West Los Angeles, VA) for their expert consultation and generous technical assistance with all elements of histology work. NR 35 TC 17 Z9 17 U1 3 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD DEC 1 PY 2013 VL 19 IS 12 BP 961 EP 969 DI 10.1089/ten.tec.2012.0710 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 256IZ UT WOS:000327304900006 PM 23566043 ER PT J AU Jones, RC Capen, DE AF Jones, Rosemary C. Capen, Diane E. TI Alveolar Oxygen Tension and Angio-architecture of the Distal Adult Lung SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE High oxygen; hyperoxia-regression; hypoxia-regeneration; pulmonary capillary remodeling; relative hypoxia ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; HYPEROXIC PULMONARY-HYPERTENSION; VASCULAR DEVELOPMENT; BLOOD-VESSELS; RAT LUNGS; INJURY; EXPOSURE; EXPRESSION; NEOVASCULARIZATION AB The present study demonstrates the fine structure of pulmonary capillaries first injured and then undergoing growth in response to a change in the ambient alveolar oxygen tension. Breathing a high fraction of inspired oxygen (FiO(2) 0.75) triggers restriction by endothelial cell injury and effacement leading to segment narrowing and shortening and segment loss as demonstrated by a fall in density. Subsequently, breathing a relatively low fraction (FiO(2) 0.21) triggers capillary assembly (angiogenesis), which reverses the changes. The data underscore the structural reprogramming (reduction and restoration) of pulmonary capillaries in response to significant shifts in oxygen tension. C1 [Jones, Rosemary C.; Capen, Diane E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Jones, Rosemary C.] Harvard Univ, Sch Med, Boston, MA USA. RP Jones, RC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM rcjones@partners.org FU NIH [HL R01 089252] FX Supported by NIH HL R01 089252. NR 46 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD DEC PY 2013 VL 37 IS 6 BP 395 EP 407 DI 10.3109/01913123.2013.831156 PG 13 WC Microscopy; Pathology SC Microscopy; Pathology GA 251WL UT WOS:000326963200003 PM 24144043 ER PT J AU Lyddon, R Dwork, AJ Keddache, M Siever, LJ Dracheva, S AF Lyddon, Rebecca Dwork, Andrew J. Keddache, Mehdi Siever, Larry J. Dracheva, Stella TI Serotonin 2c receptor RNA editing in major depression and suicide SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE RNA editing; ADAR; serotonin receptor; major depressive disorder; suicide ID PRE-MESSENGER-RNA; 5-HT2C RECEPTOR; PREFRONTAL CORTEX; SIGNAL-TRANSDUCTION; GENE; ANTAGONIST; AGONIST; PROTEIN; BRAIN; ANTIDEPRESSANTS AB Objectives. mRNA for serotonin 2C receptor (5-HT2CR) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT2CR editing in suicide victims with prior bipolar disorder (BPD) or schizophrenia (SZ) compared with non-suicide patients and normal controls (NC). This study compares suicides and non-suicides with major depressive disorder (MDDSuic and MDDNoSuic) and non-suicide NC. Methods. mRNA editing was assessed in prefrontal cortex of 24 MDDSuic, 21 MDDNoSuic, and 56 NC using next generation sequencing. mRNA expression of 5-HT2CR and editing enzymes (ADAR1-2) was assessed by real-time PCR. Results. Editing was lower in MDDNoSuic than in MDDSuic, which did not differ from NC. No differences in the 5-HT2CR or ADAR1 expression were detected. ADAR2 expression was higher in NC than in MDD subjects, but did not differ between MDDNoSuic and MDDSuic. Conclusions. Our findings suggest the presence of two factors associated with 5-HT2CR editing. One factor, which probably stems from decreased ADAR2 expression, is linked to MDD and is associated with less editing. The other, seen also in our previous study of suicide in BP and SZ, is linked to suicide alone and is associated with more editing and, therefore, less receptor function. C1 [Lyddon, Rebecca; Siever, Larry J.; Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Lyddon, Rebecca; Siever, Larry J.; Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Dwork, Andrew J.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Dwork, Andrew J.] Columbia Univ, Dept Psychiat, New York, NY USA. [Dwork, Andrew J.] New York State Psychiat Inst & Hosp, Div Mol Imaging & Neuropathol, New York, NY 10032 USA. [Keddache, Mehdi] Cincinnati Childrens Hosp Res Fdn, Div Human Genet, Cincinnati, OH USA. RP Dracheva, S (reprint author), Bronx VA Med Ctr, Psychiat Res 4F-02,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu FU VA Merit; Hope for Depression Foundation; American Foundation for Suicide Prevention; VISN3 Mental Illness Research and Education Clinical Center (MIRECC) FX We are grateful to Mr Scott Navarrett and Ms Katie Lutz for their superb technical assistance and to Dr D.J. Jamison for his help with bioinformatics. Postmortem brain tissue was donated by The Stanley Medical Research Institute courtesy of Drs Michael B. Knable, E. Fuller Torrey, Maree J. Webster, and Robert H. Yolken. This study was supported by VA Merit award to SD, by grants from the Hope for Depression Foundation and the American Foundation for Suicide Prevention (SD), and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC) (SD, LJS). NR 57 TC 10 Z9 11 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 EI 1814-1412 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD DEC PY 2013 VL 14 IS 8 BP 590 EP 601 DI 10.3109/15622975.2011.630406 PG 12 WC Psychiatry SC Psychiatry GA 256JT UT WOS:000327307100006 PM 22404657 ER PT J AU Tsao, CK Small, AC Kates, M Moshier, EL Wisnivesky, JP Gartrell, BA Sonpavde, G Godbold, JH Palese, MA Hall, SJ Oh, WK Galsky, MD AF Tsao, Che-kai Small, Alexander C. Kates, Max Moshier, Erin L. Wisnivesky, Juan P. Gartrell, Benjamin A. Sonpavde, Guru Godbold, James H. Palese, Michael A. Hall, Simon J. Oh, William K. Galsky, Matthew D. TI Cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy in the United States: a SEER analysis SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Cytoreductive nephrectomy; SEER; Targeted therapy; Tyrosine kinase inhibitor; Disparities ID SURVIVAL; CANCER; IMPACT; SURGERY; DISEASE; GENDER AB Two randomized trials published in 2001 provided level 1 evidence for the use of cytoreductive nephrectomy (CyNx) for the treatment of metastatic renal cell carcinoma (mRCC). However, the regulatory approval of vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) in 2005 has left an "evidence void" regarding the use of CyNx. We evaluated the patterns in the use of CyNx in the cytokine and VEGFR-TKI eras, and the patient characteristics associated with the use of CyNx. The Surveillance, Epidemiology, and End Results registry was used to identify patients with histologically or cytologically confirmed stage IV RCC between 2001 and 2008. Patients were classified as treated during the cytokine (2001-2005) or VEGFR-TKI (2006-2008) eras. A multivariate logistic regression analysis was performed to calculate the odds of undergoing CyNx according to treatment era and socioeconomic characteristics. Overall, 1,112 of 2,448 patients (45 %) underwent CyNx. CyNx use remained stable between 2001 and 2005 (50 %), but decreased to 38 % in 2008. Logistic regression analysis revealed that older age (OR 0.82, 95 % CI: 0.68, 0.99), black race (OR 0.64, 95 % CI: 0.46, 0.91), Hispanic ethnicity (OR 0.71, 95 % CI: 0.54, 0.93), and treatment in the VEGFR-TKI era (OR 0.82, 95 % CI: 0.68, 0.99) were independently associated with decreased use of CyNx. Use of CyNx in the United States has declined in the VEGFR-TKI era. Older patients and minorities are less likely to receive CyNx. Results of ongoing phase III trials are needed to refine the role of this treatment modality. C1 [Tsao, Che-kai; Small, Alexander C.; Kates, Max; Moshier, Erin L.; Gartrell, Benjamin A.; Godbold, James H.; Oh, William K.; Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Wisnivesky, Juan P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Houston, TX 77030 USA. [Palese, Michael A.; Hall, Simon J.] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu FU Pfizer; GlaxoSmithKline FX Dr. Sonpavde receives research support from Pfizer and is an ad board/speaker for Pfizer, Novartis, and GlaxoKlineSmith. Dr. Wisnivesky is a member of the research board of EHE International, has been a consultant for UBS and IMS Health, and received a research grant from GlaxoSmithKline. NR 23 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD DEC PY 2013 VL 31 IS 6 BP 1535 EP 1539 DI 10.1007/s00345-012-1001-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 253ZY UT WOS:000327130700033 PM 23223962 ER PT J AU Eswara, JR Lee, H Dretler, SP Sacco, D AF Eswara, Jairam R. Lee, Hang Dretler, Stephen P. Sacco, Dianne TI The effect of delayed percutaneous nephrolithotomy on the risk of bacteremia and sepsis in patients with neuromuscular disorders SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Percutaneous nephrolithotomy; Infection; Neuromuscular diseases; Sepsis; Bacteremia ID SPINAL-CORD-INJURY; TRACT INFECTION; URINARY-TRACT; RENAL-CALCULI; MANAGEMENT; COMPLICATIONS; PROPHYLAXIS; SURGERY AB To determine whether a delayed percutaneous nephrolithotomy (PCNL) reduces the rate of bacteremia/sepsis in patients with neuromuscular disorders. Patients with neuromuscular disorders are at higher risk of developing complications after PCNL. One strategy to reduce the risk of infectious complications is to place a percutaneous nephrostomy tube at least 24 h prior to performing PCNL. We analyzed the rates of bacteremia/sepsis in patients with neuromuscular disorders who had access on the day of PCNL (same-day) versus more than 24 h prior to the treatment for the stone (delayed). We identified 246 consecutive patients who underwent PCNL at our institution between 8/2003 and 8/2008, 35 of whom (14 %) had neuromuscular disorders. The primary end point was postoperative bacteremia (fever and positive blood culture) or sepsis (SIRS and documented infection), which was compared between those who had percutaneous access on the day of surgery versus those who had access at least 24 h prior to the operative event. All patients had negative urine cultures preoperatively or were treated with antibiotics for 4-7 days prior to the surgery for a positive preoperative urine culture. The neuromuscular disorders in the 35 patients were multiple sclerosis (16), spina bifida (10), quadriplegia (4), paraplegia/Guillain-Barre (3), and cerebral palsy (2). The rate of bacteremia/sepsis among patients with neuromuscular disorders was 14 %. The rate of sepsis/bacteremia was 26 % for same-day PCNL versus 0 % for delayed PCNL (OR 8.4, p = 0.05). Delayed PCNL results in lower rates of bacteremia and/or sepsis in patients with neuromuscular disorders. C1 [Eswara, Jairam R.; Dretler, Stephen P.; Sacco, Dianne] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM jeswara@partners.org NR 19 TC 5 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD DEC PY 2013 VL 31 IS 6 BP 1611 EP 1615 DI 10.1007/s00345-013-1044-0 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 253ZY UT WOS:000327130700045 PM 23443410 ER PT J AU Ioannou, GN Scott, JD Yang, Y Green, PK Beste, LA AF Ioannou, G. N. Scott, J. D. Yang, Y. Green, P. K. Beste, L. A. TI Rates and predictors of response to anti-viral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HIV-INFECTED PATIENTS; ALPHA-2A PLUS RIBAVIRIN; SUSTAINED VIROLOGICAL RESPONSE; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER-RELATED DEATHS; GENOTYPE 1; HEPATOCELLULAR-CARCINOMA; PEGYLATED INTERFERON; UNITED-STATES; THERAPY AB BackgroundThe effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in real world', clinical practice is unclear. AimsTo determine the rates and predictors of sustained virological response (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and ribavirin in HIV/HCV co-infected patients. MethodsWe identified all HIV/HCV co-infected patients who received anti-viral treatment with PEG-IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n=665). ResultsSustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1 HCV (n=491) and 44% among patients with genotype 2 or 3 HCV (n=116). Among genotype 1-infected patients, characteristics that were negatively associated with SVR independently included baseline HCV viral load >2million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI 0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)], baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio 1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR 0.41 (0.2-0.9)]; characteristics positively associated with SVR included a starting dose of ribavirin 1000-1200mg/day [AOR 2.0 (1.1-3.7)] and erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor of SVR [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800mg/day was not associated with SVR. ConclusionsSustained virological response rates achieved with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated with SVR. C1 [Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, G. N.; Yang, Y.; Green, P. K.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Ioannou, G. N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Scott, J. D.] Univ Washington, Seattle, WA 98195 USA. [Beste, L. A.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Abbott; Gilead; Genentech; Janssen; Merck; Vertex; Clinical Science Research and Development, Office of Research and Development, Department of Veterans Affairs [I01CX000320] FX John Scott speaks for Vertex, Merck, Gilead and Genentech, has received grant funding from Abbott, Gilead, Genentech, Janssen, Merck and Vertex, and has served as a consultant for Vertex.; The study was funded in full by Merit Review Award, grant number I01CX000320, from the Clinical Science Research and Development, Office of Research and Development, Department of Veterans Affairs (GNI). NR 38 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD DEC PY 2013 VL 38 IS 11-12 BP 1373 EP 1384 DI 10.1111/apt.12524 PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 248FR UT WOS:000326681400006 PM 24127691 ER PT J AU McGrath, LM Cornelis, MC Lee, PH Robinson, EB Duncan, LE Barnett, JH Huang, J Gerber, G Sklar, P Sullivan, P Perlis, RH Smoller, JW AF McGrath, Lauren M. Cornelis, Marilyn C. Lee, Phil H. Robinson, Elise B. Duncan, Laramie E. Barnett, Jennifer H. Huang, Jie Gerber, Gloria Sklar, Pamela Sullivan, Patrick Perlis, Roy H. Smoller, Jordan W. TI Genetic Predictors of Risk and Resilience in Psychiatric Disorders: A Cross-Disorder Genome-Wide Association Study of Functional Impairment in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE SF-12; health-related quality of life; disability; genetics; ADAMTS16 ID QUALITY-OF-LIFE; FORM HEALTH SURVEY; STAR-ASTERISK-D; TREATMENT ENHANCEMENT PROGRAM; SEQUENCED TREATMENT ALTERNATIVES; SEVERE MENTAL-ILLNESS; SURVEY SF-36; STEP-BD; RELIABILITY; VALIDITY AB Functional impairment is one of the most enduring, intractable consequences of psychiatric disorders and is both familial and heritable. Previous studies have suggested that variation in functional impairment can be independent of symptom severity. Here we report the first genome-wide association study (GWAS) of functional impairment in the context of major mental illness. Participants of European-American descent (N=2,246) were included from three large treatment studies of bipolar disorder (STEP-BD) (N=765), major depressive disorder (STAR*D) (N=1091), and schizophrenia (CATIE) (N=390). At study entry, participants completed the SF-12, a widely used measure of health-related quality of life. We performed a GWAS and pathway analysis of the mental and physical components of health-related quality of life across diagnosis (approximate to 1.6 million single nucleotide polymorphisms), adjusting for psychiatric symptom severity. Psychiatric symptom severity was a significant predictor of functional impairment, but it accounted for less than one-third of the variance across disorders. After controlling for diagnostic category and symptom severity, the strongest evidence of genetic association was between variants in ADAMTS16 and physical functioning (P=5.87x10(-8)). Pathway analysis did not indicate significant enrichment after correction for gene clustering and multiple testing. This study illustrates a phenotypic framework for examining genetic contributions to functional impairment across psychiatric disorders. (c) 2013 Wiley Periodicals, Inc. C1 [McGrath, Lauren M.; Lee, Phil H.; Duncan, Laramie E.; Gerber, Gloria; Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Cornelis, Marilyn C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Robinson, Elise B.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Duncan, Laramie E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Barnett, Jennifer H.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Huang, Jie] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Sklar, Pamela] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. [Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP McGrath, LM (reprint author), Amer Univ, Sch Educ Teaching & Hlth, 4400 Massachusetts Ave, Washington, DC 20016 USA. EM mcgrath@american.edu OI Robinson, Elise/0000-0003-2314-2792; McGrath, Lauren/0000-0001-6928-9656 FU National Institute of Mental Health FX Grant sponsor: National Institute of Mental Health. NR 67 TC 13 Z9 13 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC PY 2013 VL 162 IS 8 BP 779 EP 788 DI 10.1002/ajmg.b.32190 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246AE UT WOS:000326506700001 PM 24039173 ER PT J AU Derks, EM Ayub, M Chambert, K Del Favero, J Johnstone, M MacGregor, S Maclean, A McKechanie, AG McRae, AF Moran, JL Pickard, BS Purcell, S Sklar, P StCLair, DM Wray, NR Visscher, PM Blackwood, DHR AF Derks, Eske M. Ayub, Muhammad Chambert, Kimberly Del Favero, Jurgen Johnstone, Mandy MacGregor, Stuart Maclean, Alan McKechanie, Andrew G. McRae, Allan F. Moran, Jennifer L. Pickard, Benjamin S. Purcell, Shaun Sklar, Pamela StCLair, David M. Wray, Naomi R. Visscher, Peter M. Blackwood, Douglas H. R. TI A Genome Wide Survey Supports the Involvement of Large Copy Number Variants in Schizophrenia With and Without Intellectual Disability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; intellectual disability; copy number variants; genetics ID MENTAL-RETARDATION; LEARNING-DISABILITY; ASSOCIATION AB BackgroundCopy number variants (CNVs) have been shown to play a role in schizophrenia and intellectual disability. MethodsWe compared the CNV burden in 66 patients with intellectual disability and no symptoms of psychosis (ID-only) with the burden in 64 patients with intellectual disability and schizophrenia (ID+SCZ). Samples were genotyped on three plates by the Broad Institute using the Affymetrix 6.0 array. ResultsFor CNVs larger than 100kb, there was no difference in the CNV burden of ID-only and ID+SCZ. In contrast, the number of duplications larger than 1Mb was increased in ID+SCZ compared to ID-only. We detected seven large duplications and two large deletions at chromosome 15q11.2 (18.5-20.1Mb) which were all present in patients with ID+SCZ. The involvement of this region in schizophrenia was confirmed in Scottish samples from the ISC study (N=2,114; 1,130 cases and 984 controls). Finally, one of the patients with schizophrenia and low IQ carrying a duplication at 15q11.2, is a member of a previously described pedigree with multiple cases of mild intellectual disability, schizophrenia, hearing impairment, retinitis pigmentosa and cataracts. DNA samples were available for 11 members of this family and the duplication was present in all 10 affected individuals and was absent in an unaffected individual. ConclusionsDuplications at 15q11.2 (18.5-20.1Mb) are highly prevalent in a severe group of patients characterized by intellectual disability and comorbid schizophrenia. It is also associated with a phenotype that includes schizophrenia, low IQ, hearing and visual impairments resembling the spectrum of symptoms described in ciliopathies. (c) 2013 Wiley Periodicals, Inc. C1 [Derks, Eske M.] Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Derks, Eske M.] Univ Amsterdam, Dept Psychiat, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands. [Ayub, Muhammad] Queens Univ, Dept Dev Disabil, Kingston, ON K7L 3N6, Canada. [Chambert, Kimberly; Moran, Jennifer L.; Purcell, Shaun; Sklar, Pamela] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Del Favero, Jurgen] Univ Antwerp, Appl Mol Genom Unit, Dept Mol Genet, VIB, B-2020 Antwerp, Belgium. [Johnstone, Mandy; Maclean, Alan; McKechanie, Andrew G.; Blackwood, Douglas H. R.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [MacGregor, Stuart; McRae, Allan F.; Wray, Naomi R.; Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [McKechanie, Andrew G.] Univ Edinburgh, Patrick Wild Ctr, Edinburgh, Midlothian, Scotland. [Pickard, Benjamin S.] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland. [Purcell, Shaun; Sklar, Pamela] Mass Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Purcell, Shaun; Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [StCLair, David M.] Univ Aberdeen, Dept Mental Hlth, Aberdeen, Scotland. RP Derks, EM (reprint author), AMC APC, Room PA1-194,Meibergdreef 5, NL-1105 AZ Amsterdam, Netherlands. EM e.m.derks@amc.uva.nl RI Macgregor, Stuart/C-6442-2009; McRae, Allan/J-2644-2014; Wray, Naomi/C-8639-2015; Derks, Eske/A-1652-2017; OI Pickard, Benjamin/0000-0002-2374-6329; Macgregor, Stuart/0000-0001-6731-8142; McRae, Allan/0000-0001-5286-5485; Wray, Naomi/0000-0001-7421-3357; Derks, Eske/0000-0002-6292-6883; Del Favero, jurgen/0000-0002-7427-7489; Moran, Jennifer/0000-0002-5664-4716; McKechanie, Andrew/0000-0003-4273-9906; Visscher, Peter/0000-0002-2143-8760 FU Netherlands Scientific Organization [451-080-010]; Academy of Medical Sciences; Office of the Chief Scientist, the Scottish Government FX Grant sponsor: Netherlands Scientific Organization; Grant number: 451-080-010; Grant sponsor: Starter grant from the Academy of Medical Sciences; Grant sponsor: The Office of the Chief Scientist, the Scottish Government. NR 23 TC 9 Z9 9 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC PY 2013 VL 162 IS 8 BP 847 EP 854 DI 10.1002/ajmg.b.32189 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246AE UT WOS:000326506700007 PM 24115684 ER PT J AU Green, JR Yunusova, Y Kuruvilla, MS Wang, J Pattee, GL Synhorst, L Zinman, L Berry, JD AF Green, Jordan R. Yunusova, Yana Kuruvilla, Mili S. Wang, Jun Pattee, Gary L. Synhorst, Lori Zinman, Lorne Berry, James D. TI Bulbar and speech motor assessment in ALS: Challenges and future directions SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Review DE Bulbar motor; amyotrophic lateral sclerosis; oral motor; speech assessment; speech intelligibility; speaking rate; speech movement analysis ID AMYOTROPHIC-LATERAL-SCLEROSIS; FUNCTIONAL RATING-SCALE; ARTICULATORY MOVEMENTS; PERCEPTUAL EVALUATION; DYSARTHRIC PATIENTS; ACOUSTIC ANALYSIS; SPEAKING RATE; VOICE; SURVIVAL; TONGUE AB Bulbar motor deterioration due to amyotrophic lateral sclerosis (ALS) leads to the eventual impairment of speech and swallowing functions. Despite these devastating consequences, no standardized diagnostic procedure for assessing bulbar dysfunction in ALS exists and adequate objective markers of bulbar deterioration have not been identified. In this paper, we consider objective measures of speech motor function, which show promise for forming the basis of a comprehensive, quantitative bulbar motor assessment in ALS. These measures are based on the assessment of four speech subsystems: respiratory, phonatory, articulatory, and resonatory. The goal of this research is to design a non-invasive, comprehensive bulbar motor assessment instrument intended for early detection, monitoring of disease progression, and clinical trial application. Preliminary data from an ongoing study of bulbar motor decline are presented, which demonstrate the potential clinical efficacy of the speech subsystem approach. C1 [Green, Jordan R.] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02129 USA. [Yunusova, Yana] Univ Toronto, Dept Speech Language Pathol, Toronto, ON, Canada. [Yunusova, Yana; Zinman, Lorne] Sunnybrook Hlth Sci Ctr, ALS MN Clin, Toronto, ON M4N 3M5, Canada. [Kuruvilla, Mili S.; Pattee, Gary L.] Univ Nebraska, Med Ctr, Munroe Meyer Inst, Lincoln, NE 68583 USA. [Wang, Jun] Univ Texas Dallas, Callier Ctr Commun Disorders, Dallas, TX 75235 USA. [Synhorst, Lori] Univ Nebraska Lincoln, Dept Special Educ & Commun Disorders, Lincoln, NE USA. [Zinman, Lorne] Univ Toronto, Dept Neurol, Toronto, ON, Canada. [Berry, James D.] Massachusetts Gen Hosp, MDA ALS Clin, Boston, MA 02114 USA. RP Green, JR (reprint author), MGH Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM jgreen2@.mghihp.edu RI Wang, Jun/G-8572-2015; Yunusova, Yana/E-3428-2010; OI Yunusova, Yana/0000-0002-2353-2275; Kuruvilla-Dugdale, Mili/0000-0001-7900-2364 FU NIH-NIDCD; ALS Canada; Barkley Trust at the University of Nebraska-Lincoln FX This research was funded by an NIH-NIDCD grant, Bernice Ramsey Discovery Grant from ALS Canada, and the Barkley Trust at the University of Nebraska-Lincoln. The authors do not have financial and/or business in any company that may be affected by the research reported in this manuscript. The authors alone are responsible for the content and writing of the paper. NR 64 TC 12 Z9 14 U1 4 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD DEC PY 2013 VL 14 IS 7-8 BP 494 EP 500 DI 10.3109/21678421.2013.817585 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 247OA UT WOS:000326626500002 PM 23898888 ER PT J AU Brady, CB Trevor, KT Stein, TD Deykin, EY Perkins, SD Averill, JG Guilderson, L McKee, AC Renner, SW Kowall, NW AF Brady, Christopher B. Trevor, Katrina T. Stein, Thor D. Deykin, Eva Y. Perkins, Sally D. Averill, James G. Guilderson, Latease McKee, Ann C. Renner, Stephen W. Kowall, Neil W. TI The Department of Veterans Affairs Biorepository Brain Bank: A national resource for amyotrophic lateral sclerosis research SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Neuropathology; brain banking; amyotrophic lateral sclerosis; tissue banking; survival; prognostic ID MOTOR-NEURON DISEASE; CHRONIC TRAUMATIC ENCEPHALOPATHY; GULF-WAR VETERANS; GENE-EXPRESSION; LONG SURVIVAL; TISSUE PH; ALSFRS-R; QUALITY; TDP-43; PROGRESSION AB Our objective was to describe a unique national resource to facilitate amyotrophic lateral sclerosis (ALS) research, the Department of Veterans Affairs Biorepository Brain Bank. Enrolled veterans receive biannual telephone follow-up to collect clinical data until death including the ALS Functional Rating Scale-Revised (ALSFRS-R). A comprehensive post mortem examination is performed and a wide range of fixed and frozen brain and spinal cord samples are banked. As of December 2012, 240 veterans were enrolled from 47 states and post mortem tissue recoveries were performed on 100 veterans from 37 states. Average disease duration was 13.5 (range 3-45) years. Average follow-up for living subjects was 3.1 years and average ALSFRS-R score was 23.5 compared to 25.9 (12-24 months earlier), indicating slow disease progression. ALS was confirmed by post mortem examination in 97% of cases. Eighty-six percent of cases were TDP-43-positive. Additional neuropathological diagnoses include Lewy body disease (13%), frontotemporal lobar degeneration (6.3%), chronic traumatic encephalopathy with motor neuron disease (3.2%), and Alzheimer's disease (2.1%). Tissue RIN values were >= 4.0 in 88% of cases. In conclusion, the availability of high quality fixed and frozen CNS tissue from this well characterized cohort is an important resource to facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS. C1 [Brady, Christopher B.; Deykin, Eva Y.; Perkins, Sally D.; Guilderson, Latease] VA Boston Healthcare Syst, Res & Dev, Boston, MA USA. [Stein, Thor D.; McKee, Ann C.] VA Boston Healthcare Syst, Pathol, Boston, MA USA. [Kowall, Neil W.] VA Boston Healthcare Syst, Neurol Serv, Boston, MA USA. [Brady, Christopher B.; McKee, Ann C.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Stein, Thor D.; McKee, Ann C.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Brady, Christopher B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Trevor, Katrina T.; Averill, James G.; Renner, Stephen W.] Southern Arizona VA Healthcare Syst, Tucson, AZ USA. [Trevor, Katrina T.; Renner, Stephen W.] Univ Arizona, Dept Pathol, Tucson, AZ USA. RP Brady, CB (reprint author), VA Boston Healthcare Syst 151C, 150 South Huntington Ave, Boston, MA 02130 USA. EM christopher.brady2@va.gov RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Stein, Thor/0000-0001-6954-4477 FU VABBB FX We thank those who assisted with the telephone assessments, tissue recovery coordination, data scoring, entry and accuracy checks at the Boston site: Shelley Amberg, Owen Harris and Therasia Roland. We also thank those who assisted in the processing and storage of the tissue samples at the following sites: Tucson, Sean Walker; Boston/Bedford, Kerry Cormier. Additionally, we thank Marianna Bledsoe and Kristina Hill at VAORD for their assistance in the administration and funding of the VABBB, and coordination of the tissue access committee. We thank Jean Paul Vonsattel and the New York Brain Bank at Columbia University, and Anil Prasad and Louis Fiore for their support in the initiation of the VABBB. NR 41 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD DEC PY 2013 VL 14 IS 7-8 BP 591 EP 597 DI 10.3109/21678421.2013.822516 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 247OA UT WOS:000326626500016 PM 23971854 ER PT J AU Quinn, C Macklin, EA Atassi, N Bowser, R Boylan, K Cudkowicz, M Fournier, C Ladha, SS Lacomis, D Berry, J AF Quinn, Colin Macklin, Erik A. Atassi, Nazem Bowser, Robert Boylan, Kevin Cudkowicz, Merit Fournier, Christina Ladha, Shafeeq S. Lacomis, David Berry, James TI Post-lumbar puncture headache is reduced with use of atraumatic needles in ALS SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Letter ID DIAGNOSTIC LUMBAR PUNCTURE; STANDARD; TRIAL C1 [Quinn, Colin] Univ Massachusetts, Mem Med Ctr, Dept Neurol, Worcester, MA 01655 USA. [Macklin, Erik A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Atassi, Nazem; Cudkowicz, Merit; Berry, James] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA. [Bowser, Robert; Ladha, Shafeeq S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Boylan, Kevin] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Fournier, Christina] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Lacomis, David] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Quinn, C (reprint author), Univ Massachusetts, Mem Med Ctr, Dept Neurol, 55 Lake Ave North, Worcester, MA 01655 USA. EM colincq@gmail.com RI Ladha, Shafeeq/A-4948-2010; OI Ladha, Shafeeq/0000-0003-1955-4292; Macklin, Eric/0000-0003-1618-3502 NR 6 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD DEC PY 2013 VL 14 IS 7-8 BP 632 EP 634 DI 10.3109/21678421.2013.808227 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 247OA UT WOS:000326626500024 PM 23834161 ER PT J AU Tsai, AC Bangsberg, DR Kegeles, SM Katz, IT Haberer, JE Muzoora, C Kumbakumba, E Hunt, PW Martin, JN Weiser, SD AF Tsai, Alexander C. Bangsberg, David R. Kegeles, Susan M. Katz, Ingrid T. Haberer, Jessica E. Muzoora, Conrad Kumbakumba, Elias Hunt, Peter W. Martin, Jeffrey N. Weiser, Sheri D. TI Internalized Stigma, Social Distance, and Disclosure of HIV Seropositivity in Rural Uganda SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE HIV; Social stigma; Disclosure; Uganda ID AIDS-RELATED STIGMA; MEASURING TIE STRENGTH; RISK-SHARING NETWORKS; ANTIRETROVIRAL THERAPY; SEROSTATUS DISCLOSURE; POSITIVE MEN; SOUTH-AFRICA; MEDICATION ADHERENCE; FOOD INSECURITY; SELF-DISCLOSURE AB HIV is highly stigmatized, compromising both treatment and prevention in resource-limited settings. We sought to study the relationship between internalized HIV-related stigma and serostatus disclosure and to determine the extent to which this association varies with the degree of social distance. We fit multivariable Poisson regression models, with cluster-correlated robust estimates of variance, to data from 259 persons with HIV enrolled in an ongoing cohort study in rural Uganda. Persons with more internalized stigma were less likely to disclose their seropositivity. The magnitude of association increased with social distance such that the largest association was observed for public disclosures and the smallest association was observed for disclosures to sexual partners. Among persons with HIV in rural Uganda, internalized stigma was negatively associated with serostatus disclosure. The inhibiting effect of stigma was greatest for the most socially distant ties. C1 [Tsai, Alexander C.] Care of Pierce CM, Massachusetts Gen Hosp, Dept Psychiat, Div Global Psychiat, Boston, MA USA. [Tsai, Alexander C.; Bangsberg, David R.; Haberer, Jessica E.] MGH Ctr Global Hlth, Boston, MA USA. [Tsai, Alexander C.; Bangsberg, David R.; Katz, Ingrid T.; Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.; Muzoora, Conrad; Kumbakumba, Elias] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Kegeles, Susan M.; Weiser, Sheri D.] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. [Katz, Ingrid T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hunt, Peter W.; Weiser, Sheri D.] UCSF, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Martin, Jeffrey N.] UCSF Dept Epidemiol & Biostat, San Francisco, CA USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Room 1529-E3,100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI-027763, P30 AI-060354, P30 AI027763, P30 AI060354]; NIMH NIH HHS [K23 MH079713, K23 MH-079713, K23 MH-087228, K23 MH-096620, K23 MH-097667, K23 MH087228, K23 MH096620, K23 MH097667, K24 MH-087227, K24 MH087227, MH-079713-03S1, R01 MH-054907, R01 MH054907] NR 89 TC 39 Z9 41 U1 3 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2013 VL 46 IS 3 BP 285 EP 294 DI 10.1007/s12160-013-9514-6 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 248HX UT WOS:000326690300007 PM 23690283 ER PT J AU Pendergraft, WF McGrath, MM Murphy, AP Murphy, P Laliberte, KA Greene, MF Niles, JL AF Pendergraft, William F. McGrath, Martina M. Murphy, Andrew P. Murphy, Patrick Laliberte, Karen A. Greene, Michael F. Niles, John L. TI Fetal outcomes after rituximab exposure in women with autoimmune vasculitis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material DE Autoimmunity; Systemic vasculitis; B cells ID CYCLOPHOSPHAMIDE C1 [Pendergraft, William F.] Brigham & Womens Hosp BWH & Massachusetts Gen Hos, Joint Nephrol Fellowship Program, Boston, MA USA. [Pendergraft, William F.; Murphy, Andrew P.; Laliberte, Karen A.; Niles, John L.] Div Nephrol, Dept Med, MGH, Boston, MA USA. [Pendergraft, William F.; McGrath, Martina M.; Murphy, Andrew P.; Murphy, Patrick; Laliberte, Karen A.; Niles, John L.] Vasculitis & Glomerulonephritis Clin, MGH, Boston, MA USA. [McGrath, Martina M.] Div Renal, Dept Med, BWH, Boston, MA USA. [Greene, Michael F.] Dept Obstet & Gynecol, MGH, Boston, MA USA. RP Pendergraft, WF (reprint author), Massachusetts Gen Hosp MGH, Div Nephrol, Dept Med, Dr John L Niles, 151 Merrimac St, Boston, MA 02114 USA. EM jlniles@partners.org FU NIDDK NIH HHS [T32 DK007527] NR 6 TC 5 Z9 6 U1 0 U2 2 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 DEC PY 2013 VL 72 IS 12 BP 2051 EP 2053 DI 10.1136/annrheumdis-2013-203833 PG 3 WC Rheumatology SC Rheumatology GA 250TJ UT WOS:000326877500032 PM 23864238 ER PT J AU Bateman, BT Hernandez-Diaz, S Huybrechts, KF Palmsten, K Mogun, H Ecker, JL Seely, EW Fischer, MA AF Bateman, B. T. Hernandez-Diaz, S. Huybrechts, K. F. Palmsten, K. Mogun, H. Ecker, J. L. Seely, E. W. Fischer, M. A. TI Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Calcium-channel blockers; hypertensive disorders of pregnancy; postpartum haemorrhage ID HOSPITAL DISCHARGE DATA; OBSTETRIC HEMORRHAGE; PRETERM LABOR; UNITED-STATES; PREGNANCY; POPULATION; MANAGEMENT; EPIDEMIOLOGY; HYPERTENSION; PREVENTION AB ObjectiveTo determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DesignCohort study. SettingUnited States of America. Population or sampleMedicaid beneficiaries. MethodsWe identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. Main outcome measuresThe occurrence of PPH during the delivery hospitalisation. ResultsThere were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. ConclusionsThe outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH. C1 [Bateman, B. T.; Huybrechts, K. F.; Mogun, H.; Fischer, M. A.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. [Bateman, B. T.; Huybrechts, K. F.; Mogun, H.; Fischer, M. A.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, B. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Hernandez-Diaz, S.; Palmsten, K.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ecker, J. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Sci, Boston, MA USA. [Seely, E. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM bbateman@partners.org FU National Institutes of Health [T32 GM007592, K24 HL096141]; Agency for Healthcare Research and Quality (AHRQ) [R01HS018533]; National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454] FX This study was supported by the National Institutes of Health T32 GM007592 (BTB) and K24 HL096141 (EWS). The MAX pregnancy cohort was supported by the Agency for Healthcare Research and Quality (AHRQ) (Grant R01HS018533). Kristin Palmsten was supported by a Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. NR 36 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2013 VL 120 IS 13 BP 1668 EP 1677 DI 10.1111/1471-0528.12428 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 248OW UT WOS:000326712000011 PM 24020971 ER PT J AU Gallipoli, P Stobo, J Heaney, N Nicolini, FE Clark, R Wilson, G Tighe, J McLintock, L Hughes, T Michor, F Paul, J Drummond, M Holyoake, TL AF Gallipoli, Paolo Stobo, Jon Heaney, Nicholas Nicolini, Franck E. Clark, Richard Wilson, George Tighe, Jane McLintock, Lorna Hughes, Timothy Michor, Franziska Paul, James Drummond, Mark Holyoake, Tessa L. TI Safety and efficacy of pulsed imatinib with or without G-CSF versus continuous imatinib in chronic phase chronic myeloid leukaemia patients at 5 years follow-up SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE therapy; BCR-ABL1; chronic myeloid leukaemia; trials; stem cells ID STEM-CELLS; IN-VITRO; QUIESCENT C1 [Gallipoli, Paolo; Holyoake, Tessa L.] Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Glasgow, Lanark, Scotland. [Stobo, Jon; Wilson, George; Paul, James] Univ Glasgow, Canc Res UK, Clin Trials Unit, Glasgow, Lanark, Scotland. [Heaney, Nicholas; Drummond, Mark] Beatson West Scotland Canc Ctr, Dept Haematol, Glasgow, Lanark, Scotland. [Nicolini, Franck E.] Ctr Hosp Lyon Sud, Dept Haematol, Lyon, France. [Clark, Richard] Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England. [Tighe, Jane] Aberdeen Royal Infirm, Dept Haematol, Aberdeen, Scotland. [Hughes, Timothy] SA Pathol, Dept Haematol, Adelaide, SA, Australia. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Gallipoli, P (reprint author), Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Glasgow, Lanark, Scotland. EM tessa.holyoake@glasgow.ac.uk RI Holyoake, Tessa/M-3668-2015; OI Holyoake, Tessa/0000-0002-0608-6066; Gallipoli, Paolo/0000-0001-7254-2253 FU Cancer Research UK [C11074/A11008]; Chief Scientist Office; Medical Research Council [G1000288, G1000288,] NR 6 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2013 VL 163 IS 5 BP 674 EP 676 DI 10.1111/bjh.12532 PG 3 WC Hematology SC Hematology GA 249VI UT WOS:000326807400016 PM 24032404 ER PT J AU Assi, M Martin, S Wheat, LJ Hage, C Freifeld, A Avery, R Baddley, JW Vergidis, P Miller, R Andes, D Young, JAH Hammoud, K Huprikar, S McKinsey, D Myint, T Garcia-Diaz, J Esguerra, E Kwak, EJ Morris, M Mullane, KM Prakash, V Burdette, SD Sandid, M Dickter, J Ostrander, D Abou Antoun, S Kaul, DR AF Assi, Maha Martin, Stanley Wheat, L. Joseph Hage, Chadi Freifeld, Alison Avery, Robin Baddley, John W. Vergidis, Paschalis Miller, Rachel Andes, David Young, Jo-Anne H. Hammoud, Kassem Huprikar, Shirish McKinsey, David Myint, Thein Garcia-Diaz, Julia Esguerra, Eden Kwak, E. J. Morris, Michele Mullane, Kathleen M. Prakash, Vidhya Burdette, Steven D. Sandid, Mohammad Dickter, Jana Ostrander, Darin Abou Antoun, Smyrna Kaul, Daniel R. TI Histoplasmosis After Solid Organ Transplant SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE histoplasmosis; fungal infection; solid organ transplant ID RENAL-ALLOGRAFT RECIPIENTS; FUNGAL-INFECTIONS; DIAGNOSIS; UPDATE; TRANSMISSION; SENSITIVITY; GUIDELINES; SOCIETY AB Background. To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. Methods. All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. Results. One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. Conclusions. Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse. C1 [Assi, Maha; Sandid, Mohammad; Abou Antoun, Smyrna] Univ Kansas, Sch Med, Dept Internal Med, Wichita, KS 67214 USA. [Martin, Stanley] Ohio State Univ, Med Ctr, Div Infect Dis, Columbus, OH 43210 USA. [Wheat, L. Joseph] MiraVista Diagnost, Indianapolis, IN USA. [Hage, Chadi] Indiana Univ, Dept Internal Med Pulm Crit Care & Infect Dis, Indianapolis, IN 46204 USA. [Freifeld, Alison] Univ Nebraska, Med Ctr, Dept Internal Med, Div Infect Dis, Omaha, NE USA. [Avery, Robin] Johns Hopkins Univ Med, Div Infect Dis Transplant Oncol, Baltimore, MD USA. [Baddley, John W.] Univ Alabama Birmingham, Div Infect Dis, Rochester, MN USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Rochester, MN USA. [Vergidis, Paschalis] Mayo Clin, Div Clin Microbiol, Rochester, MN USA. [Miller, Rachel] Univ Iowa, Div Infect Dis, Iowa City, IA USA. [Andes, David] Univ Wisconsin, Dept Med & Med Microbiol & Immunol, Madison, WI 53706 USA. [Young, Jo-Anne H.] Univ Minnesota, Dept Med, Div Infect Dis, Minneapolis, MN 55455 USA. [Hammoud, Kassem] Univ Kansas, Med Ctr, Div Infect Dis, Kansas City, MO USA. [Huprikar, Shirish] Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY USA. [McKinsey, David] Infect Dis Associates Kansas City, Kansas City, MO USA. [Myint, Thein] Univ Kentucky, Div Infect Dis, Lexington, KY 40506 USA. [Garcia-Diaz, Julia] Ochsner Med Fdn, New Orleans, LA USA. [Esguerra, Eden] St Johns Reg Med Ctr, Joplin, MO USA. [Kwak, E. J.] Univ Pittsburgh, Div Transplant Infect Dis, Pittsburgh, PA 15260 USA. [Morris, Michele] Univ Miami, Miller Sch Med, Div Infect Dis, Coral Gables, FL 33124 USA. [Mullane, Kathleen M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Prakash, Vidhya] Wright Patterson Med Ctr, Dept Infect Dis, Dayton, OH USA. [Burdette, Steven D.] Wright State Univ, Boonshoft Sch Med, Div Infect Dis, Dayton, OH 45435 USA. [Dickter, Jana] Kaiser Permanente, Div Infect Dis, Fontana, CA USA. [Ostrander, Darin] Johns Hopkins Univ, Sch Med, Div Infect Dis, Transplant & Oncol Infect Dis Clin Res Ctr, Baltimore, MD 21205 USA. [Kaul, Daniel R.] Univ Michigan, Sch Med, Dept Internal Med, Div Infect Dis, Ann Arbor, MI USA. RP Kaul, DR (reprint author), Univ Michigan, Sch Med, 3120 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM kauld@umich.edu RI Martin, Stanley/E-3600-2011 FU National Institutes of Health [K24 A1085118] FX This work was supported by the National Institutes of Health (grant number K24 A1085118), which supplied funds for the database from which the data were extracted (Johns Hopkins University). NR 20 TC 26 Z9 28 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2013 VL 57 IS 11 BP 1542 EP 1549 DI 10.1093/cid/cit593 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 247XK UT WOS:000326657000010 PM 24046304 ER PT J AU Ribaudo, HJ Smith, KY Robbins, GK Flexner, C Haubrich, R Chen, Y Fischl, MA Schackman, BR Riddler, SA Gulick, RM AF Ribaudo, Heather J. Smith, Kimberly Y. Robbins, Gregory K. Flexner, Charles Haubrich, Richard Chen, Yun Fischl, Margaret A. Schackman, Bruce R. Riddler, Sharon A. Gulick, Roy M. TI Racial Differences in Response to Antiretroviral Therapy for HIV Infection: An AIDS Clinical Trials Group (ACTG) Study Analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV-1; antiretroviral therapy; racial disparity; virologic failure ID EFAVIRENZ-CONTAINING REGIMENS; RANDOMIZED CONTROLLED-TRIAL; SEQUENTIAL 3-DRUG REGIMENS; SELF-REPORTED ADHERENCE; INITIAL TREATMENT; HIV-1-INFECTED PATIENTS; VIROLOGICAL FAILURE; EQUAL ACCESS; CARE; DISPARITIES AB Background. In the United States, black individuals infected with human immunodeficiency virus (HIV) have higher rates of virologic failure on antiretroviral therapy (ART) and of death compared to white individuals. The cause for these disparities is uncertain. We sought to examine differences in virologic outcomes among antiretroviral-naive clinical trial participants starting randomized ART and to investigate factors to explain the differences. Methods. Individual-level data from participants initiating ART in 5 AIDS Clinical Trials Group studies were analyzed. Included studies were those conducted during 1998-2006 with a primary outcome of virologic failure. The primary outcome measure was time to virologic failure, regardless of ART changes. Results. A total of 2495 individuals (1151 black; 1344 white) were included with a median follow-up of 129 weeks. Compared to whites, blacks had an increased hazard of virologic failure (hazard ratio [HR]; 1.7; 95% confidence interval [CI], 1.4-1.9; P < .001), with no evidence of heterogeneity across regimens (P = .97); the association remained after adjustment for measured confounders (HR, 1.4; 95% CI, 1.2-1.6; P < .001). Increased hazard of virologic failure was associated with younger age, higher pretreatment HIV type 1 RNA level, lower pretreatment CD4 cell count, hepatitis C antibody, less education, and recent nonadherence to treatment. Sensitivity analyses with different endpoint definitions demonstrated similar results. Conclusions. In this analysis, blacks had a 40% higher virologic failure risk than whites that was not explained by measured confounders. The observation was consistent over a range of regimens, suggesting that the difference may be driven by social factors; however, biological factors cannot be ruled out. Further research should identify the sources of racial disparities and develop strategies to reduce them. C1 [Ribaudo, Heather J.; Chen, Yun] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Smith, Kimberly Y.] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Robbins, Gregory K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Flexner, Charles] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Flexner, Charles] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Haubrich, Richard] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Fischl, Margaret A.] Univ Miami, Miller Sch Med, Dept Med, Coral Gables, FL 33124 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Riddler, Sharon A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Gulick, Roy M.] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Ribaudo, HJ (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Dept Biostat, 651 Huntington Ave,Bagnoud Bldg,FXB 509, Boston, MA 02115 USA. EM ribaudo@sdac.harvard.edu FU National Institute of Allergy and Infectious Diseases; National Institute of Mental Health; National Institute of Dental and Craniofacial Research; National Center for Research Resources at the National Institutes of Health [UM1-AI068636, AI38858, AI51966, AI069465, AI062435, AI069432, AI69472, AI68634, AI69419, AI38855, AI069474, AI069434, AI27670, AI36214, AI064086, UL1 RR024996] FX This work was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Dental and Craniofacial Research, and the National Center for Research Resources at the National Institutes of Health (grant numbers UM1-AI068636, AI38858, AI51966, AI069465, AI062435, AI069432, AI69472, AI68634, AI69419, AI38855, AI069474, AI069434, AI27670, AI36214, AI064086, and UL1 RR024996). NR 39 TC 15 Z9 15 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2013 VL 57 IS 11 BP 1607 EP 1617 DI 10.1093/cid/cit595 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 247XK UT WOS:000326657000019 PM 24046302 ER PT J AU Leonard, DA Kurtz, JM Cetrulo, CL AF Leonard, David A. Kurtz, Josef M. Cetrulo, Curtis L., Jr. TI Vascularized composite allotransplantation: towards tolerance and the importance of skin-specific immunobiology SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE immunosuppression; skin immunobiology; tolerance; transplant; vascularized composite allotransplantation ID REGULATORY T-CELLS; EPIDERMAL LANGERHANS CELLS; MAINTAIN IMMUNE HOMEOSTASIS; DERMAL DENDRITIC CELLS; RECONSTRUCTIVE TRANSPLANTATION; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; ALLOGRAFT TOLERANCE; MINIATURE SWINE; MIXED CHIMERISM AB Purpose of reviewVascularized composite allotransplantation (VCA) is increasingly utilized in the restoration of complex injuries and tissue loss. Acute skin-targeted rejection episodes are common and concerns remain regarding the risks of conventional immunosuppression. We review current immunosuppressive regimens for VCA, progress with immunomodulatory and tolerance protocols, and highlight recent advances in cutaneous immunobiology which will have significant implications for future development in the field.Recent findingsAdvances in induction protocols have demonstrated effective prevention of early graft loss in hand transplantation, although long-term outcomes are still pending. Furthermore, recent findings in leukocyte populations within the skin and their mechanisms of communication reveal that considerable numbers of resident T-effector memory cells, including a T-regulatory subset, exist, and that epidermal Langerhans' cells communicate with these cells, mediating both immunity and tolerance to maintain skin homeostasis.SummaryThe majority of VCA centers utilize antibody-mediated induction, followed by double or triple-agent maintenance immunosuppression. A clinical trial of a minimal-immunosuppression protocol based on bone marrow infusion reports encouraging interim results, but long-term follow-up will be required. Skin remains the primary target of rejection in VCA. New data demonstrate extensive T-cell memory resident in skin, and complex interactions between these cells and epidermal Langerhans' cells will have implications for VCA rejection and tolerance, and warrant further investigation in the allogeneic setting. C1 [Leonard, David A.; Kurtz, Josef M.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Vascularized Composite, Boston, MA USA. [Kurtz, Josef M.] Emmanuel Coll, Dept Biol, Boston, MA USA. RP Cetrulo, CL (reprint author), Transplantat Biol Res Ctr, Vascularized Composite Allotransplantat Lab, MGH East Bldg 149-9019,13th St, Boston, MA 02129 USA. EM ccetrulo@partners.org FU Melina Nakos Foundation; Musculoskeletal Transplant Foundation; American Society for Transplantation; American Society of Transplant Surgeons FX The authors would like to acknowledge funding support from the Melina Nakos Foundation, the Musculoskeletal Transplant Foundation, the American Society for Transplantation and the American Society of Transplant Surgeons. NR 51 TC 7 Z9 7 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2013 VL 18 IS 6 BP 645 EP 651 DI 10.1097/MOT.0000000000000022 PG 7 WC Transplantation SC Transplantation GA 251QY UT WOS:000326946400004 PM 24126805 ER PT J AU Farhat, NA Faquin, WC Sadow, PM AF Farhat, Nada A. Faquin, William C. Sadow, Peter M. TI Primary Mucoepidermoid Carcinoma of the Thyroid Gland: A Report of Three Cases and Review of the Literature SO ENDOCRINE PATHOLOGY LA English DT Review DE Thyroid Carcinoma; Mucoepidermoid Carcinoma; Thyroid Cancer ID COMPOSITE FOLLICULAR VARIANT; SOLID CELL NESTS; PAPILLARY CARCINOMA; EOSINOPHILIA; FEATURES; TUMOR AB Mucoepidermoid carcinoma is the most common salivary gland malignancy and it may arise anywhere that salivary tissue is present. Mucoepidermoid carcinoma has been reported to arise de novo within the thyroid gland, and here, we describe three cases of primary mucoepidermoid carcinoma of the thyroid, including clinical presentation, diagnostic evaluation, and clinical follow-up, along with a discussion of tumor origin and a review of the literature. C1 [Farhat, Nada A.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Faquin, William C.; Sadow, Peter M.] WRN219 Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Faquin, William C.; Sadow, Peter M.] Harvard Univ, Sch Med, Boston, MA USA. RP Sadow, PM (reprint author), WRN219 Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM psadow@partners.org NR 34 TC 3 Z9 3 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 EI 1559-0097 J9 ENDOCR PATHOL JI Endocr. Pathol. PD DEC PY 2013 VL 24 IS 4 BP 229 EP 233 DI 10.1007/s12022-013-9267-6 PG 5 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 248IQ UT WOS:000326692900009 PM 24096806 ER PT J AU Pusztaszeri, MP Sadow, PM Faquin, WC AF Pusztaszeri, Marc P. Sadow, Peter M. Faquin, William C. TI Images in Endocrine Pathology: Psammomatoid Calcifications in Oncocytic Neoplasms of the Thyroid, a Potential Pitfall for Papillary Carcinoma SO ENDOCRINE PATHOLOGY LA English DT Editorial Material ID BODIES C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Sadow, Peter M.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadow, Peter M.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 8 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 EI 1559-0097 J9 ENDOCR PATHOL JI Endocr. Pathol. PD DEC PY 2013 VL 24 IS 4 BP 246 EP 247 DI 10.1007/s12022-013-9242-2 PG 2 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 248IQ UT WOS:000326692900012 PM 23589120 ER PT J AU Calcagno, C Ramachandran, S Izquierdo-Garcia, D Mani, V Millon, A Rosenbaum, D Tawakol, A Woodward, M Bucerius, J Moshier, E Godbold, J Kallend, D Farkouh, ME Fuster, V Rudd, JHF Fayad, ZA AF Calcagno, Claudia Ramachandran, Sarayu Izquierdo-Garcia, David Mani, Venkatesh Millon, Antoine Rosenbaum, David Tawakol, Ahmed Woodward, Mark Bucerius, Jan Moshier, Erin Godbold, James Kallend, David Farkouh, Michael E. Fuster, Valentin Rudd, James H. F. Fayad, Zahi A. TI The complementary roles of dynamic contrast-enhanced MRI and F-18-fluorodeoxyglucose PET/CT for imaging of carotid atherosclerosis SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE DCE-MRI; PET/CT; Atherosclerosis.; Inflammation; Neovascularization ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-RISK PLAQUE; NONINVASIVE ASSESSMENT; KINETIC-PARAMETERS; DAL-PLAQUE; INFLAMMATION; HYPOXIA; MACROPHAGES; RABBITS; ATHEROTHROMBOSIS AB Purpose Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and F-18-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473). Methods The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and F-18-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and F-18-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model. Results We found a significant inverse relationship between several perfusion indices by DCE-MRI and F-18-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and F-18-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or F-18-FDG PET metrics. Conclusion In this study we observed a significant, weak inverse relationship between inflammation measured as F-18-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. F-18-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events. C1 [Calcagno, Claudia; Ramachandran, Sarayu; Mani, Venkatesh; Millon, Antoine; Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Calcagno, Claudia; Ramachandran, Sarayu; Mani, Venkatesh; Millon, Antoine; Fayad, Zahi A.] Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. [Izquierdo-Garcia, David] Harvard Univ MIT Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Rosenbaum, David] Hop La Pitie Salpetriere, Paris, France. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Woodward, Mark] Univ Sydney, George Inst, Sydney, NSW 2006, Australia. [Bucerius, Jan] Maastricht Univ, Med Ctr, Dept Nucl Med, Maastricht, Netherlands. [Bucerius, Jan] Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. [Bucerius, Jan] Rhein Westfal TH Aachen, Dept Nucl Med, Aachen, Germany. [Moshier, Erin; Godbold, James] Mt Sinai Sch Med, Biostat Shared Res Facil, New York, NY 10029 USA. [Kallend, David] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Farkouh, Michael E.; Fuster, Valentin; Fayad, Zahi A.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA. [Farkouh, Michael E.] Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, Michael E.] Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Fuster, Valentin] CNIC, Madrid, Spain. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. RP Fayad, ZA (reprint author), Mt Sinai Sch Med, Translat & Mol Imaging Inst, 1 Gustave L Levy Pl,Box 1234, New York, NY 10029 USA. EM zahi.fayad@mssm.edu RI Mani, Venkatesh/B-8939-2011; Woodward, Mark/D-8492-2015; Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Rudd, James/0000-0003-2243-3117; Mani, Venkatesh/0000-0002-0432-2918 FU National Institutes of Health [NIH/NHLBI R01 HL071021, NIH/NHLBI R01 HL078667, NIH/NCRR UL1RR029887]; F. Hoffmann-La Roche Ltd; National Heart Lung and Blood Institute [NIH/NHLBI R01 HL071021, NIH/NHLBI R01 HL078667, NIH/NCRR UL1RR029887] FX F. Hoffmann-La Roche Ltd funded the dal-PLAQUE study and provided third-party editorial support, through Prime Healthcare Ltd, for the preparation of the manuscript. C.C. acknowledges grant and research support from the National Institutes of Health and National Heart Lung and Blood Institute (NIH/NHLBI R01 HL071021, NIH/NHLBI R01 HL078667 and NIH/NCRR UL1RR029887). NR 41 TC 20 Z9 22 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD DEC PY 2013 VL 40 IS 12 BP 1884 EP 1893 DI 10.1007/s00259-013-2518-4 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 248HZ UT WOS:000326690600013 PM 23942908 ER PT J AU Vachha, B Brodoefel, H Wilcox, C Hackney, DB Moonis, G AF Vachha, Behroze Brodoefel, Harald Wilcox, Carol Hackney, David B. Moonis, Gul TI Radiation dose reduction in soft tissue neck CT using adaptive statistical iterative reconstruction (ASIR) SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Radiation dose; ASIR; Neck; CT ID FILTERED BACK-PROJECTION; IMAGE QUALITY; PROTOCOLS AB Purpose: To compare objective and subjective image quality in neck CT images acquired at different tube current-time products (275 mA s and 340 mA s) and reconstructed with filtered-back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Materials and methods: HIPAA-compliant study with IRB approval and waiver of informed consent. 66 consecutive patients were randomly assigned to undergo contrast-enhanced neck CT at a standard tubecurrent-time-product (340 mA s; n=33) or reduced tube-current-time-product (275 mA s, n= 33). Data sets were reconstructed with FBP and 2 levels (30%, 40%) of ASIR-FBP blending at 340 mA s and 275 mA s. Two neuroradiologists assessed subjective image quality in a blinded and randomized manner. Volume CT dose index (CTDIvol), dose-length-product (DLP), effective dose, and objective image noise were recorded. Signal-to-noise ratio (SNR) was computed as mean attenuation in a region of interest in the sternocleidomastoid muscle divided by image noise. Results: Compared with FBP, ASIR resulted in a reduction of image noise at both 340 mA s and 275 mA s. Reduction of tube current from 340 mA s to 275 mA s resulted in an increase in mean objective image noise (p= 0.02) and a decrease in SNR (p= 0.03) when images were reconstructed with FBP. However, when the 275 mA s images were reconstructed using ASIR, the mean objective image noise and SNR were similar to those of the standard 340 mA s CT images reconstructed with FBP (p> 0.05). Subjective image noise was ranked by both raters as either average or less-than-average irrespective of the tube current and iterative reconstruction technique. Conclusion: Adapting ASIR into neck CT protocols reduced effective dose by 17% without compromising image quality. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Vachha, Behroze] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. [Brodoefel, Harald; Wilcox, Carol; Hackney, David B.; Moonis, Gul] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Vachha, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Div, 55 Fruit St, Boston, MA 02114 USA. EM bvachha@partners.org RI Hackney, David/A-5337-2010 NR 24 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD DEC PY 2013 VL 82 IS 12 BP 2222 EP 2226 DI 10.1016/j.ejrad.2011.08.014 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 248GB UT WOS:000326683100052 PM 24016832 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Personalizing the Management of Men with Intermediate-risk Prostate Cancer SO EUROPEAN UROLOGY LA English DT Editorial Material ID GLEASON SCORE; DISEASE; MORTALITY; BIOPSIES C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM adamico@partners.org NR 10 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD DEC PY 2013 VL 64 IS 6 BP 903 EP 904 DI 10.1016/j.eururo.2013.03.038 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 248EY UT WOS:000326678100006 PM 23545122 ER PT J AU Bergman, J Litwin, MS AF Bergman, Jonathan Litwin, Mark S. TI Mapping a New Truth SO EUROPEAN UROLOGY LA English DT Editorial Material ID PROSTATE-CANCER; LIFE LOST; OUTCOMES C1 [Bergman, Jonathan; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90024 USA. [Bergman, Jonathan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bergman, Jonathan] Univ Calif Los Angeles, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA 90024 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, 924 Westwood Blvd,Suite 1000, Los Angeles, CA 90024 USA. EM jbergman@mednet.ucla.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD DEC PY 2013 VL 64 IS 6 BP 929 EP 930 DI 10.1016/j.eururo.2013.03.048 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 248EY UT WOS:000326678100011 PM 23597588 ER PT J AU Eikermann, M Latronico, N AF Eikermann, Matthias Latronico, Nicola TI What is new in prevention of muscle weakness in critically ill patients? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; REHABILITATION; INJURY; UNIT; ICU C1 [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Eikermann, Matthias] Essen Duisburg Univ, Klin Anaesthesiol & Intens Med, Essen, Germany. [Latronico, Nicola] Univ Brescia, Dept Anesthesia & Crit Care Med, Brescia, Italy. [Latronico, Nicola] Spedali Civil Brescia, I-25125 Brescia, Italy. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02115 USA. EM meikermann@partners.org RI LATRONICO, Nicola/F-1557-2010 OI LATRONICO, Nicola/0000-0002-2521-5871 NR 19 TC 13 Z9 13 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2013 VL 39 IS 12 BP 2200 EP 2203 DI 10.1007/s00134-013-3132-4 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 248JG UT WOS:000326694900016 PM 24154675 ER PT J AU Carrion, IV Nedjat-Haiem, FR Marquez, DX AF Carrion, Iraida V. Nedjat-Haiem, Frances R. Marquez, David X. TI Examining Cultural Factors that Influence Treatment Decisions: a Pilot Study of Latino Men with Cancer SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Cancer; Latino men; Treatment decisions; Cultural beliefs ID PROSTATE-CANCER; HEALTH DISPARITIES; CARE; LIFE; RACE/ETHNICITY; ACCULTURATION; INFORMATION; DIAGNOSIS; WOMEN; RACE AB The objective of this study was to explore beliefs and treatment decisions of foreign-born Latino men from Cuba, Mexico, Colombia, and Venezuela, who have been diagnosed with cancer and who live in Central Florida, USA. Experiences related to knowledge of diagnosis, treatment decisions, communication with health providers, family involvement, and advance care planning (ACP) discussions following the diagnosis of cancer are central to this study. This study used qualitative in-depth semi-structured interviews and thematic analysis. The interviews were conducted with 15 Latino men who have been diagnosed with cancer within the past 5 years and who reside in the community. The interviews were conducted and transcribed in Spanish and then translated into English. The median age was 55.4 years. Nine Latino men had prostate cancer, two had brain cancer, two had colorectal cancer, and two had lung cancer. Emerging themes involved the suddenness of the diagnosis, fear of dying, expectations of diagnosis-related communication, reliance on physicians for treatment decisions, limited information pertaining to ACP, family support, and role changes. Latino men's limited knowledge of cancer diagnosis and treatment options coupled with their fear led them to immediately believe that they were going to die. Knowledge gaps regarding diagnosis-related communication, treatment decisions, and ACP varied among the men. The forthright diagnosis communication and the expectation to engage in decision making are contrary to Latinos men's beliefs of reliance on health providers decisions. The findings contribute to understanding Latino men's beliefs about a cancer diagnosis and treatment decisions. C1 [Carrion, Iraida V.] Univ S Florida, Sch Social Work, Tampa, FL 33612 USA. [Nedjat-Haiem, Frances R.] Vet Affairs Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provide Beh, Los Angeles, CA USA. [Nedjat-Haiem, Frances R.] USC Sch Social Work, Los Angeles, CA USA. [Marquez, David X.] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL 60612 USA. RP Carrion, IV (reprint author), Univ S Florida, Sch Social Work, 13301 Bruce B Downs Blvd MHC 1438, Tampa, FL 33612 USA. EM icarrion@usf.edu; nedjatha@gmail.com; marquezd@uic.edu OI Carrion, Iraida/0000-0003-4076-6644 FU Division of Population Sciences; H. Lee Moffitt Cancer Center; Research Institute and the Division for Equal Health at University of South Florida in Tampa, Florida FX The authors thank Dr. Lee Green, Dr. Richard Roetzheim, the Division of Population Sciences, H. Lee Moffitt Cancer Center and Research Institute and the Division for Equal Health at University of South Florida in Tampa, Florida for their support. They also honor the Latino men who generously participated in the study and thank Ingrid Asmar for all of her contributions as research assistant. NR 39 TC 9 Z9 9 U1 3 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD DEC PY 2013 VL 28 IS 4 BP 729 EP 737 DI 10.1007/s13187-013-0522-9 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 242ZQ UT WOS:000326286200021 PM 23881820 ER PT J AU Vij, A Kowalkowski, MA Hart, T Goltz, HH Hoffman, DJ Knight, SJ Caroll, PR Latini, DM AF Vij, Alok Kowalkowski, Marc A. Hart, Tae Goltz, Heather Honore Hoffman, David J. Knight, Sara J. Caroll, Peter R. Latini, David M. TI Symptom Management Strategies for Men with Early-Stage Prostate Cancer: Results from the Prostate Cancer Patient Education Program (PC (PEP) ) SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Prostate cancer; Symptom management; Quality of life; Survivorship ID QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; SEXUAL REHABILITATION; OUTCOMES; INTERVENTION; CARCINOMA; PATTERNS; NEEDS AB While the literature on prostate cancer health-related quality of life has grown extensively, little is known about symptom management strategies used by men to manage treatment-related side effects and the effectiveness of those strategies. We collected 628 symptom management reports from 98 men treated for localized prostate cancer. Participants were recruited from email lists and a prostate cancer clinic in Northern California. Data were collected using the Critical Incident Technique. Symptom management reports were assigned to categories of urinary, sexual, bowel, mental health, systemic, or "other." We calculated descriptive statistics by symptom type and management strategy effectiveness. The most common symptoms were urinary (26 %) and sexual (23 %). Participants' symptom management strategies varied widely, from medical and surgical interventions (20 %) to behavioral strategies (11 %) to diet and lifestyle interventions (12 %). The effectiveness of symptom management strategies varied, with sexual symptoms being managed effectively only 47 % of the time to mental health symptom management strategies considered effective 89 % of the time. Doing nothing was a commonly reported (15 %) response to symptoms and was effective only 14 % of the time. Men report the least effectiveness in symptom management for sexual dysfunction after prostate cancer treatment. Including men's experience with managing treatment side effects may be an important way to improve survivorship programs and make them more acceptable to men. More work is needed to find out why men frequently do nothing in response to symptoms when effective solutions exist and how providers can successfully engage such men. C1 [Vij, Alok; Kowalkowski, Marc A.; Goltz, Heather Honore] Baylor Coll Med, Houston, TX 77030 USA. [Kowalkowski, Marc A.; Goltz, Heather Honore] Michael E DeBakey VA Med Ctr, VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Hart, Tae] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Hoffman, David J.] Univ Texas Southwestern, Sch Med, Dallas, TX USA. [Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.; Caroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Knight, Sara J.; Caroll, Peter R.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Latini, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Latini, David M.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. RP Latini, DM (reprint author), Michael E DeBakey VA Med Ctr, Mental Hlth Care Line 116,2002 Holcombe Blvd, Houston, TX 77030 USA. EM latini@bcm.edu RI Hart, Stacey/E-4819-2011; OI Kowalkowski, Marc/0000-0003-2624-4209; Goltz, Heather/0000-0002-2875-7764; Latini, David/0000-0002-6161-4861 FU National Cancer Institute [R03 CA101586]; Health Services Research & Development Center of Excellence [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical Center; American Cancer Society [06-083-01-CPPB] FX This work was funded by grant R03 CA101586 from the National Cancer Institute to David M. Latini. This material is partly the result of work supported with resources and the use of facilities at the Health Services Research & Development Center of Excellence (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center. Dr. Latini is supported by Mentored Research Scholar Grant 06-083-01-CPPB from the American Cancer Society. We also would like acknowledge the assistance of Sarah Howard Joost in recruiting participants, David V. Flores and Thomas D. McNeese II in data management and coding, and Sonora Hudson, MA, in editing the manuscript. Sandra R. Wilson, PhD, provided her expertise with the Critical Incident Technique to the study team. The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs/Baylor College of Medicine. NR 32 TC 2 Z9 2 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD DEC PY 2013 VL 28 IS 4 BP 755 EP 761 DI 10.1007/s13187-013-0538-1 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 242ZQ UT WOS:000326286200025 PM 23996206 ER PT J AU Wilson, R Sethi, S Anzueto, A Miravitlles, M AF Wilson, Robert Sethi, Sanjay Anzueto, Antonio Miravitlles, Marc TI Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease SO JOURNAL OF INFECTION LA English DT Review DE Acute bacterial exacerbation of COPD; Chronic inflammation; Inhalation therapy; Long-term outcome; Antibiotics; Fluoroquinolones; Macrolides ID ACUTE BACTERIAL EXACERBATIONS; PSEUDOMONAS-AERUGINOSA INFECTION; CYSTIC FIBROSIS BRONCHIECTASIS; MECHANICALLY VENTILATED PATIENTS; RANDOMIZED CONTROLLED-TRIAL; CHRONIC BRONCHIAL INFECTION; COURSE 5-DAY MOXIFLOXACIN; INHALED AZTREONAM LYSINE; INHALATION SOLUTION AZLI; PLACEBO-CONTROLLED TRIAL AB Acute exacerbations (AE) can be recurrent problems for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) increasing morbidity and mortality. Evidence suggests that >= 50% of acute exacerbations involve bacteria requiring treatment with an antibiotic which should have high activity against the causative pathogens. However, sputum analysis is not a pre-requisite for antibiotic prescription in outpatients as results are delayed and patients are likely to be colonised with bacteria in the stable state. Clinicians rely on the clinical symptoms, sputum appearance and the patient's medical history to decide if an AE-COPD should be treated with antibiotics. This article reviews the available data of antibiotic trials in AE-COPD. Management of frequent exacerbators is particularly challenging for physicians. This may include antibiotic prophylaxis, especially macrolides because of anti-inflammatory properties; though successful in reducing exacerbations, concerns about resistance development remain. Inhalation of antibiotics achieves high local concentrations and minimal systemic exposure; therefore, it may represent an attractive alternative for antibiotic prophylaxis in certain COPD patients. Inhaled antibiotic prophylaxis has been successfully used in other respiratory conditions such as non-cystic fibrosis bronchiectasis which itself might be present in COPD patients who have chronic bacterial infection, particularly with Pseudomonas aeruginosa. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Wilson, Robert] Royal Brompton Hosp, Host Def Unit, London SW3 6NP, England. [Sethi, Sanjay] SUNY Buffalo, Div Pulm Crit Care & Sleep Med, Buffalo, NY 14260 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Miravitlles, Marc] Hosp Univ Vall dHebron, Ciber Enfermedades Resp CIBERES, Dept Pneumol, Barcelona, Spain. RP Wilson, R (reprint author), Royal Brompton Hosp, Host Def Unit, Sydney St, London SW3 6NP, England. EM r.wilson@rbht.nhs.uk OI Miravitlles, Marc/0000-0002-9850-9520 FU University of Texas Health Science Center (San Antonio, TX, USA); GlaxoSmithKline; Bayer; Lilly; National Institutes of Health; Boehringer Ingelheim; Pfizer; AstraZeneca; Bayer Schering; Novartis; Talecris-Grifols; Takeda-Nycomed; Merck, Sharp Dohme; GSK; Almirall; Forest; Mpex; Sanofi-Aventis FX Antonio Anzueto has participated as a speaker in scientific meetings or courses organised and financed by various pharmaceutical companies including: AstraZeneca, Boehringer Ingelheim, Bayer, Pfizer, GlaxoSmithKline, Sanofi-Aventis. A. Anzueto has been a consultant for AstraZeneca, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Sanofi-Aventis, Bayer. He has also been the principal investigator for research grants for the University of Texas Health Science Center (San Antonio, TX, USA) and was paid for participating in a multicentre clinical trial sponsored by: GlaxoSmithKline, Bayer, Lilly and National Institutes of Health. Marc Miravitlles has received speaker fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Bayer Schering, Novartis, Talecris-Grifols, Takeda-Nycomed, Merck, Sharp & Dohme and Novartis, and consulting fees from Boehringer Ingelheim, Pfizer, GSK, AstraZeneca, Bayer Schering, Novartis, Almirall, Merck, Sharp & Dohme, Talecris-Grifols and Takeda-Nycomed. Sanjay Sethi has received institutional research funds from AstraZeneca and GlaxoSmithKline. He has received lecture and/or consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Forest, Pfizer, GlaxoSmithKline, Mpex, and Novartis. Robert Wilson has received honoraria for taking part in advisory boards and presenting at meetings from Almirall, Aperion Advisors LLC, AstraZeneca, Athena Medical PR, Bayer HealthCare, Forest Laboratories (Bronchiectasis symposium), Genactis Ltd, Opticom International, Penn Technology Partnership, Resolutions Group, Rivervest, Transave, VacZine Analytics and Wyeth Pharmaceuticals. NR 124 TC 14 Z9 14 U1 3 U2 24 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD DEC PY 2013 VL 67 IS 6 BP 497 EP 515 DI 10.1016/j.jinf.2013.08.010 PG 19 WC Infectious Diseases SC Infectious Diseases GA 247BK UT WOS:000326588400001 PM 23973659 ER PT J AU Ryan, ET AF Ryan, Edward T. TI The Intestinal Pathobiome: Its Reality and Consequences Among Infants and Young Children in Resource-Limited Settings SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE Pathobiome; enteric pathogens; infants, diarrhea; intestinal infection; resource-limited C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Jackson 504, Boston, MA 02114 USA. EM etryan@partners.org NR 1 TC 8 Z9 8 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2013 VL 208 IS 11 BP 1732 EP 1733 DI 10.1093/infdis/jit509 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 247WQ UT WOS:000326654300002 PM 24041794 ER PT J AU Fitch, KV Srinivasa, S Abbara, S Burdo, TH Williams, KC Eneh, P Lo, J Grinspoon, SK AF Fitch, Kathleen V. Srinivasa, Suman Abbara, Suhny Burdo, Tricia H. Williams, Kenneth C. Eneh, Peace Lo, Janet Grinspoon, Steven K. TI Noncalcified Coronary Atherosclerotic Plaque and Immune Activation in HIV-Infected Women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; atherosclerosis; cardiovascular disease; non-calcified coronary plaque; immune activation; age ID CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; COMPUTED-TOMOGRAPHY; FLOW-CYTOMETRY; CAROTID-ARTERY; SOLUBLE CD163; HEART-DISEASE; RISK-FACTORS; ASSOCIATION; INFLAMMATION AB Background. Little is known about coronary plaque in human immunodeficiency virus (HIV)-infected women. Methods. Sixty HIV-infected and 30 non-HIV-infected women without symptoms or history of cardiovascular disease were recruited to assess coronary plaque with coronary computed tomographic angiography and immune activation. Data from 102 HIV-infected men and 41 non-HIV-infected male controls were compared. Results. HIV-infected women demonstrated significantly higher percentages of segments with noncalcified plaque (mean +/- SD, 74% +/- 28% vs 23% +/- 39% compared to female control subjects; median [interquartile range], 75% [63%-100%] vs 0% [0%-56%]; P = .007) and more segments with noncalcified plaque (mean +/- SD, 0.92 +/- 1.48 vs 0.40 +/- 1.44; median [interquartile range], 0 [0-2] vs 0 [0-0]; P = .04). Immune activation parameters, including soluble CD163 (sCD163; P = .006), CXCL10 (P = .002), and percentages of CD14(+)CD16(+) monocytes (P = .008), were higher in HIV-infected women than in female control subjects, but no differences were seen in general inflammatory markers. Among HIV-infected women with noncalcified coronary plaque, sCD163 levels were significantly higher than in HIV-infected women without noncalcified plaque (P = .04). In multivariate modeling for sCD163 levels among male and female subjects, significant effects of HIV (P < .0001), age (P = .002), and sex (P = .0002) were seen. Conclusions. Young, asymptomatic, HIV-infected women, demonstrate increased noncalcified coronary plaque and increased immune activation, particularly monocyte activation. Independent effects of sex, HIV status, and aging on immune activation may contribute to cardiovascular disease in this population. C1 [Fitch, Kathleen V.; Srinivasa, Suman; Eneh, Peace; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiovasc Imaging Sect, Boston, MA 02114 USA. [Abbara, Suhny] Harvard Univ, Sch Med, Boston, MA USA. [Burdo, Tricia H.; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU Bristol Myers Squibb; National Institutes of Health [K24 DK064545, R01 HL095123-04, K23 HL092792, NS37654, NS40237]; National Institutes of Health (NIH) [M01-RR-01066, 1 ULI RR025758-01]; National Institutes of Health (National Center for Research Resources) [P30 DK40561] FX This work was supported by Bristol Myers Squibb and the National Institutes of Health (grants K24 DK064545 and R01 HL095123-04 to S. K. G., K23 HL092792 to J. L., NS37654 and NS40237 to K.C.W; NIH M01-RR-01066 and 1 ULI RR025758-01 to the Clinical Translational and Science Center and National Center for Research Resources; and P30 DK40561 to the Nutrition Obesity Research Center at Harvard). Funding sources had no role in the design of the study, data analysis, or the writing of the manuscript. NR 25 TC 55 Z9 55 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2013 VL 208 IS 11 BP 1737 EP 1746 DI 10.1093/infdis/jit508 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 247WQ UT WOS:000326654300004 PM 24041790 ER PT J AU Alves, CP Moraes, MH Sousa, JF Pontes, CLS Ramao, A Yokoyama, S Trindade, DM Fisher, DE Espreafico, EM AF Alves, Cleidson P. Moraes, Milene H. Sousa, Josane F. Pontes, Carmen Lucia S. Ramao, Anelisa Yokoyama, Satoru Trindade, Daniel M. Fisher, David E. Espreafico, Enilza M. TI Myosin-Va Contributes to Manifestation of Malignant-Related Properties in Melanoma Cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID TUMOR MICROENVIRONMENT; CANCER; APOPTOSIS; BMF C1 [Alves, Cleidson P.; Moraes, Milene H.; Sousa, Josane F.; Pontes, Carmen Lucia S.; Ramao, Anelisa; Trindade, Daniel M.; Espreafico, Enilza M.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol & Pathogen Bioagents, BR-14049 Ribeirao Preto, SP, Brazil. [Yokoyama, Satoru] Toyama Univ, Inst Nat Med, Div Pathogen Biochem, Toyama 930, Japan. [Yokoyama, Satoru; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Cutaneous Biol Res Ctr, Boston, MA 02115 USA. RP Alves, CP (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol & Pathogen Bioagents, BR-14049 Ribeirao Preto, SP, Brazil. EM emesprea@fmrp.usp.br RI Espreafico, Enilza/O-3053-2016; OI Maragno Trindade, Daniel/0000-0002-8005-8784 FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 19 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2013 VL 133 IS 12 BP 2809 EP 2812 DI 10.1038/jid.2013.218 PG 4 WC Dermatology SC Dermatology GA 252OE UT WOS:000327015400029 PM 23652798 ER PT J AU Gros, DF Morland, LA Greene, CJ Acierno, R Strachan, M Egede, LE Tuerk, PW Myrick, H Frueh, BC AF Gros, Daniel F. Morland, Leslie A. Greene, Carolyn J. Acierno, Ron Strachan, Martha Egede, Leonard E. Tuerk, Peter W. Myrick, Hugh Frueh, B. Christopher TI Delivery of Evidence-Based Psychotherapy via Video Telehealth SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Psychotherapy; Evidence-based; Telehealth; Telemental health; Telepsychology; Telepsychiatry ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; HOME-BASED TELEHEALTH; FACE-TO-FACE; MENTAL-HEALTH RESEARCH; TELEMENTAL HEALTH; NONINFERIORITY TRIAL; EXPOSURE THERAPY; RANDOMIZED-TRIAL; SERVICE DELIVERY AB There has been increasing interest in using video telehealth to deliver evidence-based psychotherapies (EBPs). Telehealth may have numerous advantages over standard in-person care, including decreasing patients' and providers' costs and increasing system coverage area. However, little is known regarding the effectiveness of EBPs via video telehealth. This review had two goals, including a review of the existing literature and ongoing research on using video telehealth technologies to deliver EBPs as well as an informal survey of telehealth experts to discuss the special considerations and challenges present in adapting practices to video telehealth. Together, findings suggest that telehealth practices could represent an important component of the future of psychotherapy and clinical practice, especially in dissemination and implementation of EBPs in traditionally underserved areas and populations. C1 [Gros, Daniel F.; Acierno, Ron; Strachan, Martha; Egede, Leonard E.; Tuerk, Peter W.; Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.; Acierno, Ron; Strachan, Martha; Egede, Leonard E.; Tuerk, Peter W.; Myrick, Hugh] Med Univ S Carolina, Charleston, SC 29425 USA. [Morland, Leslie A.] Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI USA. [Greene, Carolyn J.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Gros, Daniel F.] Ralph H Johnson VAMC, Charleston, SC 29401 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116,109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 62 TC 28 Z9 28 U1 1 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2013 VL 35 IS 4 BP 506 EP 521 DI 10.1007/s10862-013-9363-4 PG 16 WC Psychology, Clinical SC Psychology GA 248WE UT WOS:000326735400009 ER PT J AU Gros, DF Gros, KS Acierno, R Frueh, BC Morland, LA AF Gros, Daniel F. Gros, Kirstin Stauffacher Acierno, Ron Frueh, B. Christopher Morland, Leslie A. TI Relation Between Treatment Satisfaction and Treatment Outcome in Veterans with Posttraumatic Stress Disorder SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Charleston Psychiatric Outpatient Satisfaction Scale; CPOSS; Treatmentsatisfaction; PTSD; Psychometrics ID PSYCHIATRIC-DISORDERS; HEALTH-CARE; PTSD; DEPRESSION; EXPOSURE; PREDICTORS; SERVICES; THERAPY; SCALE AB Existing measures of patient treatment satisfaction are largely characterized by a lack of psychometric evaluation, varied definitions across studies, and small numbers of items. The present study evaluated a patient treatment satisfaction questionnaire specifically designed for psychiatric outpatient treatment satisfaction, the Charleston Psychiatric Outpatient Satisfaction Scale (CPOSS), to extend previous findings by examining: 1) the psychometric properties of the CPOSS and the common domains within patient treatment satisfaction, and 2) the preliminary relations between the CPOSS and treatment outcome during exposure therapy in patients with posttraumatic stress disorder (PTSD). The present investigation included two studies. The first involved 170 combat veterans with PTSD who completed brief psychotherapy, and whose post-treatment CPOSS scores were used for the factor analytic investigations. The second study involved 63 combat veterans with PTSD who received a course of brief exposure-based psychotherapy and completed pre- and post-treatment assessments to investigate the relations between the CPOSS and treatment outcome. The first study supported the psychometric properties of the CPOSS, including identifying four psychometrically-sound subscales for: respectful care, appearance of facility, convenience of facility, and recommendation to friends/family. The second study demonstrated that the CPOSS was a significant predictor of post-treatment PTSD symptoms, relative to demographics and pre-treatment symptoms. Together, these findings support the use of the CPOSS as a valuable addition in psychiatric outpatient settings to both assess and potentially improve patient treatment satisfaction. C1 [Gros, Daniel F.; Gros, Kirstin Stauffacher; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.; Gros, Kirstin Stauffacher; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Morland, Leslie A.] Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI USA. [Morland, Leslie A.] Ralph H Johnson VAMC, Charleston, SC 29401 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116,109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 31 TC 2 Z9 2 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2013 VL 35 IS 4 BP 522 EP 530 DI 10.1007/s10862-013-9361-6 PG 9 WC Psychology, Clinical SC Psychology GA 248WE UT WOS:000326735400010 ER PT J AU Mueller-Pfeiffer, C Rufibach, K Wyss, D Perron, N Pitman, RK Rufer, M AF Mueller-Pfeiffer, Christoph Rufibach, Kaspar Wyss, Daniela Perron, Noelle Pitman, Roger K. Rufer, Michael TI Screening for Dissociative Disorders in Psychiatric Out- and Day Care-Patients SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Dissociative disorders; Dissociation; Sensitivity and specificity; Predictive value of tests; Correct classification rate; Rating scales ID IDENTITY DISORDER; QUESTIONNAIRE SDQ-20; EXPERIENCE SCALE; GERMAN VERSION; PSYCHOMETRIC CHARACTERISTICS; AXIS-I; VALIDITY; RELIABILITY; OUTPATIENTS; PSYCHOTHERAPY AB Dissociative disorders are frequent and clinically relevant conditions in psychiatric populations. Yet, their recognition in clinical practice is often poor. This study evaluated the performance of three well known and internationally used dissociation scales in screening for dissociative disorders. Consecutively treated out- and day care-patients (n = 160) from several psychiatric units in Switzerland completed the Dissociative Experiences Scale (DES), Somatoform Dissociation Questionnaire (SDQ-20), and Multidimensional Inventory for Dissociation (MID). The Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised (SCID-D-R) was then administered. Test performance of the scales was analyzed by receiver operating characteristic curves. The diagnostic accuracy, represented by the area under the curve, did not differ significantly between the three summary scales. Cut-off scores for detecting at least 80 % of any dissociative disorder and dissociative disorder-not-otherwise-specified/dissociative identity disorder, respectively, were 12 and 20 for the DES, 30 and 33 for the SDQ-20, and 28 and 28 for the MID summary scale. The diagnostic accuracy of the DES subscale 'absorption' and the MID subscale 'somatic symptoms' was equal or slightly lower than the corresponding summary scale. The DES, SDQ-20, and MID summary scales are suitable in screening for dissociative disorders in general psychiatric out- and day care-patients. Adequate cut-off scores in the German-adapted DES are lower than in non-German versions. Screening with the DES subscale 'absorption' and the MID subscale 'somatic symptoms' could be more efficient without the loss of diagnostic accuracy. C1 [Mueller-Pfeiffer, Christoph; Rufer, Michael] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph; Wyss, Daniela; Perron, Noelle] Psychiat Serv Cty St Gallen North, Ctr Educ & Res COEUR, CH-9500 Wil, Switzerland. [Mueller-Pfeiffer, Christoph; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [Rufibach, Kaspar] Univ Zurich, Div Biostat, Inst Social & Prevent Med, CH-8001 Zurich, Switzerland. [Perron, Noelle] Univ Bern, CH-3012 Bern, Switzerland. RP Mueller-Pfeiffer, C (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Culmannstr 8, CH-8091 Zurich, Switzerland. EM christoph.mueller-pfeiffer@access.uzh.ch RI Rufibach, Kaspar/F-1163-2010 NR 51 TC 4 Z9 4 U1 0 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2013 VL 35 IS 4 BP 592 EP 602 DI 10.1007/s10862-013-9367-0 PG 11 WC Psychology, Clinical SC Psychology GA 248WE UT WOS:000326735400016 ER PT J AU Martin, JL Dzierzewski, JM Mitchell, M Fung, CH Jouldjian, S Alessi, CA AF Martin, Jennifer L. Dzierzewski, Joseph M. Mitchell, Michael Fung, Constance H. Jouldjian, Stella Alessi, Cathy A. TI Patterns of sleep quality during and after postacute rehabilitation in older adults: a latent class analysis approach SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE ageing; latent class analysis; rehabilitation; sleep ID POST-ACUTE REHABILITATION; ILLNESS RATING-SCALE; ELDERLY PERSONS; POOR SLEEP; DEPRESSION; PAIN; POPULATION; COMPLAINTS; SYMPTOMS; RECOVERY AB Sleep quality is related to emotional, physical, psychological and cognitive functioning and functional independence in later life. After acute health events, older adults are likely to utilize postacute rehabilitation services to improve functioning and facilitate return to independent living. Patterns of how sleep changes with postacute rehabilitation, and predictors of such patterns, are unknown. The current investigation employed latent class analysis (LCA) methods to classify older adults (n=233) into groups based on patterns of self-reported sleep quality pre-illness, during postacute rehabilitation and up to 1year following postacute rehabilitation. Using LCA, older adults were grouped into (1) consistently good sleepers (46%), (2) good sleepers who transitioned into poor sleepers (34%), (3) consistently poor sleepers (14%) and (4) poor sleepers who transitioned into good sleepers (6%). In three planned analyses, pain was an independent predictor of membership in classes 1 or 2 (good pre-illness sleep quality) versus classes 3 or 4 (poor pre-illness sleep quality), and of membership in class 1 (consistently good sleep) versus class 2 (good sleep that transitioned to poor sleep). A lower Mini-Mental State Examination score was a predictor of membership in class 1 versus class 2. There were no statistically significant predictors of membership in class 3 versus class 4. Demographics, comorbidities and depressive symptoms were not significant predictors of class membership. These findings have implications for identification of older adults at risk for developing poor sleep associated with changes in health and postacute rehabilitation. The findings also suggest that pain symptoms should be targeted to improve sleep during postacute rehabilitation. C1 [Martin, Jennifer L.; Dzierzewski, Joseph M.; Fung, Constance H.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Jennifer L.; Dzierzewski, Joseph M.; Mitchell, Michael; Fung, Constance H.; Jouldjian, Stella; Alessi, Cathy A.] Geriatr Res Educ & Clin Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Martin, JL (reprint author), VA GRECC 11E,16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU NIA [K23 AG028452]; UCLA Claude Pepper Older Americans Independence Center [AG-10415]; VA Health Services Research Development [IIR-01-053-1, IIR 04-321-2, AIA-03-047]; VA Advanced Geriatrics Fellowship Program; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center FX This work was supported by NIA K23 AG028452; UCLA Claude Pepper Older Americans Independence Center (AG-10415), VA Health Services Research & Development IIR-01-053-1, IIR 04-321-2 and AIA-03-047; VA Advanced Geriatrics Fellowship Program and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. We thank the participating facilities and their staff and the members of the research team who made this study possible; in particular, Terry Vandenberg MA, Sergio Martinez, Maryanne Devereaux, Christina Kurtz RN, Rebecca Saia, Crystal Barker RN, Jae Lee MD, David Kim PA, and Adam Webber BSc (Hons), MRCP (UK). NR 27 TC 1 Z9 1 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2013 VL 22 IS 6 BP 640 EP 647 DI 10.1111/jsr.12066 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 250VI UT WOS:000326884000006 PM 23834036 ER PT J AU Richards, A Metzler, TJ Ruoff, LM Inslicht, SS Rao, M Talbot, LS Neylan, TC AF Richards, Anne Metzler, Thomas J. Ruoff, Leslie M. Inslicht, Sabra S. Rao, Madhu Talbot, Lisa S. Neylan, Thomas C. TI Sex differences in objective measures of sleep in post-traumatic stress disorder and healthy control subjects SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE polysomnography; post-traumatic stress disorder; quantitative electroencephalography; rapid eye movement sleep; sex differences; slow wave sleep ID REM-SLEEP; EMOTIONAL MEMORY; QUALITY INDEX; PTSD; DISTURBANCES; METYRAPONE; VETERANS; HUMANS; SCALE; RISK AB A growing literature shows prominent sex effects for risk for post-traumatic stress disorder and associated medical comorbid burden. Previous research indicates that post-traumatic stress disorder is associated with reduced slow wave sleep, which may have implications for overall health, and abnormalities in rapid eye movement sleep, which have been implicated in specific post-traumatic stress disorder symptoms, but most research has been conducted in male subjects. We therefore sought to compare objective measures of sleep in male and female post-traumatic stress disorder subjects with age- and sex-matched control subjects. We used a cross-sectional, 2x2 design (post-traumatic stress disorder/controlxfemale/male) involving83 medically healthy, non-medicated adults aged 19-39years in the inpatient sleep laboratory. Visual electroencephalographic analysis demonstrated that post-traumatic stress disorder was associated with lower slow wave sleep duration (F-(3,F-82)=7.63, P=0.007) and slow wave sleep percentage (F-(3,F-82)=6.11, P=0.016). There was also a groupxsex interaction effect for rapid eye movement sleep duration (F-(3,F-82)=4.08, P=0.047) and rapid eye movement sleep percentage (F-(3,F-82)=4.30, P=0.041), explained by greater rapid eye movement sleep in post-traumatic stress disorder females compared to control females, a difference not seen in male subjects. Quantitative electroencephalography analysis demonstrated that post-traumatic stress disorder was associated with lower energy in the delta spectrum (F-(3,F-82)=6.79, P=0.011) in non-rapid eye movement sleep. Slow wave sleep and delta findings were more pronounced in males. Removal of post-traumatic stress disorder subjects with comorbid major depressive disorder, who had greater post-traumatic stress disorder severity, strengthened delta effects but reduced rapid eye movement effects to non-significance. These findings support previous evidence that post-traumatic stress disorder is associated with impairment in the homeostatic function of sleep, especially in men with the disorder. These findings suggest that groupxsex interaction effects on rapid eye movement may occur with more severe post-traumatic stress disorder or with post-traumatic stress disorder comorbid with major depressive disorder. C1 [Richards, Anne; Inslicht, Sabra S.; Rao, Madhu; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Richards, Anne; Metzler, Thomas J.; Ruoff, Leslie M.; Inslicht, Sabra S.; Rao, Madhu; Talbot, Lisa S.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Richards, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St Box 116-C, San Francisco, CA 94121 USA. EM anne.richards@ucsf.edu FU National Institute for Mental Health [TCN: 5R01MH073978-04, 5R34MH077667-03]; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant [UL1 RR024131] FX This project was supported by grants from the National Institute for Mental Health (TCN: 5R01MH073978-04, 5R34MH077667-03), the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration and the Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This material is the result of work supported with resources and the use of facilities at the Veterans Administration Medical Center, San Francisco, California. We are grateful to Ian Campbell PhD for his scientific input and to Maryann Lenoci for her logistical and technical support. NR 30 TC 10 Z9 10 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2013 VL 22 IS 6 BP 679 EP 687 DI 10.1111/jsr.12064 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 250VI UT WOS:000326884000011 PM 23763708 ER PT J AU Press, MJ Scanlon, DP Navathe, AS Zhu, JS Chen, W Mittler, JN Volpp, KG AF Press, Matthew J. Scanlon, Dennis P. Navathe, Amol S. Zhu, Jingsan Chen, Wei Mittler, Jessica N. Volpp, Kevin G. TI The Importance of Clinical Severity in the Measurement of Hospital Readmission Rates for Medicare Beneficiaries, 1997-2007 SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE readmission; quality measurement; risk adjustment; hospital care ID ACUTE MYOCARDIAL-INFARCTION; DUTY HOUR REFORM; CARE; TRANSITIONS; DISCHARGE; MORTALITY; REDUCTION; TRIAL AB In the coming years, assessing the impact of efforts to reduce hospital readmissions will be important to policy makers and hospitals. To inform such assessments, we sought to define preexisting trends in readmission rates for patients by level of clinical severity using a difference-in-differences analysis of Medicare inpatient claims data from 1997, 2002, and 2007 for patients with acute myocardial infarction and congestive heart failure. We also examined trends in length of stay, in-hospital mortality, and postdischarge mortality by severity level to provide additional context for interpreting readmission rate trends. From 1997 to 2007, the difference in readmission rates between the highest and lowest severity quartiles increased. Length of stay and in-hospital mortality decreased for all patients; however, postdischarge mortality increased for the highest-severity patients and decreased for the lowest-severity patients. Assessments of recent policy reforms and quality improvement programs should account for underlying differential trends in readmission rates based on patient severity. C1 [Press, Matthew J.] Weill Cornell Med Coll, New York, NY 10065 USA. [Scanlon, Dennis P.; Mittler, Jessica N.] Penn State Univ, State Coll, PA USA. [Navathe, Amol S.; Zhu, Jingsan; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Navathe, Amol S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Chen, Wei; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Press, MJ (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 402 E 67th St, New York, NY 10065 USA. EM map9069@med.cornell.edu FU Commonwealth Fund; Public Health at Weill Cornell Medical College FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research was funded by a grant from the Commonwealth Fund. Dr. Press is supported in part by funds provided to him as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell Medical College. NR 21 TC 3 Z9 3 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD DEC PY 2013 VL 70 IS 6 BP 653 EP 665 DI 10.1177/1077558713496167 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 250ZD UT WOS:000326895000005 PM 23877956 ER PT J AU Iglesias, JE Sabuncu, MR Van Leemput, K AF Iglesias, Juan Eugenio Sabuncu, Mert Rory Van Leemput, Koen TI A unified framework for cross-modality multi-atlas segmentation of brain MRI SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Label fusion; Generative model; Registration; Demons algorithm ID IMAGE SEGMENTATION; LABEL FUSION; HIPPOCAMPAL SUBFIELDS; NONRIGID REGISTRATION; MUTUAL-INFORMATION; ALGORITHM; PERFORMANCE; STRATEGIES; SELECTION; ACCURACY AB Multi-atlas label fusion is a powerful image segmentation strategy that is becoming increasingly popular in medical imaging. A standard label fusion algorithm relies on independently computed pairwise registrations between individual atlases and the (target) image to be segmented. These registrations are then used to propagate the atlas labels to the target space and fuse them into a single final segmentation. Such label fusion schemes commonly rely on the similarity between intensity values of the atlases and target scan, which is often problematic in medical imaging - in particular, when the atlases and target images are obtained via different sensor types or imaging protocols. In this paper, we present a generative probabilistic model that yields an algorithm for solving the atlas-to-target registrations and label fusion steps simultaneously. The proposed model does not directly rely on the similarity of image intensities. Instead, it exploits the consistency of voxel intensities within the target scan to drive the registration and label fusion, hence the atlases and target image can be of different modalities. Furthermore, the framework models the joint warp of all the atlases, introducing interdependence between the registrations. We use variational expectation maximization and the Demons registration framework in order to efficiently identify the most probable segmentation and registrations. We use two sets of experiments to illustrate the approach, where proton density (PD) MRI atlases are used to segment T1-weighted brain scans and vice versa. Our results clearly demonstrate the accuracy gain due to exploiting within-target intensity consistency and integrating registration into label fusion. (C) 2013 Elsevier B.V. All rights reserved. C1 [Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Van Leemput, Koen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, Lyngby, Denmark. [Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, Espoo, Finland. [Van Leemput, Koen] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. RP Iglesias, JE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. EM iglesias@nmr.mgh.harvard.edu RI Van Leemput, Koen/A-9197-2009; Iglesias, Juan Eugenio/K-1184-2014 OI Van Leemput, Koen/0000-0001-6466-5309; Iglesias, Juan Eugenio/0000-0001-7569-173X FU NIH NCRR [P41-RR14075]; NIBIB [R01EB013565]; Academy of Finland [133611]; Finnish Funding Agency for Technology and Innovation (ComBrain); NIH NIBIB [1K25EB013649-01]; BrightFocus Alzheimer's pilot Grant [AHAF-A2012333] FX This research was supported by the NIH NCRR (P41-RR14075), the NIBIB (R01EB013565), the Academy of Finland (133611), and the Finnish Funding Agency for Technology and Innovation (ComBrain). M.R. Sabuncu is also supported by NIH NIBIB 1K25EB013649-01 and a BrightFocus Alzheimer's pilot Grant (AHAF-A2012333). NR 44 TC 22 Z9 22 U1 1 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD DEC PY 2013 VL 17 IS 8 BP 1181 EP 1191 DI 10.1016/j.media.2013.08.001 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 247YX UT WOS:000326662000022 ER PT J AU Peroni, M Spadea, MF Riboldi, M Falcone, S Vaccaro, C Sharp, GC Baroni, G AF Peroni, M. Spadea, M. F. Riboldi, M. Falcone, S. Vaccaro, C. Sharp, G. C. Baroni, G. TI Validation of Automatic Contour Propagation for 4D Treatment Planning using Multiple Metrics SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Contour propagation; Deformable registration; Validation metrics; 4D computed tomography ID DEFORMABLE IMAGE REGISTRATION; RADIATION-THERAPY; RADIOTHERAPY; SEGMENTATION; CT; DELINEATION; ALGORITHMS; ACCURACY; MODEL; MRI AB The aim of this work is to provide insights into multiple metrics clinical validation of deformable image registration and contour propagation methods in 4D lung radiotherapy planning. The following indices were analyzed and compared: Volume Difference (VD), Dice Similarity Coefficient (DSC), Positive Predictive Value (PPV) and Surface Distances (SD). The analysis was performed on three patient datasets, using as reference a ground-truth volume generated by means of Simultaneous Truth And Performance Level Estimation (STAPLE) algorithm from the outlines of five experts. Significant discrepancies in the quality assessment provided by the different metrics in all the examined cases were found. Metrics sensitivity was more evident in presence of image artifacts and particularly for tubular anatomical structures, such as esophagus or spinal cord. Volume Differences did not account for position and DSC exhibited criticalities due to its intrinsic symmetry (i.e. over- and under-estimation of the reference contours cannot be discriminated) and dependency on the total volume of the structure. PPV analysis showed more robust performance, as each voxel concurs to the classification of the propagation, but was not able to detect inclusion of propagated and ground-truth volumes. Mesh distances could interpret the actual shape of the structures, but might report higher mismatches in case of large local differences in the contour surfaces. According to our study, the combination of VD and SD for the validation of contour propagation algorithms in 4D could provide the necessary failure detection accuracy. C1 [Peroni, M.; Riboldi, M.; Baroni, G.] Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy. [Spadea, M. F.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Riboldi, M.; Baroni, G.] Ctr Nazl Adroterapia Oncol, Bioengn Unit, I-27100 Pavia, Italy. [Falcone, S.; Vaccaro, C.] Policlin Mater Domini, Radiat Oncol Dept, Catanzaro, Italy. [Sharp, G. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sharp, G. C.] Harvard Univ, Sch Med, Boston, MA USA. RP Peroni, M (reprint author), Politecn Milan, Dept Elect Informat & Bioengn, Via Golgi 39, I-20133 Milan, Italy. EM marta.peroni@psi.ch RI Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU NIH from National Center for Research Resources [R01 RR021885]; Neuroscience Blueprint I/C from the National Institute of Biomedical Imaging and Bioengineering [R01 EB008015]; Rocca foundation FX The authors would like to thank the Rocca foundation for the support and the Computational Radiology Laboratory at the Department of Radiology (Children's Hospital, Boston, MA) for providing the software for STAPLE algorithm. The authors of the STAPLE algorithm used in this paper would like to acknowledge partial support by NIH R01 RR021885 from the National Center for Research Resources, and by an award from the Neuroscience Blueprint I/C through R01 EB008015 from the National Institute of Biomedical Imaging and Bioengineering. NR 43 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2013 VL 12 IS 6 BP 501 EP 510 DI 10.7785/tcrt.2012.500347 PG 10 WC Oncology SC Oncology GA 251DH UT WOS:000326907500003 PM 23745788 ER PT J AU Dehghan, S Seto, J Jones, MS Dyer, DW Chodosh, J Seto, D AF Dehghan, Shoaleh Seto, Jason Jones, Morris S. Dyer, David W. Chodosh, James Seto, Donald TI Simian adenovirus type 35 has a recombinant genome comprising human and simian adenovirus sequences, which predicts its potential emergence as a human respiratory pathogen SO VIROLOGY LA English DT Article DE Simian adenovirus; Recombination; Viral genomics; Human adenovirus ID US MILITARY RECRUITS; EPIDEMIC KERATOCONJUNCTIVITIS; COMPUTATIONAL ANALYSIS; MOLECULAR EVOLUTION; DNA-REPLICATION; IN-VIVO; CHIMPANZEE ADENOVIRUSES; BIOINFORMATICS ANALYSIS; VECTOR DEVELOPMENT; GENE-TRANSFER AB Emergent human and simian adenoviruses (HAdVs) may arise from genome recombination. Computational analysis of SAdV type 35 reveals a genome comprising a chassis with elements mostly from two simian adenoviruses, SAdV-B21 and -B27, and regions of high sequence similarity shared with HAdV-B21 and HAdV-B16. Although recombination direction cannot be determined, the presence of these regions suggests prior infections of humans by an ancestor of SAdV-B35, and/or vice versa. Absence of this virus in humans may reflect non-optimal conditions for zoonosis or incomplete typing, e.g., limited epitope-based. The presence of both a critical viral replication element found in HAdV genomes and genes that are highly similar to ones in HAdVs suggest the potential to establish in a human host. This allows a prediction that this virus may be a nascent human respiratory pathogen. The recombination potential of human and simian adenovirus genomes should be considered in the use of SAdVs as vectors for gene delivery in humans. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dehghan, Shoaleh] Amer Univ, Dept Chem, Washington, DC 20016 USA. [Dehghan, Shoaleh; Seto, Jason; Seto, Donald] George Mason Univ, Sch Syst Biol, Bioinformat & Computat Biol Program, Manassas, VA 20110 USA. [Jones, Morris S.] Naval Med Ctr, Div Infect Dis, San Diego, CA 92134 USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. RP Seto, D (reprint author), George Mason Univ, Sch Syst Biol, Bioinformat & Computat Biol Program, 10900 Univ Blvd,MSN 5B3, Manassas, VA 20110 USA. EM dseto@gmu.edu FU Office of the Provost at George Mason University; NIH [EY013124]; Research to Prevent Blindness Senior Scientific Investigator Award FX D.S. thanks the Office of the Provost at George Mason University for funding a Sabbatical Study Leave; Professor James Chodosh, his research group, and the Massachusetts Eye and Ear Infirmary, Harvard Medical School (Boston, MA) for providing a stimulating intellectual environment; and outstanding, quiet writing environments at Slaughter Beach (DE; U.S.) provided by Brenda L Desjardins and Providenciales (Turks and Caicos) by Craig Wess, and Duane Zentgraf. We thank Anthony J. Geneva and Marc W. Allard for discussions and insights on phylogenetic data analyses, methods, and conclusions. J.C. was supported by NIH Grant EY013124 and a Research to Prevent Blindness Senior Scientific Investigator Award. NR 68 TC 4 Z9 5 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 DEC PY 2013 VL 447 IS 1-2 BP 265 EP 273 DI 10.1016/j.virol.2013.09.009 PG 9 WC Virology SC Virology GA 246QF UT WOS:000326553500030 PM 24210123 ER PT J AU Onur, TS Sitron, CS Dang, A AF Onur, T. S. Sitron, C. S. Dang, A. TI Co-administration of hyaluronic acid with local anaesthetics shows lower cytotoxicity than local anaesthetic treatment alone in bovine articular chondrocytes SO BONE & JOINT RESEARCH LA English DT Article DE Hyaluronic acid; Local anaesthetic; Osteoarthritis; Intra-articular injections; Chondrocytes ID KNEE OSTEOARTHRITIS; MOLECULAR-WEIGHT; BUPIVACAINE; CHONDROTOXICITY; ROPIVACAINE; EXPOSURE AB Objective To study the effect of hyaluronic acid (HA) on local anaesthetic chondrotoxicity in vitro. Methods Chondrocytes were harvested from bovine femoral condyle cartilage and isolated using collagenase-containing media. At 24 hours after seeding 15 000 cells per well onto a 96-well plate, chondrocytes were treated with media (DMEM/F12 + ITS), PBS, 1:1 lidocaine (2%): PBS, 1:1 bupivacaine (0.5%): PBS, 1:1 lidocaine (2%): HA, 1:1 bupivacaine (0.5%): HA, or 1:1 HA:PBS for one hour. Following treatment, groups had conditions removed and 24-hour incubation. Cell viability was assessed using PrestoBlue and confirmed visually using fluorescence microscopy. Results Media-treated groups had a mean of 1.55x10(4) cells/well (SEM 783). All treated cells showed statistically significant reduced viability when compared with media alone (all p < 0.003). Cells treated with bupivacaine + HA (6.70x10(3) cells/well (SEM 1.10x10(3))) survived significantly more than bupivacaine (2.44x10(3) cells/well (SEM 830)) (p < 0.001). Lidocaine + HA (1.45x10(3) cells/well (SEM 596)) was not significantly more cytotoxic than lidocaine (2.24x10(3) cells/well (SEM 341)) (p = 0.999). There was no statistical difference between the chondrotoxicities of PBS (8.49x10(3) cells/well (SEM 730) cells/well) and HA (4.75x10(3) cells/well (SEM 886)) (p = 0.294). Conclusions HA co-administration reduced anaesthetic cytotoxicity with bupivacaine but not lidocaine, suggesting different mechanisms of injury between the two. Co-administered intra-articular injections of HA with bupivacaine, but not lidocaine, may protect articular chondrocytes from local anaesthetic-associated death. C1 [Onur, T. S.; Sitron, C. S.; Dang, A.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Dang, A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Onur, TS (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. EM t.s.onur17@gmail.com FU UCSF Department of Orthopaedic Surgery, Northern California Institute of Research and Education FX The authors would like to acknowledge Smith & Nephew for providing the Supartz (R) used in this study. The authors would also like to thank the following funding sources for their support of this project: UCSF Department of Orthopaedic Surgery, Northern California Institute of Research and Education. NR 20 TC 5 Z9 5 U1 1 U2 1 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2046-3758 J9 BONE JOINT RES JI Bone Jt. Res. PD DEC PY 2013 VL 2 IS 12 BP 270 EP 275 DI 10.1302/2046-3758.212.2000216 PG 6 WC Cell & Tissue Engineering; Orthopedics SC Cell Biology; Orthopedics GA AT2JP UT WOS:000344761200003 PM 24333946 ER PT J AU Haley, KE Greenberg, SM Gurol, ME AF Haley, Kellen E. Greenberg, Steven M. Gurol, M. Edip TI Cerebral Microbleeds and Macrobleeds: Should They Influence Our Recommendations for Antithrombotic Therapies? SO CURRENT CARDIOLOGY REPORTS LA English DT Article DE Intracerebral hemorrhage; Cerebral; Microbleed; Macrobleed; Anticoagulation; Antithrombotic therapy; Stroke prevention; Leukoaraiosis; Sulcal Siderosis ID NONVALVULAR ATRIAL-FIBRILLATION; RECURRENT INTRACEREBRAL HEMORRHAGE; WHITE-MATTER LESIONS; AMYLOID ANGIOPATHY; RISK-FACTORS; SUPERFICIAL SIDEROSIS; SPATIAL-DISTRIBUTION; ALZHEIMER-DISEASE; LOBAR HEMORRHAGE; ISCHEMIC-STROKE AB Intracerebral hemorrhage (ICH, or macrobleeds) and cerebral microbleeds-smaller foci of hemosiderin deposits commonly detected by magnetic resonance imaging of older adults with or without ICH-are both associated with an increased risk of future ICH. These hemorrhagic pathologies also share risk factors with ischemic thromboembolic conditions that may require antithrombotic therapy, requiring specialists in cardiology, internal medicine, and neurology to weigh the benefits vs hemorrhagic risks of antithrombotics in individual patients. This paper will review recent advances in our understanding of hemorrhage prone cerebrovascular pathologies with a particular emphasis on use of these markers in decision making for antithrombotic use. C1 [Haley, Kellen E.] Boston Univ, Boston, MA 02215 USA. [Haley, Kellen E.; Greenberg, Steven M.; Gurol, M. Edip] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Haley, Kellen E.; Greenberg, Steven M.; Gurol, M. Edip] Harvard Univ, Sch Med, Boston, MA USA. [Gurol, M. Edip] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Gurol, ME (reprint author), Massachusetts Gen Hosp, Stroke Serv, 175 Cambridge St 300, Boston, MA 02114 USA. EM kellen.haley@gmail.com; sgreenberg@partners.org; edip@mail.harvard.edu RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU National Institute of Health [NIH 5RO1NS070834-03, 5R01AG026484, NIH 5 P50NS051343-08] FX Dr. Greenberg and Dr. Gurol have research grant funding from the National Institute of Health (NIH 5RO1NS070834-03, 5R01AG026484, NIH 5 P50NS051343-08). NR 63 TC 6 Z9 6 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD DEC PY 2013 VL 15 IS 12 AR 425 DI 10.1007/s11886-013-0425-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT6YW UT WOS:000345083900005 PM 24122195 ER PT J AU Galofre, JC Chacon, AM Latif, R AF Galofre, Juan C. Chacon, Ana M. Latif, Rauf TI Targeting thyroid diseases with TSH receptor analogs SO ENDOCRINOLOGIA Y NUTRICION LA English DT Review DE Small molecules; Thyrotropin (TSH); Thyroid; TSH-receptor; Thyroid cancer; Graves' disease AB The thyroid -stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radio-iodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. (C) 2012 SEEN. Published by Elsevier Espana, S.L. All rights reserved. C1 [Galofre, Juan C.; Chacon, Ana M.] Univ Navarra, Univ Navarra Clin, Dept Endocrinol & Nutr, E-31080 Pamplona, Spain. [Latif, Rauf] James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY USA. RP Galofre, JC (reprint author), Univ Navarra, Univ Navarra Clin, Dept Endocrinol & Nutr, E-31080 Pamplona, Spain. EM jcgalofre@unav.es NR 47 TC 9 Z9 12 U1 0 U2 3 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 1575-0922 EI 1579-2021 J9 ENDOCRINOL NUTR JI Endocrinol. Nutr. PD DEC PY 2013 VL 60 IS 10 BP 590 EP 598 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA V43XW UT WOS:000209715100008 PM 23538281 ER PT J AU Shimada, YJ Passeri, JJ Baggish, AL O'Callaghan, C Lowry, PA Yannekis, G Abbara, S Ghoshhajra, BB Rothman, RD Ho, CY Januzzi, JL Seidman, CE Fifer, MA AF Shimada, Yuichi J. Passeri, Jonathan J. Baggish, Aaron L. O'Callaghan, Caitlin Lowry, Patricia A. Yannekis, Gia Abbara, Suhny Ghoshhajra, Brian B. Rothman, Richard D. Ho, Carolyn Y. Januzzi, James L. Seidman, Christine E. Fifer, Michael A. TI Effects of Losartan on Left Ventricular Hypertrophy and Fibrosis in Patients With Nonobstructive Hypertrophic Cardiomyopathy SO JACC-HEART FAILURE LA English DT Article AB Objectives The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Background Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging. Methods Results In double-blind fashion, 20 patients (3 women, 17 men; age: 51 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement. RESULTS There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. 5% [-11% to 0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% 26% with placebo vs. 23% 45% with losartan; p = 0.03). Conclusions This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT131150461) (1 Am Coll Cardiol HF 2013;1:480-7) (C) 2013 by the American College of Cardiology Foundation C1 [Shimada, Yuichi J.; Ho, Carolyn Y.; Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Passeri, Jonathan J.; Baggish, Aaron L.; O'Callaghan, Caitlin; Lowry, Patricia A.; Yannekis, Gia; Rothman, Richard D.; Januzzi, James L.; Fifer, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Abbara, Suhny; Ghoshhajra, Brian B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA USA. [Abbara, Suhny; Ghoshhajra, Brian B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Cardiol Div, Boston, MA USA. [Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Gray Bigelow 800,Mailstop 843, Boston, MA 02114 USA. EM mfifer@partners.org OI Ho, Carolyn/0000-0002-7334-7924; Shimada, Yuichi/0000-0002-3494-307X FU National Institutes of Health; Roche; Critical Diagnostics; BG Medicine; Siemens; Singulex; Novartis; Amgen; Zensun; Thermo Fisher Scientific; Howard Hughes Medical Institute; Merck Co., Inc. FX Dr. Ho has received financial support from the National Institutes of Health. Dr. Januzzi has received grants from Roche, Critical Diagnostics, BG Medicine, Siemens, Singulex, Novartis, Amgen, Zensun, and Thermo Fisher Scientific. Dr. Seidman is a founder and owns shares of Myokardia Inc., a startup company that is developing therapeutics that target the sarcomere; and has received financial support from the National Institutes of Health and the Howard Hughes Medical Institute. Dr. Fifer has received financial support from Merck & Co., Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 27 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD DEC PY 2013 VL 1 IS 6 BP 480 EP 487 DI 10.1016/j.jchf.2013.09.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GZ UT WOS:000209536000005 PM 24621999 ER PT J AU Greene, SJ Vaduganathan, M Wilcox, JE Harinstein, ME Maggioni, AP Subacius, H Zannad, F Konstam, MA Chioncel, O Yancy, CW Swedberg, K Butler, J Bonow, RO Gheorghiade, M AF Greene, Stephen J. Vaduganathan, Muthiah Wilcox, Jane E. Harinstein, Matthew E. Maggioni, Aldo P. Subacius, Haris Zannad, Faiez Konstam, Marvin A. Chioncel, Ovidiu Yancy, Clyde W. Swedberg, Karl Butler, Javed Bonow, Robert O. Gheorghiade, Mihai CA EVEREST Trial Investigators TI The Prognostic Significance of Heart Rate in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in Sinus Rhythm SO JACC-HEART FAILURE LA English DT Article AB Objectives The purpose of this study was to characterize the relationship between heart rate and post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction (EF) in sinus rhythm. Background A reduction in heart rate improves clinical outcomes in patients with chronic heart failure and in sinus rhythm, but the association between heart rate and post-discharge outcomes in patients with HHF is presently unclear. Methods This post-hoc analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial examined 1,947 patients with HHF and EF <40% not in atrial fibrillation/flutter or pacemaker dependent. Results The median follow-up period was 9.9 months. At baseline, patients with a higher heart rate tended to be younger with lower EF and were more likely to have worse New York Heart Association functional class and higher natriuretic peptide levels. After adjustment for clinical risk factors, baseline heart rate was not predictive of all-cause mortality (p > 0.066). However, at >70 beats/min, every 5-beat increase in 1-week post-discharge heart rate was independently associated with increased all-cause mortality (hazard ratio: 1.13 [95% confidence interval: 1.05 to 1.22]; p = 0.002). Similarly, every 5-beat increase >70 beats/min in 4-week post-discharge heart rate was predictive of all-cause mortality (hazard ratio: 1.12 [95% confidence interval: 1.05 to 1.19]; p = 0.001). Conclusions In this large cohort of patients with HHF with reduced EF and in sinus rhythm, baseline heart rate did not correlate with all-cause mortality. In contrast, at >70 beats/min, higher heart rate in the early post-discharge period was independently predictive of death during subsequent follow-up. Further study of post-discharge heart rate as a potential therapeutic target in this high-risk population is encouraged. (1 Am Coll Cardiol HF 2013;1:488-96) (C) 2013 by the American College of Cardiology Foundation C1 [Greene, Stephen J.; Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Wilcox, Jane E.; Subacius, Haris; Yancy, Clyde W.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Harinstein, Matthew E.] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, INSERM, CIC 9501, Nancy, France. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, INSERM, U961, Nancy, France. [Konstam, Marvin A.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Chioncel, Ovidiu] Inst Boli Cardiovasc CC Iliescu, Cardiol 1, Bucharest, Romania. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 201 East Huron St,Galter 3-150, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu FU Otsuka Inc. (Rockville, Maryland); Roche Diagnostics; Otsuka Pharmaceuticals; National Institutes of Health; European Union; Health Resource Services Administration; Food and Drug Administration; Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, Illinois) FX Otsuka Inc. (Rockville, Maryland) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. Haris Subacius conducted all final analyses for this manuscript with funding from the Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, Illinois). Dr. Zannad has served as a steering committee member for Bayer, Boston Scientific, Gambro, Janssen, Novartis, Pfizer, ResMed, and Takeda; served as an event committee member for Biotronik; served as a consultant/advisory board member for Servier; and received grant support from Roche Diagnostics. Dr. Konstam has served as a consultant for Amgen, Johnson & Johnson, Novartis Pharma AG, Otsuka Pharmaceuticals, and Merck & Co., Inc.; and received research support from Otsuka Pharmaceuticals. Dr. Butler has received research support from the National Institutes of Health, the European Union, the Health Resource Services Administration, and the Food and Drug Administration; and has served as a consultant for Alere, Amgen, Bayer, BG Medicine, Celladon, Covis, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, Stemedica, Trevena, and Takeda. Dr. Gheorghiade has served as a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, Corthera, Cytokinetics, Debiopharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck & Co., Inc., Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, PeriCor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceuticals, and Trevena Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 26 TC 20 Z9 21 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD DEC PY 2013 VL 1 IS 6 BP 488 EP 496 DI 10.1016/j.jchf.2013.08.005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GZ UT WOS:000209536000006 PM 24622000 ER PT J AU Ruddy, KJ Greaney, ML Sprunck-Harrild, K Meyer, ME Emmons, KM Partridge, AH AF Ruddy, Kathryn J. Greaney, Mary L. Sprunck-Harrild, Kim Meyer, Meghan E. Emmons, Karen M. Partridge, Ann H. TI Young Women with Breast Cancer: A Focus Group Study of Unmet Needs SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article DE breast cancer; survivorship; oncofertility; social support AB Purpose: Young women with breast cancer suffer distress both at the time of diagnosis and afterwards. This study aimed to elucidate which issues are most disturbing to this population and which might be amenable to intervention. Methods: English-speaking women treated or involved in research at the Dana-Farber Cancer Institute for stage I-III breast cancer while aged 18-42 years were invited to participate in one of four focus groups. A trained moderator led each 90-minute audio-recorded group using a semi-structured interview guide. All transcripts were coded using thematic content analysis with NVivo software. Results: Thirty-six women participated. Three major themes emerged from the analyses of these focus groups' data: (1) participants felt different from older breast cancer patients with regard to relationships, fertility, menopausal symptoms, treatment side effects, and work/finances; (2) participants faced unique challenges transitioning into the survivorship phase of care; and (3) participants desired assistance, including connections with other young patients, help navigating the healthcare system, educational materials, and lists of appropriate counselors. Conclusion: Young women with breast cancer have unmet needs for psychosocial support, education, and symptom management, and can identify potential support that may help meet these needs. C1 [Ruddy, Kathryn J.; Meyer, Meghan E.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Sprunck-Harrild, Kim; Emmons, Karen M.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM katieruddy@gmail.com FU Improving Cancer Care Grant from the ASCO Cancer Foundation; National Cancer Institute [NIH 5K05 CA124415-05]; Susan G. Komen for the Cure FX This work was supported by an Improving Cancer Care Grant from the ASCO Cancer Foundation (PI: Partridge), by a Scholar Grant from Susan G. Komen for the Cure (PI: Partridge), and by the National Cancer Institute (NIH 5K05 CA124415-05; PI: Emmons). We would like to thank all the women who participated in the focus groups. We also would like to thank Josh Gagne, MA, who moderated, coded, and performed thematic content analysis for all four focus groups. NR 23 TC 8 Z9 8 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PD DEC PY 2013 VL 2 IS 4 BP 153 EP 160 DI 10.1089/jayao.2013.0014 PG 8 WC Oncology SC Oncology GA V39IL UT WOS:000209404600004 ER PT J AU Kerry, VB Walensky, RP Tsai, AC Bergmark, RW Bergmark, BA Rouse, C Bangsberg, DR AF Kerry, Vanessa B. Walensky, Rochelle P. Tsai, Alexander C. Bergmark, Regan W. Bergmark, Brian A. Rouse, Chaturia Bangsberg, David R. TI US medical specialty global health training and the global burden of disease SO JOURNAL OF GLOBAL HEALTH LA English DT Article AB Background: Rapid growth in global health activity among US medical specialty education programs has lead to heterogeneity in types of activities and global health training models. The breadth and scope of this activity is not well chronicled. Methods: Using a standardized search protocol, we examined the characteristics of US medical residency global health programs by number of programs, clinical specialty, nature of activity (elective, research, extended curriculum based field training), and geographic location across seven different clinical medical residency education specialties. We tabulated programmatic activity by clinical discipline, region and country. We calculated the Spearman's rank correlation coefficient to estimate the association between programmatic activity and country-level disease burden. Results: Of the 1856 programs assessed between January and June 2011, there were 380 global health residency training programs (20%) working in 141 countries. 529 individual programmatic activities (elective-based rotations, research programs, extended curriculum-based field training, or other) occurred at 1337 specific sites. The majority of the activities consisted of elective-based rotations. At the country level, disease burden had a statistically significant association with programmatic activity (Spearman's rho = 0.17) but only explained 3% of the total variation between countries. Conclusions: There were a substantial number of US medical specialty global health programs, but a relative paucity of surgical and mental health programs. Elective-based programs were more common than programs that offer longitudinal experiences. Despite heterogeneity, there was a small but statistically significant association between program location and the global burden of disease. Areas for further study include the degree to which US-based programs develop partnerships with their program sites, the significance of this activity for training, and number and breadth of programs in medical specialty global health education in other countries around the world. C1 [Kerry, Vanessa B.; Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kerry, Vanessa B.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Kerry, Vanessa B.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA. [Walensky, Rochelle P.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Bangsberg, David R.] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Bergmark, Regan W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Bergmark, Regan W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bergmark, Brian A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rouse, Chaturia] Boston Univ, Boston, MA 02215 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Kerry, VB (reprint author), 100 Cambridge St,15th Floor,Suite 1541-A, Boston, MA 02114 USA. EM vkerry@partners.org FU Mark and Lisa Schwartz Foundation; Klingenstein Family Foundation; Harvard University Center for AIDS Research NIAID [P30 AI060354]; National Institute of Allergy and Infectious Diseases [R01 AI058736]; London School of Hygiene and Tropical Medicine; NIH [K23 MH-096620]; [K24 MH87227] FX This work was supported by the Mark and Lisa Schwartz Foundation, the Klingenstein Family Foundation, and the Harvard University Center for AIDS Research NIAID P30 AI060354. Dr Bangsberg was supported by K24 MH87227. Dr Walensky was supported by National Institute of Allergy and Infectious Diseases R01 AI058736. Dr R. Bergmark and Dr B. Bergmark received funding through Benjamin Kean Traveling Fellowships from the London School of Hygiene and Tropical Medicine. All authors receive a portion of their salary from global health activities. Dr Tsai receives salary support from NIH K23 MH-096620. The sponsors had no role in interpretation of data or decision to publish. NR 46 TC 3 Z9 3 U1 0 U2 0 PU UNIV EDINBURGH, GLOBAL HEALTH SOC PI EDINBURGH PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, ENGLAND SN 2047-2978 EI 2047-2986 J9 J GLOB HEALTH JI J. Glob. Health PD DEC PY 2013 VL 3 IS 2 BP 120 EP 128 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V42SI UT WOS:000209633100011 ER PT J AU Sorensen, G McLellan, D Dennerlein, JT Pronk, NP Allen, JD Boden, LI Okechukwu, CA Hashimoto, D Stoddard, A Wagner, GR AF Sorensen, Glorian McLellan, Deborah Dennerlein, Jack T. Pronk, Nicolaas P. Allen, Jennifer D. Boden, Leslie I. Okechukwu, Cassandra A. Hashimoto, Dean Stoddard, Anne Wagner, Gregory R. TI Integration of Health Protection and Health Promotion Rationale, Indicators, and Metrics SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article AB Objective: To offer a definition of an "integrated" approach to worker health and operationalize this definition using indicators of the extent to which integrated efforts are implemented in an organization. Methods: Guided by the question-How will we know it when we see it?-we reviewed relevant literature to identify available definitions and metrics, and used a modified Delphi process to review and refine indicators and measures of integrated approaches. Results: A definition of integrated approaches to worker health is proposed and accompanied by indicators and measures that may be used by researchers, employers, and workers. Conclusions: A shared understanding of what is meant by integrated approaches to protect and promote worker health has the potential to improve dialogue among researchers and facilitate the research-to-practice process. C1 [Sorensen, Glorian; McLellan, Deborah; Allen, Jennifer D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sorensen, Glorian; Pronk, Nicolaas P.; Okechukwu, Cassandra A.; Wagner, Gregory R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.] Northeastern Univ, Boston, MA 02115 USA. [Pronk, Nicolaas P.] HealthPartners Inc, Minneapolis, MN USA. [Boden, Leslie I.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hashimoto, Dean] Partners HealthCare Inc, Boston, MA USA. [Hashimoto, Dean] Boston Coll, Sch Law, Newton Ctr, MA USA. [Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA. [Wagner, Gregory R.] NIOSH, Washington, DC USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM glorian_sorensen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015; OI Dennerlein, Jack/0000-0001-7703-643X FU NCI NIH HHS [K05 CA108663, K05 CA124415]; NIOSH CDC HHS [U19 OH008861] NR 55 TC 25 Z9 25 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2013 VL 55 IS 12 SU S BP S12 EP S18 DI 10.1097/JOM.0000000000000032 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V44HY UT WOS:000209741300002 PM 24284762 ER PT J AU Umukoro, PE Arias, OE Stoffel, SD Hopcia, K Sorensen, G Dennerlein, JT AF Umukoro, Peter E. Arias, Oscar E. Stoffel, Sonja D. Hopcia, Karen Sorensen, Glorian Dennerlein, Jack T. TI Physical Activity at Work Contributes Little to Patient Care Workers' Weekly Totals SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article AB Objective: To determine the number of minutes of moderate and vigorous physical activity at work in comparison to weekly total minutes in a pilot study of 50 hospital patient care workers. Methods: Workers wore accelerometers during work and nonwork hours for 7 days, and completed surveys at the end of the seventh day. Results: Although the participants reported on average 206 minutes of moderate activity at work, the accelerometers recorded on average 30 minutes of moderate activity at work. For the 7 days the accelerometers measured a total of 165 minutes of moderate activity. Self-reported fatigue and functional limitations were negatively correlated albeit weakly with measured minutes of vigorous activity outside of work. Conclusions: Physical activity at work on patient care units contributes a small fraction to these workers' weekly totals, and in turn meeting guidelines. C1 [Umukoro, Peter E.; Arias, Oscar E.; Dennerlein, Jack T.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Stoffel, Sonja D.] Camosun Coll, Ctr Sport & Exercise Educ, Victoria, BC, Canada. [Stoffel, Sonja D.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Hopcia, Karen] Partners HealthCare Inc, Dept Occupat Hlth, Boston, MA USA. [Hopcia, Karen] Univ Illinois, Dept Hlth Syst Sci, Chicago, IL USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Dennerlein, Jack T.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Phys Therapy, Boston, MA 02115 USA. RP Dennerlein, JT (reprint author), Northeastern Univ, 6 Robinson Hall,360 Huntington Ave, Boston, MA 02115 USA. EM j.dennerlein@northeastern.edu OI Dennerlein, Jack/0000-0001-7703-643X FU National Institute for Occupational Safety and Health for Total Worker Health Centers of Excellence to Promote a Healthier Workforce [U19 OH008861] FX This work was supported by a grant from the National Institute for Occupational Safety and Health for Total Worker Health Centers of Excellence to Promote a Healthier Workforce (U19 OH008861). NR 26 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2013 VL 55 IS 12 SU S BP S63 EP S68 DI 10.1097/JOM.0000000000000046 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V44HY UT WOS:000209741300010 PM 24284756 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI NATIVE HISTORIANS WRITE BACK: Decolonizing American Indian History SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 EI 1930-0115 J9 J WEST JI J. West PD WIN PY 2013 VL 52 IS 1 BP 72 EP 74 PG 3 WC History SC History GA V39AL UT WOS:000209383800009 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI IN THE SMALLER SCOPE OF CONSCIENCE: The Struggle for National Repatriation Legislation, 1986-1990 SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 EI 1930-0115 J9 J WEST JI J. West PD WIN PY 2013 VL 52 IS 1 BP 84 EP 85 PG 2 WC History SC History GA V39AL UT WOS:000209383800026 ER PT J AU Cusin, C Eikermann, M Zaremba, S Pavone, K Durham, K Chang, T Cassano, P Dording, C Soskin, D Mischoulon, D Fava, M AF Cusin, Cristina Eikermann, Matthias Zaremba, Sebastian Pavone, Kara Durham, Kelley Chang, Trina Cassano, Paolo Dording, Christina Soskin, David Mischoulon, David Fava, Maurizio TI Preliminary Investigation of EEG Predictors in an Open-label, Flexible-dose, Repeated Infusions of Ketamine as Augmentation in Treatment Resistant Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE ketamine; treatment-resistant; depression; EEG; biomarker C1 [Cusin, Cristina; Eikermann, Matthias; Zaremba, Sebastian; Pavone, Kara; Durham, Kelley; Chang, Trina; Cassano, Paolo; Dording, Christina; Soskin, David; Mischoulon, David; Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA W137 BP S526 EP S528 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100813 ER PT J AU Davis, FC VanElzakker, MB Staples, LK Lasko, NB Orr, S Pitman, RK Shin, LM AF Davis, F. Caroline VanElzakker, Michael B. Staples, Lindsay K. Lasko, Natasha B. Orr, Scott Pitman, Roger K. Shin, Lisa M. TI A Twin Study Identifying the Origin of Abnormal Automatic Responses to Threat Related Stimuli in PTSD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE ptsd dorsal; anterior cingulate cortex; biomarkers emotion; fMRI C1 [Davis, F. Caroline; VanElzakker, Michael B.; Staples, Lindsay K.; Lasko, Natasha B.; Orr, Scott; Pitman, Roger K.; Shin, Lisa M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M151 BP S211 EP S212 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100361 ER PT J AU Deckersbach, T Peters, A Kaur, N Corse, AK Arulpragasam, AR Sylvia, L da Silva, PV Otto, M Frank, E Miklowitz, D Berk, M Dougherty, D Nierenberg, AA AF Deckersbach, Thilo Peters, Amy Kaur, Navneet Corse, Andrew K. Arulpragasam, Amanda R. Sylvia, Louisa da Silva, Pedro Vieira Otto, Michael Frank, Ellen Miklowitz, David Berk, Michael Dougherty, Darin Nierenberg, Andrew A. TI Anxiety Moderates Response to Psychosocial Treatment for Depression in Bipolar Disorder: Results from Systematic Treatment Enhancement Program for Bipolar Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE anxiety; psychosocial treatment; depression; bipolar disorder; STEP-BD C1 [Deckersbach, Thilo; Peters, Amy; Kaur, Navneet; Corse, Andrew K.; Arulpragasam, Amanda R.; Sylvia, Louisa; da Silva, Pedro Vieira; Otto, Michael; Frank, Ellen; Miklowitz, David; Berk, Michael; Dougherty, Darin; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA T220 BP S422 EP S423 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100663 ER PT J AU Evins, AE AF Evins, A. Eden TI Extended Duration Pharmacotherapy with Varenicline Prevents Relapse to Smoking in Adult Smokers with Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA 38.2 BP S63 EP S64 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100125 ER PT J AU Fava, M AF Fava, Maurizio TI A Pilot, Placebo-controlled Study of Buspirone Plus Melatonin in Major Depressive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA 53.1 BP S93 EP S94 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100184 ER PT J AU Gilman, JM Kuster, J Lee, S Lee, MJ Kim, BW Makris, N van der Kouwe, A Blood, A Breiter, HC AF Gilman, Jodi M. Kuster, John Lee, Sang Lee, Myung Joo Kim, Byoung Woo Makris, Nikos van der Kouwe, Andre Blood, Anne Breiter, Hans C. TI Cannabis Use Is Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE cannabis; imaging; nucleus accumbens; morphometry; amygdala C1 [Gilman, Jodi M.; Kuster, John; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne; Breiter, Hans C.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M147 BP S208 EP S209 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100357 ER PT J AU Hirano, Y Oribe, N Kanba, S Onitsuka, T Hosokawa, T Shenton, M McCarley, RW Spencer, KM AF Hirano, Yoji Oribe, Naoya Kanba, Shigenobu Onitsuka, Toshiaki Hosokawa, Taiga Shenton, Martha McCarley, Robert W. Spencer, Kevin M. TI Electrophysiological and Anatomical Evidence for Two Distinct but Interacting Neural Circuit Abnormalities in the Auditory Cortex in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE Electroencephalogram; Evoked gamma; Baseline gamma; Resting gamma; Structural MRI; Auditory cortex; Schizophrenia; Auditory hallucinations C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M154 BP S213 EP S214 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100364 ER PT J AU Holt, DJ Boeke, EA Holmes, AJ Coombs, G Farabaugh, A Nyer, M Ward, M Crowell, S Cassiello, C Pisoni, A Pedrelli, P Buckner, RL Fava, M AF Holt, Daphne J. Boeke, Emily A. Holmes, Avram J. Coombs, Garth Farabaugh, Amy Nyer, Maren Ward, Maeve Crowell, Susanna Cassiello, Clair Pisoni, Angela Pedrelli, Paola Buckner, Randy L. Fava, Maurizio TI Poor Amygdalofrontal Connectivity Predicts Symptomatic Deterioration in At-risk Youth SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE amygdalofrontal; functional connectivity; longitudinal; psychosis; depression C1 [Holt, Daphne J.; Boeke, Emily A.; Holmes, Avram J.; Coombs, Garth; Farabaugh, Amy; Nyer, Maren; Ward, Maeve; Crowell, Susanna; Cassiello, Clair; Pisoni, Angela; Pedrelli, Paola; Buckner, Randy L.; Fava, Maurizio] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M133 BP S198 EP S199 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100343 ER PT J AU Hwang, MJ Song, HJ Zsido, R Pace-Schott, EF Miller, KKK Milad, MR AF Hwang, Moon Jung Song, Huijin Zsido, Rachel Pace-Schott, Edward F. Miller, Karen Klahr K. Milad, Mohammed R. TI Contributions of Estrogen and Oral Contraceptive Use to Sex Differences in Functional Responding to Conditioned Cues During Fear Conditioning SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE estrogen; oral contraceptive; sex difference; fear conditioning; fMRI C1 Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA W234 BP S591 EP S591 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100908 ER PT J AU Kokel, D AF Kokel, David TI High-throughput Behavior-based Neuroactive Drug Discovery in Zebrafish SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE drug-discovery; zebrafish; phenotype-based screening; HTS C1 [Kokel, David] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA T20 BP S283 EP S284 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100466 ER PT J AU Marin, MF Song, HJ Staples, LK VanElzakker, MB Lasko, NB Pitman, RK Shin, LM Milad, MR AF Marin, Marie-France Song, Huijin Staples, Lindsay K. VanElzakker, Michael B. Lasko, Natasha B. Pitman, Roger K. Shin, Lisa M. Milad, Mohammed R. TI Brain Glucose Metabolism Predicts Fear Extinction Recall and Global Functioning in Trauma-exposed Populations With and Without PTSD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE PET Resting Metabolism; PTSD; Extinction Memory; Skin Conductance Responses; Global Assessment of Functioning C1 [Marin, Marie-France; Song, Huijin; Staples, Lindsay K.; VanElzakker, Michael B.; Lasko, Natasha B.; Pitman, Roger K.; Shin, Lisa M.; Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M219 BP S258 EP S259 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100428 ER PT J AU McCarley, R Oribe, N Hirano, Y Kanba, S del Re, E Seidman, LJ Mesholam-Gately, R Shenton, M Goldstein, JM Spencer, KM Niznikiewicz, M AF McCarley, Robert Oribe, Naoya Hirano, Yoji Kanba, Shigenobu del Re, Elisabetta Seidman, Larry J. Mesholam-Gately, Raquelle Shenton, Martha Goldstein, Jill M. Spencer, Kevin M. Niznikiewicz, Margaret TI Progressive Reduction of Visual P300 Amplitude in Patients with First Episode Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE neurophysiology; first episode; schizophrenia; visual P300; longitudinal progression of schizophrenia biomarkers C1 [McCarley, Robert; Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu; del Re, Elisabetta; Seidman, Larry J.; Mesholam-Gately, Raquelle; Shenton, Martha; Goldstein, Jill M.; Spencer, Kevin M.; Niznikiewicz, Margaret] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA W20 BP S447 EP S447 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100698 ER PT J AU Raskind, MA Froehlich, JC Peskind, ER Rasmussen, DD AF Raskind, Murray A. Froehlich, Janice C. Peskind, Elaine R. Rasmussen, Dennis D. TI Effects of Combined Adrenoreceptor Antagonist Treatment with Prazosin and Propranolol on Alcohol Drinking in Humans and Rodents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE PTSD; alcohol; prazosin; propranolol C1 [Raskind, Murray A.; Froehlich, Janice C.; Peskind, Elaine R.; Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M199 BP S245 EP S246 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100408 ER PT J AU Reddy, F Horan, W Wynn, JK Corey-Lisle, P Maglinte, G Barch, DM Buchanan, RW Gold, J Young, J Green, MF AF Reddy, Felice Horan, William Wynn, Jonathan K. Corey-Lisle, Patricia Maglinte, Gregory Barch, Deanna M. Buchanan, Robert W. Gold, James Young, Jared Green, Michael F. TI Assessing Effort-based Decision-making in Schizophrenia with Two Novel Behavioral Paradigms SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE Schizophrenia; Negative symptoms; Effort-based tasks; Motivation C1 [Reddy, Felice; Horan, William; Wynn, Jonathan K.; Corey-Lisle, Patricia; Maglinte, Gregory; Barch, Deanna M.; Buchanan, Robert W.; Gold, James; Young, Jared; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M195 BP S242 EP S243 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100404 ER PT J AU Ripke, S AF Ripke, Stephan TI Psychiatric GWAS Consortium Triples Schizophrenia GWAS Sample-size to 31,000 Cases and 37,000 Controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Ripke, Stephan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA 57.3 BP S102 EP S102 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100202 ER PT J AU Roffman, JL AF Roffman, Joshua L. TI Longitudinal Effects of In Utero Folate Exposure on Cortical Thickness: Implications for Neurodevelopmental Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Roffman, Joshua L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Roffman, Joshua L.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA 24.2 BP S38 EP S39 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100074 ER PT J AU Simon, NM Walton, Z Prescott, J Hoge, E Keshaviah, A Bui, THE Schwarz, N Dryman, T Ojserkis, RA Mischoulon, D Worthington, J DeVivo, I Fava, M Wong, KK AF Simon, Naomi M. Walton, Zandra Prescott, Jennifer Hoge, Elizabeth Keshaviah, Aparna Bui, T. H. Eric Schwarz, Noah Dryman, Taylor Ojserkis, Rebecca A. Mischoulon, David Worthington, John DeVivo, Immaculata Fava, Maurizio Wong, Kwok-Kin TI A Cross-sectional Examination of Telomere Length and Telomerase in a Well-Characterized Sample of Individuals with Major Depressive Disorder Compared to Controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Simon, Naomi M.; Walton, Zandra; Prescott, Jennifer; Hoge, Elizabeth; Keshaviah, Aparna; Bui, T. H. Eric; Schwarz, Noah; Dryman, Taylor; Ojserkis, Rebecca A.; Mischoulon, David; Worthington, John; DeVivo, Immaculata; Fava, Maurizio; Wong, Kwok-Kin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA T83 BP S322 EP S323 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100527 ER PT J AU Song, HJ Milad, MR AF Song, Huijin Milad, Mohammed R. TI Input-information Processing During Fear Acquisition in PTSD Using Dynamic Causal Modeling and fMRI SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE dynamic causal modeling; DCM; fMRI; effective connectivity; PTSD; fear circuit; fear acquisition C1 [Song, Huijin; Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA W51 BP S467 EP S468 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100729 ER PT J AU Stoeckel, L AF Stoeckel, Luke TI The Effect of Real Time fMRI Neurofeedback on Food and Cigarette Craving SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE fMRI; neurofeedback; addiction; craving; food C1 [Stoeckel, Luke] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stoeckel, Luke] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA M203 BP S248 EP S249 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100412 ER PT J AU Thomas, C Sears, C Very, E Salles, J Bui, THE AF Thomas, Charmaine Sears, Christopher Very, Etienne Salles, Juliette Bui, T. H. Eric TI Relationship Between Peritraumatic Distress and Attentional Avoidance of Trauma-relevant Threat in the Prediction of Posttraumatic Stress Disorder: Preliminary Results from a Prospective Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract DE attentional biais; trauma; peritraumatic reactions; PTSD C1 [Thomas, Charmaine; Sears, Christopher; Very, Etienne; Salles, Juliette; Bui, T. H. Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2013 VL 38 SU 2 MA W14 BP S443 EP S443 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40KI UT WOS:000209477100692 ER PT J AU Kawabori, M Hokari, M Zheng, Z Kim, JY Calosing, C Hsieh, CL Nakamura, MC Yenari, MA AF Kawabori, Masahito Hokari, Masaaki Zheng, Zhen Kim, Jong Youl Calosing, Cyrus Hsieh, Christine L. Nakamura, Mary C. Yenari, Midori A. TI Triggering Receptor Expressed on Myeloid Cells-2 Correlates to Hypothermic Neuroprotection in Ischemic Stroke SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Article AB Hypothermia is neuroprotective against many acute neurological insults, including ischemic stroke. We and others have previously shown that protection by hypothermia is partially associated with an anti-inflammatory effect. Phagocytes are thought to play an important role in the clearance of necrotic debris, paving the way for endogenous repair mechanisms to commence, but the effect of cooling and phagocytosis has not been extensively studied. Triggering receptor expressed on myeloid cells-2 (TREM2) is a newly identified surface receptor shown to be involved in phagocytosis. In this study, we examined the effect of therapeutic hypothermia on TREM2 expression. Mice underwent permanent middle cerebral artery occlusion (MCAO) and were treated with one of the two cooling paradigms: one where cooling (30 degrees C) began at the onset of MCAO (early hypothermia [eHT]) and another where cooling began 1 hour later (delayed hypothermia [dHT]). In both groups, cooling was maintained for 2 hours. A third group was maintained at normothermia (NT) as a control (37 degrees C). Mice from the NT and dHT groups had similar ischemic lesion sizes and neurological performance, but the eHT group showed marked protection as evidenced by a smaller lesion size and less neurological deficits up to 30 days after the insult. Microglia and macrophages increased after MCAO as early as 3 days, peaked at 7 days, and decreased by 14 days. Both hypothermia paradigms were associated with decreased numbers of microglia and macrophages at 3 and 7 days, with greater decreases in the early paradigm. However, the proportion of the TREM2-positive microglia/macrophages was actually increased among the eHT group at day 7. eHT showed a long-term neurological benefit, but neuroprotection did not correlate to immune suppression. However, hypothermic neuroprotection was associated with a relative increase in TREM2 expression, and suggests that TREM2 may serve a beneficial role in brain ischemia. C1 [Kawabori, Masahito; Hokari, Masaaki; Zheng, Zhen; Kim, Jong Youl; Calosing, Cyrus; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94115 USA. [Hsieh, Christine L.; Nakamura, Mary C.] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94115 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94115 USA. EM yenari@alum.mit.edu FU National Institutes of Health (NIH) [NS40516, AR0038]; Veteran's Merit Awards; Uehara Foundation Research Fellowship; Veterans Affairs Career Development Award; Rosalind Russell Arthritis Center FX This work was supported by grants from National Institutes of Health (NIH) (NS40516 to M.Y. and AR0038 to M.N.) and the Veteran's Merit Awards to M.Y. and M.C.N., the Uehara Foundation Research Fellowship to M.K. and a Veterans Affairs Career Development Award to C.H. Grants to M.Y. and M.N. were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. M.N. also received support from the Rosalind Russell Arthritis Center. NR 51 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD DEC 1 PY 2013 VL 3 IS 4 BP 189 EP 198 DI 10.1089/ther.2013.0020 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA V38QL UT WOS:000209357800007 PM 24380032 ER PT J AU Sever, S Chang, J Gu, C AF Sever, Sanja Chang, Joann Gu, Changkyu TI Dynamin Rings: Not Just for Fission SO TRAFFIC LA English DT Review DE dynamin actin; endocytosis; microtubules; oligomerization ID CLATHRIN-MEDIATED ENDOCYTOSIS; MEMBRANE FISSION; GTPASE ACTIVITY; MECHANOCHEMICAL ENZYME; ACTIN CYTOSKELETON; LIVING CELLS; COATED PITS; DOMAIN; PROTEINS; MICROTUBULES AB The GTPase dynamin has captivated researchers for over two decades, even managing to establish its own research field. Dynamin's allure is partly due to its unusual biochemical properties as well as its essential role in multiple cellular processes, which include the regulation of clathrin-mediated endocytosis and of actin cytoskeleton. On the basis of the classic model, dynamin oligomerization into higher order oligomers such as rings and helices directly executes the final fission reaction in endocytosis, which results in the generation of clathrin-coated vesicles. Dynamin's role in the regulation of actin cytoskeleton is mostly explained by its interactions with a number of actin-binding and -regulating proteins; however, the molecular mechanism of dynamin's action continues to elude us. Recent insights into the mechanism and role of dynamin oligomerization in the regulation of actin polymerization point to a novel role for dynamin oligomerization in the cell C1 [Sever, Sanja; Chang, Joann; Gu, Changkyu] Massachusetts Gen Hosp, Nephrol Div, Charlestown, MA 02129 USA. RP Sever, S (reprint author), Massachusetts Gen Hosp, Nephrol Div, CNY 149 8-113,149 13th St, Charlestown, MA 02129 USA. EM ssever@partners.org FU National Institutes of Health [R01 DK093773] FX This work was supported by the National Institutes of Health (R01 DK093773 to S. S.) NR 60 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-9219 EI 1600-0854 J9 TRAFFIC JI Traffic PD DEC PY 2013 VL 14 IS 12 BP 1194 EP 1199 DI 10.1111/tra.12116 PG 6 WC Cell Biology SC Cell Biology GA 248TR UT WOS:000326727300003 PM 23980695 ER PT J AU Berkowitz, SA Meigs, JB Wexler, DJ AF Berkowitz, Seth A. Meigs, James B. Wexler, Deborah J. TI Age at type 2 diabetes onset and glycaemic control: results from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 SO DIABETOLOGIA LA English DT Article DE Ageing; Diabetes mellitus; Epidemiology; Prevention and control ID SELF-RATED HEALTH; PERCEIVED HEALTH; FOLLOW-UP; MELLITUS; COHORT AB We tested the hypothesis that age younger than 65 years at type 2 diabetes diagnosis is associated with worse subsequent glycaemic control. A cross-sectional analysis of data from participants in the 2005-2010 National Health and Nutrition Examination Survey was performed. For adults with self-reported diabetes, we dichotomised age at diabetes diagnosis as younger (< 65 years) vs older (a parts per thousand yen65 years). The primary outcome of interest was HbA(1c) > 9.0% (75 mmol/mol). Secondary outcomes were HbA(1c) > 8.0% (64 mmol/mol) and > 7.0% (53 mmol/mol). We used multivariable logistic regression for analysis. Among 1,438 adults with diabetes, a higher proportion of those < 65 years at diagnosis compared with those a parts per thousand yen65 at diagnosis had an HbA(1c) > 9.0% (14.4% vs 2.5%, p < 0.001). After adjustment for sex, race/ethnicity, education, income, insurance, usual source of care, hyperglycaemia medication, duration of diabetes, family history, BMI and waist circumference, age < 65 years at diagnosis remained significantly associated with greater odds of HbA(1c) > 9.0% (OR 3.22, 95% CI 1.54, 6.72), HbA(1c) > 8.0% (OR 2.72, 95% CI 1.43, 5.16) and HbA(1c) > 7.0% (OR 1.92, 95% CI 1.18, 3.11). The younger group reported fewer comorbidities, but were less likely to report good health (OR 0.54, 95% CI 0.36, 0.83). Younger age at type 2 diabetes diagnosis is significantly associated with worse subsequent glycaemic control. Because patients who are younger at diagnosis have fewer competing comorbidities and complications, safe, aggressive, individualised treatment could benefit this higher-risk group. C1 [Berkowitz, Seth A.; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Berkowitz, Seth A.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wexler, Deborah J.] Harvard Univ, Ctr Diabet, Dept Med, Massachusetts Gen Hospital,Sch Med, Boston, MA USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM SABerkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; General Medicine Division at Massachusetts General Hospital; National Institutes of Health [R03DK090196]; [K24 DK080140] FX SAB was supported by an institutional National Research Service Award T32HP10251, the Ryoichi Sasakawa Fellowship Fund, and by the General Medicine Division at Massachusetts General Hospital. DJW receives funding from the National Institutes of Health under award R03DK090196. JBM is supported in part by K24 DK080140. The funding organisations had no role in the design and conduct of the study, the collection, management, analysis and interpretation of data, or the preparation, review and approval of the manuscript. NR 23 TC 18 Z9 19 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2013 VL 56 IS 12 BP 2593 EP 2600 DI 10.1007/s00125-013-3036-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247ET UT WOS:000326599300007 PM 23995472 ER PT J AU Griffith, HR Okonkwo, OC Stewart, CC Stoeckel, LE den Hollander, JA Elgin, JM Harrell, LE Brockington, JC Clark, DG Ball, KK Owsley, C Marson, DC Wadley, VG AF Griffith, H. Randall Okonkwo, Ozioma C. Stewart, Christopher C. Stoeckel, Luke E. den Hollander, Jan A. Elgin, Jennifer M. Harrell, Lindy E. Brockington, John C. Clark, David G. Ball, Karlene K. Owsley, Cynthia Marson, Daniel C. Wadley, Virginia G. TI Lower Hippocampal Volume Predicts Decrements in Lane Control Among Drivers With Amnestic Mild Cognitive Impairment SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE mild cognitive impairment; volumetric MRI; driving performance ID EARLY ALZHEIMERS-DISEASE; DRIVING PERFORMANCE; OLDER-ADULTS; TAXI DRIVERS; DEMENTIA; MRI; NAVIGATION; BRAIN; SEGMENTATION; METAANALYSIS AB Objectives: There are few methods to discern driving risks in patients with early dementia and mild cognitive impairment (MCI). We aimed to determine whether structural magnetic resonance imaging (MRI) of the hippocampusa biomarker of probable Alzheimer pathology and a measure of disease severity in those affectedis linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI. Methods: In all, 49 consensus-diagnosed participants from an Alzheimer's Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments. Results: Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the patients with MCI (B = -1.63, standard error [SE] = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio and 95% confidence interval for below-optimal lane control in the MCI group was 4.41 (1.18-16.36), which was attenuated to 3.46 (0.88-13.60) after accounting for the contribution of left hippocampal volume. Conclusion: These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and Alzheimer disease and whether these could be early markers of clinically meaningful driving risk. C1 [Griffith, H. Randall; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Ball, Karlene K.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Ball, Karlene K.; Marson, Daniel C.; Wadley, Virginia G.] Univ Alabama Birmingham, Dept Neurol, Alzheimers Dis Res Ctr, Birmingham, AL 35294 USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Stewart, Christopher C.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA. [Stoeckel, Luke E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoeckel, Luke E.] Harvard Univ, Sch Med, Boston, MA USA. [den Hollander, Jan A.; Wadley, Virginia G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Elgin, Jennifer M.; Owsley, Cynthia] Univ Alabama Birmingham, Dept Opthalmol, Birmingham, AL USA. [Elgin, Jennifer M.; Ball, Karlene K.; Owsley, Cynthia; Wadley, Virginia G.] Univ Alabama Birmingham, Dept Psychol, Edward R Roybal Ctr Translat Res Aging & Mobil, Birmingham, AL 35294 USA. [Harrell, Lindy E.; Clark, David G.] Birmingham Reg Vet Affairs Med Ctr, Dept Neurol, Birmingham, AL USA. RP Griffith, HR (reprint author), Ackerson & Associates, 1025 23rd St South,Suite 100, Birmingham, AL 35205 USA. EM henrygriffithphd@yahoo.com; vwadley@uab.edu FU National Institute on Aging (Alzheimer's Disease Research Center [[ADRC]-1P50 AG16582-10]; Alzheimer's of Central Alabama [1R01 AG021927-05, -1P30 AG022838-06] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grants from the National Institute on Aging (Alzheimer's Disease Research Center [ADRC]-1P50 AG16582-10: Marson, PI; Ball, Co-PI, and Wadley, Co-PI and Project Leader of the MILES Study), (1R01 AG021927-05: Marson, PI), (Edward R. Roybal Center -1P30 AG022838-06: Ball, PI), from Alzheimer's of Central Alabama (Griffith, PI). NR 50 TC 6 Z9 6 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2013 VL 26 IS 4 BP 259 EP 266 DI 10.1177/0891988713509138 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 248JX UT WOS:000326696800008 PM 24212246 ER PT J AU Gong, B Pan, Y Zhao, W Knable, L Vempati, P Begum, S Ho, L Wang, J Yemul, S Barnum, S Bilski, A Gong, BY Pasinetti, GM AF Gong, Bing Pan, Yong Zhao, Wei Knable, Lindsay Vempati, Prashant Begum, Shimul Ho, Lap Wang, Jun Yemul, Shrishailam Barnum, Scott Bilski, Amanda Gong, Ben Y. Pasinetti, Giulio M. TI IVIG immunotherapy protects against synaptic dysfunction in Alzheimer's disease through complement anaphylatoxin C5a-mediated AMPA-CREB-C/EBP signaling pathway SO MOLECULAR IMMUNOLOGY LA English DT Article DE Alzheimer's disease; Complement component C5a; IVIG; pCREB; LTP; Cognitive function ID LONG-TERM POTENTIATION; CULTURED HIPPOCAMPAL-NEURONS; INTRAVENOUS IMMUNOGLOBULIN; C5A RECEPTOR; GENE-EXPRESSION; MOUSE MODEL; CELL-DEATH; REGULATED KINASE; TRANSGENIC MICE; IN-VIVO AB Background: Complement component C5-derived C5a locally generated in the brain has been shown to protect against glutamate-induced neuronal apoptosis and beta-amyloid (A beta) toxicity, but the mechanism is not clear. In this study, we tested the hypothesis that C5a influences upstream signal transduction pathways associated with cAMP-response element-binding protein (CREB) activation, in which alterations of CREB levels are associated with cognitive deterioration in AD. Methods: CREB signaling pathway, synaptic plasticity and cognitive function were studied in C5a receptor knockout mice (C5aR(-/-)), C5a over expressing mice (C5a/GFAP) and in Tg2576 mice, an AD mouse model. Results: (1) Cognitive function is severely impaired in C5aR(-/-) mice, coincident with the down-regulated CREB/CEBP pathway in brain. (2) Either the application of recombinant-human-C5a (hrC5a) or exogenous expression of C5a in the brain of a mouse model (C5a/GFAP) enhances this pathway. (3) Application of hrC5a in brain slices from Tg2576 mice significantly improves deficits in long-term potentiation (LTP), while this effect is blocked by a specific AMPA receptor antagonist. (4) Searching for a pharmacological approach to locally mediate C5a responses in the brain, we found that low-dose human intravenous immunoglobulin (IVIG) treatment improves synaptic plasticity and cognitive function through C5a-mediated induction of the CREB/CEBP pathway, while the levels of A beta in the brain are not significantly affected. Conclusion: This study for the first time provides novel evidence suggesting that C5a may beneficially influence cognitive function in AD through an up-regulation of AMPA-CREB signaling pathway. IVIG may systematically improve cognitive function in AD brain by passing A beta toxicity. Published by Elsevier Ltd. C1 [Gong, Bing; Pan, Yong; Zhao, Wei; Knable, Lindsay; Vempati, Prashant; Begum, Shimul; Ho, Lap; Wang, Jun; Yemul, Shrishailam; Bilski, Amanda; Gong, Ben Y.; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, Ctr Excellence Novel Approaches Neurotherapeut, New York, NY 10029 USA. [Barnum, Scott] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU Veterans Administration by the US National Institutes of Health; Alzheimer's Association [IIRG-08-89354, IIRG-12-242345] FX The studies described here were supported in part from a grant from the Veterans Administration by the US National Institutes of Health grants to G.M.P and by grants from Alzheimer's Association (IIRG-08-89354 and IIRG-12-242345) to B.G. We thank Dr. Ottavio Arancio for providing technical support of reported electrophysiological recording. We thank Dr. Jorg Kohl for sharing the c5a receptor antagonist reagent. NR 63 TC 17 Z9 19 U1 1 U2 49 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2013 VL 56 IS 4 BP 619 EP 629 DI 10.1016/j.molimm.2013.06.016 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 241XZ UT WOS:000326203300036 PM 23911420 ER PT J AU Blevins, JE Ho, JM AF Blevins, James E. Ho, Jacqueline M. TI Role of oxytocin signaling in the regulation of body weight SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Review DE Satiety; Meal size; Oxytocin; Hindbrain ID GLUCAGON-LIKE PEPTIDE-1; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PROLACTIN-RELEASING PEPTIDE; DIET-INDUCED OBESITY; C-FOS EXPRESSION; CENTRAL-NERVOUS-SYSTEM; DORSAL VAGAL COMPLEX; VENTRAL TEGMENTAL AREA; BRAIN-STEM NUCLEI; HIGH-FAT DIET AB Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models. C1 [Blevins, James E.; Ho, Jacqueline M.] VA Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Dept Vet Affairs Med Ctr, Seattle, WA 98108 USA. [Blevins, James E.; Ho, Jacqueline M.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Dept Vet Affairs Med Ctr, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA); Department of VA Merit Review Research Program FX This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA). The research in our laboratory has been supported by the Department of VA Merit Review Research Program. The authors are appreciative of the efforts by Vishwanath Anekonda, Benjamin Thompson, Denis Baskin and Bang Hwang for their assistance in critically reviewing this manuscript. NR 234 TC 22 Z9 23 U1 2 U2 26 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 EI 1573-2606 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2013 VL 14 IS 4 BP 311 EP 329 DI 10.1007/s11154-013-9260-x PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 245JG UT WOS:000326459300002 PM 24065622 ER PT J AU Zhou, C Cai, X Grottkau, BE Lin, Y AF Zhou, C. Cai, X. Grottkau, B. E. Lin, Y. TI BMP4 promotes vascularization of human adipose stromal cells and endothelial cells in vitro and in vivo SO CELL PROLIFERATION LA English DT Article ID MESENCHYMAL STEM-CELLS; IFATS COLLECTION; PROGENITOR CELLS; BONE-MARROW; TISSUE; ANGIOGENESIS; DIFFERENTIATION; EXPRESSION; REGULATOR; NETWORKS AB ObjectivesVascularization is a major obstacle to clinical application of regenerative medicine. Engineered tissues must be able to generate an early vascular network that can quickly connect with the host vasculature. Recent research demonstrates that natural adipose tissues contain abundant stromal cells, which can give rise to pericytes. In this study, we aimed to investigate the application of human adipose stromal cells (ASCs) to vascularization, and the function of BMP4 protein during vascularization. Materials and methodsImmunofluorescence staining for -SMA and PDGFR- were utilized to identify characteristics of ASCs/pericytes. They were then loaded into a collagen-fibronectin gel with endothelial cells to assess their vascularization ability, both in vitro and in vivo. ResultsWe showed that the ASCs expressed some of the essential markers of pericytes and they were able to promote vascularization with endothelial cells in 3D culture, both in vitro and in vivo. BMP4 protein further promoted this vascularization. ConclusionAdipose stromal cells promoted vascularization by endothelial cells and BMP4 protein further enhanced this effect. C1 [Zhou, C.; Cai, X.; Lin, Y.] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. [Grottkau, B. E.; Lin, Y.] MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA 02114 USA. [Grottkau, B. E.; Lin, Y.] Harvard Univ, Sch Med, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA 02114 USA. RP Grottkau, BE (reprint author), MassGen Hosp Children, Dept Orthopaed Surg, 15 Parkman St, Boston, MA 02114 USA. EM bgrottkau@partners.org; yunfenglin@scu.edu.cn RI Lin, Yunfeng/M-5438-2013; Lin, Yunfeng/H-3393-2011; OI Lin, Yunfeng/0000-0003-1224-6561; Lin, Yunfeng/0000-0003-1224-6561; Cai, Xiaoxiao/0000-0002-5654-7414 FU Peabody Foundation, Inc.; Constance and Anthony A Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children; National Natural Science Foundation of China [81071273, 31170929, 81201211]; Foundation for the Author of National Excellent Doctoral Dissertation of China [FANEDD 200977]; Ministry of Education of China [20110181120071] FX This work was funded by the Peabody Foundation, Inc., the Constance and Anthony A Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children, and National Natural Science Foundation of China (81071273, 31170929, 81201211), Foundation for the Author of National Excellent Doctoral Dissertation of China (FANEDD 200977), Doctoral Fund of Ministry of Education of China (20110181120071). NR 34 TC 3 Z9 3 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7722 EI 1365-2184 J9 CELL PROLIFERAT JI Cell Prolif. PD DEC PY 2013 VL 46 IS 6 BP 695 EP 704 DI 10.1111/cpr.12073 PG 10 WC Cell Biology SC Cell Biology GA 242IV UT WOS:000326233800010 PM 24460721 ER PT J AU Pekkala, S Wiener, D Himali, JJ Beiser, AS Obler, LK Liu, YL McKee, A Auerbach, S Seshadri, S Wolf, PA Au, R AF Pekkala, Seija Wiener, Debra Himali, Jayandra J. Beiser, Alexa S. Obler, Loraine K. Liu, Yulin McKee, Ann Auerbach, Sanford Seshadri, Sudha Wolf, Philip A. Au, Rhoda TI Lexical retrieval in discourse: An early indicator of Alzheimer's dementia SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE Alzheimer's disease; discourse; early markers; naming; neuropathology ID MILD COGNITIVE IMPAIRMENT; VERBAL FLUENCY TASKS; BOSTON NAMING TEST; SEMANTIC MEMORY; WORKING-MEMORY; WORD PRODUCTION; OLD-AGE; FRONTOTEMPORAL DEMENTIA; ASSOCIATION WORKGROUPS; EXECUTIVE DYSFUNCTION AB We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n=23) and a comparison group without criteria for AD (n=24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7-9 years prior to death and FAS and BNT only at 2-4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD. C1 [Pekkala, Seija] Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland. [Wiener, Debra] Bromfield Sch, Harvard, MA USA. [Himali, Jayandra J.; Beiser, Alexa S.; Obler, Loraine K.; McKee, Ann; Auerbach, Sanford; Seshadri, Sudha; Au, Rhoda] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Himali, Jayandra J.; Beiser, Alexa S.; Liu, Yulin; Auerbach, Sanford; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Himali, Jayandra J.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Obler, Loraine K.] CUNY, Grad Ctr, Program Speech Language Hearing Sci, New York, NY USA. [Obler, Loraine K.; McKee, Ann] VA Boston Hlth Care Syst, Boston, MA USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol Med & Publ Hlth, Boston, MA 02118 USA. RP Pekkala, S (reprint author), Univ Helsinki, Inst Behav Sci, POB 9,Siltavuorenpenger 3 A, FIN-00014 Helsinki, Finland. EM seija.pekkala@helsinki.fi OI Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU National Health Institute, National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [NS17950]; National Institute of Aging [AG08122, AG16495]; Academy of Finland [213023] FX This manuscript has been supported by the National Health Institute, National Heart, Lung, and Blood Institute N01-HC-25195, National Institute of Neurological Disorders and Stroke NS17950, and the National Institute of Aging AG08122, AG16495. The manuscript has also been supported by the Academy of Finland (S. Pekkala, project number 213023). The authors report no conflicts of interest. NR 122 TC 8 Z9 8 U1 4 U2 24 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9206 EI 1464-5076 J9 CLIN LINGUIST PHONET JI Clin. Linguist. Phon. PD DEC PY 2013 VL 27 IS 12 BP 905 EP 921 DI 10.3109/02699206.2013.815278 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 240TD UT WOS:000326119000005 PM 23985011 ER PT J AU Wang, SB Park, WM Gadikota, HR Miao, J Kim, YH Wood, KB Li, GA AF Wang, Shaobai Park, Won Man Gadikota, Hemanth R. Miao, Jun Kim, Yoon Hyuk Wood, Kirkham B. Li, Guoan TI A combined numerical and experimental technique for estimation of the forces and moments in the lumbar intervertebral disc SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Article DE lumbar spine; intervertebral disc; finite element analysis; imaging techniques; robotic experiment; joint force ID FINITE-ELEMENT-ANALYSIS; LOW-BACK-PAIN; IN-VIVO; MOTION SEGMENT; LOADING CONDITIONS; SPINE; DEGENERATION; BODY; MECHANICS; BONE AB Evaluation of the loads on lumbar intervertebral discs (IVD) is critically important since it is closely related to spine biomechanics, pathology and prosthesis design. Non-invasive estimation of the loads in the discs remains a challenge. In this study, we proposed a new technique to estimate in vivo loads in the IVD using a subject-specific finite element (FE) model of the disc and the kinematics of the disc endplates as input boundary conditions. The technique was validated by comparing the forces and moments in the discs calculated from the FE analyses to the in vitro experiment measurements of three corresponding lumbar discs. The results showed that the forces and moments could be estimated within an average error of 20%. Therefore, this technique can be a promising tool for non-invasive estimation of the loads in the discs and may be extended to be used on living subjects. C1 [Wang, Shaobai; Park, Won Man; Gadikota, Hemanth R.; Miao, Jun; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Park, Won Man; Kim, Yoon Hyuk] Kyung Hee Univ, Dept Mech Engn, Suwon, South Korea. [Miao, Jun] Tianjin Hosp, Tianjin, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NASS; SRS; NIH [R21AR057989]; NAP [P-09-JC-LU63-C01] FX We would like to acknowledge the financial supports from NASS, SRS, NIH (R21AR057989) and NAP (P-09-JC-LU63-C01). NR 43 TC 5 Z9 5 U1 4 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-5842 EI 1476-8259 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PD DEC 1 PY 2013 VL 16 IS 12 BP 1278 EP 1286 DI 10.1080/10255842.2012.668537 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA 243XF UT WOS:000326351000004 PM 22551235 ER PT J AU Markowitz, JT Harrington, KR Laffel, LMB AF Markowitz, Jessica T. Harrington, Kara R. Laffel, Lori M. B. TI Technology to Optimize Pediatric Diabetes Management and Outcomes SO CURRENT DIABETES REPORTS LA English DT Article DE Pediatric diabetes; Technology; Psychosocial; Continuous glucose monitoring; Insulin pump; Management; Outcomes ID AUGMENTED PUMP THERAPY; LOOP GLUCOSE CONTROL; RANDOMIZED CONTROLLED-TRIAL; GLYCEMIC CONTROL; ARTIFICIAL PANCREAS; BLOOD-GLUCOSE; TREATMENT SATISFACTION; INSULIN DELIVERY; CLINICAL-TRIAL; YOUNG-PEOPLE AB Technology for diabetes management is rapidly developing and changing. With each new development, there are numerous factors to consider, including medical benefits, impact on quality of life, ease of use, and barriers to use. It is also important to consider the interaction between developmental stage and technology. This review considers a number of newer diabetes-related technologies and explores issues related to their use in the pediatric diabetes population (including young adults), with a focus on psychosocial factors. Areas include trend technology in blood glucose monitoring, continuous glucose monitoring, sensor-augmented insulin pumps and low glucose suspend functions, internet applications including videoconferencing, mobile applications (apps), text messaging, and online gaming. C1 [Markowitz, Jessica T.; Harrington, Kara R.; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu; kara.harrington@joslin.harvard.edu; lori.laffel@joslin.harvard.edu RI Emchi, Karma/Q-1952-2016 FU National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK092335, 1R01DK095273, 5R01DK089349]; William Randolph Hearst Foundation; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; Eleanor Chesterman Beatson Fund FX This work was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant 1K23DK092335, the William Randolph Hearst Foundation, the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Fund, the Eleanor Chesterman Beatson Fund, National Institute of Diabetes and Digestive and Kidney Diseases Grant 1R01DK095273 and National Institute of Diabetes and Digestive and Kidney Diseases Grant 5R01DK089349 Reference List. NR 55 TC 8 Z9 8 U1 2 U2 19 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2013 VL 13 IS 6 BP 877 EP 885 DI 10.1007/s11892-013-0419-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 241SR UT WOS:000326188500013 PM 24046146 ER PT J AU Hanlan, ME Griffith, J Patel, N Jaser, SS AF Hanlan, Margo E. Griffith, Julie Patel, Niral Jaser, Sarah S. TI Eating Disorders and Disordered Eating in Type 1 Diabetes: Prevalence, Screening, and Treatment Options SO CURRENT DIABETES REPORTS LA English DT Article DE Adolescents; Adolescence; Type 1 diabetes; Diabetes mellitus; Eating disorder; Disordered eating; Anorexia nervosa; Bulimia nervosa; Disordered eating behavior; Screening tool; Treatment; Glycemic control; Insulin; Prevalence ID COMORBIDITY SURVEY REPLICATION; SUPPLEMENT NCS-A; ADOLESCENT GIRLS; YOUNG-ADULTS; MICROVASCULAR COMPLICATIONS; ANOREXIA-NERVOSA; MENTAL-DISORDERS; BULIMIA-NERVOSA; BEHAVIOR; MELLITUS AB This review is focused on the prevalence of eating disorders and disordered eating behaviors in individuals with type 1 diabetes. Recent research indicates higher prevalence rates of eating disorders among people with type 1 diabetes compared with their peers without diabetes. Eating disorders and disordered eating behaviors-especially insulin omission-are associated with poorer glycemic control and serious risk for increased morbidity and mortality. Screening should begin in pre-adolescence and continue through early adulthood, as many disordered eating behaviors begin during the transition to adolescence and may persist for years. Available screening tools and treatment options are reviewed. Given the complexity of diabetes management in combination with eating disorder treatment, it is imperative to screen early and often, in order to identify those most vulnerable and begin appropriate treatment in a timely manner. C1 [Hanlan, Margo E.] Preferred Pediat, Fredericksburg, VA USA. [Griffith, Julie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Patel, Niral; Jaser, Sarah S.] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. RP Jaser, SS (reprint author), Vanderbilt Univ, Dept Pediat, 2200 Childrens Way, Nashville, TN 37232 USA. EM MHanlan@ppfred.com; julie.griffith@joslin.harvard.edu; niral.patel@vanderbilt.edu; sarah.jaser@vanderbilt.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 NK088454] FX Sarah S. Jaser is supported by an award from the National Institute of Diabetes and Digestive and Kidney Diseases (K23 NK088454). NR 51 TC 9 Z9 9 U1 2 U2 24 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2013 VL 13 IS 6 BP 909 EP 916 DI 10.1007/s11892-013-0418-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 241SR UT WOS:000326188500017 ER PT J AU Celano, CM Beale, EE Moore, SV Wexler, DJ Huffman, JC AF Celano, Christopher M. Beale, Eleanor E. Moore, Shannon V. Wexler, Deborah J. Huffman, Jeff C. TI Positive Psychological Characteristics in Diabetes: A Review SO CURRENT DIABETES REPORTS LA English DT Review DE Diabetes; Positive affect; Well-being; Self-efficacy; Optimism; Resilience; Positive psychological characteristics ID RANDOMIZED CONTROLLED-TRIAL; SELF-MANAGEMENT EDUCATION; CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; GLYCEMIC CONTROL; PHYSICAL-ACTIVITY; RATE-VARIABILITY; PSYCHOSOCIAL FACTORS; DEPRESSIVE SYMPTOMS; CORTISOL RESPONSES AB Positive psychological characteristics, such as optimism, self-efficacy, and resilience, have been increasingly associated with improved outcomes in medically ill individuals. However, there has been minimal systematic review of these characteristics and their associations with outcomes in people with diabetes. We aim to review these associations, their potential mediating mechanisms, and the evidence supporting interventions targeting these qualities. In people with diabetes, positive psychological characteristics are significantly associated with improved glycemic control, fewer complications, and reduced rates of mortality. Potential mechanisms mediating these associations include behavioral factors (e.g., improved treatment adherence), reduced inflammation, and improved neuroendocrine and autonomic functioning. Most psychosocial treatments in this population have focused on improving self-efficacy and resilience; such interventions may improve quality of life, well-being, and diabetes self-care. While untested in diabetes, interventions to boost other positive characteristics have been effective in other medically ill patients and may warrant further study in this cohort. C1 [Celano, Christopher M.; Wexler, Deborah J.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Celano, Christopher M.; Beale, Eleanor E.; Moore, Shannon V.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wexler, Deborah J.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. RP Celano, CM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM ccelano@partners.org; eebeale@partners.org; svmoore@partners.org; dwexler@partners.org; jhuffman@partners.org FU NIH/NHLBI FX Christopher M. Celano was provided a Dupont-Warren Fellowship to study positive psychological interventions in patients in the depressed phase of bipolar disorder from Harvard Medical School. Jeff C. Huffman has received grant funding for positive psychology research in cardiac patients from NIH/NHLBI. NR 136 TC 10 Z9 10 U1 2 U2 30 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2013 VL 13 IS 6 BP 917 EP 929 DI 10.1007/s11892-013-0430-8 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 241SR UT WOS:000326188500018 PM 24048687 ER PT J AU Stollenwerk, B Gandjour, A Lungen, M Siebert, U AF Stollenwerk, Bjoern Gandjour, Afschin Luengen, Markus Siebert, Uwe TI Accounting for increased non-target-disease-specific mortality in decision-analytic screening models for economic evaluation SO EUROPEAN JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Screening; Decision-analytic modelling; Mortality; Model; Hazard ratio ID COST-EFFECTIVENESS MODELS; CORONARY-ARTERY-DISEASE; RISK-FACTORS; CERVICAL-CANCER; COMPUTED-TOMOGRAPHY; UTILITY ANALYSIS; LIFE EXPECTANCY; DIAGNOSTIC-TEST; HEART-DISEASE; MARKOV MODEL AB Positive screening results are often associated not only with target-disease-specific but also with non-target-disease-specific mortality. In general, this association is due to joint risk factors. Cost-effectiveness estimates based on decision-analytic models may be biased if this association is not reflected appropriately. To develop a procedure for quantifying the degree of bias when an increase in non-target-disease-specific mortality is not considered. We developed a family of parametric functions that generate hazard ratios (HRs) of non-target-disease-specific mortality between subjects screened positive and negative, with the HR of target-disease-specific mortality serving as the input variable. To demonstrate the efficacy of this procedure, we fitted a function within the context of coronary artery disease (CAD) risk screening, based on HRs related to different risk factors extracted from published studies. Estimates were embedded into a decision-analytic model, and the impact of 'modelling increased non-target-disease-specific mortality' was assessed. In 55-year-old German men, based on a risk screening with 5 % positively screened subjects, and a CAD risk ratio of 6 within the first year after screening, incremental quality-adjusted life-years were 19 % higher and incremental costs were 8 % lower if no adjustment was made. The effect varied depending on age, gender, the explanatory power of the screening test and other factors. Some bias can occur when an increase in non-target-disease-specific mortality is not considered when modelling the outcomes of screening tests. C1 [Stollenwerk, Bjoern] Helmholtz Zentrum Munchen GmbH, Inst Hlth Econ & Hlth Care Management, D-85764 Neuherberg, Germany. [Stollenwerk, Bjoern; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, A-6060 Hall Intirol, Austria. [Gandjour, Afschin] Frankfurt Sch Finance & Management, D-60314 Frankfurt, Germany. [Luengen, Markus] Univ Appl Sci, Hsch Osnabruck, Fac Business Management & Social Sci, D-49076 Osnabruck, Germany. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment,Dept Radiol, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling Hlth Technol Assess, Innsbruck, Austria. RP Stollenwerk, B (reprint author), Helmholtz Zentrum Munchen GmbH, Inst Hlth Econ & Hlth Care Management, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM bjoern.stollenwerk@helmholtz-muenchen.de NR 61 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1618-7598 EI 1618-7601 J9 EUR J HEALTH ECON JI Eur. J. Health Econ. PD DEC PY 2013 VL 14 IS 6 BP 1035 EP 1048 DI 10.1007/s10198-012-0454-z PG 14 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 240QE UT WOS:000326111200019 PM 23275043 ER PT J AU Billings, CJ McMillan, GP Penman, TM Gille, SM AF Billings, Curtis J. McMillan, Garnett P. Penman, Tina M. Gille, Sun Mi TI Predicting Perception in Noise Using Cortical Auditory Evoked Potentials SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE cortical auditory evoked potentials (CAEPs); event-related potentials (ERPs); signals in noise; signal-to-noise ratio (SNR); background noise; N1 ID RATE-INTENSITY FUNCTIONS; SENSORY GAIN-CONTROL; BROAD-BAND NOISE; SPEECH; RECOGNITION; CORTEX; SOUND; AMPLIFICATION; FREQUENCY; STIMULI AB Speech perception in background noise is a common challenge across individuals and health conditions (e.g., hearing impairment, aging, etc.). Both behavioral and physiological measures have been used to understand the important factors that contribute to perception-in-noise abilities. The addition of a physiological measure provides additional information about signal-in-noise encoding in the auditory system and may be useful in clarifying some of the variability in perception-in-noise abilities across individuals. Fifteen young normal-hearing individuals were tested using both electrophysiology and behavioral methods as a means to determine (1) the effects of signal-to-noise ratio (SNR) and signal level and (2) how well cortical auditory evoked potentials (CAEPs) can predict perception in noise. Three correlation/regression approaches were used to determine how well CAEPs predicted behavior. Main effects of SNR were found for both electrophysiology and speech perception measures, while signal level effects were found generally only for speech testing. These results demonstrate that when signals are presented in noise, sensitivity to SNR cues obscures any encoding of signal level cues. Electrophysiology and behavioral measures were strongly correlated. The best physiological predictors (e.g., latency, amplitude, and area of CAEP waves) of behavior (SNR at which 50 % of the sentence is understood) were N1 latency and N1 amplitude measures. In addition, behavior was best predicted by the 70-dB signal/5-dB SNR CAEP condition. It will be important in future studies to determine the relationship of electrophysiology and behavior in populations who experience difficulty understanding speech in noise such as those with hearing impairment or age-related deficits. C1 [Billings, Curtis J.; McMillan, Garnett P.; Penman, Tina M.; Gille, Sun Mi] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Billings, Curtis J.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97239 USA. RP Billings, CJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM curtis.billings2@va.gov FU National Institute on Deafness and Other Communication Disorders [R03DC10914]; VA Rehabilitation Research and Development Service [C4844C, C8006W] FX We wish to thank Drs. Marjorie Leek, Robert Burkard, and Kelly Tremblay for the comments on the design of this experiment and earlier versions of this manuscript. This work was supported by a grant from the National Institute on Deafness and Other Communication Disorders (R03DC10914) and career development awards from the VA Rehabilitation Research and Development Service (C4844C and C8006W). NR 35 TC 10 Z9 12 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2013 VL 14 IS 6 BP 891 EP 903 DI 10.1007/s10162-013-0415-y PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 243AR UT WOS:000326289200008 PM 24030818 ER PT J AU Wolf, EJ Harrington, KM Clark, SL Miller, MW AF Wolf, Erika J. Harrington, Kelly M. Clark, Shaunna L. Miller, Mark W. TI Sample Size Requirements for Structural Equation Models: An Evaluation of Power, Bias, and Solution Propriety SO EDUCATIONAL AND PSYCHOLOGICAL MEASUREMENT LA English DT Article DE structural equation modeling; confirmatory factor analysis; sample size; statistical power; Monte Carlo simulation; bias; solution propriety ID MAXIMUM-LIKELIHOOD-ESTIMATION; CONFIRMATORY FACTOR-ANALYSIS; MONTE-CARLO; STATISTICAL POWER; MISSING DATA; FIT INDEXES; VALUES; NUMBER; IMPACT AB Determining sample size requirements for structural equation modeling (SEM) is a challenge often faced by investigators, peer reviewers, and grant writers. Recent years have seen a large increase in SEMs in the behavioral science literature, but consideration of sample size requirements for applied SEMs often relies on outdated rules-of-thumb. This study used Monte Carlo data simulation techniques to evaluate sample size requirements for common applied SEMs. Across a series of simulations, we systematically varied key model properties, including number of indicators and factors, magnitude of factor loadings and path coefficients, and amount of missing data. We investigated how changes in these parameters affected sample size requirements with respect to statistical power, bias in the parameter estimates, and overall solution propriety. Results revealed a range of sample size requirements (i.e., from 30 to 460 cases), meaningful patterns of association between parameters and sample size, and highlight the limitations of commonly cited rules-of-thumb. The broad lessons learned for determining SEM sample size requirements are discussed. C1 [Wolf, Erika J.; Harrington, Kelly M.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wolf, Erika J.; Harrington, Kelly M.; Miller, Mark W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Clark, Shaunna L.] Virginia Commonwealth Univ, Sch Pharm, Ctr Biomarker Res & Personalized Med, Richmond, VA USA. RP Wolf, EJ (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 South Huntington Ave, Boston, MA 02130 USA. EM erika.wolf@va.gov FU VA Career Development Award; National Institute on Alcohol Abuse and Alcoholism [K01AA021266] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by a VA Career Development Award to Erika J. Wolf, and by National Institute on Alcohol Abuse and Alcoholism grant K01AA021266 awarded to Shaunna L. Clark. NR 36 TC 84 Z9 84 U1 3 U2 50 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0013-1644 EI 1552-3888 J9 EDUC PSYCHOL MEAS JI Educ. Psychol. Meas. PD DEC PY 2013 VL 73 IS 6 BP 913 EP 934 DI 10.1177/0013164413495237 PG 22 WC Psychology, Educational; Mathematics, Interdisciplinary Applications; Psychology, Mathematical SC Psychology; Mathematics GA 239RV UT WOS:000326044000001 PM 25705052 ER PT J AU Bzdok, D Laird, AR Zilles, K Fox, PT Eickhoff, SB AF Bzdok, Danilo Laird, Angela R. Zilles, Karl Fox, Peter T. Eickhoff, Simon B. TI An Investigation of the Structural, Connectional, and Functional Subspecialization in the Human Amygdala SO HUMAN BRAIN MAPPING LA English DT Article DE amygdala; data mining; parcellation; connectivity; behavior; social cognition ID BRAINS DEFAULT NETWORK; RHESUS-MONKEY; LIKELIHOOD ESTIMATION; CINGULATE CORTEX; MACAQUE MONKEY; IN-VIVO; CYTOARCHITECTONIC MAPS; ORBITOFRONTAL CORTEX; SUPERFICIAL AMYGDALA; BASOLATERAL AMYGDALA AB Although the amygdala complex is a brain area critical for human behavior, knowledge of its subspecialization is primarily derived from experiments in animals. We here employed methods for large-scale data mining to perform a connectivity-derived parcellation of the human amygdala based on whole-brain coactivation patterns computed for each seed voxel. Voxels within the histologically defined human amygdala were clustered into distinct groups based on their brain-wide coactivation maps. Using this approach, connectivity-based parcellation divided the amygdala into three distinct clusters that are highly consistent with earlier microstructural distinctions. Meta-analytic connectivity modelling then revealed the derived clusters' brain-wide connectivity patterns, while meta-data profiling allowed their functional characterization. These analyses revealed that the amygdala's laterobasal nuclei group was associated with coordinating high-level sensory input, whereas its centromedial nuclei group was linked to mediating attentional, vegetative, and motor responses. The often-neglected superficial nuclei group emerged as particularly sensitive to olfactory and probably social information processing. The results of this model-free approach support the concordance of structural, connectional, and functional organization in the human amygdala and point to the importance of acknowledging the heterogeneity of this region in neuroimaging research. Hum Brain Mapp 34:3247-3266, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Bzdok, Danilo; Eickhoff, Simon B.] Rhein Westfal TH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany. [Bzdok, Danilo; Zilles, Karl; Eickhoff, Simon B.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Bzdok, Danilo; Zilles, Karl; Eickhoff, Simon B.] Julich Aachen Res Alliance JARA Translat Brain Me, Aachen, Germany. [Zilles, Karl] Univ Dusseldorf, C&O Vogt Inst Brain Res, Dusseldorf, Germany. [Laird, Angela R.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Laird, Angela R.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. RP Eickhoff, SB (reprint author), Forschungszentrum Julich, Inst Neurowissensch & Med INM 2, D-52425 Julich, Germany. EM S.Eickhoff@fz-juelich.de RI Zilles, Karl/J-9704-2013; Fox, Peter/B-4725-2010; Eickhoff, Simon/K-2061-2013 OI Zilles, Karl/0000-0001-9296-9959; Zilles, Karl/0000-0002-4705-4175; Fox, Peter/0000-0002-0465-2028; Eickhoff, Simon/0000-0001-6363-2759 FU German Research Council [IRTG 1328]; Human Brain Project [R01-MH074457-01A1]; Helmholtz Initiative on Systems-Biology FX Contract grant sponsor: German Research Council; Contract grant number: DFG, IRTG 1328; Contract grant sponsor: Human Brain Project; Contract grant number: R01-MH074457-01A1; Contract grant sponsor: Helmholtz Initiative on Systems-Biology. NR 134 TC 71 Z9 72 U1 3 U2 43 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2013 VL 34 IS 12 BP 3247 EP 3266 DI 10.1002/hbm.22138 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 240BC UT WOS:000326068700011 PM 22806915 ER PT J AU Wang, MQ Rahnama, R Cheng, T Grotkopp, E Jacobs, L Limburg, S Kim, HT Kuo, AC AF Wang, Miqi Rahnama, Ruyan Cheng, Tiffany Grotkopp, Eva Jacobs, Linsey Limburg, Sonja Kim, Hubert T. Kuo, Alfred C. TI Trophic Stimulation of Articular Chondrocytes by Late-Passage Mesenchymal Stem Cells in Coculture SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE coculture; mesenchymal stem cells; chondrogenesis; trophic ID CHONDROGENIC DIFFERENTIATION; PROLIFERATION; CULTURE; HYPERTROPHY; CARTILAGE AB Coculture of mesenchymal stem cells (MSCs) with articular chondrocytes (ACs) increases glycosaminoglycan (GAG) accumulation compared to monoculture. MSCs might (1) differentiate into ACs (progenitor role) and/or (2) stimulate AC matrix metabolism (trophic role). MSCs lose the ability to undergo chondrogenesis after extended passaging. We hypothesized that MSCs act predominantly as progenitors, and that late-passage MSCs without chondrogenic potential would be unable to increase GAG in coculture. Early- and late-passage human MSCs (hMSCs) were grown in pellet monoculture under chondrogenic conditions and in pellet coculture with bovine ACs. Chondrogenesis was assessed with GAG quantification, safranin-O staining, and quantitative PCR (qPCR). Contributions of human and bovine cells were assessed with species-specific qPCR and human-specific immunostaining. Late-passage hMSCs did not undergo chondrogenesis in monoculture with chondrogenic stimuli or in coculture with ACs. Early-passage hMSCs underwent chondrogenesis only in response to chondrogenic stimuli. Coculture pellets in both cases accumulated as much GAG/DNA as monoculture AC pellets. Aggrecan transcription was not increased in coculture. Late-passage hMSCs that do not undergo chondrogenesis are capable of stimulating GAG accumulation in coculture with ACs. This supports a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after prolonged passaging. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 31:1936-1942, 2013 C1 [Wang, Miqi; Rahnama, Ruyan; Cheng, Tiffany; Jacobs, Linsey; Limburg, Sonja; Kim, Hubert T.; Kuo, Alfred C.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Grotkopp, Eva; Kim, Hubert T.; Kuo, Alfred C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Kuo, AC (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. EM kuoac@orthosurg.ucsf.edu FU Orthopaedic Research and Education Foundation; Musculoskeletal Transplant Foundation FX This study was performed with the support of the Orthopaedic Research and Education Foundation and the Musculoskeletal Transplant Foundation and with the resources of the San Francisco Veterans Affairs Medical Center. NR 17 TC 11 Z9 11 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD DEC PY 2013 VL 31 IS 12 BP 1936 EP 1942 DI 10.1002/jor.22466 PG 7 WC Orthopedics SC Orthopedics GA 238ZG UT WOS:000325990300011 PM 24038580 ER PT J AU Taneja, AK Simeone, FJ Chang, CY Kumar, V Daley, S Bredella, MA Torriani, M AF Taneja, Atul K. Simeone, F. Joseph Chang, Connie Y. Kumar, Vidhya Daley, Scott Bredella, Miriam A. Torriani, Martin TI Peroneal tendon abnormalities in subjects with an enlarged peroneal tubercle SO SKELETAL RADIOLOGY LA English DT Article DE Peroneal tubercle; Retrotrochlear eminence; Calcaneus; Peroneal tendons; MRI ID MR-IMAGING FEATURES; LONGUS TENDON; STENOSING TENOSYNOVITIS; HYPERTROPHY; VARIANTS AB To examine the association between inframalleolar peroneal tendon abnormalities and an enlarged peroneal tubercle. Two independent readers evaluated consecutive ankle MR imaging studies to classify inframalleolar peroneal tendon findings as normal, tenosynovitis, partial tear or complete tear. The size and morphology of the peroneal tubercle was also recorded. We performed statistical analyses for inter-observer agreement and to assess differences in peroneal tubercle size between groups with and without peroneal tendon abnormalities. The study group comprised 121 subjects (mean age, 45.5 years) of whom 28 % (34 out of 121) had lateral ankle symptoms. The peroneal tubercle was absent in 56 % of subjects (68 out of 121). In subjects with a peroneal tubercle (> 0 mm), the mean size was 3.5 mm (37 % triangular and 7 % plateau-shaped). Male subjects had significantly larger mean peroneal tubercle size than female subjects (2.1 +/- 2.5 vs 1.2 +/- 1.9 mm, P = 0.04). Overall, 26 % (32 out of 121) of subjects had some peroneal tendon abnormality: 17 % (20 out of 121) had tenosynovitis and 17 % (20 out of 121) had partial thickness tears. The peroneal tubercle size was significantly larger in subjects with peroneal tendon partial tears (P = 0.036), tenosynovitis (P < 0.001), and when both abnormalities were present (P = 0.007). ROC statistic showed 73 % sensitivity and 74 % specificity for detection of partial tears for peroneal tubercle size a parts per thousand yen4.3 mm. Our study shows a significantly larger peroneal tubercle in subjects with inframalleolar peroneal tendon abnormalities. A cut-off of 4.3 mm showed good sensitivity and specificity for the presence of partial tears of the peroneal tendon. C1 [Taneja, Atul K.; Simeone, F. Joseph; Chang, Connie Y.; Kumar, Vidhya; Daley, Scott; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Taneja, Atul K.; Simeone, F. Joseph; Chang, Connie Y.; Kumar, Vidhya; Daley, Scott; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM torriani.martin@mgh.harvard.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 15 TC 1 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2013 VL 42 IS 12 BP 1703 EP 1709 DI 10.1007/s00256-013-1725-1 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 238LC UT WOS:000325947000008 PM 24057440 ER PT J AU Reese, HE Rosenfield, E Wilhelm, S AF Reese, Hannah E. Rosenfield, Elizabeth Wilhelm, Sabine TI Reflections on the Theory-Practice Gap in Cognitive Behavior Therapy SO BEHAVIOR THERAPY LA English DT Editorial Material DE cognitive behavioral therapy; theory; practice; dissemination AB The papers in this special series, edited by Pilecki and McKay (2013 this issue), are devoted to examining the theory-practice gap in cognitive-behavior therapy (CBT). A gap between theory and practice can occur at more than one level. First, there exists a substantial and concerning gap between the theories and interventions supported by research and those being offered to patients in the community (i.e., research-practice gap). There is also a growing concern in the field that the techniques and procedures that characterize cognitive-behavioral therapies are becoming increasingly divorced from underlying theories (i.e., theory-procedure gap). In the present commentary we hope to summarize and comment on some of the themes, issues, and future directions raised by our contributors. C1 [Reese, Hannah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Reese, HE (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hreese@parmers.org NR 16 TC 2 Z9 2 U1 3 U2 17 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD DEC PY 2013 VL 44 IS 4 BP 609 EP 613 PG 5 WC Psychology, Clinical SC Psychology GA 236GI UT WOS:000325783100008 PM 24094786 ER PT J AU Aderka, IM Pollack, MH Simon, NM Smits, JAJ Van Ameringen, M Stein, MB Hofmann, SG AF Aderka, Idan M. Pollack, Mark H. Simon, Naomi M. Smits, Jasper A. J. Van Ameringen, Michael Stein, Murray B. Hofmann, Stefan G. TI Development of a Brief Version of the Social Phobia Inventory Using Item Response Theory: The Mini-SPIN-R SO BEHAVIOR THERAPY LA English DT Article DE social anxiety disorder; social phobia inventory; item response theory; psychometric properties; assessment ID AVOIDANT PERSONALITY-DISORDER; ANXIETY INVENTORY; PSYCHOMETRIC PROPERTIES; CONCURRENT VALIDITY; POSITIVE EVALUATION; DEPRESSION SCALE; DSM-IV; SAMPLE; FEAR; SUBTYPE AB The Social Phobia Inventory (SPIN) is a widely used measure in mental health settings and a 3-item version (mini-SPIN) has been developed as a screening instrument for social anxiety disorder. In the present study, we examined the psychometric properties of the SPIN and developed a brief version (mini-SPIN-R) designed to assess social anxiety severity using item response theory. Our sample included 569 individuals with social anxiety disorder who participated in 2 clinical trials and filled out a battery of self-report measures. Using a nonparametric kernel smoothing method we identified the most sensitive items of the SPIN. These 3 items comprised the mini-SPIN-R, which was found to have greater internal consistency, and to capture a greater range of symptoms compared to the mini-SPIN. The mini-SPIN-R evidenced superior convergent validity compared to the mini-SPIN and both measures had similar divergent validity. Thus, the mini-SPIN-R is a promising brief measure of social anxiety severity. C1 [Aderka, Idan M.; Hofmann, Stefan G.] Boston Univ, Boston, MA 02215 USA. [Aderka, Idan M.] Univ Haifa, IL-31999 Haifa, Israel. [Pollack, Mark H.; Simon, Naomi M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smits, Jasper A. J.] So Methodist Univ, Dallas, TX 75275 USA. [Van Ameringen, Michael] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Stein, Murray B.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Aderka, IM (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,4th Floor, Boston, MA 02215 USA. EM iaderka@bu.edu RI Hofmann, Stefan/B-8769-2014; Smits, Jasper/A-4350-2008; OI Hofmann, Stefan/0000-0002-3548-9681; Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU NIDA NIH HHS [R01DA027533, R34DA031038]; NIMH NIH HHS [1R01MH078308] NR 41 TC 4 Z9 4 U1 3 U2 22 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD DEC PY 2013 VL 44 IS 4 BP 651 EP 661 PG 11 WC Psychology, Clinical SC Psychology GA 236GI UT WOS:000325783100012 PM 24094790 ER PT J AU Granziera, C Romascano, D Daducci, A Roche, A Vincent, M Krueger, G Hadjikhani, N AF Granziera, C. Romascano, D. Daducci, A. Roche, A. Vincent, M. Krueger, G. Hadjikhani, N. TI Migraineurs Without Aura Show Microstructural Abnormalities in the Cerebellum and Frontal Lobe SO CEREBELLUM LA English DT Article DE Cerebellum; Migraine; Cortical spreading depression; Structural MRI ID FAMILIAL HEMIPLEGIC MIGRAINE; CORTICAL SPREADING DEPRESSION; STATIC STABILOMETRY; HEADACHE; MECHANISMS; MRI; NUCLEI; GENE; HYPEREXCITABILITY; SUSCEPTIBILITY AB The involvement of the cerebellum in migraine pathophysiology is not well understood. We used a biparametric approach at high-field MRI (3 T) to assess the structural integrity of the cerebellum in 15 migraineurs with aura (MWA), 23 migraineurs without aura (MWoA), and 20 healthy controls (HC). High-resolution T1 relaxation maps were acquired together with magnetization transfer images in order to probe microstructural and myelin integrity. Clusterwise analysis was performed on T1 and magnetization transfer ratio (MTR) maps of the cerebellum of MWA, MWoA, and HC using an ANOVA and a non-parametric clusterwise permutation F test, with age and gender as covariates and correction for familywise error rate. In addition, mean MTR and T1 in frontal regions known to be highly connected to the cerebellum were computed. Clusterwise comparison among groups showed a cluster of lower MTR in the right Crus I of MWoA patients vs. HC and MWA subjects (p = 0.04). Univariate and bivariate analysis on T1 and MTR contrasts showed that MWoA patients had longer T1 and lower MTR in the right and left pars orbitalis compared to MWA (p < 0.01 and 0.05, respectively), but no differences were found with HC. Lower MTR and longer T1 point at a loss of macromolecules and/or micro-edema in Crus I and pars orbitalis in MWoA patients vs. HC and vs. MWA. The pathophysiological implications of these findings are discussed in light of recent literature. C1 [Granziera, C.; Hadjikhani, N.] Ecole Polytech Fed Lausanne, SV, BMI, GRHAD, CH-1015 Lausanne, VD, Switzerland. [Granziera, C.] CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, VD, Switzerland. [Granziera, C.] CHU Vaudois, Univ Lausanne, CH-1011 Lausanne, VD, Switzerland. [Granziera, C.; Romascano, D.; Daducci, A.; Roche, A.; Krueger, G.] Ecole Polytech Fed Lausanne, Siemens CIBM, Adv Clin Imaging Technol Grp, CH-1015 Lausanne, VD, Switzerland. [Daducci, A.] Ecole Polytech Fed Lausanne, STI IEL LTS5, CH-1015 Lausanne, VD, Switzerland. [Krueger, G.] Siemens Schweiz AG, Healthcare Sect IM&WS S, Renens, VD, Switzerland. [Vincent, M.] HUCFF UFRJ, Serv Neurol, Rio De Janeiro, Brazil. [Hadjikhani, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Granziera, C (reprint author), Ecole Polytech Fed Lausanne, SV, BMI, GRHAD, CH-1015 Lausanne, VD, Switzerland. EM cristina.granziera@epfl.ch RI Vincent, Maurice/B-1415-2009; Centre d'imagerie Biomedicale, CIBM/B-5740-2012; OI Hadjikhani, Nouchine/0000-0003-4075-3106; Granziera, Cristina/0000-0002-4917-8761 FU Stoicescu Foundation; Swiss National Science Foundation [PZ00P3_131914/1]; Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL); Swiss Federal Institute of Technology Lausanne (EPFL); University of Geneva (UniGe); Centre Hospitalier Universitaire Vaudois (CHUV); Hopitaux Universitaires de Geneve (HUG); Leenaards Foundation; Jeantet Foundation FX This work was supported by the Stoicescu Foundation, the Swiss National Science Foundation Grant PZ00P3_131914/1 and by the Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hopitaux Universitaires de Geneve (HUG), and the Leenaards and the Jeantet Foundations. NR 60 TC 6 Z9 6 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 EI 1473-4230 J9 CEREBELLUM JI Cerebellum PD DEC PY 2013 VL 12 IS 6 BP 812 EP 818 DI 10.1007/s12311-013-0491-x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 236VK UT WOS:000325827300004 PM 23703313 ER PT J AU Shelton, RC Snavely, AC De Jesus, M Othus, MD Allen, JD AF Shelton, Rachel C. Snavely, Anna C. De Jesus, Maria Othus, Megan D. Allen, Jennifer D. TI HPV Vaccine Decision-Making and Acceptance: Does Religion Play a Role? SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE HPV vaccine; Religion; Vaccine acceptance; Cancer prevention ID SCHOOL IMMUNIZATION REQUIREMENTS; HUMAN-PAPILLOMAVIRUS VACCINATION; HEALTH-CARE UTILIZATION; NONMEDICAL EXEMPTIONS; PARENTAL ACCEPTANCE; ATTITUDES; PERTUSSIS; WOMEN; INFORMATION; PREDICTORS AB We conducted a web-based survey among 476 white, Black, and Hispanic parents or caregivers with daughter(s) between the ages of 9-17 to better understand how religion influences HPV vaccine acceptance. Catholic parents were more likely than nonaffiliated parents to have already vaccinated their daughters (vs. being undecided) (OR = 3.26, 95% CI = 1.06, 10.06). Parents with frequent attendance at religious services were more likely than parents who do not attend services to have decided against vaccination (vs. being undecided) (OR = 2.92, 95% CI = 1.25, 6.84). Directions for research and implications for interventions are addressed. C1 [Shelton, Rachel C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10032 USA. [Snavely, Anna C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Snavely, Anna C.; Allen, Jennifer D.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [De Jesus, Maria] American Univ, Sch Int Serv, Washington, DC 20016 USA. [Othus, Megan D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shelton, RC (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, 722 West 168th St,Room 548, New York, NY 10032 USA. EM rs3108@columbia.edu RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [R25 CA081137] NR 31 TC 9 Z9 9 U1 2 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 EI 1573-6571 J9 J RELIG HEALTH JI J. Relig. Health PD DEC PY 2013 VL 52 IS 4 BP 1120 EP 1130 DI 10.1007/s10943-011-9553-x PG 11 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 231PX UT WOS:000325430600009 PM 22076049 ER PT J AU Saini, KS Loi, S de Azambuja, E Metzger-Filho, O Saini, ML Ignatiadis, M Dancey, JE Piccart-Gebhart, MJ AF Saini, Kamal S. Loi, Sherene de Azambuja, Evandro Metzger-Filho, Otto Saini, Monika Lamba Ignatiadis, Michail Dancey, Janet E. Piccart-Gebhart, Martine J. TI Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer SO CANCER TREATMENT REVIEWS LA English DT Review DE Breast cancer; PI3K; mTOR; MAPK; Ras/Raf/MEK/ERK; Cross-talk; Dual inhibition; Targeted therapy; Personalized medicine ID ACTIVATED PROTEIN-KINASE; INHIBITOR AZD6244 ARRY-142886; I PI3K INHIBITOR; SIGNALING PATHWAYS; PIK3CA MUTATIONS; PHASE-II; GENE-EXPRESSION; MEK INHIBITORS; CELL-GROWTH; NEOADJUVANT CHEMOTHERAPY AB Alterations of signal transduction pathways leading to uncontrolled cellular proliferation, survival, invasion, and metastases are hallmarks of the carcinogenic process. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and the Raf/mitogen-activated and extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways are critical for normal human physiology, and also commonly dysregulated in several human cancers, including breast cancer (BC). In vitro and in vivo data suggest that the PI3K/AKT/mTOR and Raf/MEK/ERK cascades are interconnected with multiple points of convergence, cross-talk, and feedback loops. Raf/MEK/ERK and PI3K/AKT/mTOR pathway mutations may co-exist. Inhibition of one pathway can still result in the maintenance of signaling via the other (reciprocal) pathway. The existence of such "escape" mechanisms implies that dual targeting of these pathways may lead to superior efficacy and better clinical outcome in selected patients. Several clinical trials targeting one or both pathways are already underway in BC patients. The toxicity profile of this novel approach of dual pathway inhibition needs to be closely monitored, given the important physiological role of PI3K/AKT/mTOR and Raf/MEK/ERK signaling. In this article, we present a review of the current relevant pre-clinical and clinical data and discuss the rationale for dual inhibition of these pathways in the treatment of BC patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Saini, Kamal S.; Piccart-Gebhart, Martine J.] Breast Int Grp, Brussels, Belgium. [Saini, Kamal S.; de Azambuja, Evandro; Ignatiadis, Michail; Piccart-Gebhart, Martine J.] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Loi, Sherene] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Metzger-Filho, Otto] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA. [Saini, Monika Lamba] Catholic Univ Louvain, B-1200 Brussels, Belgium. [Dancey, Janet E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. RP Piccart-Gebhart, MJ (reprint author), Inst Jules Bordet, Dept Med, 121 Blvd Waterloo, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Loi, Sherene/H-1979-2016; OI Loi, Sherene/0000-0001-6137-9171 NR 179 TC 92 Z9 98 U1 8 U2 161 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD DEC PY 2013 VL 39 IS 8 BP 935 EP 946 DI 10.1016/j.ctrv.2013.03.009 PG 12 WC Oncology SC Oncology GA 229CC UT WOS:000325238400011 PM 23643661 ER PT J AU Johnson, JM Legesse, B Camprodon, JA Murray, E Price, BH AF Johnson, Justin M. Legesse, Benalfew Camprodon, Joan A. Murray, Evan Price, Bruce H. TI The Clinical Significance of Bilateral Basal Ganglia Calcification Presenting With Mania and Delusions SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID BIPOLAR DISORDER; FMRI AB The authors present the case of a 37-year-old man who developed a psychotic manic episode and was found to have bilateral basal ganglia calcification (BGC). The authors present this case report along with a discussion of the literature on the neuropsychiatry of BGC. (The Journal of Neuropsychiatry and Clinical Neurosciences 2013; 25:68-71) C1 [Johnson, Justin M.; Legesse, Benalfew; Camprodon, Joan A.; Murray, Evan; Price, Bruce H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Dept Neurol, Cambridge, MA 02138 USA. [Johnson, Justin M.; Legesse, Benalfew; Camprodon, Joan A.; Murray, Evan; Price, Bruce H.] Harvard Univ, Sch Med, McLean Hosp, Cambridge, MA 02138 USA. RP Johnson, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jjohnson54@partners.org FU NARSAD Young Investigator Award [R25MH094612-01]; Sydney R. Baer, Jr. Foundation FX Dr. Camprodon received funding from the NARSAD Young Investigator Award (R25MH094612-01). Dr. Price received funding from the Sydney R. Baer, Jr. Foundation. NR 15 TC 2 Z9 2 U1 2 U2 41 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2013 VL 25 IS 1 BP 68 EP 71 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 123SK UT WOS:000317410800051 PM 23487196 ER PT J AU Malone, JC Stein, MB Slavin-Mulford, J Bello, I Sinclair, SJ Blais, MA AF Malone, Johanna C. Stein, Michelle B. Slavin-Mulford, Jenelle Bello, Iruma Sinclair, S. Justin Blais, Mark A. TI Seeing red: Affect modulation and chromatic color responses on the Rorschach SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID VALIDITY; DETERMINANTS; INVENTORY AB Psychoanalytic theories suggest that color perception on the Rorschach relates to affective modulation. However, this idea has minimal empirical support. Using a clinical sample, the authors explored the cognitive and clinical correlates of Rorschach color determinants and differences among four affective modulation subtypes: Controlled, Balanced, Under-Controlled, and Flooded. Subtypes were differentiated by measures of affective regulation, reality testing/confusion, and personality traits. Initial support for the relationship of chromatic color response styles and affective modulation was found. (Bulletin of the Menninger Clinic, 77[1], 70-93) C1 [Malone, Johanna C.; Stein, Michelle B.; Sinclair, S. Justin; Blais, Mark A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malone, Johanna C.; Stein, Michelle B.; Sinclair, S. Justin; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Slavin-Mulford, Jenelle] Augusta State Univ, Dept Psychol, Augusta, GA USA. [Bello, Iruma] NYU, Med Ctr, New York, NY 10016 USA. [Bello, Iruma] Bellevue Hosp, New York, NY USA. RP Malone, JC (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,Suite 701, Boston, MA 02114 USA. EM johanna.malone@gmail.com NR 36 TC 5 Z9 7 U1 0 U2 51 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD WIN PY 2013 VL 77 IS 1 BP 70 EP 93 PG 24 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 100CT UT WOS:000315673900004 PM 23428172 ER PT J AU Braehler, C Valiquette, L Holowka, D Malla, AK Joober, R Ciampi, A Pawliuk, N King, S AF Braehler, Christine Valiquette, Luc Holowka, Darren Malla, Ashok K. Joober, Ridha Ciampi, Antonio Pawliuk, Nicole King, Suzanne TI Childhood trauma and dissociation in first-episode psychosis, chronic schizophrenia and community controls SO PSYCHIATRY RESEARCH LA English DT Article DE Psychosis; Childhood abuse; Childhood neglect; Emotional abuse; Physical abuse; Sexual abuse; Physical neglect ID POSTTRAUMATIC-STRESS-DISORDER; GENERAL-POPULATION SAMPLE; SEXUAL-ABUSE; AUDITORY-HALLUCINATIONS; SYMPTOMS; SELF; RELIABILITY; ADVERSITIES; PREVALENCE; VALIDITY AB Increasing evidence supports the role of childhood trauma in the etiology of psychosis but underlying mechanisms are poorly understood. Early maltreatment has been linked to dissociative symptoms in psychosis patients. We explored associations between childhood trauma (Childhood Trauma Questionnaire) and dissociation (Dissociative Experiences Scale) in first-episode psychotic patients (n=62), chronic psychotic patients (n=43), and non-psychotic community controls (n=66). Multivariate analyses of covariance were used to test associations between childhood trauma and dissociation by group while controlling for sex. Chronic patients reported the highest level of dissociation. More severe childhood trauma was associated with greater dissociative symptoms in all groups although most strongly in chronic patients. Emotional abuse showed the strongest associations with dissociation, with these being strongest for chronic patients, followed by first-episode patients and least for controls. Men showed a stronger association between physical neglect and dissociation than women, irrespective of group. There were no significant group by sex interactions. Our findings replicate the strong association between childhood trauma and dissociative symptoms in chronic and first-episode psychotic patients relative to non-psychotic control subjects. We also demonstrate the salience of emotional abuse in explaining variance in dissociation, especially in chronic patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Braehler, Christine] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland. [Valiquette, Luc; Malla, Ashok K.; Joober, Ridha; Pawliuk, Nicole; King, Suzanne] Douglas Mental Hlth Univ Inst, Verdun, PQ, Canada. [Valiquette, Luc; Malla, Ashok K.; Joober, Ridha; Ciampi, Antonio; King, Suzanne] McGill Univ, Montreal, PQ, Canada. [Holowka, Darren] VA Natl Ctr PTSD, Boston, MA USA. [Holowka, Darren] VA Boston Healthcare Syst, Boston, MA USA. [Holowka, Darren] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP King, S (reprint author), Douglas Mental Hlth Univ Inst, Perry Pavil,Room E-3131,6875 LaSalle Blvd, Quebec City, PQ H4H 1R3, Canada. EM suzanne.king@douglas.mcgill.ca OI King, Suzanne/0000-0003-3055-6846 NR 53 TC 17 Z9 18 U1 2 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2013 VL 210 IS 1 BP 36 EP 42 DI 10.1016/j.psychres.2013.05.033 PG 7 WC Psychiatry SC Psychiatry GA 250NL UT WOS:000326859400006 PM 23816517 ER PT J AU Gros, DF McCabe, RE Antony, MM AF Gros, Daniel F. McCabe, Randi E. Antony, Martin M. TI Using a hybrid model to investigate the comorbidity and symptom overlap between social phobia and the other anxiety disorders and unipolar mood disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Social anxiety disorder; Transdiagnostic; Multidimensional Assessment of Social; Anxiety; MASA ID POSTTRAUMATIC-STRESS-DISORDER; DIMENSIONAL CLASSIFICATION-SYSTEM; RANDOMIZED CONTROLLED-TRIAL; DSM-IV ANXIETY; EMOTIONAL DISORDERS; SPECIAL SECTION; PSYCHOPATHOLOGY; FEATURES AB New hybrid models of psychopathology have been proposed that combine the current categorical approach with symptom dimensions that are common across various disorders. The present study investigated the new hybrid model of social anxiety in a large sample of participants with anxiety disorders and unipolar mood disorders to improve understanding of the comorbidity and symptom overlap between social phobia (SOC) and the other anxiety disorders and unipolar mood disorders. Six hundred and eighty two participants from a specialized outpatient clinic for anxiety treatment completed a semi-structured diagnostic interview and the Multidimensional Assessment of Social Anxiety (MASA). A hybrid model symptom profile was identified for SOC and compared with each of the other principal diagnoses. Significant group differences were identified on each of the MASA scales. Differences also were identified when common sets of comorbidities were compared within participants diagnosed with SOC. The findings demonstrated the influence of both the principal diagnosis of SOC and other anxiety disorders and unipolar mood disorders as well as the influence of comorbid diagnoses with SOC on the six symptom dimensions. These findings highlight the need to shift to transdiagnostic assessment and treatment practices that go beyond the disorder-specific focus of the current categorical diagnostic systems. Published by Elsevier Ireland Ltd. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [McCabe, Randi E.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [McCabe, Randi E.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Office of Research and Development; Medical Research Service; Department of Veterans Affairs FX This work was partially supported by the Office of Research and Development, Medical Research Service, and Department of Veterans Affairs. There are no conflicts of interest to disclose. We would like to thank Dr. Matthew Price for his consultation on the statistical approach in the revision of this manuscript. NR 26 TC 7 Z9 7 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2013 VL 210 IS 1 BP 188 EP 192 DI 10.1016/j.psychres.2013.05.005 PG 5 WC Psychiatry SC Psychiatry GA 250NL UT WOS:000326859400029 PM 23809463 ER PT J AU Ripoll, LH Zaki, J Perez-Rodriguez, MM Snyder, R Strike, KS Boussi, A Bartz, JA Ochsner, KN Siever, LJ New, AS AF Ripoll, Luis H. Zaki, Jamil Perez-Rodriguez, Maria Mercedes Snyder, Rebekah Strike, Kathryn Sloan Boussi, Ayelet Bartz, Jennifer A. Ochsner, Kevin N. Siever, Larry J. New, Antonia S. TI Empathic accuracy and cognition in schizotypal personality disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Schizotypal personality disorder; Empathy; Personality; Working memory; Attachment; Social support ID SCHIZOPHRENIA SPECTRUM DISORDERS; SOCIAL COGNITION; WORKING-MEMORY; ADULT ATTACHMENT; EMOTION RECOGNITION; INTERPERSONAL RELATIONSHIPS; PSYCHOMETRIC SCHIZOTYPY; GENETIC VULNERABILITY; 1ST-DEGREE RELATIVES; NONCLINICAL SAMPLE AB Interpersonal dysfunction contributes to significant disability in the schizophrenia spectrum. Schizotypal Personality Disorder (SPD) is a schizophrenia-related personality demonstrating social cognitive impairment in the absence of frank psychosis. Past research indicates that cognitive dysfunction or schizotypy may account for social cognitive dysfunction in this population. We tested SPD subjects and healthy controls on the Empathic Accuracy (EA) paradigm and the Reading of the Mind in the Eyes Test (RMET), assessing the impact of EA on social support. We also explored whether EA differences could be explained by intelligence, working memory, trait empathy, or attachment avoidance. SPD subjects did not differ from controls in RMET, but demonstrated lower EA during negative valence videos, associated with lower social support. Dynamic, multimodal EA paradigms may be more effective at capturing interpersonal dysfunction than static image tasks such as RMET. Schizotypal severity, trait empathy, and cognitive dysfunction did not account for empathic dysfunction in SPD, although attachment avoidance is related to empathic differences. Empathic dysfunction for negative affect contributes to decreased social support in the schizophrenia spectrum. Future research may shed further light on potential links between attachment avoidance, empathic dysfunction, and social support. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Ripoll, Luis H.; Perez-Rodriguez, Maria Mercedes; Siever, Larry J.; New, Antonia S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ripoll, Luis H.; Perez-Rodriguez, Maria Mercedes; Strike, Kathryn Sloan; Boussi, Ayelet; Siever, Larry J.; New, Antonia S.] MIRECC, James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Zaki, Jamil] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Snyder, Rebekah; Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Bartz, Jennifer A.] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. RP Ripoll, LH (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 FU US Dept. of Veterans' Affairs MIRECC pilot grant FX The present study was funded entirely through a US Dept. of Veterans' Affairs MIRECC pilot grant, and the authors have no other significant financial relationships to disclose. NR 121 TC 11 Z9 11 U1 5 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2013 VL 210 IS 1 BP 232 EP 241 DI 10.1016/j.psychres.2013.05.025 PG 10 WC Psychiatry SC Psychiatry GA 250NL UT WOS:000326859400036 PM 23810511 ER PT J AU Smucny, J Wylie, K Rojas, D Stevens, K Olincy, A Kronberg, E Zheng, LJ Tregellas, J AF Smucny, Jason Wylie, Korey Rojas, Donald Stevens, Karen Olincy, Ann Kronberg, Eugene Zheng, Lijun Tregellas, Jason TI Evidence for gamma and beta sensory gating deficits as translational endophenotypes for schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Gamma; Beta; Nicotinic; Schizophrenia; Gating ID REPEATED AUDITORY-STIMULI; RECEPTOR SUBUNIT GENE; HIPPOCAMPAL INTERNEURONS; ACETYLCHOLINE-RECEPTOR; P50 SUPPRESSION; BRAIN OSCILLATIONS; EVOKED-RESPONSE; IN-VITRO; AGONIST; HUMANS AB Thorough analysis of translational endophenotypes is needed to improve therapeutic development in schizophrenia. Abnormal sensory gating, one such endophenotype, is associated with reduced expression of the alpha 7 nicotinic receptor. However, typical gating measures such as the P50 evoked response are often low-pass filtered, and it is unclear how a7 expression affects gating at higher frequencies. Therefore, this study used time -frequency analysis to compare sensory gating at the beta and gamma frequencies between human patients and healthy controls as well as between alpha 7 heterozygote mutant mice and wild type Gating of Loral beta (15-26 Hz) and gamma (30-50 Hz) power during paired clicks was assessed from mouse in vivo hippocampal CA3 recordings. Gating was also assessed in schizophrenia patients and healthy controls using electroencephalography. Relative to wild type. u7 heLerozygore mice showed impaired gating of Loral beta and gamma power. Similarly, relative to controls, patients showed impaired gating of Loral beta and gamma power. Poor beta gating was associated with negative symptoms. These results demonstrate that schizophrenia patients and alpha 7 heLerozygoLe mice show similar deficits in gaLing high frequency power. Time frequency analysis of beta and gamma gating may thus be a translational method of assessing the genetic basis of gating deficits in schizophrenia. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Smucny, Jason; Rojas, Donald; Tregellas, Jason] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Wylie, Korey; Rojas, Donald; Stevens, Karen; Olincy, Ann; Tregellas, Jason] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Smucny, Jason; Wylie, Korey; Rojas, Donald; Stevens, Karen; Olincy, Ann; Kronberg, Eugene; Zheng, Lijun; Tregellas, Jason] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Smucny, J (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus,East 17th Pl, Aurora, CO 80045 USA. EM Jason.Smucny@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616; Smucny, Jason/0000-0001-5656-7987 FU VA Biomedical Laboratory and Clinical Science Research and Development Service; Brain and Behavior Foundation; Blowitz-Ridgeway Foundation FX The authors thank Robert Freedman, M.D., for assistance with manuscript preparation. This research was supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service, the Brain and Behavior Foundation, and the Blowitz-Ridgeway Foundation. NR 45 TC 5 Z9 5 U1 1 U2 6 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 NOV 30 PY 2013 VL 214 IS 2 BP 169 EP 174 DI 10.1016/j.pscychresns.2013.07.002 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 231QL UT WOS:000325432300011 PM 23972946 ER PT J AU Sepucha, KR Borkhoff, CM Lally, J Levin, CA Matlock, DD Ng, CJ Ropka, ME Stacey, D Joseph-Williams, N Wills, CE Thomson, R AF Sepucha, Karen R. Borkhoff, Cornelia M. Lally, Joanne Levin, Carrie A. Matlock, Daniel D. Ng, Chirk Jenn Ropka, Mary E. Stacey, Dawn Joseph-Williams, Natalie Wills, Celia E. Thomson, Richard TI Establishing the effectiveness of patient decision aids: key constructs and measurement instruments SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; PSYCHOMETRIC EVALUATION; HEALTH; QUALITY; WOMEN; RISK; CARE; SCALE; COMMUNICATION AB Background: Establishing the effectiveness of patient decision aids (PtDA) requires evidence that PtDAs improve the quality of the decision-making process and the quality of the choice made, or decision quality. The aim of this paper is to review the theoretical and empirical evidence for PtDA effectiveness and discuss emerging practical and research issues in the measurement of effectiveness. Methods: This updated overview incorporates: a) an examination of the instruments used to measure five key decision-making process constructs (i.e., recognize decision, feel informed about options and outcomes, feel clear about goals and preferences, discuss goals and preferences with health care provider, and be involved in decisions) and decision quality constructs (i.e., knowledge, realistic expectations, values-choice agreement) within the 86 trials in the Cochrane review; and b) a summary of the 2011 Cochrane Collaboration's review of PtDAs for these key constructs. Data on the constructs and instruments used were extracted independently by two authors from the 86 trials and any disagreements were resolved by discussion, with adjudication by a third party where required. Results: The 86 studies provide considerable evidence that PtDAs improve the decision-making process and decision quality. A majority of the studies (76/ 86; 88%) measured at least one of the key decision-making process or decision quality constructs. Seventeen different measurement instruments were used to measure decision-making process constructs, but no single instrument covered all five constructs. The Decisional Conflict Scale was most commonly used (n = 47), followed by the Control Preference Scale (n = 9). Many studies reported one or more constructs of decision quality, including knowledge (n = 59), realistic expectation of risks and benefits (n = 21), and values-choice agreement (n = 13). There was considerable variability in how values-choice agreement was defined and determined. No study reported on all key decision-making process and decision quality constructs. Conclusions: Evidence of PtDA effectiveness in improving the quality of the decision-making process and decision quality is strong and growing. There is not, however, consensus or standardization of measurement for either the decision-making process or decision quality. Additional work is needed to develop and evaluate measurement instruments and further explore theoretical issues to advance future research on PtDA effectiveness. C1 [Sepucha, Karen R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sepucha, Karen R.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Borkhoff, Cornelia M.] Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada. [Lally, Joanne; Thomson, Richard] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Levin, Carrie A.] Informed Med Decis Fdn, Boston, MA 02108 USA. [Matlock, Daniel D.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Ng, Chirk Jenn] Univ Malaya, Dept Primary Care Med, Kuala Lumpur 50603, Malaysia. [Ropka, Mary E.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Stacey, Dawn] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada. [Joseph-Williams, Natalie] Cardiff Univ, Inst Primary Care & Publ Hlth, Cardiff CF14 4YS, S Glam, Wales. [Wills, Celia E.] Ohio State Univ, Columbus, OH 43210 USA. RP Sepucha, KR (reprint author), Harvard Univ, Sch Med, 50 Staniford St,9th floor, Boston, MA 02114 USA. EM ksepucha@partners.org RI NG, CHIRK JENN/C-1344-2010 FU IMDF FX KS receives salary and research support from IMDF. NR 63 TC 33 Z9 33 U1 2 U2 7 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 NOV 29 PY 2013 VL 13 SU 2 AR S12 DI 10.1186/1472-6947-13-S2-S12 PG 11 WC Medical Informatics SC Medical Informatics GA 270NA UT WOS:000328324000012 PM 24625035 ER PT J AU Ocon, S Murphy, C Dang, AT Sankaran-Walters, S Li, CS Tarara, R Borujerdpur, N Dandekar, S Paster, BJ George, MD AF Ocon, Susan Murphy, Christina Dang, Angeline T. Sankaran-Walters, Sumathi Li, Chin-Shang Tarara, Ross Borujerdpur, Niku Dandekar, Satya Paster, Bruce J. George, Michael D. TI Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; T-CELL DEPLETION; GEMELLA-MORBILLORUM; PROINFLAMMATORY CYTOKINES; ANTIMICROBIAL PEPTIDES; COMMENSAL BACTERIA; VALVE ENDOCARDITIS; PLAQUE MICROBIOTA; BARRIER FUNCTION; MUCOSA AB A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions'' of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. C1 [Ocon, Susan; Sankaran-Walters, Sumathi; Dandekar, Satya; George, Michael D.] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Murphy, Christina; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Dang, Angeline T.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Li, Chin-Shang] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Tarara, Ross] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP George, MD (reprint author), Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. EM mdgeorge@ucdavis.edu FU National Institutes of Health [1R21DE020025]; National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) [UL1 TR000002] FX The studies were funded by National Institutes of Health grant #1R21DE020025 and supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant #UL1 TR000002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 6 Z9 6 U1 0 U2 16 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 NOV 29 PY 2013 VL 8 IS 11 AR e80863 DI 10.1371/journal.pone.0080863 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261MX UT WOS:000327670300019 PM 24312248 ER PT J AU Bangsberg, D Ekra, KA Kouakou, JS Ehrenkranz, P Ao, T Alfredo, C Jobarteh, K Williams, S Shiraishi, RW Baughman, A Agolory, S Bicego, G Spira, T Zee, A Kaplan, J Ellerbrock, TV Auld, AF AF Bangsberg, David Ekra, Kunomboa A. Kouakou, Joseph S. Ehrenkranz, Peter Ao, Trong Alfredo, Charity Jobarteh, Kebba Williams, Seymour Shiraishi, Ray W. Baughman, Andrew Agolory, Simon Bicego, George Spira, Thomas Zee, Aaron Kaplan, Jonathan Ellerbrock, Tedd V. Auld, Andrew F. TI Differences Between HIV-Infected Men and Women in Antiretroviral Therapy Outcomes - Six African Countries, 2004-2012 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [Bangsberg, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ekra, Kunomboa A.; Kouakou, Joseph S.] CDC Cote Ivore, Ctr Global Hlth, Abidjan, Cote Ivoire. [Ehrenkranz, Peter; Ao, Trong] CDC Switzerland, Ctr Global Hlth, Riazzino, Switzerland. [Alfredo, Charity; Jobarteh, Kebba] CDC Mozambique, Ctr Global Hlth, Maputo, Mozambique. [Williams, Seymour] CDC South Africa, Ctr Global Hlth, Pretoria, South Africa. [Shiraishi, Ray W.; Baughman, Andrew; Agolory, Simon; Bicego, George; Spira, Thomas; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V.; Auld, Andrew F.] Ctr Global Hlth, Div Global HIV AIDS, Atlanta, GA 30333 USA. RP Auld, AF (reprint author), Ctr Global Hlth, Div Global HIV AIDS, Atlanta, GA 30333 USA. EM aauld@cdc.gov NR 10 TC 8 Z9 8 U1 0 U2 1 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD NOV 29 PY 2013 VL 62 IS 47 BP 945 EP 952 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 259NU UT WOS:000327534400001 ER PT J AU Adamala, K Szostak, JW AF Adamala, Katarzyna Szostak, Jack W. TI Nonenzymatic Template-Directed RNA Synthesis Inside Model Protocells SO SCIENCE LA English DT Article ID MAGNESIUM-IONS; MEMBRANES; CITRATE; LIFE AB Efforts to recreate a prebiotically plausible protocell, in which RNA replication occurs within a fatty acid vesicle, have been stalled by the destabilizing effect of Mg2+ on fatty acid membranes. Here we report that the presence of citrate protects fatty acid membranes from the disruptive effects of high Mg2+ ion concentrations while allowing RNA copying to proceed, while also protecting single-stranded RNA from Mg2+-catalyzed degradation. This combination of properties has allowed us to demonstrate the chemical copying of RNA templates inside fatty acid vesicles, which in turn allows for an increase in copying efficiency by bathing the vesicles in a continuously refreshed solution of activated nucleotides. C1 [Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. [Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Adamala, Katarzyna] Univ Roma Tre, Dipartimento Biol, Rome, Italy. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Adamala, Kate/0000-0003-1066-7207 FU NASA [NNX07AJ09G] FX We thank A. Engelhart, C. Hentrich, A. Larsen, N. Kamat, and A. Bjorkbom for discussions and help with manuscript preparation and A. Gifford for help with vesicle leakage experiments. This work was supported in part by NASA Exobiology grant NNX07AJ09G. J.W.S. is an investigator of the Howard Hughes Medical Institute. Raw data are presented in the supplementary materials. The instructions for assembling the Liposome Dialyzer are available at http://molbio.mgh.harvard.edu/szostakweb/. NR 12 TC 62 Z9 69 U1 8 U2 85 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 29 PY 2013 VL 342 IS 6162 BP 1098 EP 1100 DI 10.1126/science.1241888 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259HS UT WOS:000327518600058 PM 24288333 ER PT J AU Weiser, SD Yuan, C Guzman, D Frongillo, EA Riley, ED Bangsberg, DR Kushel, MB AF Weiser, Sheri D. Yuan, Caterina Guzman, David Frongillo, Edward A. Riley, Elise D. Bangsberg, David R. Kushel, Margot B. TI Food insecurity and HIV clinical outcomes in a longitudinal study of urban homeless and marginally housed HIV-infected individuals SO AIDS LA English DT Article DE adherence; antiretroviral therapy; food security; HIV; AIDS ID ACTIVE ANTIRETROVIRAL THERAPY; SAN-FRANCISCO; HEALTH-CARE; ADHERENCE; HIV/AIDS; HAART; INSUFFICIENCY; PREVALENCE; VALIDATION; INDICATORS AB Background:Food insecurity is common among HIV-infected individuals and has been associated with poor health. Little longitudinal research has examined the association of food insecurity with HIV clinical outcomes, or the extent to which adherence mediates these associations.Design:Observational cohort studyMethods:HIV-infected homeless and marginally housed individuals in the San Francisco Research on Access to Care in the Homeless cohort completed quarterly structured interviews and blood draws. We measured food insecurity using the validated Household Food Insecurity Access Scale. Primary outcomes were: antiretroviral therapy (ART) nonadherence (<90% adherence), incomplete HIV viral load suppression more than 100copies/ml, and CD4(+) cell counts less than 200 cells/l. We estimated model parameters using generalized estimating equations, adjusting for sociodemographic and clinical variables.Results:From May 2007 to March 2010, we followed 284 participants for a median of 22 months. At baseline 54.6% of participants were food-insecure. Food insecurity was associated with increased odds of ART nonadherence [adjusted odds ratio (AOR)=1.48; 95% confidence interval (CI), 1.19-1.85], incomplete viral load suppression (AOR=1.29, 95% CI 1.04-1.61), and CD4(+) cell counts less than 200 cells/l (AOR=1.26, 95% CI 1.01-1.56). When we included ART adherence in adjusted models for incomplete viral suppression and CD4(+) cell counts less than 200 cells/l, the magnitude of the effect decreased slightly.Conclusion:Food insecurity was associated with poor HIV outcomes, including nonadherence, in a longitudinal study of US-based HIV-infected unstably housed individuals. Efforts to address food insecurity should be included in HIV-treatment programs, and may help improve health outcomes. C1 [Weiser, Sheri D.; Riley, Elise D.] UCSF, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.] UCSF, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Yuan, Caterina] UCSF, Sch Med, San Francisco, CA 94143 USA. [Guzman, David; Kushel, Margot B.] UCSF, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Bangsberg, David R.] MIT, Ragon Inst MGH, Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Harvard, Boston, MA USA. RP Weiser, SD (reprint author), UCSF, San Francisco Gen Hosp, Div HIV AIDS, POB 0874, San Francisco, CA 94143 USA. EM Sheri.Weiser@ucsf.edu FU NIMH [54907]; CHRP [ID08-SF-054]; UCSF Academic Senate; Hurlbut-Johnson funds from AIDS Research Institute award; UCSF [557858-8-148]; Burke Family Foundation; [K23 MH079713]; [K24 MH-87227] FX NIMH 54907 (PI Bangsberg), CHRP ID08-SF-054 (PI Weiser); UCSF Academic Senate; Hurlbut-Johnson funds from AIDS Research Institute award, UCSF, # 557858-8-148 (PI Weiser). The authors acknowledge the following additional sources of salary support: K23 MH079713 and the Burke Family Foundation (to S. D. W.), and K24 MH-87227 (to D. R. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. NR 40 TC 20 Z9 20 U1 1 U2 7 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 NOV 28 PY 2013 VL 27 IS 18 BP 2953 EP 2958 DI 10.1097/01.aids.0000432538.70088.a3 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 295PQ UT WOS:000330128400014 PM 23921612 ER PT J AU Lindsley, RC Ebert, BL AF Lindsley, R. Coleman Ebert, Benjamin L. TI The biology and clinical impact of genetic lesions in myeloid malignancies SO BLOOD LA English DT Review ID CHRONIC MYELOMONOCYTIC LEUKEMIA; RISK MYELODYSPLASTIC SYNDROMES; DETECTABLE CLONAL MOSAICISM; DNMT3A MUTATIONS; SOMATIC MUTATIONS; ASXL1 MUTATIONS; MYELOPROLIFERATIVE NEOPLASMS; DNA METHYLATION; TP53 MUTATIONS; POOR-PROGNOSIS AB A longstanding endeavor to define the genetic lesions that drive myeloid malignances has stimulated a period of remarkable discovery. Enabled by technological advances that have sharply decreased the cost of DNA sequencing, the full compendium of common, recurrent somatic mutations in the coding genome of myeloid malignancies is nearly complete. As the focus of genetic discovery shifts to the noncoding genome, renewed attention is being applied to the clinical and biological implications of recent genomic advances. Although the potential for this newfound knowledge to influence the care of patients has not yet been realized, broad genetic surveys of patient samples are now being used to improve the accuracy of disease diagnosis, define a molecular taxonomy of myeloid malignancies, refine prognostic and predictive models, and identify novel therapeutic strategies. Here, we will review recent advances in the genetics of myeloid malignancies and discuss their potential impact on clinical practice. C1 [Lindsley, R. Coleman; Ebert, Benjamin L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindsley, R. Coleman; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Lindsley, RC (reprint author), Brigham & Womens Hosp, Karp Res Bldg,CHRB 05-210,1 Blackfan Circle, Boston, MA 02115 USA. EM bebert@partners.org OI Lindsley, Coleman/0000-0001-9822-806X FU Genoptix; Celgene; H3 Biomedicine FX B.L.E. has received consulting fees from Genoptix, Celgene, and H3 Biomedicine. R. C. L. declares no competing financial interests. NR 96 TC 19 Z9 19 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 28 PY 2013 VL 122 IS 23 BP 3741 EP 3748 DI 10.1182/blood-2013-06-460295 PG 8 WC Hematology SC Hematology GA 290EA UT WOS:000329735000012 PM 23954890 ER PT J AU Sankaran, VG Joshi, M Agrawal, A Schmitz-Abe, K Towne, MC Marinakis, N Markianos, K Berry, GT Agrawal, PB AF Sankaran, Vijay G. Joshi, Mugdha Agrawal, Akshat Schmitz-Abe, Klaus Towne, Meghan C. Marinakis, Nicholas Markianos, Kyriacos Berry, Gerard T. Agrawal, Pankaj B. TI Rare complete loss of function provides insight into a pleiotropic genome-wide association study locus SO BLOOD LA English DT Letter ID FETAL-HEMOGLOBIN LEVELS; CONSORTIUM; HBS1L-MYB; VARIANTS; CELL C1 [Sankaran, Vijay G.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Joshi, Mugdha; Agrawal, Akshat; Schmitz-Abe, Klaus; Towne, Meghan C.; Marinakis, Nicholas; Markianos, Kyriacos; Berry, Gerard T.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Joshi, Mugdha; Agrawal, Akshat; Schmitz-Abe, Klaus; Towne, Meghan C.; Marinakis, Nicholas; Markianos, Kyriacos; Berry, Gerard T.; Agrawal, Pankaj B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Agrawal, Pankaj B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet & Genom,Div Newborn Med, Boston, MA USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM sankaran@broad-institute.org; pagrawal@enders.tch.harvard.edu OI Berry, Gerard/0000-0001-5299-3313 NR 10 TC 8 Z9 8 U1 0 U2 0 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 NOV 28 PY 2013 VL 122 IS 23 BP 3845 EP 3847 DI 10.1182/blood-2013-09-528315 PG 5 WC Hematology SC Hematology GA 290EA UT WOS:000329735000026 PM 24288412 ER PT J AU Orr, MT Fox, CB Baldwin, SL Sivananthan, SJ Lucas, E Lin, S Phan, T Moon, JJ Vedvick, TS Reed, SG Coler, RN AF Orr, Mark T. Fox, Christopher B. Baldwin, Susan L. Sivananthan, Sandra J. Lucas, Elyse Lin, Susan Phan, Tony Moon, James J. Vedvick, Thomas S. Reed, Steven G. Coler, Rhea N. TI Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Vaccine formulation; Liposomes; Oil-in-water emulsions; Alum; Mycobacterium tuberculosis ID T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; CIRCUMSPOROZOITE PROTEIN; FALCIPARUM-MALARIA; PROTECTION; IMMUNOGENICITY; LIPOSOMES; EMULSIONS; ANTIGENS; SYSTEMS AB One third of the world is infected with Mycobacterium tuberculosis (Mtb) with eight million new cases of active tuberculosis (TB) each year. Development of a new vaccine to augment or replace the only approved TB vaccine, BCG, is needed to control this disease. Mtb infection is primarily controlled by TH1 cells through the production of IFN-gamma and TNF which activate infected macrophages to kill the bacterium. Here we examine an array of adjuvant formulations containing the TLR4 agonist GLA to identify candidate adjuvants to pair with ID93, a lead TB vaccine antigen, to elicit protective TH1 responses. We evaluate a variety of adjuvant formulations including alum, liposomes, and oil-in-water emulsions to determine how changes in formulation composition alter adjuvant activity. We find that alum and an aqueous nanosuspension of GLA synergize to enhance generation of ID93-specific TH1 responses, whereas neither on their own are effective adjuvants for generation of ID93-specific TH1 responses. For GLA containing oil-in-water emulsions, the selection of the oil component is critical for adjuvant activity, whereas a variety of lipid components may be used in liposomal formulations of GLA. The composition of the liposome formulation of ID93/GLA does alter the magnitude of the TH1 response. These results demonstrate that there are multiple solutions for an effective formulation of a novel TB vaccine candidate that enhances both TH1 generation and protective efficacy. (C) 2013 Elsevier B.V. All rights reserved. C1 [Orr, Mark T.; Fox, Christopher B.; Baldwin, Susan L.; Sivananthan, Sandra J.; Lucas, Elyse; Lin, Susan; Phan, Tony; Vedvick, Thomas S.; Reed, Steven G.; Coler, Rhea N.] Infect Dis Res Inst, Seattle, WA 98104 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Coler, RN (reprint author), Infect Dis Res Inst, Seattle, WA 98104 USA. EM rhea.coler@idri.org OI Fox, Christopher/0000-0002-4644-2619 FU National Institutes of Health [A1044373, A1078054, HHSN272200800045C] FX We thank Valerie Reese, David Argilla, Charles Davis, Tom Hudson, Traci Mikasa, Sarah Parker, Lucien Barnes V, and Millie Fung for their excellent technical assistance. This work was supported by the National Institutes of Health grants A1044373 and A1078054 and contract HHSN272200800045C. NR 51 TC 34 Z9 35 U1 3 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD NOV 28 PY 2013 VL 172 IS 1 BP 190 EP 200 DI 10.1016/j.jconrel.2013.07.030 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 260NI UT WOS:000327601200022 PM 23933525 ER PT J AU Barouch, DH AF Barouch, Dan H. TI The Quest for an HIV-1 Vaccine - Moving Forward SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EFFICACY TRIAL; DOUBLE-BLIND; INFECTION; THAILAND AB The challenges in the development of a prophylactic HIV-1 vaccine are unprecedented in the history of vaccinology. But there are reasons for optimism, and indeed, several promising vaccine concepts are currently moving toward clinical efficacy trials. Vaccines have historically been the most effective biomedical interventions for controlling global infectious diseases. The development of a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is therefore a critical research priority. Although other HIV-1 prevention efforts based on behavioral risk reduction, male circumcision, topical microbicides, preexposure prophylaxis, and treatment as prevention have had substantial effects on HIV-1 transmission rates, it is likely that a vaccine will be required to end the global HIV-1 epidemic. The challenges in the development of a prophylactic HIV-1 vaccine, however, are unprecedented in the history of vaccinology. First, HIV-1 exhibits tremendous ... C1 [Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Barouch, Dan H.] Harvard Univ, Sch Med, Boston, MA USA. [Barouch, Dan H.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Barouch, Dan H.] Harvard Univ, Cambridge, MA 02138 USA. RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. FU NIAID NIH HHS [U19 AI095985, U19 AI096040, U19 AI078526, R01 AI084794] NR 5 TC 9 Z9 9 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 NOV 28 PY 2013 VL 369 IS 22 BP 2073 EP 2076 DI 10.1056/NEJMp1312711 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 258OB UT WOS:000327467500003 PM 24283223 ER PT J AU Giugliano, RP Ruff, CT Braunwald, E Murphy, SA Wiviott, SD Halperin, JL Waldo, AL Ezekowitz, MD Weitz, JI Spinar, J Ruzyllo, W Ruda, M Koretsune, Y Betcher, J Shi, MG Grip, LT Patel, SP Patel, I Hanyok, JJ Mercuri, M Antman, EM Steinwender, C Kypta, A Duray, GZ Vamos, M Ritter, P Bordachar, P Lloyd, M El Chami, M Omar, R Hussin, A Girbau, JLM Tolosana, JM Morgan, JM Roberts, P De Groot, JR Tjong, FVY Boersma, LVA Soejima, K Sato, T Bongiorni, MG Soldati, E Hummel, J Augostini, R Chinitz, L Love, C Neuzil, P Reddy, V Simmers, TA Bracke, FALE Sagi, V Lee, S Gornick, C Remole, S Sra, J Nangia, V Shehata, M Swerdlow, C Schoenhard, J Milstein, S Voigt, A Saba, S Bernabei, M Bansal, S Reynolds, D Stavrakis, S AF Giugliano, Robert P. Ruff, Christian T. Braunwald, Eugene Murphy, Sabina A. Wiviott, Stephen D. Halperin, Jonathan L. Waldo, Albert L. Ezekowitz, Michael D. Weitz, Jeffrey I. Spinar, Jindrich Ruzyllo, Witold Ruda, Mikhail Koretsune, Yukihiro Betcher, Joshua Shi, Minggao Grip, Laura T. Patel, Shirali P. Patel, Indravadan Hanyok, James J. Mercuri, Michele Antman, Elliott M. Steinwender, Clemens Kypta, Alexander Duray, Gabor Z. Vamos, Mate Ritter, Philippe Bordachar, Pierre Lloyd, Michael El Chami, Mikhael Omar, Razali Hussin, Azlan Mont Girbau, Josep Lluis Maria Tolosana, Jose Morgan, John M. Roberts, Paul De Groot, Joris R. Tjong, Fleur V. Y. Boersma, Lucas V. A. Soejima, Kyoko Sato, Toshiaki Bongiorni, Maria Grazia Soldati, Ezio Hummel, John Augostini, Ralph Chinitz, Larry Love, Charles Neuzil, Petr Reddy, Vivek Simmers, Timothy Alexander Bracke, Frank A. L. E. Sagi, Venkata Lee, Scott Gornick, Charles Remole, Stephen Sra, Jasbir Nangia, Vikram Shehata, Michael Swerdlow, Charles Schoenhard, John Milstein, Simon Voigt, Andrew Saba, Samir Bernabei, Matthew Bansal, Sandeep Reynolds, Dwight Stavrakis, Stavros CA ENGAGE AF-TIMI 48 Investigators TI Edoxaban versus Warfarin in Patients with Atrial Fibrillation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FACTOR XA INHIBITOR; ORAL ANTICOAGULANTS; MISSING DATA; STROKE; PHARMACOKINETICS; METAANALYSIS; GENERATION; PREVENTION; THERAPY; TRIALS AB BackgroundEdoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. MethodsWe conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. ResultsThe annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). ConclusionsBoth once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.) C1 [Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Grip, Laura T.; Antman, Elliott M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Grip, Laura T.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Waldo, Albert L.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Ezekowitz, Michael D.] Thomas Jefferson Med Coll, Philadelphia, PA USA. [Weitz, Jeffrey I.] McMaster Univ, Hamilton, ON, Canada. [Spinar, Jindrich] Univ Hosp, Brno, Czech Republic. [Ruzyllo, Witold] Inst Cardiol, Warsaw, Poland. [Ruda, Mikhail] Cardiol Res Ctr, Moscow 121552, Russia. [Koretsune, Yukihiro] Osaka Natl Hosp, Natl Hosp Org, Osaka, Japan. [Betcher, Joshua; Patel, Shirali P.] Quintiles, Durham, NC USA. [Shi, Minggao; Patel, Indravadan; Hanyok, James J.; Mercuri, Michele] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Steinwender, Clemens; Kypta, Alexander] Johannes Kepler Univ Linz, Sch Med, Linz Gen Hosp, Linz, Austria. [Duray, Gabor Z.; Vamos, Mate] MH Honvedkorhaz, Budapest, Hungary. [Ritter, Philippe; Bordachar, Pierre] Univ Bordeaux, CHU, Pessac, France. [Lloyd, Michael; El Chami, Mikhael] Emory Univ Hosp, Atlanta, GA 30322 USA. [Omar, Razali; Hussin, Azlan] Inst Jantung Negara, Kuala Lumpur, Malaysia. [Mont Girbau, Josep Lluis; Maria Tolosana, Jose] Hosp Univ Clin Barcelona, Barcelona, Spain. [Morgan, John M.; Roberts, Paul] Southampton Gen Hosp, Southampton, Hants, England. [De Groot, Joris R.; Tjong, Fleur V. Y.] AMC, Amsterdam, Netherlands. [Boersma, Lucas V. A.] St Antonius Hosp, Nieuwegein, Netherlands. [Soejima, Kyoko; Sato, Toshiaki] Kyorin Univ Hosp, Tokyo, Japan. [Bongiorni, Maria Grazia; Soldati, Ezio] Azienda Osped Univ Pisana, Pisa, Italy. [Hummel, John; Augostini, Ralph] Ohio State Univ, Columbus, OH 43210 USA. [Chinitz, Larry; Love, Charles] NYU, New York, NY 10003 USA. [Neuzil, Petr; Reddy, Vivek] Na Homolce Hosp, Prague, Czech Republic. [Simmers, Timothy Alexander; Bracke, Frank A. L. E.] Catharina Hosp, Eindhoven, Netherlands. [Sagi, Venkata; Lee, Scott] Jacksonville Heart Ctr, Jacksonville, FL USA. [Gornick, Charles; Remole, Stephen] Minneapolis Heart Inst, Minneapolis, MN USA. [Sra, Jasbir; Nangia, Vikram] Aurora Cardiovasc Serv, Milwaukee, WI USA. [Shehata, Michael; Swerdlow, Charles] Cedars Sinai Med Ctr, Los Angeles, CA USA. [Schoenhard, John; Milstein, Simon] CentraCare Heart & Vasc Ctr, St Cloud, MN USA. [Voigt, Andrew; Saba, Samir] UPMC, Pittsburgh, PA 15260 USA. [Bernabei, Matthew; Bansal, Sandeep] Lancaster Heart & Stroke Fdn, Lancaster, PA USA. [Reynolds, Dwight; Stavrakis, Stavros] Univ Oklahoma, Oklahoma City, OK USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, 350 Longwood Ave,1st Flr, Boston, MA 02115 USA. EM rgiugliano@partners.org RI Verheugt, F.W.A./H-8105-2014; Badenhorst, Melissa/E-8214-2010; Libis, Roman/O-9193-2015; Colquhoun, David/F-9078-2013; Nagy, Ivan/I-7419-2013; De Caterina, Raffaele/K-3857-2016; Drapkina, Oxana/G-8443-2016; Flecknoe-Brown, Stephen/A-4927-2017; OI Goessling, Wolfram/0000-0001-9972-1569; Iversen, Helle Klingenberg/0000-0002-5880-6352; Macleod, Malcolm Robert/0000-0001-9187-9839; Brilakis, Emmanouil/0000-0001-9416-9701; Badenhorst, Melissa/0000-0002-4732-5027; Libis, Roman/0000-0003-0130-990X; De Caterina, Raffaele/0000-0003-1637-574X; Drapkina, Oxana/0000-0002-4453-8430; Kraydashenko, Oleg/0000-0001-8727-8889; PENCO, Maria/0000-0002-0711-9747; Villuendas-Sabate, Roger/0000-0001-9110-905X; Lappalainen, Tuuli/0000-0002-7746-8109; Fukamizu, Seiji/0000-0002-0291-9702 FU Daiichi Sankyo Pharma Development; Daiichi Sankyo; Janssen Pharmaceuticals; Merck; Bristol-Myers Squibb; Sanofi; Johnson Johnson; AstraZeneca; Boehringer Ingelheim; Genzyme; Amorcyte; Medicines Company; Cardiorentis; Eli Lilly; Menarini; Medscape; Bayer HealthCare; GlaxoSmithKline; Beckman Coulter; Roche Diagnostics; Pfizer; Eisai; Arena Pharmaceuticals; Aegerion; AngelMed; Xoma; ICON Clinical Research; Boston Clinical Research Institute; Ortho-McNeil-Janssen Pharmaceuticals; Biotronik; Boston Scientific; Medtronic; Cardio-Insight; ChanRx; Portola Pharmaceuticals; Janssen Scientific Affairs; Pozen; Coherex Medical; Gilead FX Supported by Daiichi Sankyo Pharma Development.r Dr. Giugliano reports receiving consulting fees from Daiichi Sankyo, Janssen Pharmaceuticals, and Merck; lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Merck, and Sanofi; and grant support through his institution from Daiichi Sankyo, Merck, Johnson & Johnson, Sanofi, and AstraZeneca. Dr. Ruff reports receiving consulting fees from Daiichi Sankyo, Bristol-Myers Squibb, and Boehringer Ingelheim and grant support through his institution from Daiichi Sankyo. Dr. Braunwald reports receiving consulting fees from Sanofi, Genzyme, Amorcyte, the Medicines Company, and Cardiorentis; lecture fees from Eli Lilly, Menarini, Medscape, and Bayer HealthCare; and grant support through his institution from Daiichi Sankyo, AstraZeneca, Johnson & Johnson, GlaxoSmithKline, Bristol-Myers Squibb, Beckman Coulter, Roche Diagnostics, Pfizer, Merck, and Sanofi. He also reports serving as an unpaid consultant for Merck and providing uncompensated lectures for Merck and CVRx. Dr. Wiviott reports receiving consulting fees from AstraZeneca, Bristol-Myers Squibb, Eisai, Arena Pharmaceuticals, Eli Lilly, Daiichi Sankyo, Aegerion, AngelMed, Janssen Pharmaceuticals, Xoma, ICON Clinical Research, and Boston Clinical Research Institute and grant support through his institution from AstraZeneca, Bristol-Myers Squibb, Eisai, Arena Pharmaceuticals, Merck, Eli Lilly, Daiichi Sankyo, and Sanofi. Dr. Halperin reports receiving consulting fees from Bayer HealthCare, Boehringer Ingelheim, Johnson & Johnson, Ortho-McNeil-Janssen Pharmaceuticals, Pfizer, Sanofi, Biotronik, Boston Scientific, and Medtronic. Dr. Waldo reports receiving consulting fees from Daiichi Sankyo, Sanofi, Cardio-Insight, Pfizer, and ChanRx; lecture fees from Sanofi, Pfizer, Janssen Pharmaceuticals, and Bristol-Myers Squibb; honoraria for clinical trial-related activities from Biotronik, St. Jude Medical, Daiichi Sankyo, Biosense Webster, Gilead, and AtriCure; and grant support through his institution from Gilead. Dr. Ezekowitz reports receiving consulting fees from Boehringer Ingelheim, Pfizer, Sanofi, Bristol-Myers Squibb, Portola Pharmaceuticals, Bayer HealthCare, Daiichi Sankyo, Medtronic, Aegerion, Merck, Johnson & Johnson, Gilead, Janssen Scientific Affairs, Pozen, and Coherex Medical; and lecture fees from Boehringer Ingelheim. Dr. Weitz reports receiving consulting fees from Boehringer Ingelheim, Bayer HealthCare, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, Pfizer, Merck, and Portola Pharmaceuticals. Dr. Koretsune reports receiving lecture fees from Daiichi Sankyo, Boehringer Ingelheim, Pfizer, Bayer HealthCare, and Bristol-Myers Squibb; and grant support through his institution from Daiichi Sankyo and Boehringer Ingelheim. Drs. Shi, Patel, Hanyok, and Mercuri report being employees of Daiichi Sankyo. Dr. Mercuri also reports holding a pending patent related to the clinical properties of edoxaban. Ms. Murphy, Ms. Grip, and Dr. Antman report receiving grant support through their institution from Daiichi Sankyo. No other potential conflict of interest relevant to this article was reported. NR 25 TC 852 Z9 880 U1 13 U2 132 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 NOV 28 PY 2013 VL 369 IS 22 BP 2093 EP 2104 DI 10.1056/NEJMoa1310907 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 258OB UT WOS:000327467500007 PM 24251359 ER PT J AU Kim, AY Wu, RI AF Kim, Arthur Y. Wu, Roseann I. TI Case 37-2013: A 41-Year-Old Woman with Malaise and Chest and Abdominal Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEPATITIS-C VIRUS; ALPHA-2A PLUS RIBAVIRIN; HIV-INFECTED PATIENTS; POSTEXPOSURE PROPHYLAXIS; VIRAL LOAD; REINFECTION; CLEARANCE C1 [Kim, Arthur Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wu, Roseann I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wu, Roseann I.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kim, AY (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU Vertex Pharmaceuticals; AbbVie; Gilead; Bristol-Myers Squibb FX Dr. Kim reports receiving consulting fees from Vertex Pharmaceuticals, AbbVie, and Gilead and grant funding from Bristol-Myers Squibb. No other potential conflict of interest relevant to this article was reported. NR 20 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 2013 VL 369 IS 22 BP 2138 EP 2145 DI 10.1056/NEJMcpc1209651 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 258OB UT WOS:000327467500012 PM 24283228 ER PT J AU Greene, MF Mello, MM Morain, S AF Greene, Michael F. Mello, Michelle M. Morain, Stephanie TI A New Era in Noninvasive Prenatal Testing REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter AB On March 11, 2011, a magnitude 9.0 earthquake struck the northeast region of Japan. During the first 4 weeks after the earthquake, the numbers of out-of-hospital cardiac arrests were significantly increased as compared with the numbers during the same weeks from 2005 to 2010.To the Editor: The most powerful earthquake ever recorded in Japan, with a magnitude of 9.0 on the Richter scale, struck the northeast region of Japan on March 11, 2011 (Figure 1A).(1),(2) Earthquakes are known to increase the risk of sudden cardiac arrest.(3) Using a nationwide population-based database, we assessed the association between this earthquake and the occurrence of out-of-hospital cardiac arrest of presumed cardiac origin.(4),(5) Our study involved adult patients with out-of-hospital cardiac arrest of presumed cardiac origin who were transported to medical institutions in Iwate, Miyagi, and Fukushima the three prefectures that were most damaged ... C1 [Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mello, Michelle M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Morain, Stephanie] Harvard Univ, Cambridge, MA 02138 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 2013 VL 369 IS 22 BP 2165 EP 2165 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 258OB UT WOS:000327467500028 PM 24283242 ER PT J AU McLinden, RJ LaBranche, CC Chenine, AL Polonis, VR Eller, MA Wieczorek, L Ochsenbauer, C Kappes, JC Perfetto, S Montefiori, DC Michael, NL Kim, JH AF McLinden, Robert J. LaBranche, Celia C. Chenine, Agnes-Laurence Polonis, Victoria R. Eller, Michael A. Wieczorek, Lindsay Ochsenbauer, Christina Kappes, John C. Perfetto, Stephen Montefiori, David C. Michael, Nelson L. Kim, Jerome H. TI Detection of HIV-1 Neutralizing Antibodies in a Human CD4(+)/CXCR4(+)/CCR5(+) T-Lymphoblastoid Cell Assay System SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; CROSS-CLADE NEUTRALIZATION; INFECTIOUS MOLECULAR CLONES; PROXIMAL EXTERNAL REGION; BLOOD MONONUCLEAR-CELLS; FUSION INHIBITOR T-20; SUBTYPE-C INFECTION; V3 LOOP; EFFICACY TRIAL AB Sensitive assays are needed to meaningfully assess low levels of neutralizing antibodies (NAbs) that may be important for protection against the acquisition of HIV-1 infection in vaccine recipients. The current assay of choice uses a non-lymphoid cell line (TZM-bl) that may lack sensitivity owing to over expression of CD4 and CCR5. We used transfection of a human CD4+/CXCR4+/alpha(4)beta(7)+ T-lymphoblastoid cell line (A3.01) with a CMV IE promoter-driven CCR5neo vector to stably express CCR5. The resulting line, designated A3R5, is permissive to a wide range of CCR5-tropic circulating strains of HIV-1, including HIV-1 molecular clones containing a Tat-inducible Renilla luciferase reporter gene and expressing multiple Env subtypes. Flow cytometric analysis found CCR5 surface expression on A3R5 cells to be markedly less than TZM-bl but similar to CD3.8 stimulated PBMC. More importantly, neutralization mediated by a diverse panel of monoclonal antibodies, HIV-1 positive polyclonal sera and sCD4 was consistently greater in A3R5 compared to TZM-bl cells. The A3R5 cell line provides a novel approach to guide the development and qualification of promising new HIV-1 vaccine immunogens. C1 [McLinden, Robert J.; Chenine, Agnes-Laurence; Polonis, Victoria R.; Eller, Michael A.; Wieczorek, Lindsay; Michael, Nelson L.; Kim, Jerome H.] WRAIR, Mil HIV Res Program, Silver Spring, MD USA. [LaBranche, Celia C.; Montefiori, David C.] Duke U Med Ctr, Dept Surg, Durham, NC USA. [Ochsenbauer, Christina; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. [Perfetto, Stephen] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP McLinden, RJ (reprint author), WRAIR, Mil HIV Res Program, Silver Spring, MD USA. EM rmclinden@hivresearch.org FU U.S. Army Medical Research and Material Command (USAMRMC) [Y1-AI-2642-12]; National Institute of Allergy and Infectious Diseases [Y1-AI-2642-12]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD) [W81XWH-07-2-0067]; Bill & Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery (CAVD)/Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC) [38619, 1032144]; NIH Center for HIV/AIDS Vaccine Immunology (CHAVI) [UO1-AI067854] FX This work was supported in part by an Interagency Agreement (Y1-AI-2642-12) between U.S. Army Medical Research and Material Command (USAMRMC) and the National Institute of Allergy and Infectious Diseases. This work was also supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). The contribution of DCM was supported by the Bill & Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery (CAVD)/Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC), grant numbers 38619 and 1032144. The contribution of CO and JCK was supported by NIH Center for HIV/AIDS Vaccine Immunology (CHAVI) grant, UO1-AI067854; the Bill & Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery (CAVD)/Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC), grant numbers 38619 and 1032144; and facilities of the Virology and Genetic Sequencing cores of the UAB Center for AIDS Research (P30-AI-27767). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 103 TC 15 Z9 15 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 NOV 28 PY 2013 VL 8 IS 11 AR UNSP e77756 DI 10.1371/journal.pone.0077756 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261IJ UT WOS:000327657900001 PM 24312168 ER PT J AU Wells, RE Yeh, GY Kerr, CE Wolkin, J Davis, RB Tan, Y Spaeth, R Wall, RB Walsh, J Kaptchuk, TJ Press, D Phillips, RS Kong, J AF Wells, Rebecca Erwin Yeh, Gloria Y. Kerr, Catherine E. Wolkin, Jennifer Davis, Roger B. Tan, Ying Spaeth, Rosa Wall, Robert B. Walsh, Jacquelyn Kaptchuk, Ted J. Press, Daniel Phillips, Russell S. Kong, Jian TI Meditation's impact on default mode network and hippocampus in mild cognitive impairment: A pilot study SO NEUROSCIENCE LETTERS LA English DT Article DE Mild cognitive impairment; Alzheimer's Disease; fMRI; Meditation; Default mode network; Hippocampus ID ALZHEIMERS-DISEASE; MINDFULNESS MEDITATION; FUNCTIONAL CONNECTIVITY; BRAIN; MEMORY; MECHANISMS; METAANALYSIS; EXPERIENCE; INCREASES; DISTRESS AB Those with high baseline stress levels are more likely to develop mild cognitive impairment (MCI) and Alzheimer's Disease (AD). While meditation may reduce stress and alter the hippocampus and default mode network (DMN), little is known about its impact in these populations. Our objective was to conduct a "proof of concept" trial to determine whether Mindfulness Based Stress Reduction (MBSR) would improve DMN connectivity and reduce hippocampal atrophy among adults with MCI. 14 adults with MCI were randomized to MBSR vs. usual care and underwent resting state fMRI at baseline and follow-up. Seed based functional connectivity was applied using posterior cingulate cortex as seed. Brain morphometry analyses were performed using FreeSurfer. The results showed that after the intervention, MBSR participants had increased functional connectivity between the posterior cingulate cortex and bilateral medial prefrontal cortex and left hippocampus compared to controls. In addition, MBSR participants had trends of less bilateral hippocampal volume atrophy than control participants. These preliminary results indicate that in adults with MCI, MBSR may have a positive impact on the regions of the brain most related to MCI and AD. Further research with larger sample sizes and longer-follow-up are needed to further investigate the results from this pilot study. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Wells, Rebecca Erwin; Yeh, Gloria Y.; Wolkin, Jennifer; Davis, Roger B.; Kaptchuk, Ted J.; Press, Daniel; Phillips, Russell S.] Harvard Univ, Sch Med, BIDMC, Boston, MA 02215 USA. [Kerr, Catherine E.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Tan, Ying; Spaeth, Rosa; Kong, Jian] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wall, Robert B.] Commonwealth Care Alliance, Boston, MA 02108 USA. [Walsh, Jacquelyn] Brigham & Womens Hosp, Boston, MA 02215 USA. RP Wells, RE (reprint author), Wake Forest Sch Med, Dept Neurol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM rewells@wakehealth.edu FU Harvard Medical School Osher Research Center, the Division of General Medicine; Division of General Medicine and Primary Care at BIDMC; NIH National Center for Complementary and Alternative Medicine (NCCAM) [K24 AT004095]; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Harvard University; National Research Service Award [T32AT000051]; NIH NCCAM [K24 AT004095, K24AT000589, K01 AT003459, KO1AT003883, R21AT004497, R01AT006364]; NIH NIDA [R03AT218317, NIH UL1 RR 02758] FX This study was supported by the Harvard Medical School Osher Research Center, the Division of General Medicine and Primary Care at BIDMC and NIH National Center for Complementary and Alternative Medicine (NCCAM) K24 AT004095. In addition, this work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers).; We acknowledge the research support of: National Research Service Award Number T32AT000051 (R.E.W.); NIH NCCAM funding of: K24 AT004095 (T.J.), K24AT000589 (R.S.P.), K01 AT003459 (C.E.K.), KO1AT003883 (J.K.), R21AT004497 (J.K.), R01AT006364 (J.K.); NIH NIDA funding of R03AT218317 (J.K.); NIH UL1 RR 02758 (R.D.). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 34 TC 26 Z9 27 U1 5 U2 49 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 27 PY 2013 VL 556 BP 15 EP 19 DI 10.1016/j.neulet.2013.10.001 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 273FP UT WOS:000328520900004 PM 24120430 ER PT J AU Fekadu, A Mesfin, M Medhin, G Alem, A Teferra, S Gebre-Eyesus, T Seboxa, T Assefa, A Hussein, J Lemma, MT Borba, C Henderson, DC Hanlon, C Shibre, T AF Fekadu, Abebaw Mesfin, Miraf Medhin, Girmay Alem, Atalay Teferra, Solomon Gebre-Eyesus, Tsehaysina Seboxa, Teshale Assefa, Abraham Hussein, Jemal Lemma, Martha T. Borba, Christina Henderson, David C. Hanlon, Charlotte Shibre, Teshome TI Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial SO TRIALS LA English DT Article DE Minocycline; Schizophrenia; Intervention; Clinical trial; Ethiopia ID NEGATIVE SYNDROME SCALE; NEUROPROTECTIVE AGENT; CLINICAL-COURSE; ETHIOPIA; RELIABILITY; HALOPERIDOL; OLANZAPINE; MECHANISMS; CLOZAPINE; SYMPTOMS AB Background: Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms. In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. Methods: The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years' duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level of functioning. Whether changes are maintained post intervention will also be measured (PANSS). Key assessment for the primary outcome will be conducted at the end of trial (week 12). One post-intervention assessment will be conducted 4 weeks after the end of intervention (week 16) to determine sustainability of change. C1 [Fekadu, Abebaw; Mesfin, Miraf; Alem, Atalay; Teferra, Solomon; Hanlon, Charlotte; Shibre, Teshome] Univ Addis Ababa, Sch Med, Dept Psychiat, Coll Hlth Sci, Addis Ababa, Ethiopia. [Fekadu, Abebaw] Kings Coll London, Inst Psychiat, Dept Psychol Med, Affect Disorders Res Grp, London, England. [Fekadu, Abebaw] Ctr Affect Disorders, London, England. [Medhin, Girmay] Univ Addis Ababa, Aklilu Lemma Inst Pathobiol, Addis Ababa, Ethiopia. [Gebre-Eyesus, Tsehaysina] St Paul Hosp, Dept Internal Med, Millennium Med Coll, Addis Ababa, Ethiopia. [Seboxa, Teshale] Univ Addis Ababa, Infect Dis Sect, Dept Internal Med, Coll Hlth Sci, Addis Ababa, Ethiopia. [Assefa, Abraham; Hussein, Jemal] ALERT, Armauer Hansen Res Inst, Addis Ababa, Ethiopia. [Lemma, Martha T.] Bahirdar Univ, Dept Microbiol, Bahirdar, Ethiopia. [Borba, Christina; Henderson, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MD Div Global Psychiat,MGH Schizophrenia Program, Boston, MA USA. [Hanlon, Charlotte] Kings Coll London, Inst Psychiat, Dept Hlth Serv & Populat Res, London, England. RP Fekadu, A (reprint author), Univ Addis Ababa, Sch Med, Dept Psychiat, Coll Hlth Sci, Addis Ababa, Ethiopia. EM abe.wassie@kcl.ac.uk RI Aseffa, Abraham/J-3248-2016 OI Aseffa, Abraham/0000-0002-8028-1150 FU Stanley Medical Research Institute (SMRI) FX This study is funded by a grant from the Stanley Medical Research Institute (SMRI). NR 39 TC 4 Z9 4 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD NOV 27 PY 2013 VL 14 AR 406 DI 10.1186/1745-6215-14-406 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 276NJ UT WOS:000328756700001 PM 24279305 ER PT J AU Field, AE Camargo, CA Ogino, S AF Field, Alison E. Camargo, Carlos A., Jr. Ogino, Shuji TI The Merits of Subtyping Obesity One Size Does Not Fit All SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID BODY-MASS INDEX; ASSOCIATION; PREVALENCE; CHILDREN; TRENDS C1 [Field, Alison E.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Epidemiol,Dept Med, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A., Jr.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Field, Alison E.] Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Epidemiol,Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Field, AE (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Adolescent Med, 300 Longwood Ave,AU 506, Boston, MA 02115 USA. EM alison.field@childrens.harvard.edu NR 10 TC 28 Z9 29 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 27 PY 2013 VL 310 IS 20 BP 2147 EP 2148 DI 10.1001/jama.2013.281501 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 257RS UT WOS:000327404400020 PM 24189835 ER PT J AU Morchikh, M Naughtin, M Di Nunzio, F Xavier, J Charneau, P Jacob, Y Lavigne, M AF Morchikh, Mehdi Naughtin, Monica Di Nunzio, Francesca Xavier, Johan Charneau, Pierre Jacob, Yves Lavigne, Marc TI TOX4 and NOVA1 Proteins Are Partners of the LEDGF PWWP Domain and Affect HIV-1 Replication SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRE-MESSENGER-RNA; TRANSCRIPTIONAL COACTIVATOR P75; SMALL-MOLECULE INHIBITORS; HOST MITOTIC CHROMOSOMES; INTEGRATION IN-VITRO; STRESS-RELATED GENES; DNA INTEGRATION; GROWTH-FACTOR; BINDING PROTEIN AB PWWP domains are involved in the chromatin attachment of several proteins. They bind to both DNA and proteins and their interaction with specific histone methylation marks define them as a new class of histone code readers. The lens epithelium derived growth factor (LEDGF/p75) contains an N-terminal PWWP domain necessary for its interaction with chromatin but also a C-terminal domain which interacts with several proteins, such as lentiviral integrases. These two domains confer a chromatin-tethering function to LEDGF/p75 and in the case of lentiviral integrases, this tethering participates in the efficiency and site selectivity of integration. Although proteins interacting with LEDGF/p75 C-terminal domain have been extensively studied, no data exist about partners of its PWWP domain regulating its interaction with chromatin. In this study, we report the identification by yeast-two-hybrid of thirteen potential partners of the LEDGF PWWP domain. Five of these interactions were confirmed in mammalian cells, using both a protein complementation assay and co-immunoprecipitation approaches. Three of these partners interact with full length LEDGF/p75, they are specific for PWWP domains of the HDGF family and they require PWWP amino acids essential for the interaction with chromatin. Among them, the transcription activator TOX4 and the splicing cofactor NOVA1 were selected for a more extensive study. These two proteins or their PWWP interacting regions (PIR) colocalize with LEDGF/p75 in Hela cells and interact in vitro in the presence of DNA. Finally, single round VSV-G pseudotyped HIV-1 but not MLV infection is inhibited in cells overexpressing these two PIRs. The observed inhibition of infection can be attributed to a defect in the integration step. Our data suggest that a regulation of LEDGF interaction with chromatin by cellular partners of its PWWP domain could be involved in several processes linked to LEDGF tethering properties, such as lentiviral integration, DNA repair or transcriptional regulation. C1 [Morchikh, Mehdi; Naughtin, Monica; Xavier, Johan; Lavigne, Marc] Ecole Normale Super Lyon, CNRS, Lab Joliot Curie, F-69364 Lyon, France. [Morchikh, Mehdi; Lavigne, Marc] Inst Pasteur, CNRS, Unite Virol Struct, Unite Rech Associee, Paris, France. [Morchikh, Mehdi] Univ Paris 06, Paris, France. [Di Nunzio, Francesca; Charneau, Pierre] Inst Pasteur, Unite Virol Mol & Vaccinol, CNRS, Paris, France. [Jacob, Yves] Inst Pasteur, Unite Genet Mol Virus ARN, CNRS, Paris, France. [Jacob, Yves] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Jacob, Yves] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Lavigne, M (reprint author), Ecole Normale Super Lyon, CNRS, Lab Joliot Curie, F-69364 Lyon, France. EM marc.lavigne@ens-lyon.fr RI Di Nunzio, Francesca/A-6153-2014 OI Di Nunzio, Francesca/0000-0003-2879-3164 FU Agence Nationale de la Recherche sur le SIDA et les hepatites [AO 2011-1]; Centre National de la Recherche Scientifique (CNRS, Missions Interdisciplinaires); Ecole Normale Superieure de Lyon (ENS); Ministere de la recherche et de l'enseignement superieur; Pierre Berge fundation; Pasteur Weizman fundation; CNRS; SIDACTION; ANRS FX This work was supported by grants from the Agence Nationale de la Recherche sur le SIDA et les hepatites (AO 2011-1), Centre National de la Recherche Scientifique (CNRS, Missions Interdisciplinaires) and Ecole Normale Superieure de Lyon (ENS). MM was funded by the Ministere de la recherche et de l'enseignement superieur, Pierre Berge and Pasteur Weizman fundations. MN was funded by the CNRS and ENS and FDN by SIDACTION. JX is funded by the ANRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 121 TC 7 Z9 7 U1 0 U2 14 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 NOV 27 PY 2013 VL 8 IS 11 AR e81217 DI 10.1371/journal.pone.0081217 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261GG UT WOS:000327652100065 PM 24312278 ER PT J AU Abbasi, SA Shah, RV Heydari, B Farhad, H Dodson, J Bakker, JP John, R Malhotra, A Blankstein, R Jerosch-Herold, M Kwong, RY Neilan, TG AF Abbasi, Siddique A. Shah, Ravi V. Heydari, Bobak Farhad, Hoshang Dodson, John Bakker, Jessie P. John, Roy Malhotra, Atul Blankstein, Ron Jerosch-Herold, Michael Kwong, Raymond Y. Neilan, Tomas G. TI Obesity and Sleep Apnea are Independently Associated With Adverse Left Ventricular Remodeling and Clinical Outcome in Patients With Atrial Fibrillation and Preserved Ventricular Function SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Magnetic resonance imaging; Heart failure; Obesity C1 [Abbasi, Siddique A.; Shah, Ravi V.; Heydari, Bobak; Farhad, Hoshang; Dodson, John; John, Roy; Blankstein, Ron; Kwong, Raymond Y.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Bakker, Jessie P.; Malhotra, Atul] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Div Radiol, Boston, MA 02115 USA. [Neilan, Tomas G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10761 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901209 ER PT J AU Abhishek, F Heist, EK Elmariah, S Passeri, J Palacios, I Inglessis, I Danik, S Barrett, C Baker, J Vlahakes, G Ruskin, J Mansour, M AF Abhishek, Fnu Heist, E. Kevin Elmariah, Sammy Passeri, Jonathan Palacios, Igor Inglessis, Ignacio Danik, Stephan Barrett, Conor Baker, Joshua Vlahakes, Gus Ruskin, Jeremy Mansour, Moussa TI Impact of Atrial Fibrillation on Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Valvular disease; Valvular heart disease C1 [Abhishek, Fnu; Heist, E. Kevin; Elmariah, Sammy; Passeri, Jonathan; Palacios, Igor; Inglessis, Ignacio; Danik, Stephan; Barrett, Conor; Baker, Joshua; Vlahakes, Gus; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13926 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903359 ER PT J AU Abtahian, F Yonetsu, T Karo, K Jia, HB Vergalio, R Tian, JW Hu, SN McNultv, I Lee, H Raffel, C Choi, SY Toma, C Jang, IK AF Abtahian, Farhad Yonetsu, Taishi Karo, Koji Jia, Halbo Vergalio, Rocco Tian, Jinwei Hu, Sining McNultv, Iris Lee, Hang Raffel, Christopher Choi, So-Yeon Toma, Catalin Jang, Ik-Kyung TI Smoking is Associated with Presence of Vulnerable Plaques: A Three Vessel Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Smoking; Cardiovascular imaging; Coronary artery disease; Acute coronary syndromes C1 [Abtahian, Farhad; Yonetsu, Taishi; Karo, Koji; Jia, Halbo; Vergalio, Rocco; Tian, Jinwei; Hu, Sining; McNultv, Iris; Lee, Hang; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raffel, Christopher] Prince Charles Hosp, Brisbane, Qld 4032, Australia. [Choi, So-Yeon] Ajou Univ Hosp, Suwon, South Korea. [Toma, Catalin] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12724 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902363 ER PT J AU Agboola, SO Khateeb, K Moore, SA Kvedar, JC Jethwani, K AF Agboola, Stephen O. Khateeb, Kholoud Moore, Stephanie A. Kvedar, Joseph C. Jethwani, Kamal TI Impact of the Connected Cardiac Care Program on Hospitalizations and Mortality: a Matched-control Analysis SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Self monitoring; Self care; Health education C1 [Agboola, Stephen O.; Khateeb, Kholoud; Kvedar, Joseph C.; Jethwani, Kamal] Massachusetts Gen Hosp, Cntr Connected Hlth, Boston, MA 02114 USA. [Moore, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906451 ER PT J AU Ahmad, T Wang, T Samsky, M Craig, D Felker, GM Hernandez, A Rogers, J Milano, C Januzzi, JL Bowles, D Stevens, RD Ilkayeva, O Newgard, C Shah, S Patel, C AF Ahmad, Tariq Wang, Teresa Samsky, Marc Craig, Damian Felker, Gary M. Hernandez, Adrian Rogers, Joseph Milano, Carmelo Januzzi, James L. Bowles, Dawn Stevens, Robert D. Ilkayeva, Olga Newgard, Christopher Shah, Svati Patel, Chetan TI Effects of Left Ventricular Assist Device Placement on Biomarkers of Cardiovascular Stress, Fibrosis, Fluid Homeostasis, Mitochondrial Function, Metabolism, and Endothelial Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Biomarkers; Mitochondrial energetics, heart failure, arrhythmias; Cardiac metabolism; Artificial heart/Cardiac support devices; Heart failure C1 [Ahmad, Tariq; Wang, Teresa; Samsky, Marc; Craig, Damian; Felker, Gary M.; Hernandez, Adrian; Rogers, Joseph; Milano, Carmelo; Bowles, Dawn; Stevens, Robert D.; Ilkayeva, Olga; Shah, Svati; Patel, Chetan] Duke Med Cntr, Durham, NC USA. [Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newgard, Christopher] Duke, Med, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16103 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905363 ER PT J AU Almassi, GH Wanner, TH Hattler, B Collins, JF Quin, J Ebrahimi, R Grover, FL Bishawi, M Carr, BM Shroyer, AL AF Almassi, G. Hossein Wanner, Todd H. Hattler, Brack Collins, Joseph F. Quin, Jacquelyn Ebrahimi, Ramin Grover, Frederick L. Bishawi, Muath Carr, Brendan M. Shroyer, A. L. TI Postoperative Atrial Fibrillation Impacts One Year Clinical Outcomes and Costs: The VA ROOBY Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Cardiac surgery; Quality of life; Coronary artery disease C1 [Almassi, G. Hossein] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wanner, Todd H.] Palo Alto VA Med Cntr, Hlth Econ Resource Cntr, Menlo Pk, CA USA. [Hattler, Brack] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Cardioil, Denver, CO USA. [Collins, Joseph F.] Vet Affairs Med Cntr, Cooperat Studies Program Coordinating Cntr, Perry Point, MD USA. [Quin, Jacquelyn] VA Boston Healthcare Syst, Cardiothorac Surg, West Roxbury, MA USA. [Ebrahimi, Ramin] Greater Los Angeles VA Med Cntr, Los Angeles, CA USA. [Grover, Frederick L.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Cardiothorac Surg, Denver, CO USA. [Bishawi, Muath] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. [Carr, Brendan M.] Northport VAMC, Rsch & Dev Off, Northport, NY USA. [Shroyer, A. L.] SUNY Stony Brook, Sch Med, Dept Surg, Stony Brook, NY 11794 USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12326 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902191 ER PT J AU Bagai, A Wang, YF Wang, TY Curtis, J Gurm, HS Peterson, ED Saucedo, JF Granger, CB Roe, MT Bhatt, DL McNamara, RL Alexander, KP AF Bagai, Akshay Wang, Yongfei Wang, Tracy Y. Curtis, Jeptha Gurm, Hitinder S. Peterson, Eric D. Saucedo, Jorge F. Granger, Christopher B. Roe, Matthew T. Bhatt, Deepak L. McNamara, Robert L. Alexander, Karen P. TI In-Hospital ADP Receptor Inhibitor Switching in Myocardial Infarction Patients Treated With Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry (R) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Antiplatelet drugs; Myocardial infarction; Percutaneous coronary intervention; Pharmacology C1 [Bagai, Akshay; Wang, Tracy Y.; Peterson, Eric D.; Granger, Christopher B.; Roe, Matthew T.; Alexander, Karen P.] Duke Clin Rsch Inst, Durham, NC USA. [Wang, Yongfei; Curtis, Jeptha] Yale Univ, Sch Med, New Haven, CT USA. [Gurm, Hitinder S.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Saucedo, Jorge F.] Univ Oklahoma Hlth Sci Cntr, Oklahoma City, OK USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [McNamara, Robert L.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13284 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903083 ER PT J AU Bernacki, GM Alexander, KP Newby, LK Yang, QH Schulte, P White, HD Ohman, EM Mahaffey, KW Shah, BR Giugliano, RP Armstrong, PW Harrington, RA Tricoci, P Van de Werf, F Alexander, J Califf, RM Lopes, RD AF Bernacki, Gwen M. Alexander, Karen P. Newby, L. Kristin Yang, Qinghong Schulte, Phillip White, Harvey D. Ohman, E. Magnus Mahaffey, Kenneth W. Shah, Bimal R. Giugliano, Robert P. Armstrong, Paul W. Harrington, Robert A. Tricoci, Pierluigi Van de Werf, Frans Alexander, John Califf, Robert M. Lopes, Renato D. TI Trends in Enrollment, Patient Characteristics, Treatments and Outcomes of Older Adults With Non-ST-segment Elevation Acute Coronary Syndromes (ACS) in Clinical Trials SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary Syndromes; Older population; Elderly; Clinical trials; Quality assessment C1 [Bernacki, Gwen M.] Duke Clin Rsch Inst, Div Cardiol, Durham, NC USA. [Alexander, Karen P.; Newby, L. Kristin; Ohman, E. Magnus; Mahaffey, Kenneth W.; Shah, Bimal R.; Tricoci, Pierluigi; Alexander, John; Lopes, Renato D.] Duke Univ, Dept Med, Med Cntr, Duke Clin Rsch Inst, Durham, NC USA. [Yang, Qinghong; Schulte, Phillip] Duke Clin Rsch Inst, Durham, NC USA. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Giugliano, Robert P.] Brigham & Womens Hosp, Dept Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Armstrong, Paul W.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Van de Werf, Frans] Univ Hosps Leuven, Dept Cardiol, Louvain, Belgium. [Califf, Robert M.] Duke Univ, Dept Med, Med Cntr, Duke Translat Med Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 9904 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162900452 ER PT J AU Bhatt, AB Zuflacht, JP Buck, JS Kadivar, S Singh, M Creager, MA AF Bhatt, Ami B. Zuflacht, Jonah P. Buck, J. S. Kadivar, Samoneh Singh, Michael Creager, Mark A. TI Losartan and Atenolol Exert Therapeutic Benefit via Distinct Mechanisms of Action in Marfan Syndrome SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic diseases; Adult congenital heart disease; Vascular C1 [Bhatt, Ami B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zuflacht, Jonah P.; Buck, J. S.; Kadivar, Samoneh; Singh, Michael; Creager, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16166 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905389 ER PT J AU Bittencourt, MS Hulten, E Abbara, S Ghoshhajra, B Murthy, VL Truong, OA Gowdak, LHW Riella, LV diCarli, M Hoffmann, U Blankstein, R AF Bittencourt, Marcio S. Hulten, Edward Abbara, Suhny Ghoshhajra, Brian Murthy, Venkatesh L. Truong, Ouynh A. Gowdak, Luis Henrique W. Riella, Leonardo V. diCarli, Marcelo Hoffmann, Udo Blankstein, Ron TI Incremental Prognostic Value of Coronary Artery Disease and Renal Function on the Prediction of Cardiovascular Events of Patients Evaluated by Coronary Computed Tomography: The Partners Registry SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Computed tomography; Coronary artery disease; Renal function; Prognosis C1 [Bittencourt, Marcio S.; Hulten, Edward; Riella, Leonardo V.; diCarli, Marcelo; Blankstein, Ron] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abbara, Suhny; Ghoshhajra, Brian; Truong, Ouynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Murthy, Venkatesh L.] Univ Michigan, Ann Arbor, MI USA. [Gowdak, Luis Henrique W.] Univ Sao Paulo, Heart Inst InCor, Sao Paulo, Brazil. RI Murthy, Venkatesh/B-3448-2013; Wolff Gowdak, Luis Henrique/C-4844-2012; Bittencourt, Marcio/C-1444-2011 OI Murthy, Venkatesh/0000-0002-7901-1321; Wolff Gowdak, Luis Henrique/0000-0002-6785-7506; Bittencourt, Marcio/0000-0002-3711-1754 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10683 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901175 ER PT J AU Bonaca, MP Scirica, BM Braunwald, E Wiviott, SD Murphy, SA Morrow, DA AF Bonaca, Marc P. Scirica, Benjamin M. Braunwald, Eugene Wiviott, Stephen D. Murphy, Sabina A. Morrow, David A. TI Vorapaxar Reduces Coronary Stent Thrombosis: Results From the TRA2P-TIMI 50 Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Antiplatelet drugs; Stent; Thrombosis; Coronary artery disease C1 [Bonaca, Marc P.; Scirica, Benjamin M.; Braunwald, Eugene; Wiviott, Stephen D.; Murphy, Sabina A.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18928 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162908046 ER PT J AU Bonderman, D Ghio, S Felix, SB Ghofrani, HA Michelakis, ED Mitrovic, V Oudiz, RJ Boateng, F Scalise, AV Roessig, L Semigran, M AF Bonderman, Diana Ghio, Stefano Felix, Stephan B. Ghofrani, Hossein A. Michelakis, Evangelos D. Mitrovic, Veselin Oudiz, Ronald J. Boateng, Francis Scalise, Andrea V. Roessig, Lothar Semigran, Marc CA LEft Ventricular Systolic TI Riociguat Improves Pulmonary Arterial Compliance in Patients With Pulmonary Hypertension due to Systolic Left Ventricular Dysfunction: Results From a Post-hoc Analysis of the Phase IIb Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic LEPHT Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Hemodynamics; Pulmonary circulation; Vascular resistance; Ventricular function C1 [Bonderman, Diana] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria. [Ghio, Stefano] Fdn Policlin S Matteo, Dept Cardiol, Pavia, Italy. [Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Univ Med, Dept Cardiol & Internal Med B, Greifswald, Germany. [Ghofrani, Hossein A.] Univ Hosp Giessen & Marburg, Dept Internal Med, Giessen, Germany. [Michelakis, Evangelos D.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Mitrovic, Veselin] Kerckhoff Heart Cntr, Dept Cardiol, Bad Nauheim, Germany. [Oudiz, Ronald J.] Harbor UCLA Med Cntr, Los Angeles Biomed Rsch Inst, Dept Med, Torrance, CA USA. [Boateng, Francis] Bayer HealthCare Pharmaceut, US Clin Stat, Pine Brook, NJ USA. [Scalise, Andrea V.] Bayer Hispania SL, Global Clin Dev, Barcelona, Spain. [Roessig, Lothar] Bayer Pharma AG, Global Clin Dev, Berlin, Germany. [Semigran, Marc] Massachusetts Gen Hosp, Heart Cntr, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17234 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906351 ER PT J AU Bose, A Kandala, J Friedman, D Rajabali, A Vegh, EM Heist, EK Mela, T Singh, JP AF Bose, Abhishek Kandala, Jagdesh Friedman, Daniel Rajabali, Alefiyah Vegh, Eszter M. Heist, E. Kevin Mela, Theofanie Singh, Jagmeet P. TI Myocardial Viability and Left Ventricular Lead location as Predictors of Ventricular Arrhythmias in Cardiac Resynchronization Therapy (CRT) Recipients With Ischemic Cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE CRT; Ischemic heart disease; Ventricular arrhythmia; Myocardial perfusion C1 [Bose, Abhishek; Kandala, Jagdesh; Friedman, Daniel; Rajabali, Alefiyah; Vegh, Eszter M.; Heist, E. Kevin; Mela, Theofanie; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14116 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903455 ER PT J AU Bossone, E Pyeritz, RE Braverman, AC Peterson, MD Ehrlich, MP O'Gara, P Suzuki, T Trimarchi, S Gilon, D Greason, K Desai, ND Montgomery, DG Isselbacher, EM Nienaber, CA Eagle, KA AF Bossone, Eduardo Pyeritz, Reed E. Braverman, Alan C. Peterson, Mark D. Ehrlich, Marek P. O'Gara, Patrick Suzuki, Toru Trimarchi, Santi Gilon, Dan Greason, Kevin Desai, Nimesh D. Montgomery, Daniel G. Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. TI Short- and Long-Term Outcomes of Patients With Type A Acute Aortic Dissection and Cardiogenic Shock: Contemporary Results From the International Registry of Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic diseases; Shock, cardiogenic; Outcomes C1 [Bossone, Eduardo] Univ Salerno, Div Cardiol, Brindi, Italy. [Pyeritz, Reed E.] Univ Penn, Sch Med, Div Med Genet, Philadelphia, PA 19104 USA. [Braverman, Alan C.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Ehrlich, Marek P.] Univ Vienna, Vienna, Austria. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Suzuki, Toru] Univ Tokyo, Tokyo, Japan. [Trimarchi, Santi] IRCCS Policlin San Donato, Rsch Cntr Thorac Aort Dis, Thorac Aort Rsch Cntr, San Donato Milanese, Italy. [Gilon, Dan] Hadassah Hebrew Univ, Med Cntr, Inst Heart, Jerusalem, Israel. [Greason, Kevin] Mayo Clin, Rochester, MN USA. [Desai, Nimesh D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Montgomery, Daniel G.] Univ Michigan, MCORRP, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Cntr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18106 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907221 ER PT J AU Bradley, SM Stanislawski, MA Bekelman, DB Monteith, LL Cohen, BE Hunt, SC Milek, D Schilling, JH Maddox, TM Ho, PM Shore, S Varosy, PD Rumsfeld, JS AF Bradley, Steven M. Stanislawski, Maggie A. Bekelman, David B. Monteith, Lindsey L. Cohen, Beth E. Hunt, Stephen C. Milek, Debra Schilling, John H. Maddox, Thomas M. Ho, P. Michael Shore, Supriya Varosy, Paul D. Rumsfeld, John S. TI Invasive Coronary Procedure Use and Outcomes among Patients with Post-Traumatic Stress Disorder: Insights from the VA CART Program SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Angiography; Outcomes; Longitudinal studies; Epidemiology C1 [Bradley, Steven M.; Bekelman, David B.; Maddox, Thomas M.; Ho, P. Michael; Varosy, Paul D.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Hlth Serv Rsch & Cardiol, Denver, CO USA. [Bradley, Steven M.; Bekelman, David B.; Schilling, John H.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA. [Stanislawski, Maggie A.] VA Eastern Colorado Hlth Care Syst, VA CART Program, Denver, CO USA. [Monteith, Lindsey L.] VA Eastern Colorado Hlth Care Syst, MIRECC, Denver, CO USA. [Cohen, Beth E.] San Francisco VA Med Cntr, San Francisco, CA USA. [Cohen, Beth E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hunt, Stephen C.] VA Puget Sound Healthcare Syst, Med, Seattle, WA USA. [Hunt, Stephen C.; Milek, Debra] Univ Washington, Seattle, WA 98195 USA. [Shore, Supriya] VA Eastern Colorado Hlth Care Syst, Med, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13055 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902501 ER PT J AU Carreras, ET Hochholzer, W Frelinger, AL Hoffman, EB O'Donoghue, ML Wiviott, SD Angiolillo, DJ Michelson, AD Sabatine, MS Mega, JL AF Carreras, Edward T. Hochholzer, Willibald Frelinger, Andrew L. Hoffman, Elaine B. O'Donoghue, Michelle L. Wiviott, Stephen D. Angiolillo, Dominick J. Michelson, Alan D. Sabatine, Marc S. Mega, Jessica L. TI Diabetes Mellitus, CYP2C19 Genotype, and Pharmacodynamic Response to Clopidogrel Dosing: Insights From the ELEVATE-TIMI 56 Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Clopidogrel; Type 2 Diabetes; Pharmacogenetics; Dose-response relation; drug C1 [Carreras, Edward T.; O'Donoghue, Michelle L.; Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hochholzer, Willibald] Univ Herzzentrum Freiburg, Klin Kardiol & Angiol 2, Bad Krozingen, Germany. [Frelinger, Andrew L.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cntr Platelet Rsch Studies,Boston Childrens Hosp, Boston, MA 02115 USA. [Hoffman, Elaine B.; Sabatine, Marc S.; Mega, Jessica L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12325 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902190 ER PT J AU Carson, P Anand, I Win, S Zile, M Haas, M Little, W Miller, A Lopez-Sendon, J Teerlink, J White, M Komajda, M McKelvie, RS McMurray, JJ Massie, B AF Carson, Peter Anand, Inder Win, Sithu Zile, Michael Haas, Markus Little, William Miller, Alan Lopez-Sendon, Jose Teerlink, John White, Michel Komajda, Michel McKelvie, Robert S. McMurray, John J. Massie, Barry TI Why Are patients With Heart Failure and Preserved Ejection Fraction Hospitalized? Data From I-PRESERVE SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Ejection fraction C1 [Carson, Peter] Washington VA Med Cntr, Washington, DC USA. [Anand, Inder; Win, Sithu] Minneapolis VAMC, Cardiol, Minneapolis, MN USA. [Zile, Michael] Charleston VAMC, Cardiol, Charleston, SC USA. [Zile, Michael] MUSC, Charleston, SC USA. [Haas, Markus] Theresienkrankenhaus, Mannheim, Germany. [Little, William] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Miller, Alan] Univ Florida Shands, Jacksonville, FL USA. [Lopez-Sendon, Jose] Hosp Univ LePaz, Madrid, Spain. [Teerlink, John; Massie, Barry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John; Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [White, Michel] Montreal Heart Cntr, Montreal, PQ, Canada. [Komajda, Michel] Univ Paris, Pitie Salpetriere Hosp, F-75252 Paris, France. [McKelvie, Robert S.] McMaster Univ, Hamilton Hlth Sci, Hamilton, ON, Canada. [McMurray, John J.] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Rsch Cntr, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15844 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905219 ER PT J AU Cavender, MA Scirica, BM Raz, I Steg, PG Hirshberg, B Davidson, J Im, K Hoffman, E Braunwald, E Bhatt, DL AF Cavender, Matthew A. Scirica, Benjamin M. Raz, Itamar Steg, P. G. Hirshberg, Boaz Davidson, Jaime Im, KyungAh Hoffman, Elaine Braunwald, Eugene Bhatt, Deepak L. TI Outcomes of Patients With Type 2 Diabetes at High Risk of Cardiovascular Events Treated With Saxagliptin: Outcomes by Baseline HgbA1c SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Type 2 Diabetes; Clinical trials; Myocardial infarction; Outcomes; Cardiovascular disease C1 [Cavender, Matthew A.; Scirica, Benjamin M.; Im, KyungAh; Hoffman, Elaine; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Raz, Itamar] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Steg, P. G.] Univ Paris Diderot, CHU Bichat, AP HP, Sorbonne Paris Cite,INSERM U698, Paris, France. [Hirshberg, Boaz] AstraZeneca, CVGI Clin Therapeut Area, Wilmington, DE USA. [Davidson, Jaime] Univ Texas Dallas, SW Med Sch, Dallas, TX 75230 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston VA Med Cntr, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17270 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906363 ER PT J AU Cavender, MA Scirica, B Bonaca, MP Morais, J Ophius, TO Dalby, T Murphy, S Braunwald, E Morrow, D AF Cavender, Matthew A. Scirica, Benjamin Bonaca, Marc P. Morais, Joao Ophius, Ton Oude Dalby, Tony Murphy, Sabina Braunwald, Eugene Morrow, David TI Vorapaxar in Patients With Diabetes and Prior MI: Findings From the TRA 2P-TIMI 50 Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes; Type 2 Diabetes; Platelet receptor blockers; Cardiovascular therapeutics C1 [Cavender, Matthew A.; Scirica, Benjamin; Bonaca, Marc P.; Murphy, Sabina; Braunwald, Eugene; Morrow, David] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Morais, Joao] Sta Andre Hosp, Div Cardiol, Leiria, Portugal. [Ophius, Ton Oude] Canisius Wilhelmina Hosp, Div Cardiol, Nijmegen, Netherlands. [Dalby, Tony] Milpark Hosp, South African Cardiol Clin Trials Grp, Johannesburg, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10398 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901111 ER PT J AU Cheng, S Larson, M McCabe, E Murabito, J Rhee, E Ho, J Jacques, P Ghorbani, A Magnusson, M Snuza, A Deik, A Pierce, K Bullock, K O'Donnell, C Melander, O Clish, C Vasan, R Gerszten, R Wang, T AF Cheng, Susan Larson, Martin McCabe, Elizabeth Murabito, Joanne Rhee, Eugene Ho, Jennifer Jacques, Paul Ghorbani, Anahita Magnusson, Martin Snuza, Amanda Deik, Amy Pierce, Kerry Bullock, Kevin O'Donnell, Christonher Melander, Olle Clish, Clary Vasan, Ramachandran Gerszten, Robert Wang, Thomas TI Metabolomic Correlates of Longevity in the Community SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Metabolomics; Aging; Epidemiology C1 [Cheng, Susan] Brigham & Womens Hosp, Cambridge, MA USA. [Larson, Martin] Boston Univ, Dept Math & Stat, Framingham, MA USA. [McCabe, Elizabeth; Vasan, Ramachandran] Boston Univ, Boston, MA 02215 USA. [Murabito, Joanne; Ho, Jennifer] Boston Univ, Framingham, MA USA. [Rhee, Eugene; Ghorbani, Anahita; Gerszten, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jacques, Paul] Tufts Univ, Jean Mayer USDA HNRCA, Boston, MA 02111 USA. [Magnusson, Martin] Skane Univ Hosp, Dept Cardiol, Malmo, Sweden. [Snuza, Amanda; Deik, Amy; Pierce, Kerry; Bullock, Kevin; Clish, Clary] Broad Inst, Cambridge, MA USA. [O'Donnell, Christonher] NHLBI, Div Intramural Rsch, Framingham, MA USA. [Melander, Olle] Malmo Univ Hosp, Dept Endocrinol, Malmo, Sweden. [Wang, Thomas] Vanderbilt Univ, Nashville, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10472 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901124 ER PT J AU Chirinos, J Shiva-Kumar, P Geraci, S Desai, S Chandrashekhar, R Jain, S Saif, H Haines, P Broderick, P Vakilipour, A Rawat, D Witschey, W Ferrari, V Akers, S AF Chirinos, Julio Shiva-Kumar, Prithvi Geraci, Salvatore Desai, Sanjal Chandrashekhar, Rahul Jain, Snigdha Saif, Hassam Haines, Philip Broderick, Preston Vakilipour, Amin Rawat, Deepa Witschey, Walter Ferrari, Victor Akers, Scott TI Relationship Between Effective Arterial Elastance and Specific Measures of Left Ventricular Afterload SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Arteries; Aging; Blood pressure; Blood vessel wall; Hemodynamics C1 [Chirinos, Julio; Shiva-Kumar, Prithvi; Desai, Sanjal; Chandrashekhar, Rahul; Jain, Snigdha; Haines, Philip; Broderick, Preston; Vakilipour, Amin; Ferrari, Victor] Univ Penn, Philadelphia, PA 19104 USA. [Geraci, Salvatore; Rawat, Deepa; Akers, Scott] Philadelphia VA Med Cntr, Philadelphia, PA USA. [Saif, Hassam] Lehigh Valley Hlth Network, Allentown, PA USA. [Witschey, Walter] Univ Penn, Cntr Magnet Resonance & Opt Imaging, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18641 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907478 ER PT J AU Chirinos, J Shiva-Kumar, P Chandrashekhar, R Desai, S Witschey, W Jain, S Saif, H Haines, P Broderick, P Geraci, S Vakilipour, A Rawat, D Ferrari, V Akers, S AF Chirinos, Julio Shiva-Kumar, Prithvi Chandrashekhar, Rahul Desai, Sanjal Witschey, Walter Jain, Snigdha Saif, Hassam Haines, Philip Broderick, Preston Geraci, Salvatore Vakilipour, Amin Rawat, Deepa Ferrari, Victor Akers, Scott TI Assessment of Age-Related Aortic Stiffness With Magnetic Resonance Imaging SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aging; Arteries; Magnetic resonance imaging; Vascular; Noninvasive cardiac imaging C1 [Chirinos, Julio; Shiva-Kumar, Prithvi; Chandrashekhar, Rahul; Desai, Sanjal; Jain, Snigdha; Haines, Philip; Broderick, Preston; Vakilipour, Amin; Ferrari, Victor] Univ Penn, Philadelphia, PA 19104 USA. [Witschey, Walter] Univ Penn, Cntr Magnet Resonance & Opt Imaging, Philadelphia, PA 19104 USA. [Saif, Hassam] Lehigh Valley Hlth Network, Internal Med, Philadelphia, PA USA. [Geraci, Salvatore; Rawat, Deepa; Akers, Scott] Philadelphia VA Med Cntr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18304 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907305 ER PT J AU Chun, EJ Onuma, OK Pencina, K Massaro, JM O'Donnell, CJ Hoffmann, U AF Chun, Eun Ju Onuma, Oyere K. Pencina, Karol Massaro, Joseph M. O'Donnell, Christopher J. Hoffmann, Udo TI Comparison of the Distribution and Predictive Value of Framingham Risk Factors and Coronary Artery Calcium for Major Coronary Events Between Asian (South Korean) and Framingham Cohorts SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiovascular disease prevention; Cardiac CT; Risk factors C1 [Chun, Eun Ju] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. [Onuma, Oyere K.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pencina, Karol] Boston Univ, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18337 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907325 ER PT J AU Cong, T Hung, J Hua, LQ Tan, TC Kataoka, A Zhao, YL Zeng, X AF Cong, Tao Hung, Judy Hua, Lanqi Tan, Timothy C. Kataoka, Akihisa Zhao, Yili Zeng, Xin TI Differential Effects on Left Ventricular Contractility: A Comparison Between Dobutamine vs Exercise Stress Echocardiography SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stress echocardiography; Exercise tests; Strain rate C1 [Cong, Tao; Hung, Judy; Hua, Lanqi; Tan, Timothy C.; Kataoka, Akihisa; Zhao, Yili; Zeng, Xin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15035 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904363 ER PT J AU Delling, FN Rong, J Larson, MC Benjamin, EJ Levine, RA Vasan, RS AF Delling, Francesca N. Rong, Jian Larson, Martin C. Benjamin, Emelia J. Levine, Robert A. Vasan, Ramachandran S. TI Familial Clustering of Mitral Valve Prolapse in the Community SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Mitral valve disease; Echocardiography; Epidemiology; Risk factors; Family C1 [Delling, Francesca N.] Beth Israel Deaconess Med Cntr, Cardiovasc Div, Boston, MA USA. [Rong, Jian; Larson, Martin C.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med & Framingham Heart Study, Prevent Med Sect, Framingham, MA USA. [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12116 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902090 ER PT J AU Di Eusanio, M Trimarchi, S Peterson, MD Myrmel, T Hughes, GC Korach, A Sundt, TM Greason, K Appoo, JJ Milner, R Montgomery, DG Isselbacher, EM Eagle, KA Nienaber, CA Patel, HJ AF Di Eusanio, Marco Trimarchi, Santi Peterson, Mark D. Myrmel, Truls Hughes, G. C. Korach, Amit Sundt, Thoralf M. Greason, Kevin Appoo, Jehangir J. Milner, Ross Montgomery, Daniel G. Isselbacher, Eric M. Eagle, Kim A. Nienaber, Christoph A. Patel, Himanshu J. TI Root Replacement versus More Conservative Management During Type A Acute Aortic Dissection Repair: Insights From the International Registry of Acute Aortic Dissection SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Surgery; Aortic diseases; Outcomes C1 [Di Eusanio, Marco] Univ Hosp S Orsola, Dept Cardiac Surg, Bologna, Italy. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Rsch Cntr, Rsch Cntr Thorac Aort Dis, San Donato Milanese, Italy. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway. [Hughes, G. C.] Duke Univ, Med Cntr, Div Thorac & Cardiovasc Surg, Durham, NC USA. [Korach, Amit] Hadassah Hebrew Univ Med Cntr, Jerusalem, Israel. [Sundt, Thoralf M.; Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Cntr, Boston, MA 02114 USA. [Greason, Kevin] Mayo Clin, Rochester, MN USA. [Appoo, Jehangir J.] Univ Calgary, Med Cntr, Div Cardiac Surg, Calgary, AB, Canada. [Milner, Ross] Univ Chicago, Med Cntr, Chicago, IL 60637 USA. [Montgomery, Daniel G.] Univ Michigan, MCORRP, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Patel, Himanshu J.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17606 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906522 ER PT J AU Di Eusanio, M Pape, L Braverman, AC Ehrlich, MP O'Gara, P Myrmel, T Pyeritz, RE Ballotta, A Bartnes, K Rossone, E Montgomery, DG Eagle, KA Nienaber, CA Isselbacher, EM Fattori, R AF Di Eusanio, Marco Pape, Linda Braverman, Alan C. Ehrlich, Marek P. O'Gara, Patrick Myrmel, Truls Pyeritz, Reed E. Ballotta, Andrea Bartnes, Kristian Rossone, Eduardo Montgomery, Daniel G. Eagle, Kim A. Nienaber, Christoph A. Isselbacher, Eric M. Fattori, Rossella TI Characteristics of Acute Aortic Dissection in Patients With Bicuspid Aortic Valve: Insights From the IRAD Registry SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic diseases; Genetics C1 [Di Eusanio, Marco] Univ S Orsola, Dept Cardiac Surg, Bologna, Italy. [Pape, Linda] Univ Massachusetts Hosp, Worcester, MA USA. [Braverman, Alan C.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. [Ehrlich, Marek P.] Univ Vienna, Vienna, Austria. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Myrmel, Truls; Bartnes, Kristian] Univ Tromso Hosp, N-9012 Tromso, Norway. [Pyeritz, Reed E.] Univ Penn, Sch Med, Div Med Genet, Philadelphia, PA 19104 USA. [Ballotta, Andrea] IRCCS Policlin San Donato, Div Cardiac Surg, Bologna, Italy. [Rossone, Eduardo] Univ Salerno, Div Cardiol, Brindisi, Italy. [Montgomery, Daniel G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Cntr, Boston, MA 02114 USA. [Fattori, Rossella] San Salvatore Hosp, Intervent Cardiol Unit, Pesaro, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15913 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905261 ER PT J AU Dori, Y Rychik, J Glatz, AC Gillespie, MJ Harris, MA Fogel, M Whitehead, KK Rome, JJ Keller, M Itkin, M AF Dori, Yoav Rychik, Jack Glatz, Andrew C. Gillespie, Matthew J. Harris, Matthew A. Fogel, Mark Whitehead, Kevin K. Rome, Jonathan J. Keller, Marc Itkin, Maxim TI Lymphatic Abnormalities in Patients With Congenital Heart Disease: New Insights From Non-Contrast Magnetic Resonance Lymphangiography SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Congenital hear disease; Magnetic resonance imaging; Single ventricle C1 [Dori, Yoav; Rychik, Jack; Glatz, Andrew C.; Gillespie, Matthew J.; Harris, Matthew A.; Fogel, Mark; Whitehead, Kevin K.; Rome, Jonathan J.; Keller, Marc] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Itkin, Maxim] Philadelphia VA Med Cntr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16061 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905344 ER PT J AU Emami, H Vijayakumar, J Vucic, E Subramanian, S Singh, P Solomon, DH Tawakol, A AF Emami, Hamed Vijayakumar, Jayanthi Vucic, Esad Subramanian, Sharath Singh, Parmanand Solomon, Daniel H. Tawakol, Ahmed TI Arterial Inflammation in Rheumatoid Arthritis Correlates With Joint Inflammation SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Inflammation; Positron emission tomography; Cardiovascular imaging; Arteries; Immune system C1 [Emami, Hamed; Vijayakumar, Jayanthi; Vucic, Esad; Subramanian, Sharath; Singh, Parmanand; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12061 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902067 ER PT J AU Engels, MC Rajarajan, K Feistritizer, R Sharma, A Nielsen, UB Schalij, MJ de Vries, AA Pijnappels, DA Wu, SM AF Engels, Marc C. Rajarajan, Kuppusamy Feistritizer, Rebecca Sharma, Arun Nielsen, Ulrik B. Schalij, Martin J. de Vries, Antoine A. Pijnappels, Daniel A. Wu, Sean M. TI IGF promotes Cardiac Lineage Induction by Selective Expansion of Mesoderm in vitro SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stem/progenitor cells; Cell signaling; Growth factors; Stem cell biology; Stem cells C1 [Engels, Marc C.; Rajarajan, Kuppusamy; Feistritizer, Rebecca; Wu, Sean M.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Sharma, Arun] Stanford Univ, Sch Med, Stanford, CA USA. [Nielsen, Ulrik B.] Silvercreek Pharmaeceut, Network Biol, San Francisco, CA USA. [Schalij, Martin J.; de Vries, Antoine A.; Pijnappels, Daniel A.] Leiden Univ, Med Cntr, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17539 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906482 ER PT J AU Farhan, S Clare, RM Jarai, R Newby, LK Morrow, D Giugliano, RP Lokhnygina, Y Califf, RM Harrington, RA Huber, K AF Farhan, Serdar Clare, Robert M. Jarai, Rudolf Newby, L. Kristin Morrow, David Giugliano, Robert P. Lokhnygina, Yuliya Califf, Robert M. Harrington, Robert A. Huber, Kurt TI Fasting Glucose, NT-proBNP, Treatment With Glycoprotein IIb/IIIa Inhibitors, and Outcomes in Non-ST-Segment Elevation Acute Coronary Syndromes: An Analysis From EARLY ACS SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes; Natriuretic peptide C1 [Farhan, Serdar] Wilhelminenhosp, Vienna, Austria. [Clare, Robert M.] Duke Univ Med Cntr, Duke Clin Rsch Inst, Durham, NC USA. [Jarai, Rudolf; Huber, Kurt] Wilhelminenhosp, Dept Internal Med Cardiol & Emergency Med 3, Vienna, Austria. [Newby, L. Kristin] Duke Univ Med Cntr, Dept Med, Duke Clin Rsch Inst, Durham, NC USA. [Morrow, David] Harvard Univ, Sch Med, Dept Med, TIMI Study Grp,Cardiovasc Div,Brigham & Womens Ho, Boston, MA USA. [Giugliano, Robert P.] Brigham & Womens Hosp, Dept Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Lokhnygina, Yuliya] Duke Clin Rsch Inst, Durham, NC USA. [Califf, Robert M.] Duke Univ Med Cntr, Duke Translat Med Inst, Dept Med, Durham, NC USA. [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14618 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904146 ER PT J AU Figueroa, AL MacNabb, MH Abdelbaky, A Corsini, E Lavender, ZR Kaplan, RS Grinspoon, SK Rudd, JH Nasir, K Truong, QA Hoffmann, U Tawakol, A AF Figueroa, Amparo L. MacNabb, Megan H. Abdelbaky, Amr Corsini, Erin Lavender, Zachary R. Kaplan, Rebecca S. Grinspoon, Steven K. Rudd, James H. Nasir, Khurram Truong, Quynh A. Hoffmann, Udo Tawakol, Ahmed TI Visceral Adipose Tissue Activity Independently Predicts the Risk of Future Cardiovascular Events SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Positron emission tomography; Inflammation; Adipose; Obesiy; Cardiovascular disease C1 [Figueroa, Amparo L.; MacNabb, Megan H.; Abdelbaky, Amr; Corsini, Erin; Lavender, Zachary R.; Kaplan, Rebecca S.; Grinspoon, Steven K.; Truong, Quynh A.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rudd, James H.] Univ Cambridge, Cambridge, England. [Nasir, Khurram] Johns Hopkins Univ, Baptist Hlth South Florida, Baltimore, MD USA. FU Academy of Medical Sciences (AMS) [AMS-SGCL1-Rudd]; British Heart Foundation [PG/09/083/27667, FS/12/29/29463] NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16878 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906202 ER PT J AU Fletcher, RD Amdur, RL Papademetriou, V Kheirbek, R Maron, D Faselis, C Jones, RE AF Fletcher, Ross D. Amdur, Richard L. Papademetriou, Vasilios Kheirbek, Raya Maron, David Faselis, Charles Jones, Ronald E. TI Blood Pressure Control in All VA Patients From 2000 to 2011 With Analysis of Racial Disparity and Body Mass Index for Further Improvements SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Hypertension C1 [Fletcher, Ross D.; Amdur, Richard L.; Papademetriou, Vasilios; Kheirbek, Raya; Maron, David; Faselis, Charles] US Dept Vet Affairs, Washington, DC USA. [Jones, Ronald E.] US Dept Vet Affairs, Pacemaker Cntr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16017 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905322 ER PT J AU Friedman, DJ Wang, N Meigs, JB Hoffmann, U Massaro, JM Fox, CS Magnani, JW AF Friedman, Daniel J. Wang, Na Meigs, James B. Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Magnani, Jared W. TI Pericardial Fat is Associated With Atrial Electrical Function: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Adipose; Atrial fibrillation; Electrocardiography; Cardiac CT; Epidemiology C1 [Friedman, Daniel J.; Meigs, James B.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Na; Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Magnani, Jared W.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 9885 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162900448 ER PT J AU Ghorbani, A Larson, MG Miller, KK Ho, JE Cheng, SS Rhee, EP Vasan, RS Gerszten, RE Wang, TJ AF Ghorbani, Anahita Larson, Martin G. Miller, Karen K. Ho, Jennifer E. Cheng, Susan Rhee, Eugene P. Vasan, Ramachandran S. Gerszten, Robert E. Wang, Thomas J. TI Sex-Related Differences in Plasma Metabolomic Profiles in Humans SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Metabolomics; Cardiovascular disease C1 [Ghorbani, Anahita] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.; Ho, Jennifer E.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Boston, MA USA. [Miller, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ho, Jennifer E.] Boston Med Cntr, Div Cardiol, Boston, MA USA. [Cheng, Susan] Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Vanderbilt Heart & Vasc Inst, Div Cardiovasc Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16786 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906154 ER PT J AU Goehler, A Mayrhofer, T Pursnani, A Lumish, H Barth, C Nagurney, JT Truong, QA McMahon, P Gazelle, SG Hoffmann, U AF Goehler, Alexander Mayrhofer, Thomas Pursnani, Amit Lumish, Heidi Barth, Cordula Nagurney, John T. Truong, Quynh A. McMahon, Pamela Gazelle, Scott G. Hoffmann, Udo TI Comparison of Long Term Health and Economic Outcomes of ED Triage Strategies for Patients With Acute Chest Pain SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Coronary artery disease; Acute coronary syndromes; Cardiac CT; Cost-effectiveness C1 [Goehler, Alexander; Mayrhofer, Thomas; Pursnani, Amit; Lumish, Heidi; Barth, Cordula; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR, PET CT Progam, Boston, MA 02114 USA. [Goehler, Alexander; Mayrhofer, Thomas] Inst Technol Assessment, Boston, MA USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [McMahon, Pamela; Gazelle, Scott G.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18295 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907304 ER PT J AU Gouni-Berthold, I Berthold, HK Huh, JY Krone, W Mantzoros, CS AF Gouni-Berthold, Ioanna Berthold, Heiner K. Huh, Joo Young Krone, Wilhelm Mantzoros, Christos S. TI Simvastatin Increases Irisin Concentrations in Human Subjects in Vivo and Irisin Expression and Secretion in Human Skeletal Muscle Cells ex Vivo SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Statins C1 [Gouni-Berthold, Ioanna; Krone, Wilhelm] Univ Cologne, Cntr Endocrinol Diabet & Prevent Med, D-50931 Cologne, Germany. [Berthold, Heiner K.] Charite, Evangel Geriatr Cntr Berlin, D-13353 Berlin, Germany. [Huh, Joo Young] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10390 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901108 ER PT J AU Goyal, A Steg, PG Smith, SC Eagle, KA Ohman, EM Koplan, JP Hoffman, EB Im, K Goto, S Wilson, PW Bhatt, DL AF Goyal, Abhinav Steg, Ph Gabriel Smith, Sidney C., Jr. Eagle, Kim A. Ohman, E. Magnus Koplan, Jeffrey P. Hoffman, Elaine B. Im, KyungAh Goto, Shinya Wilson, Peter W. Bhatt, Deepak L. TI Cigarette Smoking is Associated With a Greater Hazard for Adverse Outcomes in Women Compared With Men: Insights From the Global REACH Registry SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Smoking; Epidemiology; Cardiovascular disease C1 [Goyal, Abhinav; Wilson, Peter W.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Steg, Ph Gabriel] INSERM, U698, Paris, France. [Steg, Ph Gabriel] Univ Paris 07, Hop Bichat Claude Bernard, Paris, France. [Smith, Sidney C., Jr.] Univ N Carolina, Cntr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Ohman, E. Magnus] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Koplan, Jeffrey P.] Emory Global Hlth Inst, Atlanta, GA USA. [Hoffman, Elaine B.; Im, KyungAh] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Hiratsuka, Kanagawa 25912, Japan. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13411 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903152 ER PT J AU Graosa, J Demir, O Tan, TC Cabrita, IZ Hamid, S Dawson, D Sharma, R Senior, R Nihoyannopoulos, P AF Graosa, Julia Demir, Ozan Tan, Timothy C. Cabrita, Ines Z. Hamid, Safia Dawson, David Sharma, Rakesh Senior, Roxy Nihoyannopoulos, Petros TI Advanced Echocardiographic Comparison of Pulmonary Arterial Hypertension And Pulmonary Hypertension Secondary to Left Heart Disease: 3-Dimensional Speckle Tracking and 3D Tricuspid Reconstruction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Pulmonary hypertension; Tricuspid valve; Echocardiography C1 [Graosa, Julia; Demir, Ozan; Cabrita, Ines Z.; Hamid, Safia; Dawson, David; Nihoyannopoulos, Petros] Hammersmith Hosp, Dept Cardiol, London, England. [Tan, Timothy C.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Sharma, Rakesh; Senior, Roxy] Royal Brompton Hosp, Dept Cardiol, London SW3 6LY, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16727 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906129 ER PT J AU Grapsa, J Nunes, MC Tan, TC Cabrita, IZ Smith, B Dawson, D Nihoyannopoulos, P AF Grapsa, Julia Nunes, Maria C. Tan, Timothy C. Cabrita, Ines Z. Smith, Benjamin Dawson, David Nihoyannopoulos, Petros TI Precapillary Pulmonary Hypertension and Echocardiographic Determinants of Survival SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Pulmonary hypertension; Echocardiography; Remodeling C1 [Grapsa, Julia; Cabrita, Ines Z.; Smith, Benjamin; Dawson, David; Nihoyannopoulos, Petros] Hammersmith Hosp, Dept Cardiol, London, England. [Nunes, Maria C.; Tan, Timothy C.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12272 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902164 ER PT J AU Groarke, JD McGuiness, M Correia, A Tong, D Khambhati, J Hiremath, P Nohria, A Choueiri, TK Solomon, S Moslehi, J Cheng, SS AF Groarke, John D. McGuiness, Matthew Correia, Andrew Tong, Dan Khambhati, Jay Hiremath, Pranoti Nohria, Anju Choueiri, Toni K. Solomon, Scott Moslehi, Javid Cheng, Susan TI Cardiac Dysfunction Resulting From Therapeutic Inhibition of the Vascular Endothelial Growth Factor Signaling Pathway in Cancer Patients SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Strain rate; Cardiac imaging; Echocardiography; Drugs C1 [Groarke, John D.; McGuiness, Matthew; Tong, Dan; Khambhati, Jay; Hiremath, Pranoti; Nohria, Anju; Solomon, Scott; Moslehi, Javid; Cheng, Susan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Correia, Andrew] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Cntr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17397 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906415 ER PT J AU Halim, S Yang, QH Schulte, P Hochman, J Melloni, C Mahaffey, KW Moliterno, DJ Harrington, RA White, HD Armstrong, PW Ohman, EM Van de Werf, F Giugliano, RP Newby, LK AF Halim, Sharif Yang, Qinghong Schulte, Phillip Hochman, Judith Melloni, Chiara Mahaffey, Kenneth W. Moliterno, David J. Harrington, Robert A. White, Harvey D. Armstrong, Paul W. Ohman, E. Magnus Van de Werf, Frans Giugliano, Robert P. Newby, L. Kristin TI Evolution of Differences in Women and Men With Non-ST-Segment Elevation Acute Coronary Syndromes: Insights From Clinical Trials Over 15 Years SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes C1 [Halim, Sharif; Yang, Qinghong; Schulte, Phillip; Melloni, Chiara] Duke Univ, Duke Clin Rsch Inst, Med Cntr, Durham, NC USA. [Hochman, Judith] NYU, Sch Med, Dept Med, Leon Charney Div Cardiol, New York, NY USA. [Mahaffey, Kenneth W.; Ohman, E. Magnus; Newby, L. Kristin] Duke Univ, Dept Med, Med Cntr, Duke Clin Rsch Inst, Durham, NC USA. [Moliterno, David J.] Gill Heart Inst, Div Cardiovasc Med, Lexington, KY USA. [Moliterno, David J.] Univ Kentucky, Lexington, KY USA. [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Armstrong, Paul W.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Van de Werf, Frans] Univ Hosps Leuven, Dept Cardiol, Louvain, Belgium. [Giugliano, Robert P.] Brigham & Womens Hosp, Dept Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15834 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905212 ER PT J AU Hara, T Truelove, J Weissleder, R Tawakol, A Jaffer, FA AF Hara, Tetsuva Truelove, Jessica Weissleder, Ralph Tawakol, Ahmed Jaffer, Farouc A. TI Noninvasive Imaging of Inflammation Using 18F-FDG PET/CT Allows in vivo Assessment of the Biological Age of Deep Venous Thrombosis SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Thrombosis; Cardiovascular imaging; Inflammation C1 [Hara, Tetsuva; Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Truelove, Jessica; Weissleder, Ralph] Massachusetts Gen Hosp, Cntr Syst Biol, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12087 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902077 ER PT J AU Hilqendorf, I Theurl, I Gerhardt, LMS Robhins, CS Weber, GF Gonen, A Iwamoto, Y Holderried, TAW Zirlik, A Lin, HY Witztum, JL Libby, P Nahrendorf, M Weissleder, R Swirski, FK AF Hilqendorf, Ingo Theurl, Igor Gerhardt, Louisa M. S. Robhins, Clinton S. Weber, Georg F. Gonen, Ayelet Iwamoto, Yoshiko Holderried, Tobias A. W. Zirlik, Andreas Lin, Herbert Y. Witztum, Joseph L. Libby, Peter Nahrendorf, Matthias Weissleder, Ralph Swirski, Filip K. TI Innate Response Activator B Cells Aggravate Atherosclerosis by Stimulating Th1 Adaptive Immunity SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Arteriosclerosis; Dendritic cell; Growth factors; Immunology C1 [Hilqendorf, Ingo; Theurl, Igor; Gerhardt, Louisa M. S.; Robhins, Clinton S.; Weber, Georg F.; Iwamoto, Yoshiko; Lin, Herbert Y.; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Massachusetts Gen Hosp, Cntr Syst Biol, Boston, MA 02114 USA. [Gonen, Ayelet; Witztum, Joseph L.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Holderried, Tobias A. W.] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany. [Zirlik, Andreas] Univ Heart Cntr Freiburg, Dept Cardiol 1, Freiburg, Germany. [Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11539 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901488 ER PT J AU Hobai, I Buys, ES Morse, JC Edgecomb, J Hou, XY Khandelwal, A Siwik, D Cohen, RA Brouckaert, P Colucci, W AF Hobai, Ion Buys, Emmanuel S. Morse, Justin C. Edgecomb, Jessica Hou, Xiuyun Khandelwal, Alok Siwik, Deborah Cohen, Richard A. Brouckaert, Peter Colucci, Wilson TI Sulphonylation of SERCA Cysteine-674 Contributes to Cardiac Dysfunction in Endotoxemic Mice SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiomyopathy; Sarcoplasmic reticulum; Redox; Oxidative stress C1 [Hobai, Ion; Morse, Justin C.; Edgecomb, Jessica; Hou, Xiuyun; Khandelwal, Alok; Siwik, Deborah; Cohen, Richard A.; Colucci, Wilson] Boston Univ Med Cntr, Boston, MA USA. [Buys, Emmanuel S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brouckaert, Peter] Univ Ghent VIB, Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17974 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907157 ER PT J AU Hoffmann, U Massaro, JM D'Agostino, R Kathiresan, S Fox, CS O'Donnell, CJ AF Hoffmann, Udo Massaro, Joseph M. D'Agostino, Ralph Kathiresan, Sekar Fox, Caroline S. O'Donnell, Christopher J. TI Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiovascular imaging; Epidemiology; Risk factors C1 [Hoffmann, Udo; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Massaro, Joseph M.; D'Agostino, Ralph] Boston Univ, Boston, MA 02215 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14097 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903441 ER PT J AU Hu, SN Jia, HB Yonetsu, T Karanasos, A Aguirre, A Tian, JW Abtahian, F Vergallo, R Lee, H McNulty, I Zhang, SS Yu, BB Kato, K Mizuno, K Collen, D Toutouzas, K Stefanadis, C Jang, IK AF Hu, Sining Jia, Haibo Yonetsu, Taishi Karanasos, Antonios Aguirre, Aaron Tian, Jinwei Abtahian, Farhad Vergallo, Rocco Lee, Hang McNulty, Iris Zhang, Shaosong Yu, Bo Bo Kato, Koji Mizuno, Kyoichi Collen, Desire Toutouzas, Konstantinos Stefanadis, Christodoulos Jang, Ik-Kyung TI Differential Sensitivity of Plaque Rupture and Plaque Erosion to Thrombolytic Therapy in Patients With ST-segment Elevation Myocardial Infarction: an Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Plaque rupture; STEMI; Thrombosis; Thrombolysis C1 [Hu, Sining; Jia, Haibo; Tian, Jinwei; Yu, Bo Bo] Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China. [Yonetsu, Taishi; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Karanasos, Antonios; Toutouzas, Konstantinos; Stefanadis, Christodoulos] Hippokrateion Hosp, Dept Cardiol 1, Athens Med Sch, Athens, Greece. [Aguirre, Aaron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Abtahian, Farhad; Vergallo, Rocco; Lee, Hang; Kato, Koji] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zhang, Shaosong] LightLab Imaging Inc, St Jude Med, Westford, MA USA. [Mizuno, Kyoichi] Nippon Med Sch, Dept Cardiovasc Med, Tokyo 113, Japan. [Collen, Desire] Univ Louvain, Cntr Mol & Vasc Biol, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13736 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903278 ER PT J AU Hucker, WJ Chatzizisis, YS Steigner, M Winters, GL Kirshenbaum, JM AF Hucker, William J. Chatzizisis, Yiannis S. Steigner, Michael Winters, Gayle L. Kirshenbaum, James M. TI Myocardial Catastrophe: A Case of Severe, Sudden Systolic Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Cardiac MRI C1 [Hucker, William J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chatzizisis, Yiannis S.; Steigner, Michael; Winters, Gayle L.; Kirshenbaum, James M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17045 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906279 ER PT J AU Ismahil, MAM Hamid, T Bansal, SS Kingery, JR Prabhu, SD AF Ismahil, Mohamed Ameen Mohamed Hamid, Tariq Bansal, Shyam S. Kingery, Justin R. Prabhu, Sumanth D. TI Remodeling of the Mononuclear Phagocyte Network Underlies Chronic Inflammation and Disease Progression in Heart Failure: Importance of the Cardiosplenic Axis SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Inflammation; Dendritic cell; Immune system; Infarction C1 [Ismahil, Mohamed Ameen Mohamed; Hamid, Tariq; Bansal, Shyam S.; Prabhu, Sumanth D.] Univ Alabama Birmingham, Dept Cardiovasc Dis, Birmingham, AL USA. [Kingery, Justin R.] Univ Louisville, Dept Cardiovasc Dis, Louisville, KY 40292 USA. [Prabhu, Sumanth D.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14883 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904284 ER PT J AU Jbeli, AH Hagler, MA Kunkala, M Roos, CM Sundt, TM Miller, JD AF Jbeli, Aiham H. Hagler, Michael A. Kunkala, Meghana Roos, Carolyn M. Sundt, Thoralf M. Miller, Jordan D. TI Evidence for Increased mTORC1 and mTORC2 Signaling in Human Thoracic Aortic Aneurysm SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic aneurysm; Remodeling; Proteins; Signal transduction C1 [Jbeli, Aiham H.; Hagler, Michael A.; Kunkala, Meghana; Roos, Carolyn M.; Miller, Jordan D.] Mayo Clin, Dept Surg, Rochester, MN USA. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18040 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907192 ER PT J AU Kataoka, A Scherrer-Crosbie, M Dajani, KA Garceau, P Hastings, JI Kohn, JA Srbinovska-Kostovska, E Poggio, D Saric, M Senior, R Sokhon, K Shaw, L Reynolds, H Picard, MH AF Kataoka, Akihisa Scherrer-Crosbie, Marielle Dajani, Khaled A. Garceau, Patrick Hastings, Jeffrey I. Kohn, Jeffrey A. Srbinovska-Kostovska, Elizabeta Poggio, Daniele Saric, Muhamed Senior, Roxy Sokhon, Kozhaya Shaw, Leslee Reynolds, Harmony Picard, Michael H. TI Transient Ischemic Dilatation During Stress Echocardiography: A Marker of Significant Myocardial Ischemia SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Ischemic heart disease; Stress echocardiography C1 [Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Dajani, Khaled A.] Loyola Univ Med Cntr, Maywood, IL USA. [Garceau, Patrick] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Hastings, Jeffrey I.] VA North Texas Hlth Care Syst, Med, Dallas, TX USA. [Kohn, Jeffrey A.] New York Med Associates, New York, NY USA. [Srbinovska-Kostovska, Elizabeta] Univ Clin Cardiol, Skopje, Macedonia. [Poggio, Daniele] Policlin Monza, Monza, Italy. [Saric, Muhamed] New York Univ Med Cntr, New York, NY USA. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Middlesex, England. [Sokhon, Kozhaya] Medicus Alliance Clin Rsch Org Inc, Med, Houston, TX USA. [Shaw, Leslee] Emory Univ Sch Med, Atlanta, GA USA. [Reynolds, Harmony] New York Univ Langone Med Cntr, VA Med Cntr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11289 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901389 ER PT J AU Kataoka, A Scherrer-Crosbie, M Banerjee, S Goodman, D Gosselin, G Hu, B Kedev, S Mortara, A Senior, R Spizzieri, CL Shaw, L Reynolds, H Picard, MH AF Kataoka, Akihisa Scherrer-Crosbie, Marielle Banerjee, Subhash Goodman, Dennis Gosselin, Gilbert Hu, Bob Kedev, Sasko Mortara, Andrea Senior, Roxy Spizzieri, Christopher L. Shaw, Leslee Reynolds, Harmony Picard, Michael H. TI The Value of Core Lab Stress Echocardiography Interpretations: Observations From the ISCHEMIA Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stress echocardiography; Ischemic heart disease; Quality assessment C1 [Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Banerjee, Subhash] VA North Texas Hlth Care Syst, Med, Dallas, TX USA. [Goodman, Dennis] New York Med Associates, New York, NY USA. [Gosselin, Gilbert] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Hu, Bob] Palo Alto Med Fdn Rsch Inst, Palo Alto, CA USA. [Kedev, Sasko] Univ Clin Cardiol, Skopje, Macedonia. [Mortara, Andrea] Policlin Monza, Monza, Italy. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Middlesex, England. [Spizzieri, Christopher L.] Capital Cardiovasc Associates, Camp Hill, PA USA. [Shaw, Leslee] Emory Univ, Sch Med, Atlanta, GA USA. [Reynolds, Harmony] NYU, Langone Med Cntr, VA Med Cntr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11278 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901383 ER PT J AU Kathiresan, S AF Kathiresan, Sekar CA NHLI Exome Sequencing Project HDL TI Rare Loss-of-Function Mutations in the Apolipoprotein C-III gene, Plasma Triglycerides, and Risk for Coronary Heart Disease SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genetics; Apolipoproteins; Coronary heart disease; Genomics; Lipids C1 [Kathiresan, Sekar; NHLI Exome Sequencing Project HDL] Massachusetts Gen Hosp, Cntr Human Genet Rsch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17820 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907087 ER PT J AU Khalili, H Patel, V Turer, A de Lemos, J Brilakis, E Banerjee, S Bavry, AA Bhatt, DL Kumbhani, D AF Khalili, Houman Patel, Vishal Turer, Aslan de Lemos, James Brilakis, Emmanouil Banerjee, Subhash Bavry, Anthony A. Bhatt, Deepak L. Kumbhani, Dharam TI Surrogate and Clinical Outcomes Following Ischemic Postconditioning During Primary Percutaneous Coronary Intervention of ST-segment Elevation Myocardial Infarction: A Meta-analysis of 17 Randomized Trials SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc C1 [Khalili, Houman; Patel, Vishal; Turer, Aslan; de Lemos, James; Brilakis, Emmanouil; Banerjee, Subhash; Kumbhani, Dharam] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Bavry, Anthony A.] Univ Florida, Gainesville, FL USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17500 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906459 ER PT J AU Kida, K Mandeville, JB Bloch, KD Ichinose, F AF Kida, Kotaro Mandeville, Joseph B. Bloch, Kenneth D. Ichinose, Fumito TI Inhaled Nitric Oxide Improves Outcomes After Cardiac Arrest and Cardiopulmonary Resuscitation Above and Beyond Therapeutic Hypothermia in Mice SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiopulmonary resuscitation; Hypothermia; Nitric oxide synthase; Nitric oxide; Magnetic resonance imaging C1 [Kida, Kotaro; Mandeville, Joseph B.; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15842 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905218 ER PT J AU Kim, DH Handschumacher, MD Levine, RA Sun, BJ Jang, JY Yang, DH Kang, JW Song, JM Kang, DH Lim, TH Song, JK AF Kim, Dae-Hee Handschumacher, Mark D. Levine, Robert A. Sun, Byung Joo Jang, Jeong Yoon Yang, Dong Hyun Kang, Joon-Won Song, Jong-Min Kang, Duk-Hyun Lim, Tae-Hwan Song, Jae-Kwan TI Aortic Valve Adaptation to Aortic Root Dilatation: Insights into the Mechanism of Functional Aortic Regurgitation From Three-Dimensional Cardiac Computed Tomography SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc C1 [Kim, Dae-Hee; Sun, Byung Joo; Jang, Jeong Yoon; Kang, Joon-Won; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan] Asar Med Cntr, Div Cardiol, Seoul, South Korea. [Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Yang, Dong Hyun; Lim, Tae-Hwan] Asan Med Cntr, Cardiac Imaging Cntr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13438 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903164 ER PT J AU Kong, XX Banks, A Liu, TM Wang, X Kleiner, S Kang, S Rosen, ED AF Kong, Xingxing Banks, Alexander Liu, Tiemin Wang, Xun Kleiner, Sander Kang, Sona Rosen, Evan D. TI The Immune Transcriptional Factor Irf4 is a Key Regulator of Thermogenesis SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Adipose; Diet; Ablation; Gene expression; Obesity C1 [Kong, Xingxing; Liu, Tiemin; Wang, Xun; Kang, Sona; Rosen, Evan D.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Banks, Alexander; Kleiner, Sander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Banks, Alexander; Kleiner, Sander] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14096 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903440 ER PT J AU Lange, D Glidden, D Secemsky, E Ordovas, K Nitta, E Mistry, V Hur, S Deeks, S Martin, J Bolger, A Hsue, P AF Lange, David Glidden, David Secemsky, Eric Ordovas, Karen Nitta, Elaine Mistry, Vanita Hur, Sophia Deeks, Steven Martin, Jeffrey Bolger, Ann Hsue, Priscilla TI Mitral Annular Calcification and Coronary Artery Calcification are Associated With Mortality in HIV-Infected Individuals SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Computed tomography; Calcification; Mitral valve; Immune system C1 [Lange, David; Glidden, David; Ordovas, Karen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Secemsky, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Nitta, Elaine; Mistry, Vanita; Hur, Sophia; Martin, Jeffrey; Bolger, Ann; Hsue, Priscilla] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Deeks, Steven] Univ Calif San Francisco, San Francisco Gen Hosp, HIV AIDS Posit Hlth Program, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14110 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903449 ER PT J AU Lewis, GD Murphy, RM McNulty, S Semigran, MJ Borlaug, BA Mohammed, SF Stevenson, LW Deswal, A LeWinter, M Anstrom, K Hernandez, AF Braunwald, E Redfield, MM AF Lewis, Gregory D. Murphy, Ryan M. McNulty, Steven Semigran, Marc J. Borlaug, Barry A. Mohammed, Selma F. Stevenson, Lynne W. Deswal, Anita LeWinter, Martin Anstrom, Kevin Hernandez, Adrian F. Braunwald, Eugene Redfield, Margaret M. CA NHLBI Heart Failure Network TI Inefficient Ventilation is an Easily Derived Marker of Cardiovascular Reserve Capacity in Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Exercise tests; Pulmonary hypertension C1 [Lewis, Gregory D.; Murphy, Ryan M.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McNulty, Steven; Anstrom, Kevin; Hernandez, Adrian F.] Duke Univ, Durham, NC USA. [Borlaug, Barry A.; Mohammed, Selma F.; Redfield, Margaret M.] Mayo Clin, Rochester, MN USA. [Stevenson, Lynne W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [LeWinter, Martin] Univ Vermont, Burlington, VT USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15103 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904399 ER PT J AU Leyton-Mange, JS Mills, RW Macri, VS Ellinor, PT Milan, DJ AF Leyton-Mange, Jordan S. Mills, Robert W. Macri, Vincenzo S. Ellinor, Patrick T. Milan, David J. TI ArcLight: a Genetically Encoded Fluorescent Voltage Indicator Faithfully Reports Transmembrane Potentials in Embryonic Stem Cell-Derived Cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Membrane potentials; Stem cells; Cell physiology; Stem cell biology; Monitoring, physiologic C1 [Leyton-Mange, Jordan S.; Mills, Robert W.; Macri, Vincenzo S.; Ellinor, Patrick T.; Milan, David J.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15821 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905202 ER PT J AU Lopes, RD Holmes, DN Thomas, L Ansell, J Fonarow, GC Gersh, BJ Go, AS Hylek, FM Kowey, PR Piccini, JP Singer, DE Chang, P Peterson, ED Mahaffey, KW AF Lopes, Renato D. Holmes, DaJuanicia N. Thomas, Laine Ansell, Jack Fonarow, Gregg C. Gersh, Bernard J. Go, Alan S. Hylek, Flaine M. Kowey, Peter R. Piccini, Jonathan P. Singer, Daniel E. Chang, Paul Peterson, Eric D. Mahaffey, Kenneth W. TI Triple Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and History of Coronary Artery Disease: Insights From the ORBIT-AF Registry SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Anticoagulation; Antiplatelet drugs; Atrial fibrillation; Outcomes C1 [Lopes, Renato D.; Piccini, Jonathan P.; Peterson, Eric D.; Mahaffey, Kenneth W.] Duke Clin Rsch Inst, Dept Med, Div Cardiol, Durham, NC USA. [Holmes, DaJuanicia N.] Duke Univ, Duke Clin Rsch Inst, Outcomes Rsch & Assessment Grp, Med Cntr, Durham, NC USA. [Thomas, Laine] Duke Clin Rsch Inst, Dept Biostat & Bioinformat, Durham, NC USA. [Ansell, Jack] NYU, Sch Med, Dept Med, New York, NY USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Gersh, Bernard J.] Mayo Clin, Coll Med, Rochester, MN USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Rsch, Oakland, CA USA. [Hylek, Flaine M.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Kowey, Peter R.] Lankenau Inst Med Rsch, Lankenau Inst, Wynnewood, PA USA. [Kowey, Peter R.] Jefferson Med Coll, Wynnewood, PA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Chang, Paul] Janssen Pharmaceut Inc, Raritan, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15956 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905288 ER PT J AU Lopes, RD Neely, B Ohman, EM Ardissino, D Hamm, C Goodman, SG Rhatt, DL Brown, EB White, HD Prabhakaran, D Martinez, F Nicolau, JC Fox, KA Armstrong, PW Roe, MT AF Lopes, Renato D. Neely, Benjamin Ohman, E. M. Ardissino, Diego Hamm, Christian Goodman, Shaun G. Rhatt, Deepak L. Brown, Eileen B. White, Harvey D. Prabhakaran, Dorairaj Martinez, Felipe Nicolau, Jose C. Fox, Keith A. Armstrong, Paul W. Roe, Matthew T. TI Timing, Profile, and Predictors of Spontaneous Myocardial Infarction Following a Non-ST-Segment Elevation Acute Coronary Syndrome Event: Insights From the TRILOGY-ACS Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes; Clopidogrel; Antiplatelet drugs; Outcomes; Unstable angina C1 [Lopes, Renato D.; Ohman, E. M.; Roe, Matthew T.] Duke Clin Rsch Inst, Dept Med, Div Cardiol, Durham, NC USA. [Lopes, Renato D.; Ohman, E. M.; Roe, Matthew T.] Duke Sch Med, Durham, NC USA. [Neely, Benjamin] Duke Clin Rsch Inst, Durham, NC USA. [Ardissino, Diego] Univ Parma, Dept Cardiol, Azienda Osped, I-43100 Parma, Italy. [Hamm, Christian] Kerckhoff Heart & Thoraxctr, Bad Nauheim, Germany. [Goodman, Shaun G.] St Michaels Hosp, Dept Med, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Rhatt, Deepak L.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Rhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Eileen B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Rsch Unit, Green Lane Cardiovasc Serv, Auckland, New Zealand. [Prabhakaran, Dorairaj] Cntr Chron Dis Control, New Delhi, India. [Martinez, Felipe] Natl Univ Cordoba, Dept Cardiol, Cordoba, Argentina. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Fox, Keith A.] Univ Edinburgh, British Heart Fdn, Cntr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [Armstrong, Paul W.] Univ Alberta, Dept Med, Div Cardiol, Canadian VIGOUR Cntr, Edmonton, AB, Canada. RI Nicolau, Jose/E-1487-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14972 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904333 ER PT J AU Lorenzano, S Rost, NS Furie, KL AF Lorenzano, Svetlana Rost, Natalia S. Furie, Karen L. TI Molecular Correlates of Neuroimaging Findings in Acute Ischemic Stroke: Early Oxidative Stress Biomarkers of Ischemic Penumbra and Infarct Growth SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stroke; Biomarkers; Oxidative stress; Magnetic resonance imaging C1 [Lorenzano, Svetlana] Univ Roma La Sapienza, Dept Neurol & Psichiat, I-00185 Rome, Italy. [Rost, Natalia S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Furie, Karen L.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Neurol, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17543 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906484 ER PT J AU MacNabb, CM Brayanov, J Freeman, J George, E AF MacNabb, C. Marshall Brayanov, Jordan Freeman, Jenny George, Edward TI Developing a Protocol Utilizing Non-Invasive Respiratory Volume Monitoring to Identify Patients at Risk for Opioid Induced Respiratory Depression SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Ventilation; Pulmonary; Cardiopulmonary resuscitation C1 [MacNabb, C. Marshall; Freeman, Jenny] Resp Mot Inc, Clin, Waltham, MA USA. [Brayanov, Jordan] Resp Mot Inc, Rsch, Waltham, MA USA. [George, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15815 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905197 ER PT J AU MacNabb, MH Kaplan, RS Lavender, ZR Nitta, E Deeks, S Martin, J Pampaloni, MH Ganz, P Hsue, P Tawakol, A AF MacNabb, Megan H. Kaplan, Rebecca S. Lavender, Zachary R. Nitta, Elaine Deeks, Steven Martin, Jeffrey Pampaloni, Miguel Hernandez Ganz, Peter Hsue, Priscilla Tawakol, Ahmed TI Arterial Inflammation in HIV is Associated With Bone Marrow and Splenic Activation SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiac imaging; Inflammation; Positron emission tomography C1 [MacNabb, Megan H.; Kaplan, Rebecca S.; Lavender, Zachary R.; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nitta, Elaine; Martin, Jeffrey; Pampaloni, Miguel Hernandez; Ganz, Peter; Hsue, Priscilla] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Deeks, Steven] Univ Calif San Francisco, AIDS Rsch Inst, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18515 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907412 ER PT J AU Magnani, G Morrow, DA Scirica, BM Sabatine, MS Murphy, SA Bonaca, MP AF Magnani, Giulia Morrow, David A. Scirica, Benjamin M. Sabatine, Marc S. Murphy, Sabine A. Bonaca, Marc P. TI Patterns of Antiplatelet Use in Patients With Stable Atherosclerosis: Insights From the Tra 2 degrees P-timi 50 Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Antiplatelet drugs; Coronary heart disease; Peripheral arterial disease; Cerebrovascular disorders C1 [Magnani, Giulia; Morrow, David A.; Scirica, Benjamin M.; Sabatine, Marc S.; Murphy, Sabine A.; Bonaca, Marc P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18728 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907517 ER PT J AU Magnani, JW Yin, XY McManus, DD Chuang, M Cheng, S Lubitz, SA Arora, G Manning, WJ O'Donnell, CJ Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Yin, Xiaoyan McManus, David D. Chuang, Michael Cheng, Susan Lubitz, Steven A. Arora, Garima Manning, Warren J. O'Donnell, Christopher J. Ellinor, Patrick T. Benjamin, Emelia J. TI Genetic Loci Associated With Atrial Fibrillation Have Limited Relation to Left Atrial Structure in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Genetics; Epidemiology; Cardiovascular imaging C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Yin, Xiaoyan; Chuang, Michael; O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [McManus, David D.] Univ Massachusetts, Dept Med, Cardiol Sect, Worcester, MA 01605 USA. [Cheng, Susan] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Arora, Garima] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11495 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901467 ER PT J AU Malhotra, R Lavender, ZR Zhou, Q Sandoval, RM Szymonifka, J Waxman, AB Semigran, MJ Truong, QA AF Malhotra, Rajeev Lavender, Zachary R. Zhou, Qing Sandoval, Ryan M. Szymonifka, Jackie Waxman, Aaron B. Semigran, Marc J. Truong, Quynh A. TI Pulmonary Arterial Enlargement on Computed Tomography is a Powerful Predictor of Mortality in Patients Undergoing Evaluation for Pulmonary Hypertension SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Computed tomography; Pulmonary artery; Pulmonary hypertension; Pulmonary circulation; Cardiac imaging C1 [Malhotra, Rajeev; Semigran, Marc J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Malhotra, Rajeev] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Lavender, Zachary R.; Zhou, Qing; Sandoval, Ryan M.; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol & Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Waxman, Aaron B.] Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17265 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906361 ER PT J AU Marzec, LN Lambert-Kerzner, A Carey, F Del Giacco, EJ Melnyk, SD Bryson, CL Fahdi, IE Bosworth, HB Fiocchi, F Ho, M AF Marzec, Lucas N. Lambert-Kerzner, Anne Carey, Fvan Del Giacco, Eric J. Melnyk, Stephanie D. Bryson, Christopher L. Fahdi, Ibrahim E. Bosworth, Hayden B. Fiocchi, Fran Ho, Michael TI Health Illiteracy and Cognitive Dysfunction Are Common in Veterans Presenting With Acute Coronary Syndrome: Insights From the MEDICATION Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes; Cognitive function; Adherence C1 [Marzec, Lucas N.] Univ Colorado, Aurora, CO USA. [Lambert-Kerzner, Anne; Carey, Fvan; Ho, Michael] Denver VA Med Cntr, Denver, CO USA. [Del Giacco, Eric J.] John L McClellan Mem Vet Adm Med Ctr, Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Melnyk, Stephanie D.; Bosworth, Hayden B.] Durham VA Med Cntr, Durham, NC USA. [Bryson, Christopher L.] VA Puget Sound Hlth Care Syst, Seattle Div, Internal Med, Seattle, WA USA. [Fahdi, Ibrahim E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Fiocchi, Fran] Amer Coll Cardiol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16308 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905468 ER PT J AU Matteau, A Yeh, RW Camenzind, E Steg, GP Wijns, W Mills, J Gershlick, A de Belder, M Ducrocq, G Mauri, L AF Matteau, Alexis Yeh, Robert W. Camenzind, Edoardo Steg, Gabriel P. Wijns, William Mills, Joseph Gershlick, Anthony de Belder, Mark Ducrocq, Gregory Mauri, Laura TI Balancing Long-Term Risks of Ischemic and Bleeding Complications After Percutaneous Coronary Intervention With Drug-Eluting Stents SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Outcomes; Percutaneous coronary intervention; Drug eluting stents; Epidemiology; Antiplatelet drugs C1 [Matteau, Alexis; Mauri, Laura] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02114 USA. [Camenzind, Edoardo] Univ Geneva, Dept Med, Div Cardiovasc Med, Geneva, Switzerland. [Steg, Gabriel P.] Hop Bichat Claude Bernard, Dept Cardiol, F-75877 Paris, France. [Wijns, William] Onze Lieve Vrouw Hosp, Cardiovasc Cntr, Dept Med, Div Cardiovasc Med, Aalst, Belgium. [Mills, Joseph] Cardiothorac Cntr, Dept Med, Div Cardiovasc Med, Liverpool, Merseyside, England. [Gershlick, Anthony] Glenfield Hosp, Dept Med, Div Cardiovasc Med, Leicester, Leics, England. [de Belder, Mark] James Cook Univ Hosp, Dept Cardiol, Middlesbrough, Cleveland, England. [Ducrocq, Gregory] Hop Bichat Claude Bernard, Dept Med, Div Cardiovasc Med, F-75877 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16104 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905364 ER PT J AU Mauri, L Yeh, RW Nathan, A Silbaugh, TS Zelevinksy, K Normand, SL Jacobs, AK AF Mauri, Laura Yeh, Robert W. Nathan, Ashwin Silbaugh, Treacy S. Zelevinksy, Katya Normand, Sharon-Lise Jacobs, Alice K. TI Growth in Non-Emergency PCI at Hospitals Without Surgery-On-Site Since the Completion of the MASS COMM Trial - A Comparison of the MASS COMM RCT and Cohort Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Percutaneous coronary intervention; Health policy; Outcomes; Clinical trials C1 [Mauri, Laura; Nathan, Ashwin] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Silbaugh, Treacy S.; Zelevinksy, Katya; Normand, Sharon-Lise] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, Alice K.] Boston Med Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17725 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907039 ER PT J AU McCabe, JM Kennedy, KF Resnic, FS Yeh, RW AF McCabe, James M. Kennedy, Kevin F. Resnic, Frederic S. Yeh, Robert W. TI Reporting Trends and Outcomes in ST-elevation Myocardial Infarction National Hospital Quality Assessment Programs SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE STEMI; Quality assessment C1 [McCabe, James M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kennedy, Kevin F.] St Lukes Hosp, Mid Amer Heart Inst, Div Epidemiol & Stat, Kansas City, MO 64111 USA. [Resnic, Frederic S.] Lahey Hosp, Div Cardiovasc Med, Burlington, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17436 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906431 ER PT J AU McKibben, RA Grinspoon, S Li, XH Palella, F Kingsley, LA Witt, MD Brown, TT Jacobson, LP Budoff, M Post, WS AF McKibben, Rebeccah A. Grinspoon, Stephen Li, Xiuhong Palella, Frank Kingsley, Lawrence A. Witt, Mallory D. Brown, Todd T. Jacobson, Lisa P. Budoff, Matthew Post, Wendy S. TI Elevated Levels of Monocyte Activation Markers, Soluble CD14 and CD163, are Associated With Subclinical Atherosclerosis in the Multicenter AIDS Cohort Study (MACS) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Inflammation; Coronary artery disease; CT angiography C1 [McKibben, Rebeccah A.; Brown, Todd T.; Post, Wendy S.] Johns Hopkins Univ, Baltimore, MD USA. [Grinspoon, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Xiuhong; Jacobson, Lisa P.] Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Palella, Frank] Northwestern Univ, Chicago, IL 60611 USA. [Kingsley, Lawrence A.] Univ Pittsburgh, Pittsburgh, PA USA. [Witt, Mallory D.; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15501 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905039 ER PT J AU McNamara, D Damp, J Elkayam, U Hsich, E Ewald, G Cooper, L Modi, K Ramani, G Alexis, J Semigran, M Drazner, M Haythe, J Pisarcik, J Marek, J Gorcsan, J Fett, J AF McNamara, Dennis Damp, Julie Elkayam, Uri Hsich, Eileen Ewald, Gregory Cooper, Leslie Modi, Kalgi Ramani, Gautam Alexis, Jeffrey Semigran, Marc Drazner, Mark Haythe, Jennifer Pisarcik, Jessica Marek, Josef Gorcsan, John Fett, James TI Myocardial Recovery at Six Months in Peripartum Cardiomyopathy: Results of the NHLBI Multicenter IPAC study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiomyopathy; Pregnancy; Myocardium C1 [McNamara, Dennis; Marek, Josef; Gorcsan, John] Univ Pittsburgh Med Cntr, Pittsburgh, PA USA. [Damp, Julie] Vanderbilt Univ, Vanderbilt Heart & Vasc Inst, Nashville, TN 37235 USA. [Elkayam, Uri] Univ So Calif, Los Angeles, CA USA. [Hsich, Eileen] Cleveland Clinc Fdn, Cleveland, OH USA. [Ewald, Gregory] Washington Univ, St Louis, MO USA. [Cooper, Leslie] May Clin, Rochester, MN USA. [Modi, Kalgi] Lousiana State Univ Hlth Sci Cntr, Shreveport, LA USA. [Ramani, Gautam] Univ Maryland, Baltimore, MD 21201 USA. [Alexis, Jeffrey] Univ Rochester, Rochester, NY USA. [Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drazner, Mark] Univ Texas Dallas, Dallas, TX 75230 USA. [Haythe, Jennifer] Columbia Univ Med Cntr, New York, NY USA. [Pisarcik, Jessica] Univ Pittsburgh, Pittsburgh, PA USA. [Fett, James] Peripartum Cardiomyopathy Network, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12898 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902431 ER PT J AU Miller, JM Krummen, DF Clopton, P Day, JD Daubert, JP Ellenbogen, KA Hummel, JD Kowal, RC Mansour, MC Reddy, VY Shivkumar, K Steinberg, JS Swarup, V Wheelan, KR Narayan, SM AF Miller, John M. Krummen, David F. Clopton, Paul Day, John D. Daubert, James P. Ellenbogen, Kenneth A. Hummel, John D. Kowal, Robert C. Mansour, Moussa C. Reddy, Vivek Y. Shivkumar, Kalyanam Steinberg, Jonathan S. Swarup, Vijay Wheelan, Kevin R. Narayan, Sanjiv M. TI Ablation of Atrial Fibrillation Rotors and Focal Sources Improves Outcome Over Conventional Ablation Alone in Independent Laboratories: Multicenter Validation of Focal Impulse and Rotor Modulation (FIRM) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Ablation; Arrhythmia mapping C1 [Miller, John M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Krummen, David F.; Clopton, Paul; Narayan, Sanjiv M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Day, John D.] Intermt Heart Rhythm Specialists, Med, Murray, UT USA. [Daubert, James P.] Duke Univ, Sch Med, Durham, NC USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Hummel, John D.] Ohio State Univ, Sch Med, Columbus, OH 43210 USA. [Kowal, Robert C.; Wheelan, Kevin R.] Baylor Univ, Med Ctr, Dallas, TX USA. [Mansour, Moussa C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reddy, Vivek Y.] Mt Sinai Sch Med, New York, NY USA. [Shivkumar, Kalyanam] Univ Calif Los Angeles, Los Angeles, CA USA. [Steinberg, Jonathan S.] Arrhythmia & Cardiovasc Associates NY NJ, New York, NY USA. [Swarup, Vijay] Arizona Heart Rhythm Cntr, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16890 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906209 ER PT J AU Motiwala, SR Szymonifka, J Gaggin, HK Bhardwaj, A Belcher, A Weiner, RB Baggish, AL Januzzi, JL AF Motiwala, Shweta R. Szymonifka, Jackie Gaggin, Hanna K. Bhardwaj, Anju Belcher, Arianna Weiner, Rory B. Baggish, Aaron L. Januzzi, James L. TI Serial Measurement of an Ultrasensitive Cardiac Troponin-I Predicts Cardiovascular Outcomes and Ventricular Remodeling in Chronic Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Biomarkers; Troponin; Prognosis; Remodeling C1 [Motiwala, Shweta R.; Szymonifka, Jackie; Gaggin, Hanna K.; Bhardwaj, Anju; Belcher, Arianna; Weiner, Rory B.; Baggish, Aaron L.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14953 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904323 ER PT J AU Motiwala, SR Bhardwaj, A Szymonifka, J Belcher, A Weiner, RB Baggish, AL Gaggin, HK Januzzi, JL AF Motiwala, Shweta R. Bhardwaj, Anju Szymonifka, Jackie Belcher, Arianna Weiner, Rory B. Baggish, Aaron L. Gaggin, Hanna K. Januzzi, James L. TI A Remodeling Paradox? Circulating Concentrations of the Novel Biomarker Mimecan Predict Both Adverse Events and Favorable Reverse Ventricular Remodeling in Chronic Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Biomarkers; Remodeling; Prognosis; Outcomes C1 [Motiwala, Shweta R.; Bhardwaj, Anju; Szymonifka, Jackie; Belcher, Arianna; Weiner, Rory B.; Baggish, Aaron L.; Gaggin, Hanna K.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11580 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901508 ER PT J AU Natt, P Saxena, R Dib, P Ralhan, S Wander, GS Stowell, D Peyton, M Sanghera, D AF Natt, Praveen Saxena, Richa Dib, Patrick Ralhan, Sarju Wander, Gurpreet S. Stowell, Donald Peyton, Marvin Sanghera, Dharambir TI Casein Kinase II (csnk2a2) is Associated With Leucocyte Telomere Shortening and Increased Cardiovascular Disease Risk in Diabetes SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiovascular disease; Coronary heart disease; Type 2 Diabetes C1 [Natt, Praveen; Dib, Patrick; Stowell, Donald; Peyton, Marvin; Sanghera, Dharambir] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Saxena, Richa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Ralhan, Sarju; Wander, Gurpreet S.] Hero Dayanand Med Coll, Ludhiana, Punjab, India. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18797 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907552 ER PT J AU O'Brien, EC Zhao, X Fonarow, GC Smith, EE Schwamm, LH Bhatt, DL Xian, Y Saver, JL Reeves, MJ Peterson, ED Hernandez, AF AF O'Brien, Emily C. Zhao, Xin Fonarow, Gregg C. Smith, Eric E. Schwamm, Lee H. Bhatt, Deepak L. Xian, Ying Saver, Jeffrey L. Reeves, Mathew J. Peterson, Eric D. Hernandez, Adrian F. TI Readmission for Stroke and Quality of Care Among Patients Hospitalized With Transient Ischemic Attack (TIA): Findings From Get With the Guidelines (GWTG)-Stroke SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stroke; Quality of medical care; Risk factors; Outcomes; Older population C1 [O'Brien, Emily C.; Zhao, Xin; Xian, Ying; Peterson, Eric D.; Hernandez, Adrian F.] Duke Clin Rsch Inst, Durham, NC USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Cntr, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17576 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906505 ER PT J AU O'Sullivan, JF Ho, JE Rhee, EP Chen, MH Larson, MG O'Donnell, CJ Vasan, RS Wang, TJ Gerszten, RE AF O'Sullivan, John F. Ho, Jennifer E. Rhee, Eugene P. Chen, Ming-Huei Larson, Martin G. O'Donnell, Christopher J. Vasan, Ramachandran S. Wang, Thomas J. Gerszten, Robert E. TI Integration of Metabolomic and Genomic Data Highlights Novel Pathways For Mechanistic Exploration in Coronary Artery Disease SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Coronary artery disease; Genomics; Metabolomics C1 [O'Sullivan, John F.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Ho, Jennifer E.] Boston Med Cntr, Boston, MA USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wang, Thomas J.] Vanderbilt Univ, Med Cntr, Dept Cardiol, Nashville, TN 37235 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, MGH Heart Cntr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11158 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901329 ER PT J AU Onuma, OK Chun, EJ Pencina, K Massaro, JM O'Donnell, CJ Hoffmann, U AF Onuma, Oyere K. Chun, Eun Ju Pencina, Karol Massaro, Joseph M. O'Donnell, Christopher J. Hoffmann, Udo TI Performance of Framingham Risk Function With Coronary Artery Calcium in Predicting Major Coronary Events in an Asian Cohort SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiovascular disease prevention; Cardiac CT; Risk factors C1 [Onuma, Oyere K.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chun, Eun Ju] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. [Pencina, Karol] Boston Univ, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18536 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907424 ER PT J AU Patel, AP Larach, DB Peloso, GM Pirruccello, JP Gupta, N Rader, DJ Kathiresan, S AF Patel, Aniruddh P. Larach, Daniel B. Peloso, Gina M. Pirruccello, James P. Gupta, Namrata Rader, Daniel J. Kathiresan, Sekar TI Absence of Rare Coding Sequence Variants of Large Effect in GWAS Loci for High-Density Lipoprotein Cholesterol SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE HDL; Genetic techniques; Genomics; Lipids; Genetics C1 [Patel, Aniruddh P.; Peloso, Gina M.; Pirruccello, James P.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cntr Human Genet Rsch, Boston, MA 02114 USA. [Larach, Daniel B.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Larach, Daniel B.; Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gupta, Namrata] Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11298 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901391 ER PT J AU Perez, AL Lubitz, SA Guy, ML Ruskin, JN Passeri, JJ Ellinor, PT AF Perez, Antonio L. Lubitz, Steven A. Guy, Mary L. Ruskin, Jeremy N. Passeri, Jonathan J. Ellinor, Patrick T. TI Long-term Mortality of Patients With Single-Chamber versus Dual-Chamber Implantable Cardioverter-Defibrillators SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Implantable cardioconvert defibrillator C1 [Perez, Antonio L.; Lubitz, Steven A.; Guy, Mary L.; Ruskin, Jeremy N.; Passeri, Jonathan J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17491 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906454 ER PT J AU Piccini, JP Garg, J Patel, MR Lokhnygina, Y Goodman, SG Becker, RC Berkowitz, SD Breithardt, G Hacke, W Halperin, JL Hankey, GI Nessel, CC Mahaffey, KW Singer, DE Califf, RM Fox, KA AF Piccini, Jonathan P. Garg, Jyotsna Patel, Manesh R. Lokhnygina, Yuliya Goodman, Shaun G. Becker, Richard C. Berkowitz, Scott D. Breithardt, Gunter Hacke, Werner Halperin, Jonathan L. Hankey, Graeme I. Nessel, Christopher C. Mahaffey, Kenneth W. Singer, Daniel E. Califf, Robert M. Fox, Keith A. TI Management of Major Bleeding Events in Patients Treated With Rivaroxaban Versus Warfarin: Results From the ROCKET AF Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Atrial fibrillation; Stroke; Risk factors C1 [Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Mahaffey, Kenneth W.] Duke Clin Rsch Inst, Dept Med, Div Cardiol, Durham, NC USA. [Garg, Jyotsna] Duke Clin Rsch Inst, Stat Grp, Durham, NC USA. [Lokhnygina, Yuliya] Duke Clin Rsch Inst, Dept Biostat & Bioinformat, Durham, NC USA. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Canadian Heart Rsch Cntr, Toronto, ON, Canada. [Goodman, Shaun G.] Terrence Donnelly Heart Cntr, Toronto, ON, Canada. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Global Therapeut Rsch, Cardiovasc Pharmacol, Montville, NJ USA. [Breithardt, Gunter] Hosp Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Halperin, Jonathan L.] Mt Sinai, Icahn Sch Med, Mt Sinai Med Cntr, Cardiovasc Inst, New York, NY USA. [Hankey, Graeme I.] Univ Western Australia, Sch Med & Pharmacol, Dept Neurol, Perth, WA 6009, Australia. [Hankey, Graeme I.] Royal Perth Hosp, Stroke Unit, Perth, WA 6001, Australia. [Nessel, Christopher C.] Janssen Rsch & Dev, Clin Rsch, Raritan, NJ USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Califf, Robert M.] Duke Translat Med Inst, Dept Med, Div Cardiol, Durham, NC USA. [Fox, Keith A.] Univ Edinburgh, Cntr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [Fox, Keith A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15879 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905238 ER PT J AU Pursnani, A Wai, B Hoffmann, U Weiner, RB Isaacs, SK Kanayama, G Hudson, JI Pope, HG Baggish, AL AF Pursnani, Amit Wai, Bryan Hoffmann, Udo Weiner, Rory B. Isaacs, Stephanie K. Kanayama, Gen Hudson, James I. Pope, Harrison G. Baggish, Aaron L. TI Anabolic-Androgenic Steroid Use is Associated With Premature Coronary Artery Disease SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Drugs; Coronary heart disease; Cardiac CT; CT angiography; Plaque C1 [Pursnani, Amit; Wai, Bryan; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Weiner, Rory B.; Isaacs, Stephanie K.; Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kanayama, Gen; Hudson, James I.; Pope, Harrison G.] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 1 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16958 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906237 ER PT J AU Putt, M Ky, B Sawaya, H French, B Januzzi, JL Sebag, I Planas, J Cohen, V Blanchs, J Carver, J Wiegers, S Martin, RP Picard, M Gerstzen, R Halpern, E Passeri, J Irene, K Scherrer-Crosbie, M AF Putt, Mary Ky, Bonnie Sawaya, Heloisa French, Benjamin Januzzi, James L. Sebag, Igal Planas, Juan Cohen, Victor Blanchs, Jose Carver, Joseph Wiegers, Susan Martin, Randolph P. Picard, Michael Gerstzen, Robert Halpern, Elkan Passeri, Jonathan Irene, Kuter Scherrer-Crosbie, Marielle TI Early Increases in Biomarkers Predict Subsequent Cardiotoxicity in Breast Cancer Patients Treated With Doxorubicin, Taxanes, and Trastuzumab SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Biomarkers C1 [Putt, Mary; French, Benjamin; Carver, Joseph] Univ Penn, Philadelphia, PA 19104 USA. [Sawaya, Heloisa] PRA Int, Raleigh, NC USA. [Januzzi, James L.; Picard, Michael; Gerstzen, Robert; Halpern, Elkan; Passeri, Jonathan; Irene, Kuter; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Januzzi, James L.; Picard, Michael; Halpern, Elkan; Passeri, Jonathan; Irene, Kuter; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA. [Sebag, Igal; Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. [Sebag, Igal; Cohen, Victor] McGill Univ, Montreal, PQ, Canada. [Planas, Juan] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Blanchs, Jose] MD Anderson Canc Cntr, Houston, TX USA. [Wiegers, Susan] Temple Univ, Div Cardiol, Philadelphia, PA 19122 USA. [Martin, Randolph P.] Piedmont Hlth Heart Inst, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15849 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905223 ER PT J AU Rajabali, A Friedman, DJ Vegh, EM Parks, KA Moore, SA Orencole, M Singh, JP Heist, EK AF Rajabali, Alefiyah Friedman, Daniel J. Vegh, Eszter M. Parks, Kimberly A. Moore, Stephanie A. Orencole, Mary Singh, Jagmeet P. Heist, Edwin K. TI The Relationship of Percent Biventricular Pacing to Ventricular Arrhythmias and Reverse Remodeling Post Cardiac Resynchronization Therapy SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Resynchronization therapy; Ventricular arrhythmia; Remodeling C1 [Rajabali, Alefiyah; Friedman, Daniel J.; Vegh, Eszter M.; Parks, Kimberly A.; Orencole, Mary; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, Stephanie A.] Massachusetts Gen Hosp, Heart Failure & Cardiac Transplant Program, Boston, MA 02114 USA. [Heist, Edwin K.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10932 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901259 ER PT J AU Reed, GW Guo, JP Hoffman, EB Maree, AO Shekar, P Aranki, S Rosenfield, K Cannon, CP AF Reed, Grant W. Guo, Jianping Hoffman, Elaine B. Maree, Andrew O. Shekar, Prem Aranki, Sary Rosenfield, Kenneth Cannon, Christopher P. TI Aspirin Responsiveness Testing Predicts Bleeding During Coronary Artery Bypass Grafting: The Verify Pre-Op - TIMI 45 Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Antiplatelet drugs; General cardiology; Cardiac surgery; Surgery; Coronary heart disease C1 [Reed, Grant W.; Guo, Jianping; Hoffman, Elaine B.; Shekar, Prem; Aranki, Sary; Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Maree, Andrew O.] Waterford Reg Hosp, Waterford City, Ireland. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10331 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901086 ER PT J AU Ruparelia, N Lee, R Dall'Armellina, E Godec, J Medway, D Forfar, C Prendergast, B Kharbanda, RK Banning, AP Neubauer, S Lygate, CA Channon, KM Haining, WN Choudhury, RP AF Ruparelia, Neil Lee, Regent Dall'Armellina, Erica Godec, Jernei Medway, Debra Forfar, Colin Prendergast, Bernard Kharbanda, Rajesh K. Banning, Adrian P. Neubauer, Stefan Lygate, Craig A. Channon, Keith M. Haining, W. Nicholas Choudhury, Robin P. TI The Monocyte Genomic Response is Conserved Between Mice and Humans Following Acute Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genomics; Myocardial infarction; Gene expression; Leukocytes C1 [Ruparelia, Neil; Lee, Regent; Dall'Armellina, Erica; Medway, Debra; Forfar, Colin; Prendergast, Bernard; Kharbanda, Rajesh K.; Banning, Adrian P.; Neubauer, Stefan; Lygate, Craig A.; Channon, Keith M.; Choudhury, Robin P.] Univ Oxford, Oxford, England. [Godec, Jernei; Haining, W. Nicholas] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11257 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901374 ER PT J AU Schwab, PJ Buckley, EM Lynch, JM Busch, D Li, CJ Shore, D Pawlowski, TW Putt, M Montenegro, L Nicolson, S Spray, TL Gaynor, JW Fuller, S Licht, DJ Fogel, MA AF Schwab, Peter J. Buckley, Erin M. Lynch, Jennifer M. Busch, David Li, Christine J. Shore, David Pawlowski, Thomas W. Putt, Mary Montenegro, Lisa Nicolson, Susan Spray, Thomas L. Gaynor, J. W. Fuller, Stephanie Licht, Daniel J. Fogel, Mark A. TI Cerebral Co2 Reactivity is Decreased in Children With Post-Bidirectional Glenn Physiology SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Congenital heart surgery; Congenital heart disease; Perfusion imaging; Pediatric cardiology; Cerebrovascular circulation C1 [Schwab, Peter J.; Licht, Daniel J.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Buckley, Erin M.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Cntr Biomed Imaging, Opt Div,Med Sch, Charlestown, MA USA. [Lynch, Jennifer M.; Busch, David; Putt, Mary] Univ Penn, Philadelphia, PA 19104 USA. [Li, Christine J.; Shore, David; Pawlowski, Thomas W.; Fogel, Mark A.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. [Montenegro, Lisa; Nicolson, Susan] Childrens Hosp Philadelphia, Div Cardiac Anesthesia, Philadelphia, PA 19104 USA. [Spray, Thomas L.; Gaynor, J. W.; Fuller, Stephanie] Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15078 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904387 ER PT J AU Scirica, BM Raz, I Cavender, MA Steg, PG Hirshberg, B Davidson, J Im, K Hoffman, E Braunwald, E Bhatt, DL AF Scirica, Benjamin M. Raz, Itamar Cavender, Matthew A. Steg, P. G. Hirshberg, Boaz Davidson, Jaime Im, KyungAh Hoffman, Elaine Braunwald, Eugene Bhatt, Deepak L. TI Outcomes of Patients With Type 2 Diabetes and Known Congestive Heart Failure Treated With Saxagliptin: Analyses of the SAVOR-TIMI 53 Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Type 2 Diabetes; Heart failure; Outcomes; Clinical trials C1 [Scirica, Benjamin M.; Cavender, Matthew A.; Im, KyungAh; Hoffman, Elaine; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Raz, Itamar] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Steg, P. G.] Univ Paris Diderot, Sorbonne Paris Cite, CHU Bichat, AP HP,INSERM,U698, Paris, France. [Hirshberg, Boaz] AstraZeneca, CVGI Clin Therapeut Area, Wilmington, DE USA. [Davidson, Jaime] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston VA Med Cntr, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17503 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906461 ER PT J AU Secemsky, EA Scherzer, R Nitta, E Wu, A Lange, DC Deeks, SG Martin, JN Snider, J Ganz, P Hsue, PY AF Secemsky, Eric A. Scherzer, Rebecca Nitta, Elaine Wu, Alan Lange, David C. Deeks, Steven G. Martin, Jeffrey N. Snider, James Ganz, Peter Hsue, Priscilla Y. TI ST2 and GDF-15 are Associated With Structural Heart Disease and Mortality in HIV-Infected Individuals SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Biomarkers; Cardiovascular disease; Acquired immunodeficiency syndrome; Diastolic function; Echocardiography C1 [Secemsky, Eric A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scherzer, Rebecca] Univ Calif San Francisco, San Francisco Vet Affair Med Cntr, San Francisco, CA 94143 USA. [Nitta, Elaine; Wu, Alan; Deeks, Steven G.; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Lange, David C.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Snider, James] Crit Diagnost, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13364 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903125 ER PT J AU Setton, M He, W Benavidez, OJ AF Setton, Matan He, Wei Benavidez, Oscar J. TI Complications During Adult Congenital Heart Surgery Admissions: Frequency and Impact on Patient Outcomes SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Adult congenital heart disease; Congenital heart surgery; Outcomes C1 [Setton, Matan; He, Wei; Benavidez, Oscar J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [He, Wei] Massachusetts Gen Hosp, MGH Clin Rsch Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17921 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907133 ER PT J AU Shah, B Gianos, E Bangalore, S Liang, L Peacock, WF Fonarow, G Laskey, WK Hernandez, A Bhatt, DL AF Shah, Binita Gianos, Eugenia Bangalore, Srinal Liang, Li Peacock, W. Frank Fonarow, Gregg Laskey, Warren K. Hernandez, Adrian Bhatt, Deepak L. TI Temporal Trends in Clinical Characteristics of Patients Without Known Coronary Artery Disease Presenting With a First Episode of Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Myocardial infarction; Risk factors C1 [Shah, Binita; Gianos, Eugenia; Bangalore, Srinal] NYU, Sch Med, New York, NY USA. [Liang, Li; Hernandez, Adrian] Duke Clin Rsch Inst, Durham, NC USA. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Fonarow, Gregg] Univ Calif Los Angeles, Los Angeles, CA USA. [Laskey, Warren K.] Univ New Mexico, Albuquerque, NM 87131 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 11118 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901326 ER PT J AU Shah, RV Abbasi, SA McNulty, S Hernandez, A Neilan, TG Haines, PG Semigran, M Boriaug, BA Lewis, G Jerosch-Herold, M Kim, RJ Redfield, M Kwong, RY AF Shah, Ravi V. Abbasi, Siddique A. McNulty, Steven Hernandez, Adrian Neilan, Tomas G. Haines, Phillip G. Semigran, Mark Boriaug, Barry A. Lewis, Gregory Jerosch-Herold, Michael Kim, Raymond J. Redfield, Margaret Kwong, Raymond Y. TI Left Atrial Function is Associated With Cardiopulmonary Performance in Heart Failure With Preserved Ejection Fraction: A Relax Substudy SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Diastolic function; Atrial function; Magnetic resonance imaging C1 [Shah, Ravi V.; Abbasi, Siddique A.; Kwong, Raymond Y.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [McNulty, Steven; Hernandez, Adrian] Duke Clin Rsch Inst, Durham, NC USA. [Neilan, Tomas G.; Semigran, Mark; Lewis, Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haines, Phillip G.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Boriaug, Barry A.; Redfield, Margaret] Mayo Clin, Rochester, MN USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Div Radiol, Boston, MA 02115 USA. [Kim, Raymond J.] Duke Univ Med Cntr, Div Cardiol, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18524 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907417 ER PT J AU Shah, SH Kwee, L Stitziel, N Hauser, ER Haynes, C Kathiresan, S Gregory, SG Kraus, WE AF Shah, Svati H. Kwee, Lydia Stitziel, Nathan Hauser, Elizabeth R. Haynes, Carol Kathiresan, Sekar Gregory, Simon G. Kraus, William E. TI Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genetics; Insulin resistance C1 [Shah, Svati H.; Kraus, William E.] Duke Univ Med Cntr, Dept Med, Div Cardiol, Durham, NC USA. [Kwee, Lydia; Hauser, Elizabeth R.; Haynes, Carol; Gregory, Simon G.] Duke Univ Med Cntr, Dept Med, Durham, NC USA. [Stitziel, Nathan] Washington Univ, Sch Med, Dept Med, Div Cardiol, St Louis, MO 63110 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18535 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907423 ER PT J AU Shah, SH Kraus, WE Ilkaveva, O Stevens, R Haynes, C Lewis, GD Newgard, CB Gerszten, RE AF Shah, Svati H. Kraus, William E. Ilkaveva, Olga Stevens, Robert Haynes, Carol Lewis, Gregory D. Newgard, Christopher B. Gerszten, Robert E. TI Metabolomic Profiling in a Human Model of Myocardial Infarction Identifies Novel Early Biomarkers of Cellular Damage SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Metabolomics; Hypertrophic cardiomyopathy; Myocardial infarction; Biomarkers C1 [Shah, Svati H.; Kraus, William E.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Ilkaveva, Olga; Stevens, Robert; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Cntr, Durham, NC USA. [Haynes, Carol] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Lewis, Gregory D.; Gerszten, Robert E.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16632 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906080 ER PT J AU Shahid, M Spagnolli, E Ernande, L Kolodziej, S Mayeur, C Leyton, P Scherrer-Crosbie, M Bloch, KD AF Shahid, Mohd Spagnolli, Ester Ernande, Laura Kolodziej, Starsha Mayeur, Claire Leyton, Patricio Scherrer-Crosbie, Marielle Bloch, Kenneth D. TI ALK2 and ALK3 BMP Type I Receptors Are Required for the Development of Cardiac Hypertrophy SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiac hypertrophy; Cardiovascular disease; Gene expression; Natriuretic peptide C1 [Shahid, Mohd; Spagnolli, Ester; Ernande, Laura; Kolodziej, Starsha; Mayeur, Claire; Leyton, Patricio; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 19016 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162908085 ER PT J AU Sharma, AK Kandala, J Vegh, EM Orencole, M Miller, A Parks, KA Heist, EK Singh, JP AF Sharma, Ajay K. Kandala, Jagdesh Vegh, Eszter M. Orencole, Mary Miller, Alexandra Parks, Kimberly A. Heist, E. Kevin Singh, Jagmeet P. TI Hyponatremia as a Predictor for Adverse Events in Patients With Heart Failure Receiving Cardiac Resynchroniation Therapy SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE CRT; Sodium C1 [Sharma, Ajay K.; Kandala, Jagdesh; Vegh, Eszter M.; Orencole, Mary; Miller, Alexandra; Parks, Kimberly A.; Heist, E. Kevin; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17381 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906406 ER PT J AU Sharma, UC Puchner, S Lee, AM Liu, T Holmvang, G Ghoshhajra, B Hoffmann, U Abbara, S AF Sharma, Umesh C. Puchner, Stefan Lee, Ashley M. Liu, Ting Holmvang, Godtfred Ghoshhajra, Brian Hoffmann, Udo Abbara, Suhny TI Cardiac MRI and Follow-Up of AICD and Pacemaker Events to Identify the Etiology and Natural History of Sudden Cardiac Arrest and Heart Blocks SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Sudden cardiac death; Cardiac MRI; Heart block; Cardiac imaging C1 [Sharma, Umesh C.; Puchner, Stefan; Lee, Ashley M.; Liu, Ting; Holmvang, Godtfred; Ghoshhajra, Brian; Hoffmann, Udo; Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10608 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901146 ER PT J AU Shimada, YJ Passeri, JJ Raggish, AL O'Callaghan, C Lowry, PA Yannekis, G Ahbara, S Ghoshhajra, BB Rothman, RD Ho, CY Januzzi, JL Seidman, CE Fifer, MA AF Shimada, Yuichi J. Passeri, Jonathan J. Raggish, Aaron L. O'Callaghan, Caitlin Lowry, Patricia A. Yannekis, Gia Ahbara, Suhny Ghoshhajra, Brian B. Rothman, Richard D. Ho, Carolyn Y. Januzzi, James L. Seidman, Christine E. Fifer, Michael A. TI Attenuation of Left Ventricular Fibrosis by Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo Controlled, Double Blind Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Hypertrophic cardiomyopathy; Angiotensin II; Cardiac hypertrophy; Fibrosis; Cardiac MRI C1 [Shimada, Yuichi J.; Ho, Carolyn Y.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Passeri, Jonathan J.; Raggish, Aaron L.; O'Callaghan, Caitlin; Lowry, Patricia A.; Yannekis, Gia; Ahbara, Suhny; Ghoshhajra, Brian B.; Rothman, Richard D.; Januzzi, James L.; Fifer, Michael A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ahbara, Suhny; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10336 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901090 ER PT J AU Sihag, S Haas, MS Kim, KM Guerrero, JL Beaudoin, J Carroll, E Gottschall, JD Haspel, R Madsen, JC Sachs, DH Carroll, MC Allan, JS AF Sihag, Smita Haas, Michael S. Kim, Karen M. Guerrero, Jose L. Beaudoin, Jonathan Carroll, Elisabeth Gottschall, James D. Haspel, Robyn Madsen, Joren C. Sachs, David H. Carroll, Michael C. Allan, James S. TI Natural IgM Blockade Mitigates Myocardial Ischemia-Reperfusion Injury in Miniature Swine SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Ischemia reperfusion; Immunologic factors; Reperfusion injury; Infarct size; Antibodies C1 [Sihag, Smita; Kim, Karen M.; Guerrero, Jose L.; Beaudoin, Jonathan; Allan, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haas, Michael S.; Haspel, Robyn] Decimmune Therapeut, Cambridge, MA USA. [Carroll, Elisabeth; Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Gottschall, James D.; Madsen, Joren C.; Sachs, David H.] Massachusetts Gen Hosp, Transplant Biol Rsch Cntr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16004 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905314 ER PT J AU Singh, P Tawakol, A Mojena, M Pimentel-Santillana, M Vucic, E Emami, H Morss, A Swanson, J Fontanez, S Fayad, ZA Rudd, JHF Narula, J Traves, PG Fernandez-Velasco, M Martin-Sanz, P Tejedor, A Bosca, L AF Singh, Parmanand Tawakol, Ahmed Mojena, Marina Pimentel-Santillana, Maria Vucic, Esad Emami, Hamed Morss, Alex Swanson, Jeffrey Fontanez, Sara Fayad, Zahi A. Rudd, James H. F. Narula, Jagat Traves, Paqul G. Fernandez-Velasco, Maria Martin-Sanz, Paloma Tejedor, Alberto Bosca, Lisardo TI Close Interrelationship Between Macrophage Pro-inflammatory Activation and Metabolism in an Atherosclerotic Environment SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Inflammation; Metabolism; Hypoxia; Leukocytes; Plaque C1 [Singh, Parmanand; Tawakol, Ahmed; Vucic, Esad; Emami, Hamed; Morss, Alex; Swanson, Jeffrey; Fontanez, Sara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mojena, Marina; Pimentel-Santillana, Maria; Traves, Paqul G.; Fernandez-Velasco, Maria; Martin-Sanz, Paloma; Tejedor, Alberto; Bosca, Lisardo] Inst Invest Biomed Alberto Sols, Dept Metab & Cell Signaling, Madrid, Spain. [Fayad, Zahi A.] Mt Sinai Sch Med, New York, NY USA. [Rudd, James H. F.] Univ Cambridge, Cambridge, England. [Narula, Jagat] Sch Med Mt Sinai, New York, NY USA. RI G. Traves, Paqui/L-5693-2014; Pimentel-Santillana, Maria/L-9437-2014 OI G. Traves, Paqui/0000-0001-5749-8426; Pimentel-Santillana, Maria/0000-0003-1179-4259 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17560 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906495 ER PT J AU Steen, DL Umez-Eronini, AA Hoffman, EB Antman, EM Wiviott, SD AF Steen, Dylan L. Umez-Eronini, Amarachi A. Hoffman, Elaine B. Antman, Elliott M. Wiviott, Stephen D. TI Utilization of Intensive Lipid-Lowering Therapy After an Acute Coronary Syndrome: Insights From the Triton-TIMI 38 Trial SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Arteriosclerosis; Statins; Lipids; Acute coronary syndromes; Lipoproteins C1 [Steen, Dylan L.; Umez-Eronini, Amarachi A.; Hoffman, Elaine B.; Antman, Elliott M.; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17544 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906485 ER PT J AU Stein, AF Hara, T McCarthy, JR Mauskapf, A Jaffer, FA AF Stein, Ashley F. Hara, Tetsuya McCarthy, Jason R. Mauskapf, Adam Jaffer, Farouc A. TI Intravascular Near Infrared Fluorescence Molecular Imaging Identifies Macrophages in vivo in Thrombosis-Prone Plaques SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Arteriosclerosis; Inflammation; Plaque rupture; Imaging agents; Cardiovascular imaging C1 [Stein, Ashley F.; Hara, Tetsuya; McCarthy, Jason R.; Mauskapf, Adam] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16926 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906221 ER PT J AU Stitziel, N Do, R Won, HH AF Stitziel, Nathan Do, Ron Won, Hong-Hee CA NHLBI Exome Sequencing Project Ear Myocardial Infarction Genetics Exo TI Exome Sequencing Identifies Rare Alleles Contributing to the Inherited Basis of Early-Onset Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genetics; Genomics; Myocardial infarction; Gene mutations; Genome-wide association studies (GWAS) C1 [Stitziel, Nathan] Washington Univ, St Louis, MO USA. [Do, Ron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Won, Hong-Hee] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14028 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903405 ER PT J AU Sturzu, AC Kuppusamy, R Passer, D Riley, AK Tan, TC Engles, MC Feistritzer, R Robertson, KD Scherrer-Crosbie, M Domian, IJ Wu, SM AF Sturzu, Anthony C. Kuppusamy, Rajarajan Passer, Derek Riley, Alyssa K. Tan, Timothy C. Engles, Marc C. Feistritzer, Rebecca Robertson, Keston D. Scherrer-Crosbie, Marielle Domian, Ibrahim J. Wu, Sean M. TI A Novel Cell Ablation Strategy Defines the Regenerative Potential of the Embryonic Mouse Heart SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiac regeneration; Cardiac development; Stem/progenitor cells; Regenerative medicine stem cells; Myocardium C1 [Sturzu, Anthony C.; Kuppusamy, Rajarajan; Engles, Marc C.; Wu, Sean M.] Stanford Univ, Cardiovasc Inst, Stanford, CA 94305 USA. [Passer, Derek; Feistritzer, Rebecca; Robertson, Keston D.; Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Riley, Alyssa K.] Massachusetts Gen Hosp, Cardiovasc Inst, Boston, MA 02114 USA. [Tan, Timothy C.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12609 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902301 ER PT J AU Tada, H Liu, DJJ Patel, A AF Tada, Hayato Liu, Dajiang J. Patel, Aniruddh CA Global Lipids Genetics Exome Array TI A Rare View of Coding Sequence Mutations and Plasma Lipid Levels: Results From an Association Study Including similar to 82,000 Individuals Genotyped Using the Exome Array SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genetics; Lipids C1 [Tada, Hayato; Patel, Aniruddh] Massachusetts Gen Hosp, Cntr Human Genet Rsch, Boston, MA 02114 USA. [Liu, Dajiang J.] Univ Michigan, Dept Biostat, Cntr Stat Genet, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 10159 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162901042 ER PT J AU Tada, H Won, HH Yang, J Peloso, GM Do, R Kathiresan, S AF Tada, Hayato Won, Hong-hee Yang, Jian Peloso, Gina M. Do, Ron Kathiresan, Sekar TI Exploring the Missing Heritability of Complex Traits: Multiple Associated Variants Increase the Heritability Explained for Plasma Lipids and Coronary Artery Disease SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genetics; Genome-wide association studies (GWAS); Cardiovascular disease C1 [Tada, Hayato; Won, Hong-hee; Peloso, Gina M.; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Cntr Human Genet Rsch, Boston, MA 02114 USA. [Yang, Jian] Queensland Inst Med Rsch, Queensland Stat Genet Lab, Brisbane, Qld, Australia. RI Yang, Jian/A-5852-2010 OI Yang, Jian/0000-0003-2001-2474 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 9468 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162900362 ER PT J AU Tan, TC Jiao, Y Zeng, X Wei, QF Thiele, K Salgo, I Picard, MH Hung, JW AF Tan, Timothy C. Jiao, Yuan Zeng, Xin Wei, Qifeng Thiele, Karl Salgo, Ivan Picard, Michael H. Hung, Judy W. TI Comparison of an Automated Method for Quantification of Mitral Regurgitation Flow Using 3 Dimensional Color Doppler Imaging of Proximal Velocities With 2 Dimensional Echocardiographic Methods SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Mitral regurgitation; Transesophageal echocardiography; Echocardiography; Qualty assessment C1 [Tan, Timothy C.; Jiao, Yuan; Zeng, Xin; Picard, Michael H.; Hung, Judy W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wei, Qifeng] Philips Healthcare, Philips Ultrasound, Andover, MA USA. [Thiele, Karl; Salgo, Ivan] Philips Healthcare, Ultrasound Cardiol, Andover, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15980 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905301 ER PT J AU Tan, TC Pontes-Neto, OM Nunes, MC Piro, V Jiao, Y Kim, GM Helenius, Y O'Brien, C Avery, R Leavitt, MB Zeng, X Handschumacher, M Furie, K Ay, H Hung, J AF Tan, Timothy C. Pontes-Neto, Octavio M. Nunes, Maria C. Piro, Victoria Jiao, Yuan Kim, Gyeong-Moon Helenius, Yohanna O'Brien, Cashel Avery, Ross Leavitt, Marcia B. Zeng, Xin Handschumacher, Mark Furie, Karen Ay, Hakan Hung, Judy TI Left Atrial Cross Sectional Area is a Novel Risk Factor for Cardioembolic Stroke and Recurrence of Ischemic Stroke Within go Days SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stroke; Echocardiography; Cardiac imaging; Magnetic resonance C1 [Tan, Timothy C.; Pontes-Neto, Octavio M.; Nunes, Maria C.; Piro, Victoria; Jiao, Yuan; O'Brien, Cashel; Avery, Ross; Zeng, Xin; Handschumacher, Mark; Ay, Hakan; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Gyeong-Moon] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Helenius, Yohanna] Massachusetts Gen Hosp, Athinoula A Martinos Cntr Biomed Imaging, Boston, MA 02114 USA. [Leavitt, Marcia B.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Furie, Karen] Rhodes Isl Hosp, Providence, RI USA. RI Pontes-Neto, Octavio/G-4294-2012 OI Pontes-Neto, Octavio/0000-0003-0317-843X NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15274 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904481 ER PT J AU Tang, J Lobatto, ME Leong, W Sager, H van der Staay, SE van Rijs, SM Ramachandran, S Astudillo, YM Duivenvoorden, R Wang, Y Tabas, I Fuster, V Nahrendorf, M Cormode, DP Fisher, EA Fayad, ZA Mulder, WJ AF Tang, Jun Lobatto, Mark E. Leong, Wei Sager, Hendrik van der Staay, Susanne E. van Rijs, Sarian M. Ramachandran, Sarayu Astudillo, Yaritzv M. Duivenvoorden, Raphael Wang, Ying Tabas, Ira Fuster, Valentin Nahrendorf, Matthias Cormode, David P. Fisher, Edward A. Fayad, Zahi A. Mulder, Willem J. TI A Nanomedicine-Based Treatment Regimen to Induce Plaque Remodeling to a Favorable Phenotype in Mice With Advanced Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Inflammation; Arteriogenesis; Statins; HDL; Acute coronary syndromes C1 [Tang, Jun; Leong, Wei; van der Staay, Susanne E.; van Rijs, Sarian M.; Ramachandran, Sarayu; Fayad, Zahi A.; Mulder, Willem J.] Mt Sinai, Icahn Sch Med, Translat & Mol Imaging Inst, New York, NY USA. [Lobatto, Mark E.; Duivenvoorden, Raphael] Acad Med Cntr, Amsterdam, Netherlands. [Sager, Hendrik] Massachusetts Gen Hosp, Cntr Syst Biol, Boston, MA 02114 USA. [Astudillo, Yaritzv M.; Fisher, Edward A.] NYU, Sch Med, Dept Med Cardiol & Cell Biol, New York, NY USA. [Wang, Ying; Tabas, Ira] Columbia Univ, New York, NY USA. [Fuster, Valentin] Mt Sinai, Icahn Sch Med, New York, NY USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Translat & Mol Imaging Inst, Boston, MA 02114 USA. [Cormode, David P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14660 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904167 ER PT J AU Thayer, TE Shakartzi, HR Martyn, T Shahid, M Mayeur, C Jung, DY Ha, H Kim, JK Bloch, KD Malhotra, R AF Thayer, Timothy E. Shakartzi, Hannah R. Martyn, Trejeeve Shahid, Mohd Mayeur, Claire Jung, Dae Young Ha, Hyekyung Kim, Jason K. Bloch, Kenneth D. Malhotra, Rajeev TI Inhibition of Bone Morphogenetic Protein Signaling Reduces Weight Gain and Hepatic Lipid Accumulation in a Murine Model of Obesity SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Lipids; Metabolic syndrome; Obesity; Molecular biology; Metabolism C1 [Thayer, Timothy E.; Shakartzi, Hannah R.; Martyn, Trejeeve; Shahid, Mohd; Mayeur, Claire; Bloch, Kenneth D.; Malhotra, Rajeev] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jung, Dae Young; Ha, Hyekyung; Kim, Jason K.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16797 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906158 ER PT J AU Tian, JW Uemura, S Ren, XF Yonetsu, T Kato, K Jia, HB Abtahian, F Vergallo, R Hu, SN McNulty, I Lee, H Zhang, SS Yu, B Jang, IK AF Tian, Jinwei Uemura, Shiro Ren, Xuefeng Yonetsu, Taishi Kato, Koji Jia, Haibo Abtahian, Farhad Vergallo, Rocco Hu, Sining McNulty, Iris Lee, Hang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Spatial Heterogeneity of Neoatherosclerosis and Neovascularization After Stent Implantation: Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Interventional studies; Plaque; Stent C1 [Tian, Jinwei; Yonetsu, Taishi; Kato, Koji; Jia, Haibo; Abtahian, Farhad; Vergallo, Rocco; Hu, Sining; McNulty, Iris; Lee, Hang; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Uemura, Shiro] Nara Med Univ, Div Cardiol, Nara, Japan. [Ren, Xuefeng] Harbin Med Univ, Affiliated Hosp 2, Div Cardiol, Harbin, Peoples R China. [Zhang, Shaosong] LightLab Imaging Inc, St Jude Med, Boston, MA USA. [Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13952 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903373 ER PT J AU Tolenaar, JL Froehlich, W Jonker, FH Upchurch, GR Ramnoldi, V Tsai, TT Bossone, E Evangelista, A O'Gara, P Pape, L Montgomery, DG Isselbacher, EM Nienaber, CA Eagle, KA Trimarchi, S AF Tolenaar, Jip L. Froehlich, William Jonker, Frederik H. Upchurch, Gilbert R. Ramnoldi, Vincenzo Tsai, Thomas T. Bossone, Eduaro Evangelista, Arturo O'Gara, Patrick Pape, Linda Montgomery, Daniel G. Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. Trimarchi, Santi TI Predicting In-Hospital Mortality in Acute Type B Aortic Dissection: Evidences From IRAD SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic diseases; Outcomes C1 [Tolenaar, Jip L.; Jonker, Frederik H.; Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Rsch Cntr, Rsch Cntr Thorac Aort Dis, San Donato Milanese, Italy. [Froehlich, William; Montgomery, Daniel G.] Univ Michigan, Cardiovasc Cntr, MCORRP, Ann Arbor, MI 48109 USA. [Upchurch, Gilbert R.] Univ Virginia Hlth Syst, Div Vasc & Endovasc Surg, Charlottesville, VA USA. [Ramnoldi, Vincenzo] IRCCS Policlin San Donato, Thorac Aort Rsch Cntr, San Donato Milanese, Italy. [Tsai, Thomas T.] Univ Colorado Hosp, Denver, CO USA. [Bossone, Eduaro] Univ Salerno, Div Cardiol, Brindisi, Italy. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Barcelona, Spain. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pape, Linda] Univ Massachusetts Hosp, Worcester, MA USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Cntr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI USA. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18293 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907303 ER PT J AU Varughese, KK Larsen, M Harris, KM Peterson, MD Fattori, R Hutchison, S Upchurch, GR Ehrlich, MP Pyeritz, RE Montgomery, DG Trimarchi, S Nienaber, CA Isselbacher, EM Eagle, KA Myrmel, T AF Varughese, Kevin K. Larsen, Magnus Harris, Kevin M. Peterson, Mark D. Fattori, Rossella Hutchison, Stuart Upchurch, Gilbert R. Ehrlich, Marek P. Pyeritz, Reed E. Montgomery, Daniel G. Trimarchi, Santi Nienaber, Christoph A. Isselbacher, Eric M. Eagle, Kim A. Myrmel, Truls TI Does a Repaired Type A Dissection Turn into a Medical Type B Dissection? Lessons From IRAD SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Aortic diseases; Follow-up studies; Outcomes C1 [Varughese, Kevin K.; Larsen, Magnus; Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway. [Harris, Kevin M.] Minneapolis Heart Inst, Minneapolis, MN USA. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Fattori, Rossella] San Salvatore Hosp, Div Intervent Cardiol, Pesaro, Italy. [Hutchison, Stuart] Univ Calgary, Med Cntr, Calgary, AB, Canada. [Upchurch, Gilbert R.] Univ Virginia Hlth Syst, Div Vasc & Endovasc Surg, Charlottesville, VA USA. [Ehrlich, Marek P.] Univ Vienna, Vienna, Austria. [Pyeritz, Reed E.] Univ Penn, Sch Med, Div Med Genet, Philadelphia, PA 19104 USA. [Montgomery, Daniel G.] Univ Michigan, Cardiovasc Cntr, MCORRP, Ann Arbor, MI 48109 USA. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Rsch Cntr, Rsch Cntr Thorac Aort Dis, San Donato Milanese, Italy. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Cntr, Boston, MA 02114 USA. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17817 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907085 ER PT J AU Vergallo, R Papafaklis, MI Jia, HB Bourantas, CV McNulty, I Lee, H Yu, B Porto, I Biasucci, LM Crea, F Feldman, CL Michalis, LK Stone, PH Jang, IK AF Vergallo, Rocco Papafaklis, Michail I. Jia, Haibo Bourantas, Christos V. McNulty, Iris Lee, Hang Yu, Bo Porto, Italo Biasucci, Luigi M. Crea, Filippo Feldman, Charles L. Michalis, Lampros K. Stone, Peter H. Jang, Ik-Kyung TI Low Endothelial Shear Stress is Associated With High-Risk Coronary Plaque Characteristics in Humans: A Three-Dimensional Frequency-Domain Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Blood flow; Vulnerable plaque; Acute coronary syndromes C1 [Vergallo, Rocco; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Papafaklis, Michail I.; Feldman, Charles L.; Stone, Peter H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. [Jia, Haibo; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. [Bourantas, Christos V.] Erasmus Med Cntr, Thoraxctr, Dept Cardiol, Rotterdam, Netherlands. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Cntr, Boston, MA USA. [Porto, Italo] San Donato Hosp, Cardiovasc & Neurol Dept, Arezzo, Italy. [Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, I-00168 Rome, Italy. [Michalis, Lampros K.] Univ Ioannina, Dept Cardiol, GR-45110 Ioannina, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18072 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907205 ER PT J AU Vergallo, R Yonetsu, T Kato, K Uemura, S Yu, B Jia, HB Abtahian, F Tian, JW Hu, SN Aguirre, AD Lee, H McNulty, I Park, SJ Jang, Y Prasad, A Lee, SW Zhang, SS Porto, I Biasucci, LM Crea, F Jang, IK AF Vergallo, Rocco Yonetsu, Taishi Kato, Koji Uemura, Shiro Yu, Bo Jia, Haibo Abtahian, Farhad Tian, Jinwei Hu, Sining Aguirre, Aaron D. Lee, Hang McNulty, Iris Park, Seung-Jung Jang, Yangsoo Prasad, Abhiram Lee, Stephen W. Zhang, Shaosong Porto, Italo Biasucci, Luigi M. Crea, Filippo Jang, Ik-Kyung TI Pancoronary Plaque Vulnerability in Patients With Acute Coronary Syndrome and Ruptured Culprit Plaque: A Three-Vessel Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Acute coronary syndromes; Plaque rupture; Percutaneous coronary intervention C1 [Vergallo, Rocco; Yonetsu, Taishi; Kato, Koji; Abtahian, Farhad; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Yu, Bo; Jia, Haibo; Tian, Jinwei; Hu, Sining] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin, Peoples R China. [Aguirre, Aaron D.] Harvard Univ, Brigham & Womens Hosp, Dept Cardiol, Sch Med, Boston, MA 02115 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Park, Seung-Jung] Asan Med Cntr, Dept Cardiol, Seoul, South Korea. [Jang, Yangsoo] Yonsei Univ, Div Cardiol, Severance Cardiovasc Hosp, Seoul 120749, South Korea. [Prasad, Abhiram] Mayo Clin, Div Cardiovasc Dis, Dept Internal Med, Rochester, MN USA. [Lee, Stephen W.] Univ Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Zhang, Shaosong] LightLab Imaging Inc, Clin Affairs, St Jude Med, Westford, MA USA. [Porto, Italo] San Donato Hosp, Cardiovasc & Neurol Dept, Arezzo, Italy. [Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, I-00168 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 13152 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162903018 ER PT J AU Vucic, E Emami, H Lavender, ZR Mcnabb, MH Kaplan, RS Singh, P Rudd, JH Fayad, ZA Korsgren, M Fredrickson, J Nahrendorf, M Lehrer-Graiwer, J Tawakol, A AF Vucic, Esad Emami, Hamed Lavender, Zachary R. Mcnabb, Megan H. Kaplan, Rebecca S. Singh, Parmanand Rudd, James H. Fayad, Zahi A. Korsgren, Magnus Fredrickson, Jill Nahrendorf, Matthias Lehrer-Graiwer, Joshua Tawakol, Ahmed TI Up-regulation of Bone Marrow and Splenic Activity After Acute Coronary Syndrome: Close Relationship With Arterial Inflammation and CRP SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Inflammation; Acute coronary syndromes; Arteriosclerosis C1 [Vucic, Esad; Emami, Hamed; Lavender, Zachary R.; Mcnabb, Megan H.; Kaplan, Rebecca S.; Singh, Parmanand; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rudd, James H.] Univ Cambridge, Cambridge CB2 2QQ, England. [Fayad, Zahi A.] Mt Sinai Hosp, TMII Radiol, New York, NY 10029 USA. [Korsgren, Magnus] BioInvent Int AB, Lund, Sweden. [Fredrickson, Jill] Genentech Inc, Imaging Sci, San Francisco, CA 94080 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Cntr Syst Biol, Boston, MA 02114 USA. [Lehrer-Graiwer, Joshua] Genentech Inc, Early Clin Dev, San Francisco, CA 94080 USA. FU Academy of Medical Sciences (AMS) [AMS-SGCL1-Rudd] NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 17468 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906445 ER PT J AU Wang, L Isaacs, SK Weiner, MS Weyman, AE Picard, MH Baggish, AL Weiner, RB AF Wang, Lin Isaacs, Stephanie K. Weiner, Merideth S. Weyman, Arthur E. Picard, Michael H. Baggish, Aaron L. Weiner, Rory B. TI The Impact of Normal Saline Infusion on Myocardial Deformation: Mechanistic Insight Into the Frank-Starling Law SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Echocardiography; Myocardial torsion and recoil C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15168 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904428 ER PT J AU Wang, L Tan, T Szymonifka, J Picard, MH Scherrer-Crosbie, M AF Wang, Lin Tan, Timothy Szymonifka, Jackie Picard, Michael H. Scherrer-Crosbie, Marielle TI Value of Left Ventricular Ejection Fraction and Its Changes for the Prediction of Symptomatic Heart Failure in Patients Treated by Anthracyclines SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Ejection fraction; Cardiomyopathy C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14921 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904308 ER PT J AU Wasfy, JH Strom, JB Wimmer, NJ Zai, A Luttrell, J Spertus, JA Normand, SLT Mauri, L Yeh, RW AF Wasfy, Jason H. Strom, Jordan B. Wimmer, Neil J. Zai, Adrian Luttrell, Jennifer Spertus, John A. Normand, Sharon-Lise T. Mauri, Laura Yeh, Robert W. TI Preventability of 30-Day Readmission After PCI SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Percutaneous coronary intervention; Quality improvement; Quality of medical care; Systems of care C1 [Wasfy, Jason H.; Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Strom, Jordan B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wimmer, Neil J.; Mauri, Laura] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Zai, Adrian; Luttrell, Jennifer] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Spertus, John A.] St Lukes Midamer UKMC, Inst Heart, Kansas City, MO USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 14912 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904301 ER PT J AU Weiner, RB Isaacs, SK Hutter, AM Kanayama, G Hudson, JI Picard, MH Pope, HG Baggish, AL AF Weiner, Rory B. Isaacs, Stephanie K. Hutter, Adolph M. Kanayama, Gen Hudson, James I. Picard, Michael H. Pope, Harrison G. Baggish, Aaron L. TI Anabolic-Androgenic Steroid Use is Associated With Systolic and Diastolic Left Ventricular Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Ventricular function; Diastolic function C1 [Weiner, Rory B.; Isaacs, Stephanie K.; Hutter, Adolph M.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Med Cardiol Div, Boston, MA 02114 USA. [Kanayama, Gen; Hudson, James I.; Pope, Harrison G.] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 18278 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162907293 ER PT J AU Williams, LA Stewart, GC Clark, MA Lai, ECC Stevenson, LW Chen, CY Saldana, F Wong, MB Cheung, W Setoguchi, S AF Williams, Lauren A. Stewart, Garrick C. Clark, Melissa A. Lai, Edward Chia-Cheng Stevenson, Lynne W. Chen, Chih-Ying Saldana, Fidencio Wong, Monera B. Cheung, Winson Setoguchi, Soko TI Information Delivery Affects Patients' Attitudes Toward Devices More Than Toward Medicines to Treat Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Heart failure; Device; Patient education/teaching psychosocial aspects; Patient care C1 [Williams, Lauren A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stewart, Garrick C.; Stevenson, Lynne W.; Saldana, Fidencio] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Clark, Melissa A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Lai, Edward Chia-Cheng; Setoguchi, Soko] Duke Clin Rsch Inst, Durham, NC USA. [Chen, Chih-Ying] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Wong, Monera B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheung, Winson] British Columbia Canc Agcy, Vancouver Cntr Clin, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16934 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162906225 ER PT J AU Wurtz, P Havulinna, AS Prieto, D Kettunen, J Kangas, AI Soininen, P Ebrahim, S Ripatti, S Wang, TJ Gerszten, RE Ala-Korpela, M Vasan, R Salomaa, V AF Wurtz, Peter Havulinna, Aki S. Prieto, David Kettunen, Johannes Kangas, Antti I. Soininen, Pasi Ebrahim, Shah Ripatti, Samuli Wang, Thomas J. Gerszten, Robert E. Ala-Korpela, Mika Vasan, Ramachandran Salomaa, Veikko TI Metabolite Profiling Identifies Novel Biomarkers for Cardiovascular Disease Risk Across Multiple Population-Studies and Profiling Platforms SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Metabolomics; Risk factors; Biomarkers; Cardiovascular disease prevention; Epidemiology C1 [Wurtz, Peter; Kettunen, Johannes; Ripatti, Samuli] Univ Helsinki, Helsinki, Finland. [Havulinna, Aki S.; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. [Prieto, David; Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England. [Kangas, Antti I.; Ala-Korpela, Mika] Univ Oulu, Oulu, Finland. [Soininen, Pasi] Univ Eastern Finland, Kuopio, Finland. [Wang, Thomas J.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vasan, Ramachandran] Boston Univ, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15751 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905166 ER PT J AU Yeh, RW Czarny, MJ Kim, S Roe, MT Holmes, DR Brindis, RG Weaver, WD Normand, SLT Kereiakes, D Mauri, L AF Yeh, Robert W. Czarny, Matthew J. Kim, Sunghee Roe, Matthew T. Holmes, David R. Brindis, Ralph G. Weaver, W. D. Normand, Sharon-Lise T. Kereiakes, Dean Mauri, Laura TI Are "All-Comer" Clinical Trials Representative of Contemporary Clinical Practice: A Linked Analysis of the Dual Antiplatelet Therapy (DAPT) Study and the National Cardiovascular Data Registry (R) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Clinical trials; Interventional cardiology; Percutaneous coronary intervention; Disparities; Antiplatelet drugs C1 [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Czarny, Matthew J.; Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kim, Sunghee] Duke Univ, Sch Med, Duke Clin Rsch Inst, Durham, NC USA. [Roe, Matthew T.] Duke Univ, Sch Med, Durham, NC USA. [Holmes, David R.] Mayo Clin, Rochester, MN USA. [Brindis, Ralph G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weaver, W. D.] Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Kereiakes, Dean] Christ Hosp, Cincinnati, OH 45219 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 9351 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162900329 ER PT J AU Zhang, ZG Edwards, F Kolm, P Rao, SV Sepulveda, MG O'Brien, S Shahian, D Ponirakis, A Klein, LW Grover, FL Garratt, KN Mckay, C Weintraub, WS AF Zhang, Zugui Edwards, Fred Kolm, Paul Rao, Sunil V. Sepulveda, Maria Grau O'Brien, Sean Shahian, David Ponirakis, Angelo Klein, Lloyd W. Grover, Frederick L. Garratt, Kirk N. Mckay, Charles Weintraub, William S. TI Risk Factors of 30-Day Readmission for Patients Undergoing Revascularization SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Coronary artery disease; Percutaneous coronary intervention; Risk factors; Coronary heart disease; Congenital heart disease C1 [Zhang, Zugui] Christiana Care Hlth Syst, Cntr Outcomes Rsch, Newark, DE USA. [Edwards, Fred] Univ Florida Shands Jacksonville, Div Cardiothorac Surg, Jacksonville, FL USA. [Kolm, Paul; Weintraub, William S.] Christiana Care Hlth Syst, Value Inst, Newark, DE USA. [Rao, Sunil V.; Sepulveda, Maria Grau; O'Brien, Sean] Duke Clin Rsch Inst, Durham, NC USA. [Shahian, David] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David] Massachusetts Gen Hosp, Cntr Qual & Safety, Boston, MA 02114 USA. [Ponirakis, Angelo] Amer Coll Cardiol, Washington, DC USA. [Klein, Lloyd W.] Rush Univ, Med Cntr, Melrose Pk, IL USA. [Grover, Frederick L.] Univ Colorado, Sch Med, Denver Dept, Vet Affairs Med Cntr, Aurora, CO USA. [Garratt, Kirk N.] Lenox Hill Heart & Vasc Inst New York, New Yor, NY USA. [Mckay, Charles] Harbor UCLA Med Cntr, Torrance, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15924 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905269 ER PT J AU Zhao, S Xing, L Jin, CM Ren, XF Hou, JB Zhang, SS Yu, B Jang, IK AF Zhao Sun Xing Lei Jin Chengmei Ren Xuefeng Hou, Jingbo Zhang, Shaosong Yu, Bo Jang, Ik-kyung TI Impact of Age on Strut Coverage and Neointimal Response to Sirolimus Eluting Stent SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Stent C1 [Zhao Sun; Xing Lei; Jin Chengmei; Ren Xuefeng; Hou, Jingbo; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Zhang, Shaosong] St Jude Med, LightLab Imaging, Westford, MA USA. [Jang, Ik-kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904459 ER PT J AU Bucheli, ME Calderon, A Chicaiza, D Franco, C Lopez, R Digga, E Atassi, N Salameh, J Berry, JD AF Bucheli, Miriam E. Calderon, Amelia Chicaiza, Diana Franco, Carolina Lopez, Ricardo Digga, Elise Atassi, Nazem Salameh, Johnny Berry, James D. TI FEEDBACK INTERACTION OF RESEARCH, ADVOCACY, AND CLINICAL CARE APPLIED TO ALS RESEARCH IN SOUTH AMERICA SO NEUROLOGY LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS C1 [Bucheli, Miriam E.; Salameh, Johnny] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Calderon, Amelia; Chicaiza, Diana; Franco, Carolina; Lopez, Ricardo] San Francisco Univ Quito, Quito, Ecuador. [Digga, Elise] Wellesley Coll, Wellesley, MA 02181 USA. [Atassi, Nazem; Berry, James D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Bucheli, ME (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. EM Miriam.Bucheli@umassmed.edu OI Bucheli, Miriam/0000-0002-3757-8522 NR 5 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 NOV 26 PY 2013 VL 81 IS 22 BP 1959 EP 1961 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AA0FR UT WOS:000330771500019 PM 24276333 ER PT J AU Jurado, KA Engelman, A AF Jurado, Kellie Ann Engelman, Alan TI Multimodal mechanism of action of allosteric HIV-1 integrase inhibitors SO EXPERT REVIEWS IN MOLECULAR MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; SMALL-MOLECULE INHIBITORS; RETROVIRAL DNA INTEGRATION; LEDGF/P75 BINDING-SITE; PROTEIN IN-VITRO; TYPE-1 INTEGRASE; VIRAL-DNA; REVERSE-TRANSCRIPTASE; STRAND TRANSFER; HUMAN-CELLS AB Integrase (IN) is required for lentivirus replication and is a proven drug target for the prevention of AIDS in HIV-1-infected patients. While clinical strand transfer inhibitors disarm the IN active site, allosteric inhibition of enzyme activity through the disruption of IN-IN protein interfaces holds great therapeutic potential. A promising class of allosteric IN inhibitors (ALLINIs), 2-(quinolin-3-yl) acetic acid derivatives, engage the IN catalytic core domain dimerisation interface at the binding site for the host integration co-factor LEDGF/p75. ALLINIs promote IN multimerisation and, independent of LEDGF/p75 protein, block the formation of the active IN-DNA complex, as well as inhibit the IN-LEDGF/p75 interaction in vitro. Yet, rather unexpectedly, the full inhibitory effect of these compounds is exerted during the late phase of HIV-1 replication. ALLINIs impair particle core maturation as well as reverse transcription and integration during the subsequent round of virus infection. Recapitulating the pleiotropic phenotypes observed with numerous IN mutant viruses, ALLINIs provide insight into underlying aspects of IN biology that extend beyond its catalytic activity. Therefore, in addition to the potential to expand our repertoire of HIV-1 antiretrovirals, ALLINIs afford important structural probes to dissect the multifaceted nature of the IN protein throughout the course of HIV-1 replication. C1 [Jurado, Kellie Ann; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Jurado, Kellie Ann; Engelman, Alan] Harvard Univ, Sch Med, Program Virol, Boston, MA USA. [Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave,CLS 1010, Boston, MA 02215 USA. EM alan_engelman@dfci.harvard.edu FU US National Institutes of Health [AI039394, GM103368]; National Academies' Ford Foundation Predoctoral Fellowship FX The authors acknowledge funding support from the US National Institutes of Health grants AI039394 and GM103368. K.A.J. is a recipient of a National Academies' Ford Foundation Predoctoral Fellowship. NR 119 TC 20 Z9 20 U1 0 U2 14 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1462-3994 J9 EXPERT REV MOL MED JI Expert Rev. Mol. Med. PD NOV 26 PY 2013 VL 15 AR e14 DI 10.1017/erm.2013.15 PG 22 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 267UV UT WOS:000328124700001 PM 24274067 ER PT J AU Etemadmoghadam, D Weir, BA Au-Yeung, G Alsop, K Mitchell, G George, J Davis, S D'Andrea, AD Simpson, K Hahn, WC Bowtell, DDL AF Etemadmoghadam, Dariush Weir, Barbara A. Au-Yeung, George Alsop, Kathryn Mitchell, Gillian George, Joshy Davis, Sally D'Andrea, Alan D. Simpson, Kaylene Hahn, William C. Bowtell, David D. L. CA Australian Ovarian Canc Study Grp TI Synthetic lethality between CCNE1 amplification and loss of BRCA1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RNAi; pan-cancer; CDK2; cell cycle; DNA repair ID DNA COPY NUMBER; OVARIAN-CANCER; GENE AMPLIFICATION; CELLS; ONCOGENE; SURVIVAL; DISTINCT; TARGETS AB High-grade serous ovarian cancers (HGSCs) are characterized by a high frequency of TP53 mutations, BRCA1/2 inactivation, homologous recombination dysfunction, and widespread copy number changes. Cyclin E1 (CCNE1) gene amplification has been reported to occur independently of BRCA1/2 mutation, and it is associated with primary treatment failure and reduced patient survival. Insensitivity of CCNE1-amplified tumors to platinum cross-linking agents may be partly because of an intact BRCA1/2 pathway. Both BRCA1/2 dysfunction and CCNE1 amplification are known to promote genomic instability and tumor progression. These events may be mutually exclusive, because either change provides a path to tumor development, with no selective advantage to having both mutations. Using data from a genome-wide shRNA synthetic lethal screen, we show that BRCA1 and members of the ubiquitin pathway are selectively required in cancers that harbor CCNE1 amplification. Furthermore, we show specific sensitivity of CCNE1-amplified tumor cells to the proteasome inhibitor bortezomib. These findings provide an explanation for the observed mutual exclusivity of CCNE1 amplification and BRCA1/2 loss in HGSC and suggest a unique therapeutic approach for treatment-resistant CCNE1-amplified tumors. C1 [Etemadmoghadam, Dariush; Au-Yeung, George; Alsop, Kathryn; Mitchell, Gillian; George, Joshy; Davis, Sally; Bowtell, David D. L.] Peter MacCallum Canc Ctr, Dept Res, East Melbourne, Vic 3002, Australia. [Etemadmoghadam, Dariush; Mitchell, Gillian; Simpson, Kaylene; Bowtell, David D. L.] Univ Melbourne, Dept Oncol, Sir Peter MacCallum Canc Ctr, Melbourne, Vic 3010, Australia. [Etemadmoghadam, Dariush; Davis, Sally; Simpson, Kaylene; Bowtell, David D. L.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Weir, Barbara A.; D'Andrea, Alan D.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Weir, Barbara A.; D'Andrea, Alan D.; Hahn, William C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Weir, Barbara A.; Hahn, William C.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. [Au-Yeung, George; Alsop, Kathryn; George, Joshy; Bowtell, David D. L.] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia. Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW 2145, Australia. Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW 2145, Australia. [Australian Ovarian Canc Study Grp] QIMR Berghofer Med Res Inst, Canc Program, Brisbane, Qld 4006, Australia. [Simpson, Kaylene] Peter MacCallum Canc Ctr, Victorian Ctr Funct Genom, East Melbourne, Vic 3002, Australia. RP Bowtell, DDL (reprint author), Peter MacCallum Canc Ctr, Dept Res, East Melbourne, Vic 3002, Australia. EM david.bowtell@petermac.org RI Bowtell, David/H-1007-2016; OI Bowtell, David/0000-0001-9089-7525; Simpson, Kaylene/0000-0001-9136-1781 FU National Health and Medical Research Council (NHMRC) [APP 1042358]; Cancer Australia Grant [APP 1004673]; US National Institutes of Health [U01 CA176058]; US Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council Tasmania; NHMRC Grant [ID400413]; Australian Government's Education Investment Fund through the Super Science Initiative FX The authors acknowledge assistance from Daniel Thomas and Yanny Handoko in conducting siRNA experiments in the Victorian Centre for FunctionalGenomics, PeterMacCallumCancer Centre. The Australian Ovarian Cancer Study (AOCS) acknowledges the cooperation of the participating institutions in Australia and the contribution of the study nurses, research assistants, and all clinical and scientific collaborators. We thank all of thewomen who participated in the study. This study was funded by National Health and Medical Research Council (NHMRC) Project Grant APP 1042358, Cancer Australia Grant APP 1004673, and US National Institutes of Health Grant U01 CA176058. The AOCS was supported by US Army Medical Research andMateriel Command Grant DAMD17-01-1-0729, the Cancer Council Tasmania, the Cancer Foundation of Western Australia, and NHMRC Grant ID400413. Genotyping of AOCS patient samples was supported by Ovarian Cancer Research Program of the US Department of Defense Grants W81XWH-08-10684 andW81XWH-08-1-0685; Cancer Australia and National Breast Cancer Foundation Grants ID509303, CG-08-07, and ID509366; the Peter MacCallum Cancer Centre Foundation; and the Cancer Council Victoria. The Victorian Centre for Functional Genomics is funded by the Australian Cancer Research Foundation and the Victorian Department of Industry, Innovation and Regional Development. The Australian Phenomics Network is supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative, the Australasian Genomics Technologies Association, the Brockhoff Foundation, and the Peter MacCallum Cancer Centre Foundation. NR 29 TC 44 Z9 46 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 NOV 26 PY 2013 VL 110 IS 48 BP 19489 EP 19494 DI 10.1073/pnas.1314302110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 257NB UT WOS:000327390400081 PM 24218601 ER PT J AU Bao, Y Hu, FB Giovannucci, EL Wolpin, BM Stampfer, MJ Willett, WC Fuchs, CS AF Bao, Y. Hu, F. B. Giovannucci, E. L. Wolpin, B. M. Stampfer, M. J. Willett, W. C. Fuchs, C. S. TI Nut consumption and risk of pancreatic cancer in women SO BRITISH JOURNAL OF CANCER LA English DT Article DE nut consumption; pancreatic cancer; prospective cohort study ID METABOLIC SYNDROME; MEDITERRANEAN DIET; MALE SMOKERS; INFLAMMATORY MARKERS; INSULIN-RESISTANCE; RANDOMIZED-TRIAL; COHORT; POPULATION; MAGNESIUM; HEALTH AB Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts >= 2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47-0.92; P for trend = 0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48-0.95; P for trend = 0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer. C1 [Bao, Y.; Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.; Fuchs, C. S.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Bao, Y.; Hu, F. B.; Giovannucci, E. L.; Wolpin, B. M.; Stampfer, M. J.; Willett, W. C.; Fuchs, C. S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, F. B.; Giovannucci, E. L.; Stampfer, M. J.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wolpin, B. M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wolpin, B. M.; Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bao, Y (reprint author), Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu FU National Institutes of Health [P01 CA87969, R01 CA124908, 1U54CA155626-01]; International Tree Nut Council Nutrition Research & Education Foundation; Biomedical Research Institute at the Brigham and Women's Hospital FX This study is supported by the Grants P01 CA87969, R01 CA124908, and 1U54CA155626-01 from the National Institutes of Health, and by the grant from the International Tree Nut Council Nutrition Research & Education Foundation. The work is also supported in part by a micro-grant from the Biomedical Research Institute at the Brigham and Women's Hospital. In addition, we thank the participants and staff of the Nurses' Health Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. NR 42 TC 10 Z9 10 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 26 PY 2013 VL 109 IS 11 BP 2911 EP 2916 DI 10.1038/bjc.2013.665 PG 6 WC Oncology SC Oncology GA 262UG UT WOS:000327762700021 PM 24149179 ER PT J AU Merritt, MA Bentink, S Schwede, M Iwanicki, MP Quackenbush, J Woo, T Agoston, ES Reinhardt, F Crum, CP Berkowitz, RS Mok, SC Witt, AE Jones, MA Wang, B Ince, TA AF Merritt, Melissa A. Bentink, Stefan Schwede, Matthew Iwanicki, Marcin P. Quackenbush, John Woo, Terri Agoston, Elin S. Reinhardt, Ferenc Crum, Christopher P. Berkowitz, Ross S. Mok, Samuel C. Witt, Abigail E. Jones, Michelle A. Wang, Bin Ince, Tan A. TI Gene Expression Signature of Normal Cell-of-Origin Predicts Ovarian Tumor Outcomes SO PLOS ONE LA English DT Article ID SURFACE EPITHELIAL-CELLS; FALLOPIAN-TUBE EPITHELIUM; GRADE SEROUS CARCINOMA; MOLECULAR SUBTYPES; MUTATION CARRIERS; CANCER; MODEL; CARCINOGENESIS; PATHWAYS; BREAST AB The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome. C1 [Merritt, Melissa A.; Bentink, Stefan; Schwede, Matthew; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Merritt, Melissa A.; Berkowitz, Ross S.; Mok, Samuel C.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Merritt, Melissa A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Iwanicki, Marcin P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Woo, Terri; Agoston, Elin S.; Reinhardt, Ferenc; Crum, Christopher P.; Ince, Tan A.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Witt, Abigail E.; Jones, Michelle A.; Wang, Bin; Ince, Tan A.] Univ Miami, Miller Sch Med, Dept Pathol, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA. [Witt, Abigail E.; Jones, Michelle A.; Wang, Bin; Ince, Tan A.] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Miami, FL 33136 USA. RP Ince, TA (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM TInce@med.miami.edu FU National Cancer Institute (NCI) [R01-CA146445-01]; Breast Cancer Research Foundation; NCI SPORE in Ovarian Cancer [5P50 CA105009-05]; Women's Cancer Program at Dana-Farber/Harvard Cancer Center; Ovarian Cancer Research Fund; Gynecologic Cancer Foundation; NCI Nutritional Epidemiology of Cancer training program [R25CA098566]; NCI [R21 CA124688-01A1, NCI R01-CA133057-01] FX Financial support for this research was provided by grants from the National Cancer Institute (NCI) (http://www.cancer.gov/) (R01-CA146445-01), Breast Cancer Research Foundation (http://www.bcrfcure.org/), and Pilot Project Awards from the NCI SPORE in Ovarian Cancer (5P50 CA105009-05) and Women's Cancer Program at Dana-Farber/Harvard Cancer Center to T. A. Ince; grants from the Ovarian Cancer Research Fund (http://www.ocrf.org/), the Gynecologic Cancer Foundation (http://www. foundationforwomenscancer.org/) and the NCI Nutritional Epidemiology of Cancer training program (R25CA098566) to M. A. Merritt, an NCI R21 CA124688-01A1 to C. P. Crum, and an NCI R01-CA133057-01 to S. C. Mok. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 11 Z9 11 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 NOV 26 PY 2013 VL 8 IS 11 AR e80314 DI 10.1371/journal.pone.0080314 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259SK UT WOS:000327546400022 PM 24303006 ER PT J AU Martel, JM Toner, M AF Martel, Joseph M. Toner, Mehmet TI Particle Focusing in Curved Microfluidic Channels SO SCIENTIFIC REPORTS LA English DT Article ID POISEUILLE FLOW; INERTIAL MIGRATION; RIGID SPHERES; SEPARATION; MICROCHANNELS; CELLS AB The decoupled effects of Reynolds and Dean numbers are examined in inertial focusing flows. In doing so, a complex set of inertial focusing behavioral regimes is discovered within curved microfluidic channels over a range of channel Reynolds numbers, curvature ratios and particle confinement ratios. These regimes are characterized by particle migration either towards or away from the center of curvature as the channel Reynolds number is increased. The transition between these two regimes is shown to be a set of conditions where single-point equilibrium position focusing of particles of different sizes is achieved. A mechanism describing the observed motion of particles in such flows is hypothesized incorporating the redistribution of the main flow velocities caused by Dean flow and its effect on the balance forces on suspended particles. C1 [Martel, Joseph M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Martel, Joseph M.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Martel, Joseph M.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu FU National Science Foundation; National Institute of Biomedical Imaging and Bioengineering (BioMEMS Resource Center) [P41 EB002503] FX Joseph M. Martel is a National Science Foundation Graduate Research Fellow. This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering (BioMEMS Resource Center, P41 EB002503). Thanks to Ian Wong, Dino Di Carlo and Jon Edd for helpful discussion, Eugene Lim, Salil Desai and Bashar Hamza for epoxy device fabrication development. NR 40 TC 28 Z9 28 U1 4 U2 76 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 NOV 26 PY 2013 VL 3 AR 3340 DI 10.1038/srep03340 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259MH UT WOS:000327530500001 ER PT J AU Meyer, AND Payne, VL Meeks, DW Rao, R Singh, H AF Meyer, Ashley N. D. Payne, Velma L. Meeks, Derek W. Rao, Radha Singh, Hardeep TI Physicians' Diagnostic Accuracy, Confidence, and Resource Requests A Vignette Study SO JAMA INTERNAL MEDICINE LA English DT Article ID DECISION-SUPPORT; ULTRASOUND OPERATORS; MEDICINE; ERRORS; OVERCONFIDENCE; CONSULTATION; ASSOCIATION; CORRECT AB IMPORTANCE Little is known about the relationship between physicians' diagnostic accuracy and their confidence in that accuracy. OBJECTIVE To evaluate how physicians' diagnostic calibration, defined as the relationship between diagnostic accuracy and confidence in that accuracy, changes with evolution of the diagnostic process and with increasing diagnostic difficulty of clinical case vignettes. DESIGN, SETTING, AND PARTICIPANTS We recruited general internists from an online physician community and asked them to diagnose 4 previously validated case vignettes of variable difficulty (2 easier; 2 more difficult). Cases were presented in a web-based format and divided into 4 sequential phases simulating diagnosis evolution: history, physical examination, general diagnostic testing data, and definitive diagnostic testing. After each phase, physicians recorded 1 to 3 differential diagnoses and corresponding judgments of confidence. Before being presented with definitive diagnostic data, physicians were asked to identify additional resources they would require to diagnose each case (ie, additional tests, second opinions, curbside consultations, referrals, and reference materials). MAIN OUTCOMES AND MEASURES Diagnostic accuracy (scored as 0 or 1), confidence in diagnostic accuracy (on a scale of 0-10), diagnostic calibration, and whether additional resources were requested (no or yes). RESULTS A total of 118 physicians with broad geographical representation within the United States correctly diagnosed 55.3% of easier and 5.8% of more difficult cases (P < .001). Despite a large difference in diagnostic accuracy between easier and more difficult cases, the difference in confidence was relatively small (7.2 vs 6.4 out of 10, for easier and more difficult cases, respectively) (P < .001) and likely clinically insignificant. Overall, diagnostic calibration was worse for more difficult cases (P < .001) and characterized by overconfidence in accuracy. Higher confidence was related to decreased requests for additional diagnostic tests (P = .01); higher case difficulty was related to more requests for additional reference materials (P = .01). CONCLUSIONS AND RELEVANCE Our study suggests that physicians' level of confidence may be relatively insensitive to both diagnostic accuracy and case difficulty. This mismatch might prevent physicians from reexamining difficult cases where their diagnosis may be incorrect. C1 [Meyer, Ashley N. D.; Payne, Velma L.; Meeks, Derek W.; Singh, Hardeep] Vet Affairs Hlth Serv Res, Dev Ctr Excellence & Sect Hlth Serv Res, Houston, TX USA. [Meyer, Ashley N. D.; Payne, Velma L.; Meeks, Derek W.; Rao, Radha; Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Meyer, Ashley N. D.; Payne, Velma L.; Meeks, Derek W.; Rao, Radha; Singh, Hardeep] Baylor Coll Med, Houston, TX 77030 USA. RP Singh, H (reprint author), Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Meyer, Ashley/0000-0001-7993-8584 FU PHS HHS [T32HP10031] NR 29 TC 26 Z9 26 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 25 PY 2013 VL 173 IS 21 BP 1952 EP 1959 DI 10.1001/jamainternmed.2013.10081 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AA2WG UT WOS:000330954300003 PM 23979070 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI Known Unknowns and Unknown Unknowns at the Point of Care SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID DECISION-MAKING C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, Med Serv, San Francisco, CA 94143 USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@ucsf.edu NR 10 TC 3 Z9 3 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 25 PY 2013 VL 173 IS 21 BP 1959 EP 1961 DI 10.1001/jamainternmed.2013.7494 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AA2WG UT WOS:000330954300004 PM 23979528 ER PT J AU Good, CB Burk, M Cunningham, F AF Good, Chester B. Burk, Muriel Cunningham, Francesca TI Topical Anesthetic-Induced Methemoglobinemia and Veterans Affairs Hospitals SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Good, Chester B.; Burk, Muriel; Cunningham, Francesca] VA Ctr Medicat Safety, Hines, IL USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA 15240 USA. [Good, Chester B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Good, CB (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr, Pittsburgh, PA 15240 USA. EM Chester.good@va.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 25 PY 2013 VL 173 IS 21 DI 10.1001/jamainternmed.2013.9970 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA2WG UT WOS:000330954300021 ER PT J AU Sheen, J AF Sheen, Jen TI The Cytokinin Side Chain Commands Shooting SO DEVELOPMENTAL CELL LA English DT Editorial Material ID ROOT-MERISTEM; BIOSYNTHESIS; ACTIVATION C1 [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.hrvard.edu FU NIGMS NIH HHS [R01 GM070567, R01 GM060493] NR 10 TC 0 Z9 0 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD NOV 25 PY 2013 VL 27 IS 4 BP 371 EP 372 DI 10.1016/j.devce1.2013.11.008 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 263MG UT WOS:000327812100003 PM 24286823 ER PT J AU Sen, M Yuki, K Springer, TA AF Sen, Mehmet Yuki, Koichi Springer, Timothy A. TI An internal ligand-bound, metastable state of a leukocyte integrin, alpha(X)beta(2) SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ALPHA-I DOMAIN; STRUCTURAL BASIS; CRYSTAL-STRUCTURE; ROLLING ADHESION; A-DOMAIN; ACTIVATION; RECEPTOR; RECOGNITION; SUBUNIT; CONFORMATION AB How is massive conformational change in integrins achieved on a rapid timescale? We report crystal structures of a metastable, putative transition state of integrin alpha(X)beta(2). The alpha(X)beta(2) ectodomain is bent; however, a lattice contact stabilizes its ligand-binding alpha I domain in a high affinity, open conformation. Much of the alpha I alpha 7 helix unwinds, loses contact with the alpha I domain, and reshapes to form an internal ligand that binds to the interface between the beta propeller and beta I domains. Lift-off of the alpha I domain above this platform enables a range of extensional and rotational motions without precedent in allosteric machines. Movements of secondary structure elements in the beta(2) beta I domain occur in an order different than in beta(3) integrins, showing that integrin beta subunits can be specialized to assume different intermediate states between closed and open. Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness. C1 [Sen, Mehmet; Yuki, Koichi; Springer, Timothy A.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Yuki, Koichi] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Sen, Mehmet; Yuki, Koichi; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Sen, Mehmet; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu FU National Institutes of Health grant NIAID [AI072756]; GlaxoSmithKline fellowship FX This work was supported by National Institutes of Health grant NIAID AI072756 and a GlaxoSmithKline fellowship. NR 44 TC 23 Z9 23 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD NOV 25 PY 2013 VL 203 IS 4 BP 629 EP 642 DI 10.1083/jcb.201308083 PG 14 WC Cell Biology SC Cell Biology GA 260EV UT WOS:000327578700009 PM 24385486 ER PT J AU Ziakas, PD Prodromou, ML El Khoury, J Zintzaras, E Mylonakis, E AF Ziakas, Panayiotis D. Prodromou, Michael L. El Khoury, Joseph Zintzaras, Elias Mylonakis, Eleftherios TI The Role of TLR4 896 A > G and 1196 C > T in Susceptibility to Infections: A Review and Meta-Analysis of Genetic Association Studies SO PLOS ONE LA English DT Review ID TOLL-LIKE-RECEPTOR; RESPIRATORY SYNCYTIAL VIRUS; SINGLE NUCLEOTIDE POLYMORPHISMS; PATTERN-RECOGNITION RECEPTORS; CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS; THR399ILE POLYMORPHISMS; PULMONARY TUBERCULOSIS; TOLL-LIKE-RECEPTOR-4 POLYMORPHISMS; PORPHYROMONAS-GINGIVALIS AB Background: Toll-like receptor 4 plays a role in pathogen recognition, and common polymorphisms may alter host susceptibility to infectious diseases. Purpose: To review the association of two common polymorphisms (TLR4 896A>G and TLR4 1196C>T) with infectious diseases. Data Sources: We searched PubMed and EMBASE up to March 2013 for pertinent literature in English, and complemented search with references lists of eligible studies. Study Selection: We included all studies that: reported an infectious outcome; had a case-control design and reported the TLR4 896A>G and/or TLR4 1196C>T genotype frequencies; 59 studies fulfilled these criteria and were analyzed. Data Extraction: Two authors independently extracted study data. Data Synthesis: The generalized odds ratio metric (ORG) was used to quantify the impact of TLR4 variants on disease susceptibility. A meta-analysis was undertaken for outcomes reported in >1 study. Eleven of 37 distinct outcomes were significant. TLR4 896 A>G increased risk for all parasitic infections (ORG 1.59; 95% CI 1.05-2.42), malaria (1.31; 95% CI 1.04-1.66), brucellosis (2.66; 95% CI 1.66-4.27), cutaneous leishmaniasis (7.22; 95% CI 1.91-27.29), neurocysticercosis (4.39; 95% CI 2.53-7.61), Streptococcus pyogenes tonsillar disease (2.93; 95% CI 1.24-6.93), typhoid fever (2.51; 95% CI 1.18-5.34) and adult urinary tract infections (1.98; 95% CI 1.04-3.98), but was protective for leprosy (0.36; 95% CI 0.22-0.60). TLR4 1196 C>T effects were similar to TLR4 896 A>G for brucellosis, cutaneous leishmaniasis, leprosy, typhoid fever and S. pyogenes tonsillar disease, and was protective for bacterial vaginosis in pregnancy (0.55; 95% CI 0.31-0.98) and Haemophilus influenzae tonsillar disease (0.42; 95% CI 0.17-1.00). The majority of significant associations were among predominantly Asian populations and significant associations were rare among European populations. Conclusions: Depending on the type of infection and population, TLR4 polymorphisms are associated with increased, decreased or no difference in infectious disease. This may be due to differential functional expression of TLR4, the co-segregation of TLR4 variants or a favorable inflammatory response. C1 [Ziakas, Panayiotis D.; Prodromou, Michael L.; Mylonakis, Eleftherios] Rhode Isl Hosp, Div Infect Dis, Providence, RI 02903 USA. [Ziakas, Panayiotis D.; Mylonakis, Eleftherios] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Prodromou, Michael L.] Brown Univ, Dept Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [El Khoury, Joseph] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [El Khoury, Joseph] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Charlestown, MA USA. [El Khoury, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Zintzaras, Elias] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Clin Evidence Synth, Boston, MA USA. [Zintzaras, Elias] Univ Thessaly, Sch Med, Dept Biomath, Larisa, Greece. RP Mylonakis, E (reprint author), Rhode Isl Hosp, Div Infect Dis, Providence, RI 02903 USA. EM emylonakis@lifespan.org FU Warren Alpert School of Brown University; Department of Medicine; Division of Infectious Diseases FX The Brown University Infectious Diseases Program in Outcomes Research is supported through funding from the Warren Alpert School of Brown University, the Department of Medicine and the Division of Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 103 TC 8 Z9 9 U1 1 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 NOV 25 PY 2013 VL 8 IS 11 AR UNSP e81047 DI 10.1371/journal.pone.0081047 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259RH UT WOS:000327543500069 PM 24282567 ER PT J AU Pei, SS Minhajuddin, M Callahan, KP Balys, M Ashton, JM Neering, SJ Lagadinou, ED Corbett, C Ye, HB Liesveld, JL O'Dwyer, KM Li, Z Shi, L Greninger, P Settleman, J Benes, C Hagen, FK Munger, J Crooks, PA Becker, MW Jordan, CT AF Pei, Shanshan Minhajuddin, Mohammad Callahan, Kevin P. Balys, Marlene Ashton, John M. Neering, Sarah J. Lagadinou, Eleni D. Corbett, Cheryl Ye, Haobin Liesveld, Jane L. O'Dwyer, Kristen M. Li, Zheng Shi, Lei Greninger, Patricia Settleman, Jeffrey Benes, Cyril Hagen, Fred K. Munger, Joshua Crooks, Peter A. Becker, Michael W. Jordan, Craig T. TI Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Anticancer Drug; Cancer Stem Cells; Leukemia; Redox Regulation; Tumor Metabolism; CD34+; Glutathione; Human; Parthenolide ID GLUTAMATE-CYSTEINE LIGASE; ACUTE MYELOID-LEUKEMIA; SESQUITERPENE LACTONE PARTHENOLIDE; GENE-EXPRESSION; CATALYTIC SUBUNIT; CANCER-CELLS; STEM-CELLS; KAPPA-B; PROGENITOR CELLS; IN-VIVO AB The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. C1 [Pei, Shanshan; Jordan, Craig T.] Univ Rochester, Sch Med, Dept Biomed Genet, Rochester, NY 14642 USA. [Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Liesveld, Jane L.; O'Dwyer, Kristen M.; Becker, Michael W.] Univ Rochester, Sch Med, Dept Med, Rochester, NY 14642 USA. [Ye, Haobin] Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Hagen, Fred K.; Munger, Joshua] Univ Rochester, Sch Med, Dept Biochem & Biophys, Rochester, NY 14642 USA. [Pei, Shanshan; Minhajuddin, Mohammad; Ye, Haobin; Jordan, Craig T.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Li, Zheng; Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Crooks, Peter A.] Univ Arkansas, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Jordan, CT (reprint author), 12700 E 19th Ave, Aurora, CO 80045 USA. EM craig.jordan@ucdenver.edu RI PEI, SHANSHAN/D-8200-2016; OI PEI, SHANSHAN/0000-0001-9619-2614; Becker, Michael/0000-0001-9890-8815 FU National Institutes of Health [R01AI081773]; Leukemia and Lymphoma Society [6230-11]; Department of Defense [W81XWH-07-1-0601]; New York State Stem Cell Foundation [C024964, R01-CA158275] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01AI081773 (to J.M.), Leukemia and Lymphoma Society Grant 6230-11 (to C.T.J.), Department of Defense Grant W81XWH-07-1-0601 (to C.T.J.), New York State Stem Cell Foundation Grant C024964 (to C.T.J.) and R01-CA158275 (to P.A.C.). NR 60 TC 49 Z9 52 U1 2 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2013 VL 288 IS 47 BP 33542 EP 33558 DI 10.1074/jbc.M113.511170 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 255OR UT WOS:000327250200005 PM 24089526 ER PT J AU Holter, SM Stromberg, M Kovalenko, M Garrett, L Glasl, L Lopez, E Guide, J Gotz, A Hans, W Becker, L Rathkolb, B Rozman, J Schrewed, A Klingenspor, M Klopstock, T Schulz, H Wolf, E Wursta, W Gillis, T Wakimoto, H Seidman, J MacDonald, ME Cotman, S Gailus-Durner, V Fuchs, H de Angelis, MH Lee, JM Wheeler, VC AF Hoelter, Sabine M. Stromberg, Mary Kovalenko, Marina Garrett, Lillian Glasl, Lisa Lopez, Edith Guide, Jolene Goetz, Alexander Hans, Wolfgang Becker, Lore Rathkolb, Birgit Rozman, Jan Schrewed, Anja Klingenspor, Martin Klopstock, Thomas Schulz, Holger Wolf, Eckhard Wursta, Wolfgang Gillis, Tammy Wakimoto, Hiroko Seidman, Jonathan MacDonald, Marcy E. Cotman, Susan Gailus-Durner, Valerie Fuchs, Helmut de Angelis, Martin Hrabe Lee, Jong-Min Wheeler, Vanessa C. TI A Broad Phenotypic Screen Identifies Novel Phenotypes Driven by a Single Mutant Allele in Huntington's Disease CAG Knock-In Mice SO PLOS ONE LA English DT Article ID TRANSGENIC MOUSE MODEL; EARLY ALZHEIMERS-DISEASE; NEURAL STEM-CELLS; LONG-TERM-MEMORY; REPEAT INSTABILITY; GLUCOSE-TOLERANCE; BEHAVIORAL ABNORMALITIES; POLYGLUTAMINE INCLUSIONS; OLFACTORY DISCRIMINATION; HIPPOCAMPAL NEUROGENESIS AB Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing. C1 [Hoelter, Sabine M.; Garrett, Lillian; Glasl, Lisa] Helmholtz Zentrum Munchen, Inst Dev Genet, German Mouse Clin, Neuherberg, Germany. [Stromberg, Mary; Kovalenko, Marina; Lopez, Edith; Guide, Jolene; Gillis, Tammy; MacDonald, Marcy E.; Cotman, Susan; Lee, Jong-Min; Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Goetz, Alexander] Helmholtz Zentrum Munchen, Inst Lung Biol & Dis, Comprehens Pneumol Ctr, Neuherberg, Germany. [Hans, Wolfgang; Becker, Lore; Rathkolb, Birgit; Rozman, Jan; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabe] Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, Neuherberg, Germany. [Schrewed, Anja] Heidelberg Univ, Dept Med 3, Div Cardiol, Heidelberg, Germany. [Klingenspor, Martin] Tech Univ Munich, Else Kroner Fresenius Ctr, D-80290 Munich, Germany. [Klingenspor, Martin] Tech Univ Munich, ZIEL Res Ctr Nutr & Food Sci, D-80290 Munich, Germany. [Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany. [Klopstock, Thomas] Univ Munich, German Ctr Vertigo & Balance Disorders, Munich, Germany. [Schulz, Holger] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Wolf, Eckhard] Univ Munich, Gene Ctr, Chair Mol Anim Breeding & Biotechnol, Munich, Germany. [Wursta, Wolfgang] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Wursta, Wolfgang] Deutsch Zentrum Neurodegenerat Erkrankungen, Munich, Germany. [Wakimoto, Hiroko; Seidman, Jonathan] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Wheeler, VC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM Wheeler@chgr.mgh.harvard.edu RI Becker, Lore/E-3717-2010; Gailus-Durner, Valerie/M-7337-2014; Holter, Sabine/N-5868-2014; Fuchs, Helmut/M-7347-2014; Schulz, Holger/J-5643-2015; Rozman, Jan/A-2540-2010; Hrabe de Angelis, Martin/F-5531-2012 OI Holter, Sabine/0000-0003-4878-5241; Becker, Lore/0000-0002-6890-4984; Klingenspor, Martin/0000-0002-4502-6664; Fuchs, Helmut/0000-0002-5143-2677; Schulz, Holger/0000-0002-1157-200X; Rozman, Jan/0000-0002-8035-8904; Hrabe de Angelis, Martin/0000-0002-7898-2353 FU National Institutes of Health [R01NS049206, R01NS073813]; CHDI Foundation; German Federal Ministry of Education and Research [01GS0850, 01GS0851, 01KX1012]; German Center for Vertigo and Balance Disorders [01 EO 0901]; Helmholtz Alliance for Mental Health in an Ageing Society [HA-215] FX This work was supported by the National Institutes of Health R01NS049206, R01NS073813 and the CHDI Foundation. GMC researchers were funded by the German Federal Ministry of Education and Research by grants to the GMC (NGFN-Plus grants No. 01GS0850; 01GS0851; Infrafrontier grant 01KX1012), to the German Center for Diabetes Research (DZD e.V.), the German Center for Vertigo and Balance Disorders (grant 01 EO 0901), and by the Helmholtz Alliance for Mental Health in an Ageing Society (HA-215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 116 TC 11 Z9 11 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 NOV 22 PY 2013 VL 8 IS 11 AR UNSP e80923 DI 10.1371/journal.pone.0080923 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259QP UT WOS:000327541700037 PM 24278347 ER PT J AU Viaud, S Saccheri, F Mignot, G Yamazaki, T Daillere, R Hannani, D Enot, DP Pfirschke, C Engblom, C Pittet, MJ Schlitzer, A Ginhoux, F Apetoh, L Chachaty, E Woerther, PL Eberl, G Berard, M Ecobichon, C Clermont, D Bizet, C Gaboriau-Routhiau, V Cerf-Bensussan, N Opolon, P Yessaad, N Vivier, E Ryffel, B Elson, CO Dore, J Kroemer, G Lepage, P Boneca, IG Ghiringhelli, F Zitvogel, L AF Viaud, Sophie Saccheri, Fabiana Mignot, Gregoire Yamazaki, Takahiro Daillere, Romain Hannani, Dalil Enot, David P. Pfirschke, Christina Engblom, Camilla Pittet, Mikael J. Schlitzer, Andreas Ginhoux, Florent Apetoh, Lionel Chachaty, Elisabeth Woerther, Paul-Louis Eberl, Gerard Berard, Marion Ecobichon, Chantal Clermont, Dominique Bizet, Chantal Gaboriau-Routhiau, Valerie Cerf-Bensussan, Nadine Opolon, Paule Yessaad, Nadia Vivier, Eric Ryffel, Bernhard Elson, Charles O. Dore, Joel Kroemer, Guido Lepage, Patricia Boneca, Ivo Gomperts Ghiringhelli, Francois Zitvogel, Laurence TI The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide SO SCIENCE LA English DT Article ID T-CELL RESPONSES; PATHOGENIC T(H)17 CELLS; BARRIER; SYSTEM; MICE AB Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response. C1 [Viaud, Sophie; Saccheri, Fabiana; Yamazaki, Takahiro; Daillere, Romain; Hannani, Dalil; Zitvogel, Laurence] INSERM, U1015, Equipe Labellisee Ligue Natl Canc, Inst Gustave Roussy, Villejuif, France. [Zitvogel, Laurence] Inst Gustave Roussy, Ctr Invest Clin Biotherapie, CICBT 507, Villejuif, France. [Viaud, Sophie; Daillere, Romain; Zitvogel, Laurence] Univ Paris 11, Le Kremlin Bicetre, France. [Mignot, Gregoire; Apetoh, Lionel; Ghiringhelli, Francois] INSERM, U866, Ctr Georges Francois Leclerc, Dijon, France. [Mignot, Gregoire; Apetoh, Lionel; Ghiringhelli, Francois] INSERM, Grp Avenir, Dijon, France. [Ghiringhelli, Francois] Univ Bourgogne, Fac Med, Dijon, France. [Enot, David P.; Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France. [Enot, David P.; Kroemer, Guido] Inst Gustave Roussy, Villejuif, France. [Pfirschke, Christina; Engblom, Camilla; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pfirschke, Christina; Engblom, Camilla; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA USA. [Schlitzer, Andreas; Ginhoux, Florent] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore. [Chachaty, Elisabeth; Woerther, Paul-Louis] Inst Gustave Roussy, Microbiol Serv, Villejuif, France. [Eberl, Gerard] Inst Pasteur, Lymphoid Tissue Dev Unit, Paris, France. [Berard, Marion] Inst Pasteur, Nimaterie Cent, Paris, France. [Ecobichon, Chantal; Boneca, Ivo Gomperts] Inst Pasteur, Unit Biol & Genet Bacterial Cell Wall, Paris, France. [Ecobichon, Chantal; Boneca, Ivo Gomperts] INSERM, Grp Avenir, Paris, France. [Clermont, Dominique; Bizet, Chantal] Inst Pasteur, Collect Inst Pasteur, Paris, France. [Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine; Dore, Joel; Lepage, Patricia] INRA, Micatis UMR1319, F-78350 Jouy En Josas, France. [Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine] Univ Paris 05, INSERM, U989, F-75730 Paris, France. [Opolon, Paule] Inst Gustave Roussy, IFR54, Villejuif, France. [Opolon, Paule] Inst Gustave Roussy, IRCIV, Lab Pathol Expt, Villejuif, France. [Yessaad, Nadia; Vivier, Eric] Aix Marseille Univ UM2, Ctr Immunol Marseille Luminy, Marseille, France. [Yessaad, Nadia; Vivier, Eric] INSERM, UMR 1104, F-13258 Marseille, France. [Yessaad, Nadia; Vivier, Eric] Ctr Natl Rech Sci, UMR 7280, Marseille, France. [Yessaad, Nadia; Vivier, Eric] Hop Conception, Assistance Publ Hop Marseille, Marseille, France. [Ryffel, Bernhard] Univ Orleans, CNRS, Lab Mol & Expt Immunol & Neurogenet, UMR 7355, Orleans, France. [Elson, Charles O.] Univ Alabama Birmingham, Birmingham, AL USA. [Dore, Joel; Lepage, Patricia] AgroParisTech, Micalis UMR1319, F-78352 Jouy En Josas, France. [Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, Paris, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Paris, France. [Kroemer, Guido] Univ Paris 05, Paris, France. RP Zitvogel, L (reprint author), INSERM, U1015, Equipe Labellisee Ligue Natl Canc, Inst Gustave Roussy, Villejuif, France. EM laurence.zitvogel@gustaveroussy.fr RI Lepage, Patricia/D-4362-2014; Apetoh, Lionel/G-3310-2014; Schlitzer, Andreas/R-2237-2016; Boneca, Ivo/H-1677-2014; OI Apetoh, Lionel/0000-0002-2774-438X; Schlitzer, Andreas/0000-0001-7662-3712; Boneca, Ivo/0000-0001-8122-509X; Eberl, Gerard/0000-0002-1119-5638 FU Institut National du Cancer (INCa); la Ligue contre le cancer (LIGUE labelisee); SIRIC Socrates; LABEX; PACRI Onco-Immunology; European Research Council [202283]; NIH [P01DK071176] FX We thank T. Angelique (Institut Pasteur), C. Flament, M. Vetizou (Gustave Roussy), and K. LeRoux (INRA) for technical assistance. The data reported in this manuscript are tabulated in the main paper and in the supplementary materials. This work was supported by Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labelisee, L.Z., G.K.), SIRIC Socrates, LABEX, and PACRI Onco-Immunology, European Research Council Advanced Grant (to G.K.), and European Research Council starting grant (PGNfromSHAPEtoVIR no. 202283 to I.G.B.), and partially supported by NIH grant P01DK071176 (C.O.E.). NR 24 TC 230 Z9 241 U1 23 U2 106 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 22 PY 2013 VL 342 IS 6161 BP 971 EP 976 DI 10.1126/science.1240537 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EZ UT WOS:000327223500041 PM 24264990 ER PT J AU Tardiff, DF Jui, NT Khurana, V Tambe, MA Thompson, ML Chung, CY Kamadurai, HB Kim, HT Lancaster, AK Caldwell, KA Caldwell, GA Rochet, JC Buchwald, SL Lindquist, S AF Tardiff, Daniel F. Jui, Nathan T. Khurana, Vikram Tambe, Mitali A. Thompson, Michelle L. Chung, Chee Yeun Kamadurai, Hari B. Kim, Hyoung Tae Lancaster, Alex K. Caldwell, Kim A. Caldwell, Guy A. Rochet, Jean-Christophe Buchwald, Stephen L. Lindquist, Susan TI Yeast Reveal a "Druggable" Rsp5/Nedd4 Network that Ameliorates alpha-Synuclein Toxicity in Neurons SO SCIENCE LA English DT Article ID PARKINSONS-DISEASE; VESICLE TRAFFICKING; PROTEIN; PHOSPHORYLATION; CEREVISIAE; MECHANISMS; DEFECTS; MODELS; VPS35; CELLS AB alpha-Synuclein (alpha-syn) is a small lipid-binding protein implicated in several neurodegenerative diseases, including Parkinson's disease, whose pathobiology is conserved from yeast to man. There are no therapies targeting these underlying cellular pathologies, or indeed those of any major neurodegenerative disease. Using unbiased phenotypic screens as an alternative to target-based approaches, we discovered an N-aryl benzimidazole (NAB) that strongly and selectively protected diverse cell types from alpha-syn toxicity. Three chemical genetic screens in wild-type yeast cells established that NAB promoted endosomal transport events dependent on the E3 ubiquitin ligase Rsp5/Nedd4. These same steps were perturbed by alpha-syn itself. Thus, NAB identifies a druggable node in the biology of alpha-syn that can correct multiple aspects of its underlying pathology, including dysfunctional endosomal and endoplasmic reticulum-to-Golgi vesicle trafficking. C1 [Tardiff, Daniel F.; Khurana, Vikram; Chung, Chee Yeun; Lancaster, Alex K.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Jui, Nathan T.; Buchwald, Stephen L.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Khurana, Vikram] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Khurana, Vikram] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tambe, Mitali A.; Rochet, Jean-Christophe] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Thompson, Michelle L.; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Kamadurai, Hari B.] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38018 USA. [Kim, Hyoung Tae] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu RI Lancaster, Alex/K-2855-2013 OI Lancaster, Alex/0000-0002-0002-9263 FU NIH [5R01GM069530, GM58160]; National Research Service Award (NRSA) fellowship [F32NS061419, F32GM099817]; JPB Foundation; Eleanor Schwartz Charitable Foundation; HHMI; Bachmann-Strauss Dystonia & Parkinson Foundation FX We thank A. Kumar for providing the plasmid Tn7 library; B. Wendland and L. Hicke for the Rsp5 antibody; the WIBR Genome Technology Core for Illumina Sequencing; B. Schulman (B. Schulman and H.B.K. were funded by NIH grant 5R01GM069530) and A. Goldberg for help with in vitro ubiquitination assays; T. DiCesare for graphics support; and members of the Lindquist Lab for helpful comments on the manuscript. S.L. is an investigator for HHMI. D.F.T. was funded by a National Research Service Award (NRSA) fellowship F32NS061419 and research supported by the JPB Foundation (D.F.T. and S.L.), the Eleanor Schwartz Charitable Foundation, and an HHMI Collaborative Innovation Award (D.F.T., V.K., C.Y.C., and S.L.; G.A.C., K.A.C., and M.L.T.; and J.-C.R. and M.A.T.). N.T.J. was funded by a NRSA fellowship (F32GM099817), and N.T.J. and S.L.B. were funded by NIH grant GM58160. H.T.K. was funded by the Bachmann-Strauss Dystonia & Parkinson Foundation. Genome sequencing data are deposited in the National Center for Biotechnology Information under BioProject accession number PRJNA222476. WIBR and MIT have filed a patent application, on which D.F.T., N.T.J., S.L.B., and S.L. are inventors, relating to use of compounds described here in treatment of neurodegenerative diseases. In addition, S.L. is an inventor on patents and patent applications filed by the University of Chicago relating to methods of screening for compounds that decrease alpha-syn-associated toxicity using yeast that express alpha-syn. All the yeast plasmids and strains and NAB are available under a Uniform Biological Material Transfer Agreement from the Whitehead Institute. NR 25 TC 78 Z9 78 U1 3 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 22 PY 2013 VL 342 IS 6161 BP 979 EP 983 DI 10.1126/science.1245321 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EZ UT WOS:000327223500043 PM 24158909 ER PT J AU Chung, CY Khurana, V Auluck, PK Tardiff, DF Mazzulli, JR Soldner, F Baru, V Lou, YL Freyzon, Y Cho, S Mungenast, AE Muffat, J Mitalipova, M Pluth, MD Jui, NT Schule, B Lippard, SJ Tsai, LH Krainc, D Buchwald, SL Jaenisch, R Lindquist, S AF Chung, Chee Yeun Khurana, Vikram Auluck, Pavan K. Tardiff, Daniel F. Mazzulli, Joseph R. Soldner, Frank Baru, Valeriya Lou, Yali Freyzon, Yelena Cho, Sukhee Mungenast, Alison E. Muffat, Julien Mitalipova, Maisam Pluth, Michael D. Jui, Nathan T. Schuele, Birgitt Lippard, Stephen J. Tsai, Li-Huei Krainc, Dimitri Buchwald, Stephen L. Jaenisch, Rudolf Lindquist, Susan TI Identification and Rescue of alpha-Synuclein Toxicity in Parkinson Patient-Derived Neurons SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DISEASE; NEURODEGENERATION; MUTATION; YEAST; NITRATION; DEMENTIA; STRESS; RISK AB The induced pluripotent stem (iPS) cell field holds promise for in vitro disease modeling. However, identifying innate cellular pathologies, particularly for age-related neurodegenerative diseases, has been challenging. Here, we exploited mutation correction of iPS cells and conserved proteotoxic mechanisms from yeast to humans to discover and reverse phenotypic responses to alpha-synuclein (alpha syn), a key protein involved in Parkinson's disease (PD). We generated cortical neurons from iPS cells of patients harboring alpha syn mutations, who are at high risk of developing PD dementia. Genetic modifiers from unbiased screens in a yeast model of alpha syn toxicity led to identification of early pathogenic phenotypes in patient neurons. These included nitrosative stress, accumulation of endoplasmic reticulum (ER)-associated degradation substrates, and ER stress. A small molecule identified in a yeast screen (NAB2), and the ubiquitin ligase Nedd4 it affects, reversed pathologic phenotypes in these neurons. C1 [Chung, Chee Yeun; Khurana, Vikram; Auluck, Pavan K.; Tardiff, Daniel F.; Soldner, Frank; Baru, Valeriya; Lou, Yali; Freyzon, Yelena; Muffat, Julien; Mitalipova, Maisam; Jaenisch, Rudolf; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Khurana, Vikram; Mazzulli, Joseph R.; Krainc, Dimitri] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Khurana, Vikram; Auluck, Pavan K.; Mazzulli, Joseph R.; Krainc, Dimitri] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Baru, Valeriya; Lou, Yali; Tsai, Li-Huei; Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Cho, Sukhee; Mungenast, Alison E.; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Pluth, Michael D.; Jui, Nathan T.; Lippard, Stephen J.; Buchwald, Stephen L.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Schuele, Birgitt] Parkinsons Inst, Sunnyvale, CA 94085 USA. [Jaenisch, Rudolf; Lindquist, Susan] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu RI Muffat, Julien/P-2298-2014 FU Howard Hughes Medical Institute; JPB Foundation; NIH/National Institute on Aging [K01 AG038546]; American Brain Foundation; Parkinson's Disease Foundation; NIH [5 R01CA084198]; NSF FX We thank D. Dickson, L. Golbe, and J. Trojanowki for postmorterm tissue or data; D. Pincus for the UPR reporter; I. Cheeseman, J. Kim, J. Pruszak, P. Wisniewski, and W. Salmon for important technical advice; R. Alagappan, T. Lungiangwa, and P. Xu for superb technical assistance; and S. Santagata, L. Whitesell, M. Feany, D. Landgraf, and L. Clayton for fruitful discussion and critical comments on the manuscript. Grant support was provided by a Howard Hughes Medical Institute Collaborative Innovation Award (S.L.), JPB Foundation grants (S.L.), NIH/National Institute on Aging grant K01 AG038546 (C.Y.C.), an American Brain Foundation and Parkinson's Disease Foundation Clinician-Scientist Development Award (V.K.), NIH grant 5 R01CA084198 (R.J.), and the NSF (S.J.L.). Whitehead Institute for Biomedical Research has filed a patent application, on which authors V.K., C.Y.C., and S.L. are inventors, relating to the use of yeast- and iPS cell-based models of synucleinopathies and associated phenotypes for identifying compounds. In addition, author S.L. is an inventor on patents and patent applications filed by The University of Chicago relating to methods of screening for compounds that decrease alpha-synuclein-associated toxicity using yeast that expresses alpha-synuclein. All the yeast plasmids and strains and NAB2 are available under a Uniform Biological Material Transfer Agreement from the Whitehead Institute. Author contributions: C.Y.C., V.K., and S.L. conceptualized the study, designed the experiments, and wrote the paper. V.K. developed the human iPS cell-derived cortical synucleinopathy model, assisted by Y.L. Pluripotent cell lines, advice on experimental design, and technical expertise were provided by F.S., J.R.M., J.M., M.M., and R.J. F.S. reprogrammed the WIBR-IPS-SYNTRPL line from fibroblasts provided by B.S. C.Y.C. developed the rat cortical synucleinopathy model, assisted by V.B. The mKate2-tagged constructs were generated by Y.F. C.Y.C. and V.K. performed all experiments except Fig. 1, D and E, Fig. 2E, and fig. S5, A and B (P.K.A.); Fig. 4A (D.F.T.); Fig. 4C and fig. S6C (J.R.M./D.K.); fig. S2, H and I (A.E.M./S.C./L.-H.T.); and fig. S1 (Y.F./Y.L.). The small molecule NAB2 was synthesized by N.T.J. and S.L.B., based on a yeast screen performed by D.F.T. FL2 dye synthesis and technical advice were provided by M.D.P. and S.J.L. NR 28 TC 126 Z9 131 U1 14 U2 68 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 22 PY 2013 VL 342 IS 6161 BP 983 EP 987 DI 10.1126/science.1245296 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EZ UT WOS:000327223500044 PM 24158904 ER PT J AU Sankaran, VG Gallagher, PG AF Sankaran, Vijay G. Gallagher, Patrick G. TI Applications of high-throughput DNA sequencing to benign hematology SO BLOOD LA English DT Review ID DIAMOND-BLACKFAN ANEMIA; ACUTE MYELOID-LEUKEMIA; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; MONOMAC SYNDROME; INCIDENTAL FINDINGS; GATA2 MUTATIONS; FANCONI-ANEMIA; BLOOD-CELL; CONGENITAL NEUTROPENIA AB The development of novel technologies for high-throughput DNA sequencing is having a major impact on our ability to measure and define normal and pathologic variation in humans. This review discusses advances in DNA sequencing that have been applied to benign hematologic disorders, including those affecting the red blood cell, the neutrophil, and other white blood cell lineages. Relevant examples of how these approaches have been used for disease diagnosis, gene discovery, and studying complex traits are provided. High-throughput DNA sequencing technology holds significant promise for impacting clinical care. This includes development of improved disease detection and diagnosis, better understanding of disease progression and stratification of risk of disease-specific complications, and development of improved therapeutic strategies, particularly patient-specific pharmacogenomics-based therapy, with monitoring of therapy by genomic biomarkers. C1 [Sankaran, Vijay G.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.] Broad Inst, Cambridge, MA USA. [Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, New Haven, CT 06520 USA. [Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pathol, Div Neonatal Perinatal Med, New Haven, CT 06520 USA. [Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Genet, Div Neonatal Perinatal Med, New Haven, CT 06520 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, Div Hematol Oncol, 3 Blackfan Circle,CL 03001, Boston, MA 02115 USA. EM sankaran@broadinstitute.org; patrick.gallagher@yale.edu FU National Institutes of Health, National Heart, Lung, and Blood Institute [RO1HL065449, HL007574-30]; Doris Duke Research Foundation FX This work was supported in part by RO1HL065449 (P. G. G.) and HL007574-30 (V. G. S.) from the National Institutes of Health, National Heart, Lung, and Blood Institute, and a grant from the Doris Duke Research Foundation (P.G.G.). NR 87 TC 12 Z9 12 U1 1 U2 8 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 NOV 21 PY 2013 VL 122 IS 22 BP 3575 EP 3582 DI 10.1182/blood-2013-07-460337 PG 8 WC Hematology SC Hematology GA 290BE UT WOS:000329726200012 PM 24021670 ER PT J AU Shen, Q Du, F Huang, SL Rodriguez, P Watts, LT Duong, TQ AF Shen, Qiang Du, Fang Huang, Shiliang Rodriguez, Pavel Watts, Lora Talley Duong, Timothy Q. TI Neuroprotective Efficacy of Methylene Blue in Ischemic Stroke: An MRI Study SO PLOS ONE LA English DT Article ID DIFFUSION; PERFUSION AB Methylene blue (MB) has unique energy-enhancing and antioxidant properties and is FDA-approved drug to treat methemoglobinemia and cyanide poisoning. This study evaluated the efficacy of MB to treat ischemic stroke in rats using longitudinal MRI and behavioral measures. Rats were subjected to 60-minute middle-cerebral-artery occlusion. In a randomized double-blinded design, vehicle or MB was administered after reperfusion. The initial lesion volumes at 30 minutes post-ischemia were not significantly different between the two groups (P = 0.92). The final infarct volumes two days after stroke increased in the vehicle group but decreased in the MB group, yielding a 30% difference in infarct volume (P = 0.03). Tracking tissue fate on a pixel-by-pixel basis showed that MB salvaged more initial core pixels compared to controls (22 +/- 3% versus 11 +/- 3%, P = 0.03), and more mismatch pixels compared to controls (83 +/- 3% versus 61 +/- 8%, P = 0.02). This study demonstrates MB treatment minimizes ischemic brain injury and improves functional outcomes. C1 [Shen, Qiang; Du, Fang; Huang, Shiliang; Watts, Lora Talley; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Shen, Qiang; Rodriguez, Pavel; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Watts, Lora Talley] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora Talley] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH [R01NS45879, UL1TR000149]; American Heart Association [EIA0940104N, BGIA9300047] FX This work was supported in part by NIH (R01NS45879, UL1TR000149) and American Heart Association (EIA0940104N, BGIA9300047). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 17 Z9 18 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 NOV 21 PY 2013 VL 8 IS 11 AR e79833 DI 10.1371/journal.pone.0079833 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259PW UT WOS:000327539800026 PM 24278191 ER PT J AU Silberstein, L Scadden, DT AF Silberstein, Lev Scadden, David T. TI Blood Scent SO CELL LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS AB Blood cell production is tightly regulated by cell-intrinsic mechanisms and environmental factors. The study by Utpal Banerjee and colleagues and colleagues reveals that, in Drosophila, olfactory signals control hematopoietic progenitor maintenance, thus uncovering a physiological link between sensory perception and hematopoietic response to environmental stress. C1 [Silberstein, Lev; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Silberstein, Lev; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Silberstein, Lev; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Silberstein, Lev; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM david_scadden@harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 21 PY 2013 VL 155 IS 5 BP 981 EP 982 DI 10.1016/j.cell.2013.11.006 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259AU UT WOS:000327500600003 PM 24267883 ER PT J AU Praetorius, C Grill, C Stacey, SN Metcalf, AM Gorkin, DU Robinson, KC Van Otterloo, E Kim, RSQ Bergsteinsdottir, K Ogmundsdottir, MH Magnusdottir, E Mishra, PJ Davis, SR Guo, T Zaidi, MR Helgason, AS Sigurdsson, MI Meltzer, PS Merlino, G Petit, V Larue, L Loftus, SK Adams, DR Sobhiafshar, U Emre, NCT Pavan, WJ Cornell, R Smith, AG McCallion, AS Fisher, DE Stefansson, K Sturm, RA Steingrimsson, E AF Praetorius, Christian Grill, Christine Stacey, Simon N. Metcalf, Alexander M. Gorkin, David U. Robinson, Kathleen C. Van Otterloo, Eric Kim, Reuben S. Q. Bergsteinsdottir, Kristin Ogmundsdottir, Margret H. Magnusdottir, Erna Mishra, Pravin J. Davis, Sean R. Guo, Theresa Zaidi, M. Raza Helgason, Agnar S. Sigurdsson, Martin I. Meltzer, Paul S. Merlino, Glenn Petit, Valerie Larue, Lionel Loftus, Stacie K. Adams, David R. Sobhiafshar, Ulduz Emre, N. C. Tolga Pavan, William J. Cornell, Robert Smith, Aaron G. McCallion, Andrew S. Fisher, David E. Stefansson, Kari Sturm, Richard A. Steingrimsson, Eirikur TI A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway SO CELL LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; CANCER SUSCEPTIBILITY; GENETIC-DETERMINANTS; COLORECTAL-CANCER; MULTIPLE-MYELOMA; EXPRESSION; VARIANTS; ENHANCER; MELANOCYTES; MELANOMA AB Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. Here, we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a noncoding polymorphism that affects a phenotype by modulating a developmental gene regulatory network. C1 [Praetorius, Christian; Grill, Christine; Bergsteinsdottir, Kristin; Ogmundsdottir, Margret H.; Magnusdottir, Erna; Sigurdsson, Martin I.; Steingrimsson, Eirikur] Univ Iceland, Fac Med, Dept Biochem & Mol Biol, Biomed Ctr, IS-101 Reykjavik, Iceland. [Stacey, Simon N.; Helgason, Agnar S.; Stefansson, Kari] Decode Genet, IS-101 Reykjavik, Iceland. [Metcalf, Alexander M.; Kim, Reuben S. Q.; Smith, Aaron G.; Sturm, Richard A.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Gorkin, David U.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Gorkin, David U.] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA. [Robinson, Kathleen C.; Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Van Otterloo, Eric; Cornell, Robert] Univ Iowa, Iowa City, IA 52242 USA. [Kim, Reuben S. Q.; Smith, Aaron G.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. [Mishra, Pravin J.; Guo, Theresa; Zaidi, M. Raza; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Davis, Sean R.; Meltzer, Paul S.] NCI, Genet Branch, Bethesda, MD 20892 USA. [Petit, Valerie; Larue, Lionel] Inst Curie, Ctr Rech, F-91405 Orsay, France. [Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Adams, David R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Sobhiafshar, Ulduz; Emre, N. C. Tolga] Bogazici Univ, Dept Mol Biol & Genet, Lab Genome Regulat, TR-34342 Istanbul, Turkey. RP Steingrimsson, E (reprint author), Univ Iceland, Fac Med, Dept Biochem & Mol Biol, Biomed Ctr, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. EM eirikurs@hi.is RI Smith, Aaron/A-8329-2010; Sturm, Richard/C-9943-2009; Magnusdottir, Erna/H-5181-2013; Helgason, Agnar/K-1522-2015; Larue, Lionel/I-6532-2016; Zaidi, M. Raza/H-1386-2016; Sigurdsson, Martin/I-9655-2016; OI Sturm, Richard/0000-0003-1301-0294; Magnusdottir, Erna/0000-0002-3369-4390; Zaidi, M. Raza/0000-0003-0480-3188; Sigurdsson, Martin/0000-0001-7054-0844; Praetorius, Christian/0000-0001-7514-5333 FU NIH [5R01 AR043369-16]; Melanoma Research Alliance; Dr. Miriam and Sheldon Adelson Medical Research Foundation; US-Israel Binational Science Foundation; Ligue Nationale Contre le Cancer; INCa; Icelandic Research Fund; Research Fund of the University of Iceland; Haskolasjodur Student Fund; Jules Verne Fund; National Institute of General Medical Sciences [GM071648]; National Institute of Neurological Disease and Stroke [NS062972]; National Human Genome Research Institute's Intramural Research Program; NSF Graduate Research Fellowship FX We thank Thorunn Rafnar, Magnus Karl Magnusson, Unnur Thorsteinsdottir, Colin R. Goding, and Thorarinn Gudjonsson for critical comments on the manuscript. This work was supported by grants from NIH (5R01 AR043369-16), Melanoma Research Alliance, Dr. Miriam and Sheldon Adelson Medical Research Foundation, US-Israel Binational Science Foundation (to D.E.F.), Ligue Nationale Contre le Cancer (Equipe labellisee) and INCa (to L.L.), the Icelandic Research Fund and the Research Fund of the University of Iceland (to E.S.), the Haskolasjodur Student Fund (to E.S., C.P., and C.G.), the Jules Verne Fund (to E.S. and L.L.), by the National Institute of General Medical Sciences (GM071648) and National Institute of Neurological Disease and Stroke (NS062972; to A.S.M.), the National Human Genome Research Institute's Intramural Research Program (to W.J.P. and S.L.), and an NSF Graduate Research Fellowship (to D.U.G.). NR 51 TC 46 Z9 47 U1 9 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 21 PY 2013 VL 155 IS 5 BP 1022 EP 1033 DI 10.1016/j.cell.2013.10.022 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259AU UT WOS:000327500600008 PM 24267888 ER PT J AU Asch, DA Nicholson, S Vujicic, M AF Asch, David A. Nicholson, Sean Vujicic, Marko TI Are We in a Medical Education Bubble Market? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB Debt-to-income ratios for new physicians reveal the connection between what physicians can charge patients and what medical schools can charge students. If we aim to reduce the costs of health care, we need to reduce the costs of medical education. In November 1636, the prices of tulip bulbs in the Dutch market rose rapidly from their normal level to the point where a single bulb might sell for 10 times the annual earnings of a typical worker. Just as quickly, in May 1637, tulip-bulb prices returned to their previous values. The causes of this dramatic rise and fall remain in dispute. The event occurred during the Dutch Golden Age, when stock exchanges, central banking, and many of the fundamental structures that govern contemporary capital markets and the approaches deployed by MBAs today were developed. One modern economic analysis suggests that ... C1 [Asch, David A.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Nicholson, Sean] Cornell Univ, Ithaca, NY USA. [Nicholson, Sean] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Vujicic, Marko] Amer Dent Assoc, Chicago, IL USA. RP Asch, DA (reprint author), Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 5 TC 23 Z9 23 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 21 PY 2013 VL 369 IS 21 BP 1973 EP 1975 DI 10.1056/NEJMp1310778 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 254KE UT WOS:000327163000002 PM 24171508 ER PT J AU Powe, CE Evans, MK Wenger, J Zonderman, AB Berg, AH Nalls, M Tamez, H Zhang, DS Bhan, I Karumanchi, SA Powe, NR Thadhani, R AF Powe, Camille E. Evans, Michele K. Wenger, Julia Zonderman, Alan B. Berg, Anders H. Nalls, Michael Tamez, Hector Zhang, Dongsheng Bhan, Ishir Karumanchi, S. Ananth Powe, Neil R. Thadhani, Ravi TI Vitamin D-Binding Protein and Vitamin D Status of Black Americans and White Americans SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; D DEFICIENCY; 25-HYDROXYVITAMIN D; HIP-FRACTURES; SERUM 25-HYDROXYVITAMIN-D; PARATHYROID-HORMONE; AFRICAN-AMERICANS; D INSUFFICIENCY; OLDER-ADULTS AB BackgroundLow levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D-binding protein has not been considered in the assessment of vitamin D deficiency. MethodsIn the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D-binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. ResultsMean (SE) levels of both total 25-hydroxyvitamin D and vitamin D-binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.60.2 ng per milliliter vs. 25.80.4 ng per milliliter, P<0.001; vitamin D-binding protein, 1683 g per milliliter vs. 337 +/- 5 g per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D-binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05 +/- 0.01 g per square centimeter vs. 0.94 +/- 0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9 +/- 0.1 ng per milliliter and 3.1 +/- 0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration. Conclusions Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D-binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. C1 [Powe, Camille E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wenger, Julia; Tamez, Hector; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Berg, Anders H.] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Zhang, Dongsheng; Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Powe, Neil R.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Evans, MK (reprint author), NIA, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Rm 4C-222, Baltimore, MD 21224 USA. EM me42v@nih.gov; rthadhani@mgh.harvard.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging FX Funded by the National Institute on Aging and others. NR 41 TC 329 Z9 335 U1 2 U2 29 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 NOV 21 PY 2013 VL 369 IS 21 BP 1991 EP 2000 DI 10.1056/NEJMoa1306357 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 254KE UT WOS:000327163000007 PM 24256378 ER PT J AU Bao, Y Han, JL Hu, FB Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS AF Bao, Ying Han, Jiali Hu, Frank B. Giovannucci, Edward L. Stampfer, Meir J. Willett, Walter C. Fuchs, Charles S. TI Association of Nut Consumption with Total and Cause-Specific Mortality SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; MEDITERRANEAN DIET; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; WALNUT CONSUMPTION; WOMENS HEALTH; WEIGHT-GAIN; LIFE-STYLE AB BackgroundIncreased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. MethodsWe examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses' Health Study (1980-2010) and 42,498 men in the Health Professionals Follow-up Study (1986-2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. ResultsDuring 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. ConclusionsIn two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. C1 [Bao, Ying; Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Bao, Ying; Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Han, Jiali] Indiana Univ, Dept Epidemiol, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA. [Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. RP Bao, Y (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU National Institutes of Health; International Tree Nut Council Nutrition Research and Education Foundation FX Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation. NR 41 TC 85 Z9 86 U1 8 U2 62 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 NOV 21 PY 2013 VL 369 IS 21 BP 2001 EP 2011 DI 10.1056/NEJMoa1307352 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 254KE UT WOS:000327163000008 PM 24256379 ER PT J AU Wright, DE Rosovsky, RP Platt, MY AF Wright, Douglas E. Rosovsky, Rachel P. Platt, Mia Y. TI Case 36-2013: A 38-Year-Old Woman with Anemia and Thrombocytopenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AUTOIMMUNE HEMOLYTIC-ANEMIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; EVANS-SYNDROME; MYCOPHENOLATE-MOFETIL; REVISED CRITERIA; RITUXIMAB; CLASSIFICATION; INFUSION; EFFICACY; THERAPY AB A 38-year-old woman was admitted to this hospital because of fatigue, malaise, and lightheadedness, with dyspnea on exertion, bruising, dark urine, and headache. Laboratory tests revealed anemia and thrombocytopenia. Diagnostic tests were performed. Presentation of CaseDr. Joanna Lopez (Medicine): A 38-year-old woman was admitted to this hospital because of anemia and thrombocytopenia. The patient had been well until approximately 3 months before admission, when fatigue, malaise, and light-headedness developed that she attributed to a viral illness. Three weeks before admission, fatigue worsened, and dyspnea on exertion, bruising on the legs, dark urine, and headache developed. She reported that she felt like staying in a bed all day and needed assistance with showering. Two days before admission, she went to another hospital. The physical examination was reportedly normal, as were the results of ... C1 [Wright, Douglas E.; Rosovsky, Rachel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Platt, Mia Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wright, Douglas E.; Rosovsky, Rachel P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Platt, Mia Y.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wright, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. NR 36 TC 2 Z9 3 U1 1 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 NOV 21 PY 2013 VL 369 IS 21 BP 2032 EP 2043 DI 10.1056/NEJMcpc1215972 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 254KE UT WOS:000327163000012 PM 24256382 ER PT J AU Zygmanski, P Liu, B Tsiamas, P Cifter, F Petersheim, M Hesser, J Sajo, E AF Zygmanski, Piotr Liu, Bo Tsiamas, Panagiotis Cifter, Fulya Petersheim, Markus Hesser, Juergen Sajo, Erno TI Dependence of Monte Carlo microdosimetric computations on the simulation geometry of gold nanoparticles SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DOSE ENHANCEMENT; BEAM QUALITY; ENERGY; RADIOSENSITIZATION; RADIATION; ELECTRONS; DNA AB These MC simulations were carried out in simplified geometries and provided encouraging preliminary data in support of GNP radiotherapy. As these studies showed, radiation transport computations of clinical beams to obtain dose enhancement from nanoparticles has several challenges, mostly arising from the requirement of high spatial resolution and from the approximations used at the interface between the macroscopic clinical beam transport and the nanoscopic electron transport originating in the nanoparticle or its vicinity. We investigate the impact of MC simulation geometry on the energy deposition due to the presence of GNPs, including the effects of particle clustering and morphology. Dose enhancement due to a single and multiple GNPs using various simulation geometries is computed using GEANT4MC radiation transport code. Various approximations in the geometry and in the phase space transition from macro-to micro-beams incident on GNPs are analyzed. Simulations using GEANT4 are compared to a deterministic code CEPXS/ONEDANT for microscopic (nm-mu m) geometry. Dependence on the following microscopic (mu) geometry parameters is investigated: mu-source-to-GNP distance (mu SAD), mu-beam size (mu S), and GNP size (mu C). Because a micro-beam represents clinical beam properties at the microscopic scale, the effect of using different types of micro-beams is also investigated. In particular, a micro-beam with the phase space of a clinical beam versus a plane-parallel beam with an equivalent photon spectrum is characterized. Furthermore, the spatial anisotropy of energy deposition around a nanoparticle is analyzed. Finally, dependence of dose enhancement on the number of GNPs in a finite cluster of nanoparticles is determined. Simulations were performed for 100 nm GNPs irradiated in water phantom by various monoenergetic (11 keV-1 MeV) and spectral (50 kVp) sources. The dose enhancement ratio (DER) is very sensitive to the specific simulation geometry (mu SAD, mu S, mu C parameters) and mu-source type. For a single GNP the spatial distribution of DER is found to be nearly isotropic with limited magnitude and relatively short range (similar to 100-200 nm for DER significantly greater than 1). For a cluster of GNPs both the magnitude and range are found much greater (similar to 1-2 mu m). The relation between DER for a cluster of GNPs and a single GNP is strongly nonlinear. Relatively strong dependence of DER on the simulation micro-geometry cautions future studies and the interpretation of existing MC results obtained in different simulations geometries. The nonlinear relation between DER for a single and multiple GNPs suggests that parameters such as the number of adjacent nanoparticles per cell and the distances between the GNPs and the cellular target may be important in assessing the biological effectiveness associated with GNP. C1 [Zygmanski, Piotr; Liu, Bo; Tsiamas, Panagiotis] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Zygmanski, Piotr; Liu, Bo; Tsiamas, Panagiotis] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, Bo; Petersheim, Markus; Hesser, Juergen] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Radiat Oncol, D-69115 Heidelberg, Germany. [Cifter, Fulya; Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pzygmanski@LROC.harvard.edu NR 20 TC 20 Z9 21 U1 1 U2 18 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2013 VL 58 IS 22 BP 7961 EP 7977 DI 10.1088/0031-9155/58/22/7961 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 252LS UT WOS:000327006800007 PM 24169737 ER PT J AU Testa, M Verburg, JM Rose, M Min, CH Tang, SK Bentefour, E Paganetti, H Lu, HM AF Testa, Mauro Verburg, Joost M. Rose, Mark Min, Chul Hee Tang, Shikui Bentefour, El Hassane Paganetti, Harald Lu, Hsiao-Ming TI Proton radiography and proton computed tomography based on time-resolved dose measurements SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO SIMULATIONS; VIVO RANGE VERIFICATION; HEAVY-ION CT; SPATIAL-RESOLUTION; BEAM RADIOGRAPHY; THERAPY; DETECTOR; SYSTEM; RADIOTHERAPY; DENSITY AB We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time-dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (similar to 100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is similar to 0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector. C1 [Testa, Mauro; Verburg, Joost M.; Min, Chul Hee; Tang, Shikui; Bentefour, El Hassane; Paganetti, Harald; Lu, Hsiao-Ming] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Verburg, Joost M.] Eindhoven Univ Technol, Sch Med Phys & Engn, NL-5600 MB Eindhoven, Netherlands. [Rose, Mark] Sun Nucl Corp, Melbourne, FL 32940 USA. RP Testa, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM hmlu@partners.org FU [NIH/NCI P01 CA21239] FX We wish to thank Gregory Sharp, PhD at MGH for his help with the measurements during the moving target experiment. We wish to thank Thomas Ruggieri at MGH for building the rotational platform used for the pCT experiment. We also thank Xingqi Lu, PhD from Beth Israel Hospital, Boston to have lent us the human skull. This work was supported by grant number NIH/NCI P01 CA21239. NR 37 TC 15 Z9 15 U1 2 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2013 VL 58 IS 22 BP 8215 EP 8233 DI 10.1088/0031-9155/58/22/8215 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 252LS UT WOS:000327006800022 PM 24200989 ER PT J AU Aaltonen, T Behari, S Boveia, A Brau, B Bolla, G Bortoletto, D Calancha, C Carron, S Cihangir, S Corbo, M Clark, D Di Ruzza, B Eusebi, R Fernandez, JP Freeman, JC Garcia, JE Garcia-Sciveres, M Glenzinski, D Gonzalez, O Grinstein, S Hartz, M Herndon, M Hill, C Hocker, A Husemann, U Incandela, J Issever, C Jindariani, S Junk, TR Knoepfel, K Lewis, JD Lu, RS Martinez-Ballarin, R Mathis, M Mattson, M Merkel, P Miller, L Mitra, A Mondragon, MN Moore, R Mumford, JR Nahn, S Nielsen, J Nelson, TK Pavlicek, V Pursley, J Redondo, I Roser, R Schultz, K Slaughter, J Spalding, J Stancari, M Stanitzki, M Stuart, D Sukhanov, A Tesarek, R Treptow, K Wallny, R Wilson, P Worm, S AF Aaltonen, T. Behari, S. Boveia, A. Brau, B. Bolla, G. Bortoletto, D. Calancha, C. Carron, S. Cihangir, S. Corbo, M. Clark, D. Di Ruzza, B. Eusebi, R. Fernandez, J. P. Freeman, J. C. Garcia, J. E. Garcia-Sciveres, M. Glenzinski, D. Gonzalez, O. Grinstein, S. Hartz, M. Herndon, M. Hill, C. Hocker, A. Husemann, U. Incandela, J. Issever, C. Jindariani, S. Junk, T. R. Knoepfel, K. Lewis, J. D. Lu, R. S. Martinez-Ballarin, R. Mathis, M. Mattson, M. Merkel, P. Miller, L. Mitra, A. Mondragon, M. N. Moore, R. Mumford, J. R. Nahn, S. Nielsen, J. Nelson, T. K. Pavlicek, V. Pursley, J. Redondo, I. Roser, R. Schultz, K. Slaughter, J. Spalding, J. Stancari, M. Stanitzki, M. Stuart, D. Sukhanov, A. Tesarek, R. Treptow, K. Wallny, R. Wilson, P. Worm, S. TI Operational experience, improvements, and performance of the CDF Run II silicon vertex detector SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE Silicon; Vertex detector; CDF; Tevatron Run II; Detector operations ID TRACKER; UPGRADE; READOUT; TRIGGER; LINK AB The Collider Detector at Fermilab (CDF) pursues a broad physics program at Fermilab's Tevatron collider. Between Run II commissioning in early 2001 and the end of operations in September 2011, the Tevatron delivered 12 fb(-1) of integrated luminosity of p (p) over bar collisions at root s =1.96 TeV. Many physics analyses undertaken by CDF require heavy flavor tagging with large charged particle tracking acceptance. To realize these goals, in 2001 CDF installed eight layers of silicon microstrip detectors around its interaction region. These detectors were designed for 2-5 years of operation, radiation doses up to 2 Mrad (0.02 Gy), and were expected to be replaced in 2004. The sensors were not replaced, and the Tevatron run was extended for several years beyond its design, exposing the sensors and electronics to much higher radiation doses than anticipated. In this paper we describe the operational challenges encountered over the past 10 years of running the CDF silicon detectors, the preventive measures undertaken, and the improvements made along the way to ensure their optimal performance for collecting high quality physics data. In addition, we describe the quantities and methods used to monitor radiation damage in the sensors for optimal performance and summarize the detector performance quantities important to CDF's physics program, including vertex resolution, heavy flavor tagging, and silicon vertex trigger performance. (c) 2013 Elsevier B.V. All rights reserved. C1 [Lu, R. S.; Mitra, A.] Acad Sinica, Taipei 11529, Taiwan. [Grinstein, S.] Univ Autonoma Barcelona, ICREA, Inst Fis Altes Energies, E-08193 Bellaterra, Barcelona, Spain. [Clark, D.] Brandeis Univ, Waltham, MA 02453 USA. [Di Ruzza, B.] Brookhaven Natl Lab, Dept Phys, Upton, NY 11973 USA. [Worm, S.] CERN, CH-1211 Geneva, Switzerland. [Boveia, A.] Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Boveia, A.; Brau, B.; Hill, C.; Incandela, J.; Issever, C.; Stuart, D.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Nielsen, J.] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Santa Cruz, CA 95064 USA. [Stanitzki, M.] DESY, D-22603 Hamburg, Germany. [Stanitzki, M.] DESY, D-15738 Zeuthen, Germany. ETH, Inst Particle Phys, CH-8093 Zurich, Switzerland. [Behari, S.; Carron, S.; Cihangir, S.; Di Ruzza, B.; Eusebi, R.; Freeman, J. C.; Glenzinski, D.; Hocker, A.; Jindariani, S.; Junk, T. R.; Knoepfel, K.; Lewis, J. D.; Merkel, P.; Mondragon, M. N.; Moore, R.; Pavlicek, V.; Roser, R.; Schultz, K.; Slaughter, J.; Spalding, J.; Stancari, M.; Sukhanov, A.; Tesarek, R.; Treptow, K.; Wilson, P.] Fermilab Natl Accelerator Lab, Batavia, IL 60510 USA. [Sukhanov, A.] Univ Florida, Gainesville, FL 32611 USA. [Garcia, J. E.] Univ Geneva, CH-1211 Geneva 4, Switzerland. [Grinstein, S.; Miller, L.] Harvard Univ, Cambridge, MA 02138 USA. [Aaltonen, T.] Univ Helsinki, FIN-00014 Helsinki, Finland. [Aaltonen, T.] Helsinki Inst Phys, FIN-00014 Helsinki, Finland. [Behari, S.; Herndon, M.; Mathis, M.; Mumford, J. R.; Pursley, J.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Husemann, U.] Karlsruhe Inst Technol, Inst Expt Kernphys, D-76131 Karlsruhe, Germany. [Garcia-Sciveres, M.; Nielsen, J.] Ernest Orlando Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Lu, R. S.] Natl Taiwan Univ, Taipei 10764, Taiwan. [Calancha, C.; Fernandez, J. P.; Gonzalez, O.; Martinez-Ballarin, R.; Redondo, I.] Ctr Invest Energet Medioambiental & Tecnol, E-28040 Madrid, Spain. [Brau, B.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. [Moore, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Nahn, S.] MIT, Cambridge, MA 02139 USA. [Pursley, J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hill, C.] Ohio State Univ, Columbus, OH 43210 USA. [Issever, C.] Univ Oxford, Oxford OX1 3RH, England. [Corbo, M.] Univ Paris 06, CNRS, IN2P3, LPNHE,UMR7585, F-75252 Paris, France. [Garcia, J. E.] Univ Pisa, Ist Nazl Fis Nucl Pisa, I-56127 Pisa, Italy. [Garcia, J. E.] Univ Siena, I-56127 Pisa, Italy. [Garcia, J. E.] Univ Scuola Normale Super, I-56127 Pisa, Italy. [Hartz, M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Bolla, G.; Bortoletto, D.; Merkel, P.] Purdue Univ, W Lafayette, IN 47907 USA. [Husemann, U.] Univ Rochester, Rochester, NY 14627 USA. [Worm, S.] Rutgers State Univ, Piscataway, NJ 08855 USA. [Worm, S.] Sci & Technol Facil Council, Rutherford Appleton Lab, Didcot OX11 00QX, Oxon, England. [Carron, S.; Nelson, T. K.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. [Eusebi, R.] Texas A&M Univ, College Stn, TX 77843 USA. [Hartz, M.] Univ Toronto, Toronto, ON M5S 1A7, Canada. [Mattson, M.] Wayne State Univ, Detroit, MI 48202 USA. [Herndon, M.] Univ Wisconsin, Madison, WI 53706 USA. [Mathis, M.] Coll William & Mary, Williamsburg, VA 23187 USA. [Husemann, U.; Nahn, S.; Stanitzki, M.] Yale Univ, New Haven, CT 06520 USA. RP Behari, S (reprint author), Fermilab Natl Accelerator Lab, Batavia, IL 60510 USA. EM behari@fnal.gov RI Grinstein, Sebastian/N-3988-2014; Garcia, Jose /H-6339-2015; Martinez Ballarin, Roberto/K-9209-2015 OI Grinstein, Sebastian/0000-0002-6460-8694; Martinez Ballarin, Roberto/0000-0003-0588-6720 FU U.S. Department of Energy and National Science Foundation; Italian Istituto Nazionale di Fisica Nucleare; Ministry of Education, Culture, Sports, Science and Technology of Japan; Natural Sciences and Engineering Research Council of Canada; National Science Council of the Republic of China; Swiss National Science Foundation; A.P. Sloan Foundation; Bundesministerium fur Bildung und Forschung, Germany; Korean World Class University Program; National Research Foundation of Korea; Science and Technology Facilities Council; Royal Society, UK; Russian Foundation for Basic Research; Ministerio de Ciencia e Innovacion, and Programa Consolider-Ingenio, Spain; Slovak RD Agency; Academy of Finland; Australian Research Council (ARC) FX The authors would like to thank Dr. D. Christian and Dr. T. Zimmerman of Fermilab for useful discussions on radiation damage in silicon detectors and SVX3D chip functionalities, respectively. This work would not have been possible without a strong support by the CDF operations management and the spokespersons. We also thank the Fermilab staff and the technical staffs of the participating institutions for their vital contributions. This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A.P. Sloan Foundation; the Bundesministerium fur Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, UK; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovacion, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; and the Australian Research Council (ARC). NR 46 TC 17 Z9 17 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 EI 1872-9576 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD NOV 21 PY 2013 VL 729 BP 153 EP 181 DI 10.1016/j.nima.2013.07.015 PG 29 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 235WT UT WOS:000325753500023 ER PT J AU Der-Martirosian, C Heslin, KC Mitchell, MN Chu, K Tran, K Dobalian, A AF Der-Martirosian, Claudia Heslin, Kevin C. Mitchell, Michael N. Chu, Karen Kim Tran Dobalian, Aram TI Comparison of the Use of H1N1 and seasonal influenza vaccinations between veterans and non-veterans in the United States, 2010 SO BMC PUBLIC HEALTH LA English DT Article DE H1N1; Seasonal flu shot; Veterans; non-Veterans; flu vaccination ID IMMUNIZATION PRACTICES ACIP; VACCINES RECOMMENDATIONS; ADVISORY-COMMITTEE; OLDER; HEALTH; PREVENTION; RESOURCE; ADULTS; RATES; CARE AB Background: Veterans of the U.S. armed forces tend to be older and have more chronic health problems than the general adult population, which may place them at greater risk of complications from influenza. Despite Centers for Disease Control and Prevention (CDC) recommendations, seasonal influenza vaccination rates for the general adult population remain well below the national goal of 80%. Achieving this goal would be facilitated by a clearer understanding of which factors influence vaccination. Methods: Using the 2010 U.S. National Health Interview Survey (NHIS), this study estimates models of two types of vaccinations (H1N1 and seasonal flu), assesses if the correlates differ for these vaccinations, and analyses the distribution of the correlates by veteran status. Results: Veterans, women, non-Hispanic whites, non-smokers, those at high risk, educated, with health insurance, and who use clinics as a usual source of care were more likely to receive both types of vaccinations. Those who were older, married, and with higher income were more likely to get vaccinated for seasonal flu, but not for H1N1. Age and number of children living in the household were found to have different effects for H1N1 compared to seasonal flu. Conclusion: Veterans are more likely to get vaccinated for seasonal influenza and H1N1 compared to the general population. This might be due to Veterans having better access to care or Veterans participating in better health care practices. Future studies should examine potential differences in flu vaccination use among Veterans using Veterans Affairs (VA) health care system vs. non-VA users. C1 [Der-Martirosian, Claudia; Heslin, Kevin C.; Mitchell, Michael N.; Chu, Karen; Dobalian, Aram] US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, North Hills, CA USA. [Kim Tran; Dobalian, Aram] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Heslin, Kevin C.; Dobalian, Aram] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Der-Martirosian, C (reprint author), US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, North Hills, CA USA. EM claudia.der-martirosian@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Public Health (OPH) FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Public Health (OPH). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. NR 35 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD NOV 20 PY 2013 VL 13 AR 1082 DI 10.1186/1471-2458-13-1082 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 284EX UT WOS:000329300000001 PM 24252569 ER PT J AU Hudry, E Dashkoff, J Roe, AD Takeda, S Koffie, RM Hashimoto, T Scheel, M Spires-Jones, T Arbel-Ornath, M Betensky, R Davidson, BL Hyman, BT AF Hudry, Eloise Dashkoff, Jonathan Roe, Alysson D. Takeda, Shuko Koffie, Robert M. Hashimoto, Tadafumi Scheel, Maria Spires-Jones, Tara Arbel-Ornath, Michal Betensky, Rebecca Davidson, Beverly L. Hyman, Bradley T. TI Gene Transfer of Human Apoe Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; A-BETA; TRANSGENIC MICE; SYNAPSE LOSS; IN-VIVO; SENILE PLAQUES; PROTEIN; MODEL; RECEPTOR AB Inheritance of the epsilon 4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor associated with the sporadic form of Alzheimer's disease (AD), whereas the rare APOE epsilon 2 allele has the opposite effect. However, the mechanisms whereby APOE confers risk and protection remain uncertain. We used a gene transfer approach to bathe the cortex of amyloid plaque-bearing transgenic mice with virally expressed human APOE. We monitored amyloid-beta (A beta) with multiphoton imaging, in vivo microdialysis, and postmortem array tomography to study the kinetics of human APOE-mediated changes in A beta-related neurotoxicity in a mouse model of AD. We observed that human APOE4 increased the concentrations of oligomeric A beta within the interstitial fluid and exacerbated plaque deposition; the converse occurred after exposure to human APOE2. Peri-plaque synapse loss and dystrophic neurites were also worsened by APOE4 or attenuated by APOE2. Egress of A beta from the central nervous system (CNS) into the plasma was diminished by APOE3 and APOE4 compared to APOE2, in accord with isoform-specific retention of A beta in the CNS. Overall, our data show a differential effect of human APOE isoforms on amyloid deposition and clearance in transgenic mice and, more importantly, on A beta-mediated synaptotoxicity. These results suggest that the APOE genetic risk is mediated by A beta, and that therapeutic approaches aimed at decreasing APOE4, or increasing APOE2, may be beneficial in AD. C1 [Hudry, Eloise; Dashkoff, Jonathan; Roe, Alysson D.; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Hudry, Eloise; Dashkoff, Jonathan; Roe, Alysson D.; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Internal Med Neurol & Mol Physiol & Biophys, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. [Betensky, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu OI Dashkoff, Jonathan/0000-0002-1512-5661; Spires-Jones, Tara/0000-0003-2530-0598 FU NIH [R00AG33670, NS34568, HD33531, DK54759]; NIH Challenge Grant [1RC1AG026265-01]; Roy J. Carver Trust; Lefler Fellowship (Harvard Medical School); French Bettencourt-Schueller Foundation; Dreyfoos Program FX This work was supported by NIH grants R00AG33670, NS34568, HD33531, and DK54759; the NIH Challenge Grant (1RC1AG026265-01); the Roy J. Carver Trust (B. L. D.); the Lefler Fellowship (Harvard Medical School); the French Bettencourt-Schueller Foundation; and the Dreyfoos Program. NR 53 TC 24 Z9 24 U1 2 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 20 PY 2013 VL 5 IS 212 AR 212ra161 DI 10.1126/scitranslmed.3007000 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 258FF UT WOS:000327443900003 PM 24259049 ER PT J AU Rottiers, V Obad, S Petri, A McGarrah, R Lindholm, MW Black, JC Sinha, S Goody, RJ Lawrence, MS deLemos, AS Hansen, HF Whittaker, S Henry, S Brookes, R Najafi-Shoushtari, SH Chung, RT Whetstine, JR Gerszten, RE Kauppinen, S Nara, AM AF Rottiers, Veerle Obad, Susanna Petri, Andreas McGarrah, Robert Lindholm, Marie W. Black, Joshua C. Sinha, Sumita Goody, Robin J. Lawrence, Matthew S. deLemos, Andrew S. Hansen, Henrik F. Whittaker, Steve Henry, Steve Brookes, Rohn Najafi-Shoushtari, Seyed Hani Chung, Raymond T. Whetstine, Johnathan R. Gerszten, Robert E. Kauppinen, Sakari Naerae, Anders M. TI Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CHOLESTEROL HOMEOSTASIS; IN-VIVO; MIR-33; ATHEROSCLEROSIS; MICE; HDL; TRANSPORTERS; PROGRESSION; ANTAGONISM; EXPRESSION AB MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base pairing with 3' untranslated regions, primarily via seed sequences (nucleotides 2 to 8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed. miRNAs have been implicated in the etiology of a wide variety of human diseases and therefore represent promising therapeutic targets. However, potential redundancy of different miRNAs sharing the same seed sequence and the challenge of simultaneously targeting miRNAs that differ significantly in nonseed sequences complicate therapeutic targeting approaches. We recently demonstrated effective inhibition of entire miRNA families using seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiRs in short-term experiments in mammalian cells and in mice. However, the long-term efficacy and safety of this approach in higher organisms, such as humans and nonhuman primates, have not been determined. We show that pharmacological inhibition of the miR-33 family, key regulators of cholesterol/lipid homeostasis, by a subcutaneously delivered 8-mer LNA-modified antimiR in obese and insulin-resistant nonhuman primates results in derepression of miR-33 targets, such as ABCA1, increases circulating high-density lipoprotein cholesterol, and is well tolerated over 108 days of treatment. These findings demonstrate the efficacy and safety of an 8-mer LNA-antimiR against an miRNA family in a nonhuman primate metabolic disease model, suggesting that this could be a feasible approach for therapeutic targeting of miRNA families sharing the same seed sequence in human diseases. C1 [Rottiers, Veerle; Black, Joshua C.; Najafi-Shoushtari, Seyed Hani; Whetstine, Johnathan R.; Naerae, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Rottiers, Veerle; Najafi-Shoushtari, Seyed Hani; Naerae, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Obad, Susanna; Petri, Andreas; Lindholm, Marie W.; Hansen, Henrik F.; Kauppinen, Sakari] Santaris Pharma, DK-2970 Horsholm, Denmark. [Petri, Andreas; Kauppinen, Sakari] Aalborg Univ Hosp, Dept Haematol, DK-2450 Copenhagen SV, Denmark. [McGarrah, Robert; Sinha, Sumita; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [McGarrah, Robert; Sinha, Sumita; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [McGarrah, Robert] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Black, Joshua C.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [Goody, Robin J.; Lawrence, Matthew S.; Whittaker, Steve; Henry, Steve; Brookes, Rohn] RxGen Inc, Hamden, CT 06517 USA. [deLemos, Andrew S.; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Najafi-Shoushtari, Seyed Hani] Qatar Fdn, Weill Cornell Med Coll Qatar, Dept Cell & Dev Biol, Doha, Qatar. RP Kauppinen, S (reprint author), Santaris Pharma, DK-2970 Horsholm, Denmark. EM sk@bio.aau.dk; naar@helix.mgh.harvard.edu RI Lindholm, Marie/B-8736-2015; Black, Joshua/Q-2484-2015; OI Lindholm, Marie/0000-0003-4309-3203; Najafi-Shoushtari, Hani/0000-0002-7562-4083 FU U.S. NIH [R21DK084459, R01DK094184]; Partners Innovation Fund; NIH [DK078772, DK093216-01A1, R01GM097360, CA059267, RSG-13-115-01-CCG]; Neural Imaging Center as part of National Institute of Neurological Disorders and Stroke P30 Core Center [NS072030] FX This work was supported by the following grants to A.M.N.: U.S. NIH grants R21DK084459 and R01DK094184, and the Partners Innovation Fund. R. T. C. was supported by NIH grant DK078772 (mentorship grant), and A.S.d. by NIH DK093216-01A1 (F32 grant). J.R.W. was supported by NIH grants R01GM097360, CA059267, and RSG-13-115-01-CCG. The MGH Neurobiology Imaging facility is supported, in part, by the Neural Imaging Center as part of National Institute of Neurological Disorders and Stroke P30 Core Center grant NS072030. NR 33 TC 34 Z9 35 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 20 PY 2013 VL 5 IS 212 AR 212ra162 DI 10.1126/scitranslmed.3006840 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 258FF UT WOS:000327443900004 PM 24259050 ER PT J AU Kopeikina, KJ Wegmann, S Pitstick, R Carlson, GA Bacskai, BJ Betensky, RA Hyman, BT Spires-Jones, TL AF Kopeikina, Katherine J. Wegmann, Susanne Pitstick, Rose Carlson, George A. Bacskai, Brian J. Betensky, Rebecca A. Hyman, Bradley T. Spires-Jones, Tara L. TI Tau Causes Synapse Loss without Disrupting Calcium Homeostasis in the rTg4510 Model of Tauopathy SO PLOS ONE LA English DT Article ID ALZHEIMERS-DISEASE; MOUSE MODEL; AXONAL-TRANSPORT; IN-VIVO; CASPASE ACTIVATION; DENDRITIC SPINES; TANGLE FORMATION; TRANSGENIC MICE; NEURODEGENERATION; NEURONS AB Neurofibrillary tangles (NFTs) of tau are one of the defining hallmarks of Alzheimer's disease (AD), and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner. C1 [Kopeikina, Katherine J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Kopeikina, Katherine J.; Wegmann, Susanne; Bacskai, Brian J.; Hyman, Bradley T.; Spires-Jones, Tara L.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Wegmann, Susanne; Bacskai, Brian J.; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Boston, MA USA. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Spires-Jones, Tara L.] Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh, Midlothian, Scotland. RP Spires-Jones, TL (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM tara.spires-jones@ed.ac.uk FU National Institutes of Health [T32AG000277, AG026249, AG08487, R00AG33670, P50AG05134]; Alzheimer's Association; Harvard Catalyst; Harvard Neurodiscovery Center FX These studies were supported by National Institutes of HealthGrants T32AG000277, AG026249, AG08487, R00AG33670 and P50AG05134 as well as the Alzheimer's Association Zenith Award. Further support came from Harvard Catalyst and the Harvard Neurodiscovery Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 11 Z9 11 U1 1 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 NOV 20 PY 2013 VL 8 IS 11 AR UNSP e80834 DI 10.1371/journal.pone.0080834 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 256LY UT WOS:000327313100117 PM 24278327 ER PT J AU Stamatakis, AM Jennings, JH Ung, RL Blair, GA Weinberg, RJ Neve, RL Boyce, F Mattis, J Ramakrishnan, C Deisseroth, K Stuber, GD AF Stamatakis, Alice M. Jennings, Joshua H. Ung, Randall L. Blair, Grace A. Weinberg, Richard J. Neve, Rachael L. Boyce, Frederick Mattis, Joanna Ramakrishnan, Charu Deisseroth, Karl Stuber, Garret D. TI A Unique Population of Ventral Tegmental Area Neurons Inhibits the Lateral Habenula to Promote Reward SO NEURON LA English DT Article ID MIDBRAIN DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; RAT; RELEASE; STIMULATION; PROJECTIONS; PATHWAY; ACTIVATION AB Lateral habenula (LHb) neurons convey aversive and negative reward conditions through potent indirect inhibition of ventral tegmental area (VTA) dopaminergic neurons. Although VTA dopaminergic neurons reciprocally project to the LHb, the electrophysiological properties and the behavioral consequences associated with selective manipulations of this circuit are unknown. Here, we identify an inhibitory input to the LHb arising from a unique population of VTA neurons expressing dopaminergic markers. Optogenetic activation of this circuit resulted in no detectable dopamine release in LHb brain slices. Instead, stimulation produced GABA-mediated inhibitory synaptic transmission, which suppressed the firing of postsynaptic LHb neurons in brain slices and increased the spontaneous firing rate of VTA dopaminergic neurons in vivo. Furthermore, in vivo activation of this pathway produced reward-related phenotypes that were dependent on intra-LHb GABA(A) receptor signaling. These results suggest that noncanonical inhibitory signaling by these hybrid dopaminergic-GABAergic neurons act to suppress LHb output under rewarding conditions. C1 [Stamatakis, Alice M.; Jennings, Joshua H.; Stuber, Garret D.] Univ N Carolina, Neurobiol Curriculum, Chapel Hill, NC 27599 USA. [Stamatakis, Alice M.; Jennings, Joshua H.; Ung, Randall L.; Blair, Grace A.; Stuber, Garret D.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Stamatakis, Alice M.; Jennings, Joshua H.; Weinberg, Richard J.; Stuber, Garret D.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. [Weinberg, Richard J.; Stuber, Garret D.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Neve, Rachael L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Boyce, Frederick] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mattis, Joanna; Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Stuber, Garret D.] Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. RP Stuber, GD (reprint author), Univ N Carolina, Neurobiol Curriculum, Chapel Hill, NC 27599 USA. EM gstuber@med.unc.edu RI Stuber, Garret/E-1160-2011; OI Ramakrishnan, Charu/0000-0002-3474-6332; Weinberg, Richard/0000-0001-9689-7278 FU Whitehall Foundation; Brain and Behavior Research Foundation (NARSAD); Foundation of Hope; National Institutes of Health [DA032750, DA034472, NS039444] FX We thank V. Gukassyan and the University of North Carolina (UNC) Neuroscience Center Microscopy Core (P30 NS045892), and the members of the Stuber laboratory for discussion. We thank Kristen Phend and Susan Burette for technical assistance with histology and electron microscopy. We thank the UNC Vector Core Facility for viral packaging. This study was supported by The Whitehall Foundation, the Brain and Behavior Research Foundation (NARSAD), The Foundation of Hope, and National Institutes of Health grants DA032750 (to G.D.S), DA034472 (to A.M.S), and NS039444 (to R.J.W.) NR 57 TC 95 Z9 98 U1 4 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD NOV 20 PY 2013 VL 80 IS 4 BP 1039 EP 1053 DI 10.1016/j.neuron.2013.08.023 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 256AD UT WOS:000327281200019 PM 24267654 ER PT J AU Gaziano, JM Gaziano, TA AF Gaziano, J. Michael Gaziano, Thomas A. TI What's New With Measuring Cholesterol? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DISEASE C1 [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Boston, MA 02120 USA. [Gaziano, Thomas A.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02120 USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 7 TC 5 Z9 5 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 NOV 20 PY 2013 VL 310 IS 19 BP 2043 EP 2044 DI 10.1001/jama.2013.282775 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 253OQ UT WOS:000327098900018 PM 24240929 ER PT J AU Gaziano, JM Peterson, E AF Gaziano, J. Michael Peterson, Eric TI The Cardiovascular Disease Researcher SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Gaziano, J. Michael] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02120 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. [Peterson, Eric] Duke Univ, Med Ctr, Durham, NC USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 9 TC 1 Z9 1 U1 1 U2 4 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 NOV 20 PY 2013 VL 310 IS 19 BP 2048 EP 2049 DI 10.1001/jama.2013.282990 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 253OQ UT WOS:000327098900020 PM 24240931 ER PT J AU Mack, MJ Brennan, JM Brindis, R Carroll, J Edwards, F Grover, F Shahian, D Tuzcu, EM Peterson, ED Rumsfeld, JS Hewitt, K Shewan, C Michaels, J Christensen, B Christian, A O'Brien, S Holmes, D AF Mack, Michael J. Brennan, J. Matthew Brindis, Ralph Carroll, John Edwards, Fred Grover, Fred Shahian, David Tuzcu, E. Murat Peterson, Eric D. Rumsfeld, John S. Hewitt, Kathleen Shewan, Cynthia Michaels, Joan Christensen, Barb Christian, Alexander O'Brien, Sean Holmes, David CA STS ACC TVT Registry TI Outcomes Following Transcatheter Aortic Valve Replacement in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH-RISK PATIENTS; END-POINT DEFINITIONS; DEVICE SURVEILLANCE; MEDICAL DEVICES; IMPLANTATION; REGISTRY; STENOSIS AB IMPORTANCE Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for the treatment of severe, symptomatic aortic stenosis and inoperable status (in 2011) and high-risk but operable status (starting in 2012). A national registry (the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy [STS/ACC TVT] Registry) was initiated to meet a condition for Medicare coverage and also facilitates outcome assessment and comparison with other trials and international registries. OBJECTIVE To report the initial US commercial experience with TAVR. DESIGN, SETTING, AND PARTICIPANTS We obtained results from all eligible US TAVR cases (n=7710) from 224 participating registry hospitals following the Edwards Sapien XT device commercialization (November 2011-May 2013). MAIN OUTCOMES AND MEASURES Primary outcomes included all-cause in-hospital mortality and stroke following TAVR. Secondary analyses included procedural complications and outcomes by clinical indication and access site. Device implantation success was defined as successful vascular access, deployment of a single device in the proper anatomic position, appropriate valve function without either moderate or severe AR, and successful retrieval of the delivery system. Thirty-day outcomes are presented for a representative 3133 cases (40.6%) at 114 centers with at least 80% complete follow-up reporting. RESULTS The 7710 patients who underwent TAVR included 1559 (20%) cases that were inoperable and 6151 (80%) cases that were high-risk but operable. The median age was 84 years (interquartile range [IQR], 78-88 years); 3783 patients (49%) were women and the median STS predicted risk of mortality was 7% (IQR, 5%-11%). At baseline, 2176 patients (75%) were either not at all satisfied (1297 patients [45%]) or mostly dissatisfied (879 patients [30%]) with their symptom status; 2198 (72%) had a 5-m walk time longer than 6 seconds (slow gait speed). The most common vascular access approach was transfemoral (4972 patients [64%]), followed by transapical (2197 patients [29%]) and other alternative approaches (536 patients [7%]); successful device implantation occurred in 7069 patients (92%; 95% CI, 91%-92%). The observed incidence of in-hospital mortality was 5.5% (95% CI, 5.0%-6.1%). Other major complications included stroke (2.0%; 95% CI, 1.7%-2.4%), dialysis-dependent renal failure (1.9%; 95% CI, 1.6%-2.2%), and major vascular injury (6.4%; 95% CI, 5.8%-6.9%). Median hospital stay was 6 days (IQR, 4-10 days), with 4613 (63%) discharged home. Among patients with available follow-up at 30 days (n=3133), the incidence of mortality was 7.6% (95% CI, 6.7%-8.6%) (noncardiovascular cause, 52%); a stroke had occurred in 2.8% (95% CI, 2.3%-3.5%), new dialysis in 2.5% (95% CI, 2.0%-3.1%), and reintervention in 0.5% (95% CI, 0.3%-0.8%). CONCLUSIONS AND RELEVANCE Among patients undergoing TAVR at US centers in the STS/ACC TVT Registry, device implantation success was achieved in 92% of cases, the overall in-hospital mortality rate was 5.5%, and the stroke rate was 2.0%. Although these postmarket US approval findings are comparable with prior published trial data and international experience, long-term follow-up is essential to assess continued efficacy and safety. C1 [Mack, Michael J.] Heart Hosp Baylor Plano, Baylor Healthcare Syst, Plano, TX USA. [Brennan, J. Matthew; Peterson, Eric D.; Christensen, Barb; O'Brien, Sean] Duke Clin Res Inst, Durham, NC USA. [Brindis, Ralph] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carroll, John; Grover, Fred; Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA. [Edwards, Fred] Univ Florida, Jacksonville, FL USA. [Shahian, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tuzcu, E. Murat] Cleveland Clin, Cleveland, OH 44106 USA. [Hewitt, Kathleen; Michaels, Joan; Christensen, Barb] Amer Coll Cardiol, Washington, DC USA. [Shewan, Cynthia] Soc Thorac Surg, Chicago, IL USA. [Holmes, David] Mayo Clin, Rochester, MN USA. RP Mack, MJ (reprint author), Baylor Hlth Care Syst, 1100 Allied Dr, Plano, TX 75093 USA. EM michael.mack@baylorhealth.edu FU American College of Cardiology Foundation; Society of Thoracic Surgeons FX This study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. NR 22 TC 179 Z9 181 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 2013 VL 310 IS 19 BP 2069 EP 2077 DI 10.1001/jama.2013.282043 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 253OQ UT WOS:000327098900023 PM 24240934 ER PT J AU Geller, AC Clapp, RW Sober, AJ Gonsalves, L Mueller, L Christiansen, CL Shaikh, W Miller, DR AF Geller, Alan C. Clapp, Richard W. Sober, Arthur J. Gonsalves, Lou Mueller, Lloyd Christiansen, Cindy L. Shaikh, Waqas Miller, Donald R. TI Melanoma Epidemic: An Analysis of Six Decades of Data From the Connecticut Tumor Registry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; SUN PROTECTION; TRENDS; INCREASE; POPULATION; MORTALITY; PROGRAM; TIME AB Purpose Melanoma is the most commonly fatal form of skin cancer, with nearly 50,000 annual deaths worldwide. We sought to assess long-term trends in the incidence and mortality of melanoma in a state with complete and consistent registration. Methods We used data from the Connecticut Tumor Registry, the original National Cancer Institute SEER site, to determine trends in invasive melanoma (1950-2007), in situ melanoma (1973-2007), tumor thickness (1993-2007), mortality (1950-2007), and mortality to incidence (1950-2007) among the 19,973 and 3,635 Connecticut residents diagnosed with invasive melanoma (1950-2007) and who died as a result of melanoma (1950-2007), respectively. Main outcome measures included trends in incidence and mortality by age, sex, and birth cohort. Results In the initial period (1950-1954), a diagnosis of invasive melanoma was rare, with 1.9 patient cases per 100,000 for men and 2.6 patient cases per 100,000 for women. Between 1950 and 2007, overall incidence rates rose more than 17-fold in men (1.9 to 33.5 per 100,000) and more than nine-fold in women (2.6 to 25.3 per 100,000). During these six decades, mortality rates more than tripled in men (1.6 to 4.9 per 100,000) and doubled in women (1.3 to 2.6 per 100,000). Mortality rates were generally stable or decreasing in men and women through age 54 years. Conclusion Unremitting increases in incidence and mortality of melanoma call for a nationally coordinated effort to encourage and promote innovative prevention and early-detection efforts. C1 [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Clapp, Richard W.; Christiansen, Cindy L.; Miller, Donald R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, Donald R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Christiansen, Cindy L.; Miller, Donald R.] Vet Adm Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Gonsalves, Lou; Mueller, Lloyd] Connecticut Tumor Registry, Hartford, CT USA. [Shaikh, Waqas] Suny Downstate Med Ctr, New York, NY USA. RP Geller, AC (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave,Kresge 718, Boston, MA 02115 USA. EM ageller@hsph.harvard.edu FU National Cancer Institute [HHSN261201000024C]; State of Connecticut Department of Public Health [HHSN261201000024C] FX The Connecticut Tumor Registry is supported by Contract No. HHSN261201000024C between the National Cancer Institute and State of Connecticut Department of Public Health. NR 28 TC 33 Z9 34 U1 1 U2 4 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 NOV 20 PY 2013 VL 31 IS 33 BP 4172 EP 4178 DI 10.1200/JCO.2012.47.3728 PG 7 WC Oncology SC Oncology GA 253LM UT WOS:000327088000003 PM 24043747 ER PT J AU Karp, DD Lee, SJ Keller, SM Wright, GS Aisner, S Belinsky, SA Johnson, DH Johnston, MR Goodman, G Clamon, G Okawara, G Marks, R Frechette, E McCaskill-Stevens, W Lippman, SM Ruckdeschel, J Khuri, FR AF Karp, Daniel D. Lee, Sandra J. Keller, Steven M. Wright, Gail Shaw Aisner, Seena Belinsky, Steven Alan Johnson, David H. Johnston, Michael R. Goodman, Gary Clamon, Gerald Okawara, Gordon Marks, Randolph Frechette, Eric McCaskill-Stevens, Worta Lippman, Scott M. Ruckdeschel, John Khuri, Fadlo R. TI Randomized, Double-Blind, Placebo-Controlled, Phase III Chemoprevention Trial of Selenium Supplementation in Patients With Resected Stage I Non-Small-Cell Lung Cancer: ECOG 5597 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID 2ND PRIMARY TUMORS; BRONCHIAL SQUAMOUS METAPLASIA; FORMER SMOKERS; BETA-CAROTENE; VITAMIN-A; CARDIOVASCULAR-DISEASE; NECK-CANCER; PREVENTION; ISOTRETINOIN; RISK AB Purpose Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients and Methods Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 g versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. Results The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. Conclusion Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC. C1 [Karp, Daniel D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Johnson, David H.] Univ Texas Southwestern, Dallas, TX USA. [Lee, Sandra J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Keller, Steven M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Wright, Gail Shaw] Florida Canc Specialists, New Port Richey, FL USA. [Aisner, Seena] Univ Med & Dent New Jersey, New Jersey Med Sch, Canc Inst New Jersey, Newark, NJ 07103 USA. [Belinsky, Steven Alan] Lovelace Resp Res Inst, Albuquerque, NM USA. [Goodman, Gary] Swedish Med Ctr, Inst Canc, Seattle, WA USA. [Goodman, Gary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Clamon, Gerald] Univ Iowa, Iowa City, IA USA. [Marks, Randolph] Mayo Clin, Rochester, MN USA. [McCaskill-Stevens, Worta] NCI, Rockville, MD USA. [Lippman, Scott M.] Univ Calif San Diego, Ctr Canc, San Diego, CA 92103 USA. [Ruckdeschel, John] Intermt Healthcare, Salt Lake City, UT USA. [Khuri, Fadlo R.] Emory Univ, Atlanta, GA 30322 USA. [Johnston, Michael R.] Dalhousie Univ, Halifax, NS, Canada. [Johnston, Michael R.] Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. [Okawara, Gordon] McMaster Univ, Hamilton, ON, Canada. [Frechette, Eric] Hop Laval, Quebec City, PQ, Canada. RP Khuri, FR (reprint author), Emory Univ, Winship Canc Inst, 1365 C Clifton Rd NE, Atlanta, GA 30322 USA. EM fkhuri@emory.edu FU Public Health Service [CA037403, CA14958, CA80775, CA73590, CA107868, CA49957, CA31946, CA33601, CA32102, CA20319, CA25224, CA21661, CA37422]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Supported in part by Public Health Service Grants No. CA037403, CA14958, CA80775, CA73590, CA107868, CA49957, CA31946, CA33601, CA32102, CA20319, CA25224, CA21661, and CA37422 and grants from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services. NR 35 TC 21 Z9 21 U1 0 U2 8 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 NOV 20 PY 2013 VL 31 IS 33 BP 4179 EP + DI 10.1200/JCO.2013.49.2173 PG 12 WC Oncology SC Oncology GA 253LM UT WOS:000327088000004 PM 24002495 ER PT J AU Armand, P Nagler, A Weller, EA Devine, SM Avigan, DE Chen, YB Kaminski, MS Holland, HK Winter, JN Mason, JR Fay, JW Rizzieri, DA Hosing, CM Ball, ED Uberti, JP Lazarus, HM Mapara, MY Gregory, SA Timmerman, JM Andorsky, D Or, R Waller, EK Rotem-Yehudar, R Gordon, LI AF Armand, Philippe Nagler, Arnon Weller, Edie A. Devine, Steven M. Avigan, David E. Chen, Yi-Bin Kaminski, Mark S. Holland, H. Kent Winter, Jane N. Mason, James R. Fay, Joseph W. Rizzieri, David A. Hosing, Chitra M. Ball, Edward D. Uberti, Joseph P. Lazarus, Hillard M. Mapara, Markus Y. Gregory, Stephanie A. Timmerman, John M. Andorsky, David Or, Reuven Waller, Edmund K. Rotem-Yehudar, Rinat Gordon, Leo I. TI Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY; HEMATOLOGIC MALIGNANCIES; MARROW TRANSPLANTATION; SALVAGE CHEMOTHERAPY; SAFETY; PD-1; RECONSTITUTION; IMMUNOTHERAPY AB Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease. C1 [Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avigan, David E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nagler, Arnon] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Or, Reuven] Hadassah Med Ctr, IL-91120 Jerusalem, Israel. [Rotem-Yehudar, Rinat] CureTech, Yavne, Israel. [Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Kaminski, Mark S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Holland, H. Kent] Emory Univ, Northside Hosp, Atlanta, GA 30322 USA. [Waller, Edmund K.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Winter, Jane N.; Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Gregory, Stephanie A.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. [Mason, James R.] Scripps Clin, Los Angeles, CA USA. [Ball, Edward D.] Univ Calif San Diego, Moores Univ Calif San Diego Canc Ctr, Los Angeles, CA USA. [Timmerman, John M.; Andorsky, David] Univ Calif Los Angeles, Los Angeles, CA USA. [Fay, Joseph W.] Baylor Univ, Med Ctr, Baylor Res Inst, Dallas, TX USA. [Hosing, Chitra M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rizzieri, David A.] Duke Canc Ctr, Durham, NC USA. [Uberti, Joseph P.] Karmanos Canc Inst, Detroit, MI USA. [Mapara, Markus Y.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Mapara, Markus Y.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Gordon, LI (reprint author), Northwestern Univ, Feinberg Sch Med, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. EM l-gordon@northwestern.edu OI Winter, Jane/0000-0001-7542-3305; Gordon, Leo/0000-0003-1666-7064; Hosing, Chitra/0000-0003-0409-5556 FU CureTech; Millenium; Seattle Genetics; Onyx; Otsuka FX Research Funding: Arnon Nagler, CureTech; David E. Avigan, CureTech; Yi-Bin Chen, Millenium, Seattle Genetics, Onyx, Otsuka; H. Kent Holland, CureTech; Chitra M. Hosing, CureTech; Hillard M. Lazarus, CureTech NR 33 TC 188 Z9 197 U1 2 U2 16 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 NOV 20 PY 2013 VL 31 IS 33 BP 4199 EP 4206 DI 10.1200/JCO.2012.48.3685 PG 8 WC Oncology SC Oncology GA 253LM UT WOS:000327088000006 PM 24127452 ER PT J AU Yuan, C Bao, Y Wu, C Kraft, P Ogino, S Ng, K Qian, ZR Rubinson, DA Stampfer, MJ Giovannucci, EL Wolpin, BM AF Yuan, Chen Bao, Ying Wu, Chen Kraft, Peter Ogino, Shuji Kimmie Ng Qian, Zhi Rong Rubinson, Douglas A. Stampfer, Meir J. Giovannucci, Edward L. Wolpin, Brian M. TI Prediagnostic Body Mass Index and Pancreatic Cancer Survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; LIFE-STYLE; RISK; OBESITY; GROWTH; PANCREATICODUODENECTOMY; DISSEMINATION; ADIPONECTIN; DIAGNOSIS AB Purpose Although obesity is associated with increased incidence of pancreatic cancer, studies have not prospectively evaluated prediagnostic body mass index (BMI) and survival. Patients and Methods We analyzed survival by prediagnostic BMI assessed in 1986 among 902 patients from two large prospective cohorts diagnosed from 1988 to 2010. We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and stage. We evaluated the temporal association of BMI with survival by grouping reported BMI by 2-year lag-time intervals before diagnosis. Results The multivariable-adjusted HR for death was 1.53 (95% CI, 1.11 to 2.09) comparing patients with BMI 35 kg/m(2) with those with BMI < 25 kg/m(2) (P trend = .001), which was similar after adjustment for stage. The association of BMI with survival was stronger with longer lag times between reported BMI and cancer diagnosis. Among patients with BMI collected 18 to 20 years before diagnosis, HR for death was 2.31 (95% CI, 1.48 to 3.61; P trend < .001), comparing obese with healthy-weight patients. No statistically significant differences were seen by cohort, smoking status, or stage, although the association was stronger among never-smokers (HR, 1.61; 95% CI, 1.01 to 2.57; P trend = .002) than ever-smokers (HR, 1.36; 95% CI, 0.86 to 2.15; P trend = .63), comparing BMI 35 kg/m(2) with BMI < 25 kg/m(2). Higher prediagnostic BMI was associated with more advanced stage at diagnosis, with 72.5% of obese patients presenting with metastatic disease versus 59.4% of healthy-weight patients (P = .02). Conclusion Higher prediagnostic BMI was associated with statistically significantly decreased survival among patients with pancreatic cancer from two large prospective cohorts. C1 [Yuan, Chen; Ogino, Shuji; Kimmie Ng; Qian, Zhi Rong; Rubinson, Douglas A.; Wolpin, Brian M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Bao, Ying; Ogino, Shuji; Kimmie Ng; Stampfer, Meir J.; Giovannucci, Edward L.; Wolpin, Brian M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Wu, Chen; Kraft, Peter; Ogino, Shuji; Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org FU National Cancer Institute of the National Institutes of Health [K07 CA140790]; American Society of Clinical Oncology Conquer Cancer Foundation; Howard Hughes Medical Institute; Lustgarten Foundation; Promises for Purple; National Cancer Institute, National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, R01 CA49449, 1UM1 CA167552] FX Supported in part by Grant No. K07 CA140790 from the National Cancer Institute of the National Institutes of Health and by the American Society of Clinical Oncology Conquer Cancer Foundation, Howard Hughes Medical Institute, Lustgarten Foundation, and Promises for Purple (B. M. W.). The Nurses' Health Study and Health Professionals Follow-Up Study were supported by Grants No. P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, R01 CA49449, and 1UM1 CA167552 from the National Cancer Institute, National Institutes of Health. NR 34 TC 28 Z9 28 U1 0 U2 9 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 NOV 20 PY 2013 VL 31 IS 33 BP 4229 EP + DI 10.1200/JCO.2013.51.7532 PG 7 WC Oncology SC Oncology GA 253LM UT WOS:000327088000010 PM 24145341 ER PT J AU Jacobsen, ED AF Jacobsen, Eric D. TI Restoring Antitumor Immunity via PD-1 Blockade After Autologous Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID T-CELLS; EXPRESSION; CANCER; INFECTION; ANTIBODY; RECEPTOR; SAFETY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jacobsen, ED (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 3 Z9 4 U1 0 U2 2 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 NOV 20 PY 2013 VL 31 IS 33 BP 4268 EP + DI 10.1200/JCO.2013.51.7680 PG 4 WC Oncology SC Oncology GA 253LM UT WOS:000327088000015 PM 24127445 ER PT J AU Lathan, C Frank, DA AF Lathan, Christopher Frank, David A. TI Review: Low-dose CT screening reduces lung cancer and mortality in current or former smokers SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Lathan, Christopher; Frank, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lathan, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 19 PY 2013 VL 159 IS 10 AR JC3 DI 10.7326/0003-4819-159-10-201311190-02003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 276FB UT WOS:000328732700002 PM 24247693 ER PT J AU Feinberg, AW Ripplinger, CM van der Meer, P Sheehy, SP Domian, I Chien, KR Parker, KK AF Feinberg, Adam W. Ripplinger, Crystal M. van der Meer, Peter Sheehy, Sean P. Domian, Ibrahim Chien, Kenneth R. Parker, Kevin Kit TI Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes SO STEM CELL REPORTS LA English DT Article ID TISSUE IN-VITRO; CARDIAC-MUSCLE; SYNTHETIC STRANDS; PROGENITOR CELLS; THIN-FILMS; HEART; MURINE; TRANSPLANTATION; REGENERATION; ARCHITECTURE AB Stem cell-derived cardiomyocytes represent unique tools for cell-and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated. We reasoned that physiological metrics of engineered cardiac tissues offer a means of comparison. We built laminar myocardium engineered from cardiomyocytes that were differentiated from mouse embryonic stem cell-derived cardiac progenitors or harvested directly from neonatal mouse ventricles, and compared their anatomy and physiology in vitro. Tissues assembled from progenitor-derived myocytes and neonate myocytes demonstrated similar cytoskeletal architectures but different gap junction organization and electromechanical properties. Progenitor-derived myocardium had significantly less contractile stress and slower longitudinal conduction velocity than neonate-derived myocardium, indicating that the developmental state of the cardiomyocytes affects the electromechanical function of the resultant engineered tissue. These data suggest a need to establish performance metrics for future stem cell applications. C1 [Feinberg, Adam W.; Ripplinger, Crystal M.; Sheehy, Sean P.; Parker, Kevin Kit] Harvard Univ, Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA. [van der Meer, Peter; Domian, Ibrahim; Chien, Kenneth R.; Parker, Kevin Kit] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Feinberg, Adam W.; Ripplinger, Crystal M.; Sheehy, Sean P.; Domian, Ibrahim; Chien, Kenneth R.; Parker, Kevin Kit] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Feinberg, Adam W.; Ripplinger, Crystal M.; Sheehy, Sean P.; Parker, Kevin Kit] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [van der Meer, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. RP Parker, KK (reprint author), Harvard Univ, Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA. EM kkparker@seas.harvard.edu RI Feinberg, Adam/A-7103-2009 OI Feinberg, Adam/0000-0003-3338-5456 FU Progenitor Cell Biology Consortium [U01 HL100408-02]; Netherlands Organization for Scientific Research (VENI) [016106013]; National Heart Lung and Blood Institute, National Institutes of Health FX We thank the Harvard Center for Nanoscale Systems (CNS) for use of their soft-lithography facilities. This work was supported by grant U01 HL100408-02 from the Progenitor Cell Biology Consortium and the National Heart Lung and Blood Institute, National Institutes of Health. P.v.d.M. received financial support from the Netherlands Organization for Scientific Research (VENI grant 016106013). NR 44 TC 15 Z9 17 U1 2 U2 11 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 NOV 19 PY 2013 VL 1 IS 5 BP 387 EP 396 DI 10.1016/j.stemcr.2013.10.004 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1WV UT WOS:000336646800003 PM 24286027 ER PT J AU Papakostas, TD Lessell, S AF Papakostas, Thanos D. Lessell, Simmons TI Teaching Video NeuroImages: Pulsatile proptosis SO NEUROLOGY LA English DT Editorial Material ID EXOPHTHALMOS C1 [Papakostas, Thanos D.; Lessell, Simmons] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Neuroophthalmol Serv, Boston, MA 02114 USA. RP Papakostas, TD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Neuroophthalmol Serv, Boston, MA 02114 USA. EM thanos_papakostas@meei.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 19 PY 2013 VL 81 IS 21 BP E160 EP E160 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AA0FL UT WOS:000330770900003 PM 24249796 ER PT J AU Dombi, E Ardern-Holmes, SL Babovic-Vuksanovic, D Barker, FG Connor, S Evans, DG Fisher, MJ Goutagny, S Harris, GJ Jaramillo, D Karajannis, MA Korf, BR Mautner, V Plotkin, SR Poussaint, TY Robertson, K Shih, CS Widemann, BC AF Dombi, Eva Ardern-Holmes, Simone L. Babovic-Vuksanovic, Dusica Barker, Fred G. Connor, Steve Evans, D. Gareth Fisher, Michael J. Goutagny, Stephane Harris, Gordon J. Jaramillo, Diego Karajannis, Matthias A. Korf, Bruce R. Mautner, Victor Plotkin, Scott R. Poussaint, Tina Y. Robertson, Kent Shih, Chie-Schin Widemann, Brigitte C. CA REiNS Int Collaboration TI Recommendations for imaging tumor response in neurofibromatosis clinical trials SO NEUROLOGY LA English DT Article ID PHASE-I TRIAL; VESTIBULAR SCHWANNOMA GROWTH; PLEXIFORM NEUROFIBROMAS; NATURAL-HISTORY; GRADE GLIOMAS; SOLID TUMORS; TYPE-2; CHILDREN; CRITERIA; NEUROONCOLOGY AB Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors. C1 [Dombi, Eva; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Ardern-Holmes, Simone L.] Childrens Hosp Westmead, Dept Neurol, Sydney, NSW, Australia. [Babovic-Vuksanovic, Dusica] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Barker, Fred G.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Connor, Steve] Kings Coll Hosp London, Dept Neuroradiol, London, England. [Evans, D. Gareth] St Marys Hosp, Dept Med Genet, MAHSC, Manchester M13 0JH, Lancs, England. [Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Jaramillo, Diego] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Fisher, Michael J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Goutagny, Stephane] Hop Beaujon, Dept Neurosurg, Clichy, France. [Karajannis, Matthias A.] NYU Langone Med Ctr, Div Pediat Hematol Oncol, New York, NY USA. [Karajannis, Matthias A.] NYU Langone Med Ctr, NYU Canc Inst, New York, NY USA. [Korf, Bruce R.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Mautner, Victor] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany. [Poussaint, Tina Y.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Robertson, Kent; Shih, Chie-Schin] James Whitcomb Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA. RP Dombi, E (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM dombie@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 35 TC 20 Z9 20 U1 0 U2 2 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 NOV 19 PY 2013 VL 81 IS 21 SU 1 BP S33 EP S40 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 304GH UT WOS:000330734600005 PM 24249804 ER PT J AU Plotkin, SR Ardern-Holmes, SL Barker, FG Blakeley, JO Evans, DG Ferner, RE Hadlock, TA Halpin, C AF Plotkin, Scott R. Ardern-Holmes, Simone L. Barker, Fred G., II Blakeley, Jaishri O. Evans, D. Gareth Ferner, Rosalie E. Hadlock, Tessa A. Halpin, Chris CA REiNS Int Collaboration TI Hearing and facial function outcomes for neurofibromatosis 2 clinical trials SO NEUROLOGY LA English DT Article ID NERVE GRADING SYSTEMS; VESTIBULAR SCHWANNOMAS; ACOUSTIC NEUROMA; HOUSE-BRACKMANN; TYPE-2; PRESERVATION; QUESTIONNAIRE; BEVACIZUMAB; REANIMATION; EXCURSION AB Objectives: Vestibular schwannomas are the hallmark of neurofibromatosis 2 (NF2), occurring in > 95% of patients. These tumors develop on the vestibulocochlear nerve and are associated with significant morbidity due to hearing loss, tinnitus, imbalance, facial weakness, and risk of early mortality from brainstem compression. Although hearing loss and facial weakness have been identified as important functional outcomes for patients with NF2, there is a lack of consensus regarding appropriate endpoints in clinical trials. Methods: The functional outcomes group reviewed existing endpoints for hearing and facial function and developed consensus recommendations for response evaluation in NF2 clinical trials. Results: For hearing endpoints, the functional group endorsed the use of maximum word recognition score as a primary endpoint, with the 95% critical difference as primary hearing outcomes. The group recommended use of the scaled measurement of improvement in lip excursion (SMILE) system for studies of facial function. Conclusions: These recommendations are intended to provide researchers with a common set of endpoints for use in clinical trials of patients with NF2. The use of common endpoints should improve the quality of clinical trials and foster comparison among studies for hearing loss and facial weakness. C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Ardern-Holmes, Simone L.] Univ Sydney, Dept Neurol & Neurosurg, Childrens Hosp Westmead, Sydney, NSW 2006, Australia. [Blakeley, Jaishri O.] Johns Hopkins Med Inst, Dept Neurol & Oncol, Baltimore, MD USA. [Evans, D. Gareth] St Marys Hosp, Univ Dept Med Genet, Manchester M13 0JH, Lancs, England. [Ferner, Rosalie E.] Guys & St Thomas NHS Fdn Trust, Dept Neurol, London, England. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Halpin, Chris] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM splotkin@partners.org FU American Academy of Neurology; Children's Tumor Foundation; Department of Defense [W81XWH-091-0182, NF050202, W81XWH-12-1-0155]; Johns Hopkins Medical Institutes; Novartis Pharmaceuticals Australia; Children's Tumor Foundation of Australia; American Society of Clinical Oncology; GlaxoSmithKline; Sanofi-Aventis; Eli Lilly; Cancer Therapy Evaluation Program; Samantha Dickenson Brain Tumor Trust; Cancer Research-UK; Association of International Cancer Research; Medical Research Council; British Skin Foundation; CLAHRC for Greater Manchester; CMFT RfPB; BDRF; Genome Canada; Genesis Breast Cancer Prevention Appeal; Children with Cancer UK; European Neurofibromatosis Association; CLAVE; NIH/NIDCD [1R21DC012407-0181, 1U01DC010811-01A1] FX S. Plotkin has been reimbursed by the American Academy of Neurology and the Children's Tumor Foundation for travel for educational activities. He has received research support from the Department of Defense (W81XWH-091-0182, NF050202, W81XWH-12-1-0155, PI), the Children's Tumor Foundation (PI), and Johns Hopkins Medical Institutes (site PI). S. Ardern-Holmes served on a scientific advisory board for Novartis Pharmaceuticals Australia, received funding for a trip from Novartis Pharmaceuticals Australia, and receives research support from The Children's Tumor Foundation of Australia. F. Barker served as a scientific reviewer for the Department of Defense CDMRP panels on neurofibromatosis and tuberous sclerosis. He serves as section editor for Neurosurgery and has received travel expenses for lectures and educational activities not funded by industry. J. Blakeley received travel support from the Children's Tumor Foundation, the American Academy of Neurology, and the American Society of Clinical Oncology. She receives research support from GlaxoSmithKline, Sanofi-Aventis, Eli Lilly, the Cancer Therapy Evaluation Program, and the Children's Tumor Foundation. D. Evans has served on the scientific advisory boards of Breast Cancer Campaign and the Genesis Breast Cancer Prevention Appeal. He is on the editorial board of Familial Cancer. He received research support from the Samantha Dickenson Brain Tumor Trust, Cancer Research-UK, the Children's Tumor Foundation, the Association of International Cancer Research, the Medical Research Council, the British Skin Foundation, CLAHRC for Greater Manchester, CMFT RfPB, BDRF, Genome Canada, Genesis Breast Cancer Prevention Appeal, and Children with Cancer UK. R. Ferner received funding for travel from the Children's Tumor Foundation and the European Neurofibromatosis Association. She receives royalties from Springer for the book Neurofibromatoses in Clinical Practice. T. Hadlock reports no disclosures. C. Halpin received travel funding from CLAVE. He is an associate editor for the Journal of Speech, Language, and Hearing Research. He receives research support from NIH/NIDCD grants 1R21DC012407-0181 and 1U01DC010811-01A1, as well as Department of Defense grant W81XWH-12-1-0155. Go to Neurology. org for full disclosures. NR 35 TC 6 Z9 6 U1 2 U2 2 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 NOV 19 PY 2013 VL 81 IS 21 SU 1 BP S25 EP S32 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 304GH UT WOS:000330734600004 PM 24249803 ER PT J AU Plotkin, SR Blakeley, JO Dombi, E Fisher, MJ Hanemann, CO Walsh, KS Wolters, PL Widemann, BC AF Plotkin, Scott R. Blakeley, Jaishri O. Dombi, Eva Fisher, Michael J. Hanemann, C. Oliver Walsh, Karin S. Wolters, Pamela L. Widemann, Brigitte C. TI Achieving consensus for clinical trials The REiNS International Collaboration SO NEUROLOGY LA English DT Article ID PHASE-I TRIAL; NEUROFIBROMATOSIS TYPE-I; PLEXIFORM NEUROFIBROMAS; SOLID TUMORS; CHILDREN; TYPE-1; PIRFENIDONE; THERAPY AB The neurofibromatoses (NF)-including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis-are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Blakeley, Jaishri O.] Johns Hopkins, Dept Neurol Neurosurg & Oncol, Baltimore, MD USA. [Dombi, Eva; Wolters, Pamela L.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Fisher, Michael J.] Childrens Hosp Penn, Dept Pediat, Div Oncol, Philadelphia, PA USA. [Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England. [Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England. [Walsh, Karin S.] Childrens Natl Med Ctr, Jennifer & Daniel Gilbert Neurofibromatosis Inst, Washington, DC 20010 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM splotkin@partners.org FU Children's Tumor Foundation FX Supported by the Children's Tumor Foundation. NR 22 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 19 PY 2013 VL 81 IS 21 SU 1 BP S1 EP S5 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 304GH UT WOS:000330734600001 PM 24249801 ER PT J AU Widemann, BC Blakeley, JO Dombi, E Fisher, MJ Hanemann, CO Walsh, KS Wolters, PL Plotkin, SR AF Widemann, Brigitte C. Blakeley, Jaishri O. Dombi, Eva Fisher, Michael J. Hanemann, Clemens O. Walsh, Karin S. Wolters, Pamela L. Plotkin, Scott R. TI Conclusions and future directions for the REiNS International Collaboration SO NEUROLOGY LA English DT Article ID PLEXIFORM NEUROFIBROMAS; RESPONSE ASSESSMENT; GRADE GLIOMAS; WORKING GROUP; NEUROONCOLOGY; SCHWANNOMATOSIS; INHIBITOR; DEFICITS; CHILDREN; TRIALS AB The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development. The REiNS recommendations are made based on current knowledge. Experience with the use of the recommended endpoints in clinical trials, development of new tools and technologies, new knowledge of the natural history of NF, and advances in the methods used to analyze endpoints will likely lead to modifications of the currently proposed guidelines, which will be shared with the NF research community through the REiNS Web site www.reinscollaboration.org. Due to the clinical complexity of NF, there is a need to seek expertise from multiple medical disciplines, regulatory agencies, and industry to develop trial endpoints and designs, which will lead to the identification and approval of effective treatments for NF tumor and nontumor manifestations. The REiNS Collaboration welcomes anyone interested in providing his or her expertise toward this effort. C1 [Widemann, Brigitte C.; Dombi, Eva; Wolters, Pamela L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Blakeley, Jaishri O.] Johns Hopkins, Dept Neurol Neurosurg & Oncol, Baltimore, MD USA. [Fisher, Michael J.] Childrens Hosp Penn, Dept Pediat, Div Oncol, Philadelphia, PA USA. [Hanemann, Clemens O.] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England. [Hanemann, Clemens O.] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England. [Walsh, Karin S.] Childrens Natl Med Ctr, Jennifer & Daniel Gilbert Neurofibromatosis Inst, Washington, DC 20010 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov FU Children's Tumor Foundation; intramural research program of the Center for Cancer Research, NCI FX Supported by the Children's Tumor Foundation and the intramural research program of the Center for Cancer Research, NCI. NR 15 TC 6 Z9 6 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 NOV 19 PY 2013 VL 81 IS 21 SU 1 BP S41 EP S44 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 304GH UT WOS:000330734600006 PM 24249805 ER PT J AU Wolters, PL Martin, S Merker, VL Gardner, KL Hingtgen, CM Tonsgard, JH Schorry, EK Baldwin, A AF Wolters, Pamela L. Martin, Staci Merker, Vanessa L. Gardner, Kathy L. Hingtgen, Cynthia M. Tonsgard, James H. Schorry, Elizabeth K. Baldwin, Andrea CA REiNS Int Collaboration TI Patient-reported outcomes in neurofibromatosis and schwannomatosis clinical trials SO NEUROLOGY LA English DT Article ID QUALITY-OF-LIFE; PAIN INTENSITY; RATING-SCALES; PLEXIFORM NEUROFIBROMAS; SELF-REPORT; CHILDREN; CANCER; RECOMMENDATIONS; SURGERY AB Objectives: Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include patient-reported outcomes (PROs) as endpoints to assess treatment effects on various aspects of QOL, but there is no consensus on the selection and use of such measures in NF. This article describes the PRO Working Group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Collaboration, its main goals, methods for identifying appropriate PRO measures for NF clinical trials, and recommendations for assessing pain intensity. Methods: The REiNS PRO group selected core endpoint domains important to assess in NF. The members developed criteria to rate PRO measures, including patient characteristics, psychometric properties, and feasibility, and utilized a systematic process to evaluate PROs for NF clinical trials. Within the subdomain of pain intensity, the group reviewed the Numerical Rating Scale-11 (NRS-11), the Visual Analogue Scale, and the Faces Pain Scale-Revised using this process. Results: Based on the review criteria, each of these pain intensity scales is brief, reliable, valid, and widely used. However, the NRS-11 was given the highest rating for use in NF clinical trials due to recommendations from pain experts and other consensus groups, its extensive use in research, strong psychometric data including sensitivity to change, and excellent feasibility in ages >= 8 years. Conclusions: The systematic review criteria and process are effective for identifying appropriate PRO measures and provide information utilized by the REiNS Collaboration to achieve consensus regarding PROs in NF clinical trials. C1 [Wolters, Pamela L.; Martin, Staci; Baldwin, Andrea] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Merker, Vanessa L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gardner, Kathy L.] Vet Adm Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gardner, Kathy L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Hingtgen, Cynthia M.] Michigan State Univ, Dept Clin Neurosci, Spectrum Hlth Med Grp, E Lansing, MI 48824 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Tonsgard, James H.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Schorry, Elizabeth K.] Cincinnati Childrens Hosp, Div Human Genet, Cincinnati, OH USA. RP Wolters, PL (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM woltersp@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute FX This research is supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 38 TC 12 Z9 12 U1 2 U2 6 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 NOV 19 PY 2013 VL 81 IS 21 SU 1 BP S6 EP S14 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 304GH UT WOS:000330734600002 PM 24249806 ER PT J AU Goldzweig, CL Orshansky, G Paige, NM Towfigh, AA Haggstrom, DA Miake-Lye, I Beroes, JM Shekelle, PG AF Goldzweig, Caroline Lubick Orshansky, Greg Paige, Neil M. Towfigh, Ali Alexander Haggstrom, David A. Miake-Lye, Isomi Beroes, Jessica M. Shekelle, Paul G. TI Electronic Patient Portals: Evidence on Health Outcomes, Satisfaction, Efficiency, and Attitudes SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; SHARED MEDICAL-RECORD; CONGESTIVE-HEART-FAILURE; INFORMATION-TECHNOLOGY; HYPERTENSION CONTROL; COLLABORATIVE CARE; ONLINE; EXPERIENCES; INTERNET; ACCESS AB Background: Patient portals tied to provider electronic health record (EHR) systems are increasingly popular. Purpose: To systematically review the literature reporting the effect of patient portals on clinical care. Data Sources: PubMed and Web of Science searches from 1 January 1990 to 24 January 2013. Study Selection: Hypothesis-testing or quantitative studies of patient portals tethered to a provider EHR that addressed patient outcomes, satisfaction, adherence, efficiency, utilization, attitudes, and patient characteristics, as well as qualitative studies of barriers or facilitators, were included. Data Extraction: Two reviewers independently extracted data and addressed discrepancies through consensus discussion. Data Synthesis: From 6508 titles, 14 randomized, controlled trials; 21 observational, hypothesis-testing studies; 5 quantitative, descriptive studies; and 6 qualitative studies were included. Evidence is mixed about the effect of portals on patient outcomes and satisfaction, although they may be more effective when used with case management. The effect of portals on utilization and efficiency is unclear, although patient race and ethnicity, education level or literacy, and degree of comorbid conditions may influence use. Limitation: Limited data for most outcomes and an absence of reporting on organizational and provider context and implementation processes. Conclusion: Evidence that patient portals improve health outcomes, cost, or utilization is insufficient. Patient attitudes are generally positive, but more widespread use may require efforts to overcome racial, ethnic, and literacy barriers. Portals represent a new technology with benefits that are still unclear. Better understanding requires studies that include details about context, implementation factors, and cost. C1 Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. Indianapolis Vet Affairs Med Ctr, Indianapolis, IN USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Goldzweig, CL (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111-G, Los Angeles, CA 90073 USA. EM caroline.goldzweig@va.gov FU U.S. Department of Veterans Affairs FX U.S. Department of Veterans Affairs. NR 53 TC 84 Z9 84 U1 6 U2 30 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 NOV 19 PY 2013 VL 159 IS 10 BP 677 EP + DI 10.7326/0003-4819-159-10-201311190-00006 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 276FB UT WOS:000328732700016 PM 24247673 ER PT J AU Akeju, O Brown, EN AF Akeju, Oluwaseun Brown, Emery N. TI Awakened by a sleeping pill SO ELIFE LA English DT Editorial Material ID COMA C1 [Akeju, Oluwaseun; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Dept Brain & Cognit Sci, Cambridge, MA USA. RP Akeju, O (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM enb@neurostat.mit.edu NR 6 TC 0 Z9 0 U1 0 U2 4 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD NOV 19 PY 2013 VL 2 AR e01658 DI 10.7554/eLife.01658 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274YJ UT WOS:000328641800007 PM 24252876 ER PT J AU Lee, J Sugiyama, T Liu, YH Wang, J Gu, X Lei, J Markmann, JF Miyazaki, S Miyazaki, JI Szot, GL Bottino, R Kim, SK AF Lee, Jonghyeob Sugiyama, Takuya Liu, Yinghua Wang, Jing Gu, Xueying Lei, Ji Markmann, James F. Miyazaki, Satsuki Miyazaki, Jun-ichi Szot, Gregory L. Bottino, Rita Kim, Seung K. TI Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells SO ELIFE LA English DT Article ID PLURIPOTENT STEM-CELLS; ADULT HUMAN PANCREAS; BETA-LIKE CELLS; PROGENITOR CELLS; HUMAN ISLETS; IN-VITRO; HUMAN FIBROBLASTS; MOUSE PANCREAS; IPS CELLS; DIFFERENTIATION AB Pancreatic islet beta-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional beta-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native beta-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark beta-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. C1 [Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Kim, Seung K.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. [Lei, Ji; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Miyazaki, Satsuki; Miyazaki, Jun-ichi] Osaka Univ, Grad Sch Med, Div Stem Cell Regulat Res, Osaka, Japan. [Szot, Gregory L.] Univ Calif San Francisco, UCSF Transplantat Surg, San Francisco, CA 94143 USA. [Bottino, Rita] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pediat,Div Immunogenet, Pittsburgh, PA USA. [Kim, Seung K.] Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Med,Oncol Div, Stanford, CA 94305 USA. RP Kim, SK (reprint author), Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. EM seungkim@stanford.edu RI Miyazaki, Jun-ichi/N-1976-2015 OI Miyazaki, Jun-ichi/0000-0003-2475-589X FU JDRF [43-2010-347]; Howard Hughes Medical Institute; Larry L Hillblom Foundation [2008-D-018-FEL] FX JDRF 43-2010-347 Jonghyeob Lee, Jing Wang, Seung K Kim; Howard Hughes Medical Institute Seung K Kim; Larry L Hillblom Foundation 2008-D-018-FEL Jonghyeob Lee NR 70 TC 45 Z9 48 U1 2 U2 15 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD NOV 19 PY 2013 VL 2 AR e00940 DI 10.7554/eLife.00940 PG 22 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274YJ UT WOS:000328641800001 PM 24252877 ER PT J AU Masoudi, FA Ponirakis, A Yeh, RW Maddox, TM Beachy, J Casale, PN Curtis, JP De Lemos, J Fonarow, G Heidenreich, P Koutras, C Kremers, M Messenger, J Moussa, I Oetgen, WJ Roe, MT Rosenfield, K Shields, TP Spertus, JA Wei, J White, C Young, CH Rumsfeld, JS AF Masoudi, Frederick A. Ponirakis, Angelo Yeh, Robert W. Maddox, Thomas M. Beachy, Jim Casale, Paul N. Curtis, Jeptha P. De Lemos, James Fonarow, Gregg Heidenreich, Paul Koutras, Christina Kremers, Mark Messenger, John Moussa, Issam Oetgen, William J. Roe, Matthew T. Rosenfield, Kenneth Shields, Thomas P., Jr. Spertus, John A. Wei, Jessica White, Christopher Young, Christopher H. Rumsfeld, John S. TI Cardiovascular Care Facts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiovascular disease; quality of care; registries; registry ID PERCUTANEOUS CORONARY INTERVENTION; DATA REGISTRY; PROGRAM AB Objectives The aim of this report was to characterize the patients, participating centers, and measures of quality of care and outcomes for 5 NCDR (National Cardiovascular Data Registry) programs: 1) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry-GWTG (Get With The Guidelines) for acute coronary syndromes; 2) CathPCI Registry for coronary angiography and percutaneous coronary intervention; 3) CARE (Carotid Artery Revascularization and Endarterectomy) Registry for carotid revascularization; 4) ICD Registry for implantable cardioverter defibrillators; and the 5) PINNACLE (Practice INNovation And CLinical Excellence) Registry for outpatients with cardiovascular disease (CVD). Background CVD is a leading cause of death and disability in the United States. The quality of care for patients with CVD is suboptimal. National registry programs, such as NCDR, permit assessments of the quality of care and outcomes for broad populations of patients with CVD. Methods For the year 2011, we assessed for each of the 5 NCDR programs: 1) demographic and clinical characteristics of enrolled patients; 2) key characteristics of participating centers; 3) measures of processes of care; and 4) patient outcomes. For selected variables, we assessed trends over time. Results In 2011 ACTION Registry-GWTG enrolled 119,967 patients in 567 hospitals; CathPCI enrolled 632,557 patients in 1,337 hospitals; CARE enrolled 4,934 patients in 130 hospitals; ICD enrolled 139,991 patients in 1,435 hospitals; and PINNACLE enrolled 249,198 patients (1,436,328 individual encounters) in 74 practices (1,222 individual providers). Data on performance metrics and outcomes, in some cases risk-adjusted with validated NCDR models, are presented. Conclusions The NCDR provides a unique opportunity to understand the characteristics of large populations of patients with CVD, the centers that provide their care, quality of care provided, and important patient outcomes. (C) 2013 by the American College of Cardiology Foundation C1 [Masoudi, Frederick A.; Maddox, Thomas M.; Messenger, John; Rumsfeld, John S.] Univ Colorado, Dept Med, Aurora, CO USA. [Masoudi, Frederick A.; Maddox, Thomas M.; Rumsfeld, John S.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Ponirakis, Angelo; Beachy, Jim; Koutras, Christina; Oetgen, William J.; Shields, Thomas P., Jr.; Wei, Jessica] Amer Coll Cardiol Fdn, Washington, DC USA. [Yeh, Robert W.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Maddox, Thomas M.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Dept Med, Denver, CO USA. [Casale, Paul N.] Heart Grp Lancaster Gen Hlth, Lancaster, PA USA. [Curtis, Jeptha P.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [De Lemos, James] Univ Texas Southwestern, Dept Med, Dallas, TX USA. [Fonarow, Gregg] Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA 90024 USA. [Heidenreich, Paul] Vet Affairs Palo Alto Med Ctr, Dept Med, Palo Alto, CA USA. [Kremers, Mark] Mid Carolina Cardiol & Presbyterian Hosp, Charlotte, NC USA. [Moussa, Issam] Mayo Clin, Div Cardiovasc Dis, Jacksonville, FL 32224 USA. [Roe, Matthew T.] Duke Cardiovasc Res Inst, Durham, NC USA. [Spertus, John A.] Midamer Heart Inst, Div Cardiovasc Dis, Kansas City, KS USA. [White, Christopher] Ochsner Clin Fdn, Dept Cardiovasc Dis, New Orleans, LA USA. [Young, Christopher H.] Moran Co, Arlington, VA USA. RP Masoudi, FA (reprint author), Campus Box B132,12401 East 17th Ave,Room 522, Aurora, CO 80045 USA. EM fred.masoudi@ucdenver.edu FU VA Health Services Research & Development Career Development Award; American College of Cardiology; Centers for Medicaid and Medicare Services; Janssen Pharmaceuticals; Agency for Healthcare Research and Quality FX Dr. Ponirakis, Mr. Beachy, Mrs. Koutras, Dr. Oetgen, Mr. Shields, and Ms. Wei are employed by the American College of Cardiology Foundation (ACCF). Dr. Maddox is Chair of the PINNACLE (Practice INNovation And CLinical Excellence) Registry Research & Publication Committee and is funded by a VA Health Services Research & Development Career Development Award. Dr. Casale is the Chair of the PINNACLE Registry Steering Committee. Dr. Curtis receives salary support through a contract with the American College of Cardiology to provide data analytic services, salary support under contract with Centers for Medicaid and Medicare Services to develop and maintain quality measures, reports stock holding in Medtronic, and has received research funding from Boston Scientific. Dr. De Lemos receives grant support from Roche Diagnostics and Abbott Diagnostics; consulting fees from Janssen Pharmaceuticals; and honoraria from Astra Zeneca and BMS. Dr. Fonarow receives research support from the Agency for Healthcare Research and Quality; serves as a consultant for Novartis, Medtronic, and Gambro; and has served as unpaid Chair of the ACTION Registry-GWTG Steering Committee. Dr. Kremers has equity >$10K in Boston Scientific; provides consulting for Medtronic; is a member of the Speakers' bureau for Boston Scientific; and is an investigator for St. Jude Medical, Medtronic, Boston Scientific, and Cameron Health. Dr. Messenger is Chair of the CathPCI Registry Research and Publication Committee. Dr. Moussa is an investigator on research protocols sponsored by Medtronic, Gilead, Baxter, and Terumo. Dr. Roe has received research funding from Eli Lilly, Revalesio, Sanofi-Aventis, American College of Cardiology, American Heart Association; and consulting fees or honoraria from AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Merck, Regeneron, and Daiichi-Sankyo. Dr. Rosenfield has received research grants from Abbott Vascular, Atrium, LutronixBard, Baxter, and IDEV; has received consulting/advisory board fees from Abbott Vascular, Complete Conference Management, Endospan, Micell and VortexAngioDynamics; has equity in CardioMEMs, Contego, Embolitech, Icon, Micell, Primacea, and Vortex; and has served on the board of directors for VIVA Physicians (501C3). Dr. Spertus is affiliated with the Saint Luke's Mid America Heart and Institute, which is the major analytic center for the PINNACLE Registry; receives funding from the American College of Cardiology for this role; is on the Scientific Advisory Board of United Healthcare; and reports a financial relationship with Health Outcomes Sciences. Dr. Rumsfeld has a contract with the ACCF for his role as the Chief Medical Officer of the NCDR. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 7 TC 53 Z9 53 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 19 PY 2013 VL 62 IS 21 BP 1931 EP 1947 DI 10.1016/j.jacc.2013.05.099 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251ON UT WOS:000326939500006 PM 24036027 ER PT J AU Holmes, MV Simon, T Exeter, HJ Folkersen, L Asselbergs, FW Guardiola, M Cooper, JA Palmen, J Hubacek, JA Carruthers, KF Horne, BD Brunisholz, KD Mega, JL Van Iperen, EPA Li, MY Leusink, M Trompet, S Verschuren, JJW Hovingh, GK Dehghan, A Nelson, CP Kotti, S Danchin, N Scholz, M Haase, CL Rothenbacher, D Swerdlow, DI Kuchenbaecker, KB Staines-Urias, E Goel, A van 't Hooft, F Gertow, K de Faire, U Panayiotou, AG Tremoli, E Baldassarre, D Veglia, F Holdt, LM Beutner, F Gansevoort, RT Navis, GJ Leach, IM Breitling, LP Brenner, H Thiery, J Dallmeier, D Franco-Cereceda, A Boer, JMA Stephens, JW Hofker, MH Tedgui, A Hofman, A Uitterlinden, AG Adamkova, V Pitha, J Onland-Moret, NC Cramer, MJ Nathoe, HM Spiering, W Klungel, OH Kumari, M Whincup, PH Morrow, DA Braund, PS Hall, AS Olsson, AG Doevendans, PA Trip, MD Tobin, MD Hamsten, A Watkins, H Koenig, W Nicolaides, AN Teupser, D Day, INM Carlquist, JF Gaunt, TR Ford, I Sattar, N Tsimikas, S Schwartz, GG Lawlor, DA Morris, RW Sandhu, MS Poledne, R Maitland-van der Zee, AH Khaw, KT Keating, BJ van der Harst, P Price, JF Mehta, SR Yusuf, S Witteman, JCM Franco, OH Jukema, JW de Knijff, P Tybjaerg-Hansen, A Rader, DJ Farrall, M Samani, NJ Kivimaki, M Fox, KAA Humphries, SE Anderson, JL Boekholdt, SM Palmer, TM Eriksson, P Pare, G Hingorani, AD Sabatine, MS Mallat, Z Casas, JP Talmud, PJ AF Holmes, Michael V. Simon, Tabassome Exeter, Holly J. Folkersen, Lasse Asselbergs, Folkert W. Guardiola, Montse Cooper, Jackie A. Palmen, Jutta Hubacek, Jaroslav A. Carruthers, Kathryn F. Horne, Benjamin D. Brunisholz, Kimberly D. Mega, Jessica L. Van Iperen, Erik P. A. Li, Mingyao Leusink, Maarten Trompet, Stella Verschuren, Jeffrey J. W. Hovingh, G. Kees Dehghan, Abbas Nelson, Christopher P. Kotti, Salma Danchin, Nicolas Scholz, Markus Haase, Christiane L. Rothenbacher, Dietrich Swerdlow, Daniel I. Kuchenbaecker, Karoline B. Staines-Urias, Eleonora Goel, Anuj van 't Hooft, Ferdinand Gertow, Karl de Faire, Ulf Panayiotou, Andrie G. Tremoli, Elena Baldassarre, Damiano Veglia, Fabrizio Holdt, Lesca M. Beutner, Frank Gansevoort, Ron T. Navis, Gerjan J. Leach, Irene Mateo Breitling, Lutz P. Brenner, Hermann Thiery, Joachim Dallmeier, Dhayana Franco-Cereceda, Anders Boer, Jolanda M. A. Stephens, Jeffrey W. Hofker, Marten H. Tedgui, Alain Hofman, Albert Uitterlinden, Andre G. Adamkova, Vera Pitha, Jan Onland-Moret, N. Charlotte Cramer, Maarten J. Nathoe, Hendrik M. Spiering, Wilko Klungel, Olaf H. Kumari, Meena Whincup, Peter H. Morrow, David A. Braund, Peter S. Hall, Alistair S. Olsson, Anders G. Doevendans, Pieter A. Trip, Mieke D. Tobin, Martin D. Hamsten, Anders Watkins, Hugh Koenig, Wolfgang Nicolaides, Andrew N. Teupser, Daniel Day, Ian N. M. Carlquist, John F. Gaunt, Tom R. Ford, Ian Sattar, Naveed Tsimikas, Sotirios Schwartz, Gregory G. Lawlor, Debbie A. Morris, Richard W. Sandhu, Manjinder S. Poledne, Rudolf Maitland-van der Zee, Anke H. Khaw, Kay-Tee Keating, Brendan J. van der Harst, Pim Price, Jackie F. Mehta, Shamir R. Yusuf, Salim Witteman, Jaqueline C. M. Franco, Oscar H. Jukema, J. Wouter de Knijff, Peter Tybjaerg-Hansen, Anne Rader, Daniel J. Farrall, Martin Samani, Nilesh J. Kivimaki, Mika Fox, Keith A. A. Humphries, Steve E. Anderson, Jeffrey L. Boekholdt, S. Matthijs Palmer, Tom M. Eriksson, Per Pare, Guillaume Hingorani, Aroon D. Sabatine, Marc S. Mallat, Ziad Casas, Juan P. Talmud, Philippa J. TI Secretory Phospholipase A(2)-IIA and Cardiovascular Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiovascular diseases; drug development; epidemiology; genetics; Mendelian randomization ID ACUTE CORONARY SYNDROMES; MENDELIAN RANDOMIZATION; ARTERY-DISEASE; EPIC-NORFOLK; SERUM-LEVELS; HEALTHY-MEN; EVENTS; TRIAL; INHIBITOR; RISK AB Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. Results PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. Conclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. (C) 2013 by the American College of Cardiology Foundation C1 [Holmes, Michael V.; Swerdlow, Daniel I.; Kumari, Meena; Kivimaki, Mika; Hingorani, Aroon D.; Casas, Juan P.] UCL, Fac Populat Hlth Sci, London WC1E 6BT, England. [Simon, Tabassome; Kotti, Salma; Day, Ian N. M.] Hop St Antoine, AP HP, Dept Clin Pharmacol, URC EST, F-75571 Paris, France. [Simon, Tabassome] Univ Paris 06, Paris, France. [Simon, Tabassome] INSERM, U698, Paris, France. [Exeter, Holly J.; Cooper, Jackie A.; Palmen, Jutta; Humphries, Steve E.; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, Inst Cardiovasc Sci, London WC1E 6BT, England. [Folkersen, Lasse; van 't Hooft, Ferdinand; Gertow, Karl; Hamsten, Anders; Eriksson, Per] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Folkersen, Lasse; van 't Hooft, Ferdinand; Gertow, Karl; Hamsten, Anders; Eriksson, Per] Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden. [Asselbergs, Folkert W.; Cramer, Maarten J.; Nathoe, Hendrik M.; Doevendans, Pieter A.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Asselbergs, Folkert W.; Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Asselbergs, Folkert W.] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Guardiola, Montse] Univ Rovira & Virgili, CIBERDEM, Unitat Recerca Lipids & Arteriosclerosi, IISPV, E-43201 Reus, Spain. [Hubacek, Jaroslav A.; Adamkova, Vera; Pitha, Jan; Poledne, Rudolf] Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic. [Carruthers, Kathryn F.; Fox, Keith A. A.] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [Horne, Benjamin D.; Brunisholz, Kimberly D.; Carlquist, John F.; Anderson, Jeffrey L.] Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA. [Horne, Benjamin D.; Carlquist, John F.; Anderson, Jeffrey L.] Univ Utah Sch Med, Dept Med, Salt Lake City, UT USA. [Mega, Jessica L.; Morrow, David A.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Mega, Jessica L.; Morrow, David A.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Van Iperen, Erik P. A.; Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Van Iperen, Erik P. A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, NL-1105 AZ Amsterdam, Netherlands. [Li, Mingyao] Univ Penn Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA. [Leusink, Maarten; Klungel, Olaf H.; Maitland-van der Zee, Anke H.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands. [Trompet, Stella; Verschuren, Jeffrey J. W.; Jukema, J. Wouter] Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella] Leiden Univ Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Dehghan, Abbas; Hofman, Albert; Witteman, Jaqueline C. M.; Franco, Oscar H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Nelson, Christopher P.; Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England. Hop Europeen Georges Pompidou, Dept Cardiol, AP HP, Paris, France. Univ Paris 05, Paris, France. [Scholz, Markus] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany. [Scholz, Markus; Holdt, Lesca M.; Beutner, Frank; Thiery, Joachim; Teupser, Daniel] Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04109 Leipzig, Germany. [Haase, Christiane L.; Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Danchin, Nicolas; Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany. [Danchin, Nicolas; Rothenbacher, Dietrich; Breitling, Lutz P.; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Kuchenbaecker, Karoline B.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Staines-Urias, Eleonora; Casas, Juan P.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. [Goel, Anuj; Watkins, Hugh; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Goel, Anuj; Watkins, Hugh; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Panayiotou, Andrie G.] Cyprus Cardiovasc Educ & Res Trust, Nicosia, Cyprus. [Panayiotou, Andrie G.] Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth Assoc Harvar, Limassol, Cyprus. [Tremoli, Elena; Baldassarre, Damiano] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy. [Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Holdt, Lesca M.; Thiery, Joachim; Teupser, Daniel] Univ Hosp Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany. [Beutner, Frank] Univ Leipzig, Ctr Heart, Dept Internal Med Cardiol, D-04109 Leipzig, Germany. [Gansevoort, Ron T.; Navis, Gerjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Leach, Irene Mateo; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Dallmeier, Dhayana; Koenig, Wolfgang] Univ Ulm Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Boer, Jolanda M. A.] Natl Inst Publ Hlth & Environm, Dept Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands. [Stephens, Jeffrey W.] Swansea Univ, Coll Med, Inst Life Sci, Diabet Res Grp, Swansea, W Glam, Wales. [Hofker, Marten H.] Univ Groningen, Univ Med Ctr Groningen, Med Biol Sect, Dept Pathol & Med Biol, Groningen, Netherlands. [Tedgui, Alain; Mallat, Ziad] INSERM, U970, Paris Cardiovasc Res Ctr, Paris, France. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Spiering, Wilko] Univ Med Ctr Utrecht, Dept Vasc Med, Utrecht, Netherlands. [Whincup, Peter H.] Univ London, Div Populat Hlth Sci & Educ, London, England. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Olsson, Anders G.] Stockholm Heart Ctr, Stockholm, Sweden. [Olsson, Anders G.] Linkoping Univ, Linkoping, Sweden. [Trip, Mieke D.; Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Tobin, Martin D.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Nicolaides, Andrew N.] Univ London Imperial Coll Sci Technol & Med, Dept Vasc Surg, London, England. [Nicolaides, Andrew N.] Cyprus Cardiovasc Educ & Res Trust, Nicosia, Cyprus. [Holdt, Lesca M.; Teupser, Daniel] Univ Munich, Inst Lab Med, Univ Hosp Munich LMU, Munich, Germany. [Gaunt, Tom R.; Lawlor, Debbie A.] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol CAiTE, Bristol, Avon, England. [Gaunt, Tom R.; Lawlor, Debbie A.] Univ Bristol, BGEL, Sch Social & Community Med, Bristol, Avon, England. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Sattar, Naveed] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Tsimikas, Sotirios] Univ Calif San Diego, Dept Med, Div Cardiovasc Dis, La Jolla, CA 92093 USA. [Schwartz, Gregory G.; Sandhu, Manjinder S.] VA Med Ctr, Denver, CO USA. [Schwartz, Gregory G.; Sandhu, Manjinder S.] Univ Colorado Sch Med, Denver, CO USA. [Morris, Richard W.] UCL, Dept Primary Care & Populat Hlth, London, England. [Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Keating, Brendan J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Mehta, Shamir R.; Pare, Guillaume] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Mehta, Shamir R.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Mehta, Shamir R.] McMaster Univ, Hamilton, ON, Canada. [Mehta, Shamir R.; Yusuf, Salim; Pare, Guillaume] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [Mehta, Shamir R.; Yusuf, Salim; Pare, Guillaume] Hamilton Hlth Sci, Hamilton, ON, Canada. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [de Knijff, Peter] Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands. [Rader, Daniel J.] Penn Heart & Vasc Ctr, Philadelphia, PA USA. [Palmer, Tom M.] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England. [Pare, Guillaume] McMaster Univ, Dept Pathol & Lab Med, Hamilton, ON, Canada. [Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON, Canada. [Hingorani, Aroon D.] UCL, Div Med, Ctr Clin Pharmacol, London, England. [Mallat, Ziad] Univ Cambridge, Addenbrookes Hosp, Div Cardiovasc Med, Cambridge CB2 2QQ, England. RP Holmes, MV (reprint author), UCL, Dept Epidemiol & Publ Hlth, Fac Populat Hlth Sci, 1-19 Torrington Pl, London WC1E 6BT, England. EM mvholmes@gmail.com; Juan.Pablo-Casas@lshtm.ac.uk RI Boekholdt, Matthijs/G-7562-2014; Pitha, Jan/O-2348-2014; Gaunt, Tom/O-3918-2014; Onland-Moret, N. Charlotte/G-9185-2011; Veglia, Fabrizio/K-1958-2016; Klungel, Olaf/I-9563-2016; Brenner, Hermann/B-4627-2017; Baldassarre, Damiano/J-3295-2016; OI Gaunt, Tom/0000-0003-0924-3247; Veglia, Fabrizio/0000-0002-9378-8874; Brenner, Hermann/0000-0002-6129-1572; Baldassarre, Damiano/0000-0002-2766-8882; Palmer, Tom/0000-0003-4655-4511 FU BHG programme grant [RG/10/12/28456]; UK Medical Research Council (Population Health Scientist Fellowship) [G0802432]; British Heart Foundation [RG 10/12/28456, RG008/014, RG/10/001/27643, PG07/133/24260, FS 08/ 048/25628]; National Institute of Health Research University College London Hospitals Biomedical Research Centre; Dutch Kidney Foundation [E033]; Netherlands Organisation for Health Research and Development (NWO VENI) [916.761.70]; Dutch Inter University Cardiology Institute Netherlands (ICIN); Canada Research Chair in Genetic and Molecular Epidemiology; Europe Against Cancer Programme of the European Commission (SANCO), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch Cancer Society; [EU-LSHM-CT-2006037697] FX The UCLEB consortium is funded by a BHG programme grant (ref RG/10/12/28456). This work was funded by the UK Medical Research Council (Population Health Scientist Fellowship G0802432: to M. V. H.), British Heart Foundation RG 10/12/28456 (A. D. H., J. P. C., S. E. H., and Meena Kumari), RG008/014 (S. E. H., A. D. H., and P. J. T.), RG/10/001/27643 (Z. M.), PG07/133/24260 (S. E. H., A. D. H., P. J. T., and Meena Kumari), and FS 08/ 048/25628 (P. J. T. and A. D. H.). Inserm A. T. and I. M. Arron D. Hingorani has provided non-remunerated advice on the Roche Actemra (tocilizumab) cardiovascular advisory board; Aroon D. Hingorani and Juan P. Casas are supported by the National Institute of Health Research University College London Hospitals Biomedical Research Centre. PREVEND genetics is supported by EU-LSHM-CT-2006037697 and the Dutch Kidney Foundation (grant E033). P. van der Harst is supported by the Netherlands Organisation for Health Research and Development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). GP is supported by the Canada Research Chair in Genetic and Molecular Epidemiology. The EPIC-NL study was funded by the Europe Against Cancer Programme of the European Commission (SANCO), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch Cancer Society; ZonMW the Netherlands Organisation for Health Research and Development, World Cancer Research Fund (WCRF) (the Netherlands). Genotyping was funded by IOP Genomics grant IGE05012 from Agentschap NL. Folkert W. Asselbergs is supported by a clinical fellowship from the Netherlands Organisation for Health Research and Development (ZonMw grant 90700342). The FAST-MI study is sponsored by the French Society of Cardiology and has been supported by a grant from La Caisse Nationale de l'Assurance Maladie (CNAM) and unrestricted grants from Pfizer and Servier. The WHII study has been supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart, Lung, and Blood Institute (NHLBI: HL36310) and National Institute on Aging (AG13196), U. S., NIH; Agency for Health Care Policy Research (HS06516); and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. The ASAP study was supported by the Swedish Research Council (12660: P. E.), the Swedish Heart-Lung Foundation (20090541: P. E.), the European Commission (FAD, Health F2 2008 200647: P. E.), a donation by Fredrik Lundberg (A. F. C. and P. E.). Dr. Swerdlow is supported by a Medical Research Council Doctoral Training Award. M. Scholz was funded by LIFE-Leipzig Research Center for Civilization Diseases (LIFE Center, Universit t Leipzig). LIFE-Leipzig Research Center for Civilization Diseases is funded by means of the European Union, by the European Regional Development Fund (ERFD) and by means of the Free State of Saxony within the framework of the excellence initiative. This publication is supported by LIFE-Leipzig Research Center for Civilization Diseases, Universit t Leipzig). LIFE is funded by means of the European Union, by the European Regional Development Fund (ERFD) and by means of the Free State of Saxony within the framework of the excellence initiative. The British Regional Heart Study is a British Heart Foundation research group (grant number RG/08/013/25942).; DNA extraction was supported in part by British Heart Foundation Senior Research Fellowship FS05/125. The British Women's Heart and Health Study is supported by funding from the British Heart Foundation (BHF) and the Department of Health Policy Research Programme (England). Human CVD genotyping of the BWHHS was funded by the BHF PG/07/131/24254). D. A. L., T. M. P., T. R. G., and I. N. M. D. work in a center that receives funds from the UK Medical Research Council (G0600705) and University of Bristol. The EAS has been supported by grants from the British Heart Foundation. Recruitment of the CAD cases for the BHF- FHS Study was funded by the British Heart Foundation. Controls were collected as part of the Wellcome Trust Case Control Consortium Study. Genotyping was funded by the British Heart Foundation and the European Union FP6 Cardiogenics Study. Recruitment and genotyping of the GRAPHIC Study was funded by the British Heart Foundation. N. J. S. holds a Chair funded by the British Heart Foundation and is an NIHR Senior Investigator. Z. M. holds a Chair funded by the British Heart Foundation. M. D. T. is an MRC Senior Clinical Fellow. The BHF- FHS and GRAPHIC studies are part of the portfolio of research supported by the Leicester NIHR Biomedical Research Unit in Cardiovascular Disease. The IMPROVE study was supported by the European Commission (Contract number: QLG1- CT- 2002- 00896), the Swedish Heart- Lung Foundation, the Swedish Research Council (projects 8691 and 0593), Knut and Alice Wallenberg Foundation, the Torsten and Ragnar Sderberg Foundation, the Foundation for Strategic Research, the Stockholm County Council (project 562183), the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council, Academy of Finland (Grant # 110413), Ministry of Education and Culture of Finland, the City of Kuopio, the British Heart Foundation (RG2008/014), and the Italian Ministry of Health (Ricerca Corrente). The BWHHS is supported by the Department of Health (England) Policy Research Programme and British Heart Foundation (PG/09/036/26739). The Cyprus study has been supported by grants from the Cyprus Research Promotion Foundation (YGEIA/1104/17 and PENEK_ 05/04) and the Cyprus Cardiovascular Educational and Research Trust. EPIC- Norfolk study is supported by grants from the Medical Research Council UK and Cancer Research UK. G. Kees Hovingh is supported by the Netherlands Organisation for Health Research and Development (NWO VENI grant 91612122). The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911- 03- 012), the Research Institute for Diseases in the Elderly (014- 93- 015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050- 060- 810. Jacqueline Witteman is supported by NWO grant (vici, 918- 76619). Abbas Dehghan is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship.; The research of the PROSPER study has been funded by the European Union's Seventh Framework Programme (FP7/2007- 2013) under grant agreement n ~ HEALTH- F2- 2009- 223004. GRACE- Scotland was supported by an unrestricted educational grant from sanofi- aventis,. KAROLA: The study was supported in parts by the Association of German Pension Fund Agencies, the German Federal Ministry of Education and Research (# 01GD9820/0), and the Pitzer Foundation (Bad Nauheim, Germany). UDACS was supported by a clinical training fellowship (JWS: BDA: RD 01 /0001357) from Diabetes UK. GENDEMIP: supported by the project (Ministry of Health, Czech Republic) for development of research organization 00023001 (IKEM, Prague, Czech Republic)- Institutional support. UCP: The project was funded by Veni grant Organization for Scientific Research (NWO), Grant no. 2001.064 Netherlands Heart Foundation (NHS), and TI Pharma Grant T6- 101 Mondriaan. S Yusuf holds the Heart and Stroke Foundation/Marion W Burke Chair in cardiovascular diseases. PROCARDIS was supported by the British Heart Foundation; by the European Community Sixth Framework Programme (grant number LSHM- CT- 2007- 037273); and by AstraZeneca. A. B., M. F., and H. W. are supported by the British Heart Foundation Centre for Research Excellence in Oxford and the Wellcome Trust core award (090532/Z/09/Z). Anders Hamsten obtained support for this project from the Swedish Heart-Lung Foundation; from the Swedish Medical Research Council (grant number 8691); from the Knut and Alice Wallenberg Foundation; from the Karolinska Institute; and from the Stockholm County Council (grant number 560183). Dr. Schwartz, through his institution, has received research grants from Anthera, Resverlogix, Roche, and sanofi-aventis. The MIRACL study was supported by Pfizer. CCHS: Supported by The Danish Medical Research Council and The Research Fund at Rigshospitalet, Copenhagen University Hospital. The Whitehall II study is supported by the UK Medical Research Council (K013351), the British Heart Foundation, the ESRC, the U. S. NIH (R01 HL036310; R01 AG034454) Health and Safety Executive; the Department of Health; the National Heart, Lung, and Blood Institute (NHLBI; HL36310); the National Institute on Aging (AG13196); the Agency for Health Care Policy Research (HS06516); and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. Ziad Mallat, Tabassome Simon, and Alain Tedgui are listed as coinventors on patents related to the use of sPLA2 activity and/or PLA2G2A rs11573156 SNP as a cardiovascular biomarker. Wolfgang Koenig has received a research grant from Anthera to measure sPLA2 in KAROLA, was the National Coordinator for the VISTA-16 clinical trial in Germany and has acted as consultant for Roche, BioInvent, Cerenis, Novartis, and Anthera. Gregory Schwartz, through his institution, has received research grants from Anthera, Resverlogix, Roche, and sanofi-aventis and was involved in the VISTA-16 clinical trial. Alain Tedgui has acted as a consultant for Aterovax. Damiano Baldassarre has acted as a consultant for Centro Cardiologico Monzino, IRCCS. J. W.; Jukema has received research grants from and was speaker on (CME accredited) meetings sponsored by Astellas, Anthera, AstraZeneca, Biotronik, Boston Scientific, Daiichi Sankyo, Eli Lilly, Genzyme, Medtronic, Merck-Schering-Plough, Pfizer, Orbus Neich, Novartis, Roche, Servier, sanofi-aventis, the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Community Framework KP7 Programme. Martin Tobin has received funding from a Pfizer collaborative research project. Kathryn Carruthers has received an educational grant from sanofi-aventis. Ziad Mallat is a board member of AstraZeneca and acts as consultant for Aterovax. Tabassome Simon is a board member of Bayer; acts as consultant for Bayer, Eli Lilly, AstraZeneca, and sanofi-aventis; has received grants from Merck, AstraZeneca, sanofi-aventis, Eli Lilly, Daiichi Sankyo, Novartis, and GlaxoSmithKline; has received payment for lectures from sanofi-aventis and Eli Lilly. Sam Tsimikas has acted as consultant for Isis, Genzyme, and Quest; receives a grant from Pfizer; and has patents with and/receives royalties from UCSD. J. L. M. has received research grant support from AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Janssen, Sanofi-aventis and honoraria for consulting from: Boehringer Ingelheim, Janssen. M. S. S. received research grant support through Brigham and Women's Hospital from: Abbott Laboratories; Amgen; AstraZeneca; AstraZeneca/Bristol-Myers Squibb Alliance; Bristol-Myers Squibb/Sanofi-aventis Joint Venture; Critical Diagnostics; Daiichi-Sankyo; Eisai; Genzyme; GlaxoSmithKline; Intarcia; Merck; Nanosphere; Roche Diagnostics; Sanofi-aventis; Takeda. MSS received honoraria for consulting from: Aegerion; Amgen; AstraZeneca/ Bristol-Myers Squibb Alliance; GlaxoSmithKline; Intarcia; Merck; Pfizer; Sanofi-aventis; Vertex. PROVE-IT TIMI 22 was by Bristol-Myers Squibb & Sankyo. MERLIN-TIMI 36 was supported by CV Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Holmes, Simon, and Exeter are joint first authors. Drs. Hingorani, Sabatine, Mallat, Casas, and Talmud are joint last authors. Stephen Nicholls, MBBS, PHD, served as Guest Editor for this paper. NR 25 TC 40 Z9 40 U1 0 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 19 PY 2013 VL 62 IS 21 BP 1966 EP 1976 DI 10.1016/j.jacc.2013.06.044 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251ON UT WOS:000326939500010 PM 23916927 ER PT J AU Kim, ESH Olin, JW Froehlich, JB Gu, XK Bacharach, JM Gray, BH Jaff, MR Katzen, BT Kline-Rogers, E Mace, PD Matsumoto, AH McBane, RD White, CJ Gornik, HL AF Kim, Esther S. H. Olin, Jeffrey W. Froehlich, James B. Gu, Xiaokui Bacharach, J. Michael Gray, Bruce H. Jaff, Michael R. Katzen, Barry T. Kline-Rogers, Eva Mace, Pamela D. Matsumoto, Alan H. McBane, Robert D. White, Christopher J. Gornik, Heather L. TI Clinical Manifestations of Fibromuscular Dysplasia Vary by Patient Sex: A Report of the United States Registry for Fibromuscular Dysplasia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID MUTATIONS C1 [Kim, Esther S. H.; Gornik, Heather L.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA. [Olin, Jeffrey W.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Froehlich, James B.; Gu, Xiaokui; Kline-Rogers, Eva] Univ Michigan, Ann Arbor, MI 48109 USA. [Bacharach, J. Michael] North Cent Heart, Sioux Falls, SD USA. [Gray, Bruce H.] Greenville Hosp Syst, Greenville, SC USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katzen, Barry T.] Miami Baptist Cardiac Vasc Inst, Miami, FL USA. [Mace, Pamela D.] Fibromuscular Dysplasia Soc Amer, Rocky River, OH USA. [Matsumoto, Alan H.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [McBane, Robert D.] Mayo Clin, Rochester, MN USA. [White, Christopher J.] Ochsner Med Ctr, New Orleans, LA USA. RP Kim, ESH (reprint author), Cleveland Clin, Dept Cardiovasc Med, Desk J3-5 9500 Euclid Ave, Cleveland, OH 44195 USA. EM kims@ccf.org NR 4 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 19 PY 2013 VL 62 IS 21 BP 2026 EP 2028 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251ON UT WOS:000326939500021 PM 23954333 ER PT J AU Batchelor, TT Gerstner, ER Emblem, KE Duda, DG Kalpathy-Cramer, J Snuderl, M Ancukiewicz, M Polaskova, P Pinho, MC Jennings, D Plotkin, SR Chi, AS Eichler, AF Dietrich, J Hochberg, FH Lu-Emerson, C Iafrate, AJ Ivy, SP Rosen, BR Loeffler, JS Wen, PY Sorensen, AG Jain, RK AF Batchelor, Tracy T. Gerstner, Elizabeth R. Emblem, Kyrre E. Duda, Dan G. Kalpathy-Cramer, Jayashree Snuderl, Matija Ancukiewicz, Marek Polaskova, Pavlina Pinho, Marco C. Jennings, Dominique Plotkin, Scott R. Chi, Andrew S. Eichler, April F. Dietrich, Jorg Hochberg, Fred H. Lu-Emerson, Christine Iafrate, A. John Ivy, S. Percy Rosen, Bruce R. Loeffler, Jay S. Wen, Patrick Y. Sorensen, A. Greg Jain, Rakesh K. TI Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain tumor; personalized treatment ID TYROSINE KINASE INHIBITOR; GROWTH-FACTOR RECEPTOR; ANTIANGIOGENIC THERAPY; VASCULAR NORMALIZATION; RECURRENT GLIOBLASTOMA; RECTAL-CANCER; PHASE-II; TEMOZOLOMIDE; BEVACIZUMAB; RADIATION AB Antiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types. However, an incomplete understanding of the mechanisms of action of antiangiogenic agents has hindered optimization and broader application of this new therapeutic modality. In particular, the impact of antiangiogenic therapy on tumor blood flow and oxygenation status (i.e., the role of vessel pruning versus normalization) remains controversial. This controversy has become critical as multiple phase III trials of antiVEGF agents combined with cytotoxics failed to show overall survival benefit in newly diagnosed glioblastoma (nGBM) patients and several other cancers. Here, we shed light on mechanisms of nGBM response to cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, using MRI techniques and blood biomarkers in prospective phase II clinical trials of cediranib with chemoradiation vs. chemoradiation alone in nGBM patients. We demonstrate that improved perfusion occurs only in a subset of patients in cediranib-containing regimens, and is associated with improved overall survival in these nGBM patients. Moreover, an increase in perfusion is associated with improved tumor oxygenation status as well as with pharmacodynamic biomarkers, such as changes in plasma placenta growth factor and sVEGFR2. Finally, treatment resistance was associated with elevated plasma IL-8 and sVEGFR1 posttherapy. In conclusion, tumor perfusion changes after antiangiogenic therapy may distinguish responders vs. nonresponders early in the course of this expensive and potentially toxic formof therapy, and these results may provide newinsight into the selection of glioblastoma patients most likely to benefit from anti-VEGF treatments. C1 [Batchelor, Tracy T.; Gerstner, Elizabeth R.; Plotkin, Scott R.; Chi, Andrew S.; Eichler, April F.; Dietrich, Jorg; Hochberg, Fred H.; Lu-Emerson, Christine] Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA. [Batchelor, Tracy T.; Duda, Dan G.; Ancukiewicz, Marek; Loeffler, Jay S.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Polaskova, Pavlina; Pinho, Marco C.; Jennings, Dominique; Rosen, Bruce R.; Sorensen, A. Greg] Massachusetts Gen Hosp, Dept Radiol, Ctr Canc, Boston, MA 02114 USA. [Snuderl, Matija; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Polaskova, Pavlina; Pinho, Marco C.; Jennings, Dominique; Rosen, Bruce R.; Sorensen, A. Greg] Harvard Mit Div Hlth Sci & Technol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Neurooncol, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA. EM tbatchelor@partners.org; jain@steele.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Pinho, Marco/0000-0002-4645-1638; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Snuderl, Matija/0000-0003-0752-0917 FU National Institutes of Health [R01CA129371, K24CA125440A, P01CA080124, R01CA163815, N01CM-2008-00060C, 5R01NS060918, 1U01CA154601, R01CA159258]; Proton Beam/Federal Share Program; National Foundation for Cancer Research; Merck; Norwegian Research Council Grant [191088/V50]; South-Eastern Norway Regional Health Authority Grant [2013069]; Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Harvard University FX We thank A. Khachatryan, C. Koppel, O. Pulluqi, and C. Smith for outstanding technical support for biomarker studies. This work was funded by National Institutes of Health Grants R01CA129371 and K24CA125440A (to T.T.B.), P01CA080124 and R01CA163815 (to R.K.J.), N01CM-2008-00060C and 5R01NS060918 (to A.G.S.), 1U01CA154601 (to B.R.R.), and R01CA159258 (to D.G.D.); the Proton Beam/Federal Share Program (R.K.J and D.G.D.); the National Foundation for Cancer Research (R.K.J.); Merck (A.G.S. and E.R.G.); Norwegian Research Council Grant 191088/V50 and South-Eastern Norway Regional Health Authority Grant 2013069 (to K.E.E.); and the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). NR 44 TC 88 Z9 90 U1 6 U2 19 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 NOV 19 PY 2013 VL 110 IS 47 BP 19059 EP 19064 DI 10.1073/pnas.1318022110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253PD UT WOS:000327100600079 PM 24190997 ER PT J AU Benzinger, TLS Blazey, T Jack, CR Koeppe, RA Su, Y Xiong, CJ Raichle, ME Snyder, AZ Ances, BM Bateman, RJ Cairns, NJ Fagan, AM Goate, A Marcus, DS Aisen, PS Christensen, JJ Ercole, L Hornbeck, RC Farrar, AM Aldea, P Jasielec, MS Owen, CJ Xie, XY Mayeux, R Brickman, A McDade, E Klunk, W Mathis, CA Ringman, J Thompson, PM Ghetti, B Saykin, AJ Sperling, RA Johnson, KA Salloway, S Correia, S Schofield, PR Masters, CL Rowe, C Villemagne, VL Martins, R Ourselin, S Rossor, MN Fox, NC Cash, DM Weiner, MW Holtzman, DM Buckles, VD Moulder, K Morris, JC AF Benzinger, Tammie L. S. Blazey, Tyler Jack, Clifford R., Jr. Koeppe, Robert A. Su, Yi Xiong, Chengjie Raichle, Marcus E. Snyder, Abraham Z. Ances, Beau M. Bateman, Randall J. Cairns, Nigel J. Fagan, Anne M. Goate, Alison Marcus, Daniel S. Aisen, Paul S. Christensen, Jon J. Ercole, Lindsay Hornbeck, Russ C. Farrar, Angela M. Aldea, Patricia Jasielec, Mateusz S. Owen, Christopher J. Xie, Xianyun Mayeux, Richard Brickman, Adam McDade, Eric Klunk, William Mathis, Chester A. Ringman, John Thompson, Paul M. Ghetti, Bernardino Saykin, Andrew J. Sperling, Reisa A. Johnson, Keith A. Salloway, Stephen Correia, Stephen Schofield, Peter R. Masters, Colin L. Rowe, Christopher Villemagne, Victor L. Martins, Ralph Ourselin, Sebastien Rossor, Martin N. Fox, Nick C. Cash, David M. Weiner, Michael W. Holtzman, David M. Buckles, Virginia D. Moulder, Krista Morris, John C. TI Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuroimaging; aging; dementia; neurodegeneration; DIAN ID AMYLOID-BETA DEPOSITION; MILD COGNITIVE IMPAIRMENT; PRESENILIN-1 MUTATION CARRIERS; HUMAN CEREBRAL-CORTEX; HIPPOCAMPAL ATROPHY; HYPOTHETICAL MODEL; GLUCOSE-METABOLISM; DYNAMIC BIOMARKERS; LONGITUDINAL MRI; GENETIC RISK AB Major imaging biomarkers of Alzheimer's disease include amyloid deposition [imaged with [C-11]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [F-18]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now extend this work to include a larger cohort, wholebrain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease. C1 [Benzinger, Tammie L. S.; Blazey, Tyler; Su, Yi; Marcus, Daniel S.; Christensen, Jon J.; Ercole, Lindsay; Hornbeck, Russ C.; Farrar, Angela M.; Aldea, Patricia; Owen, Christopher J.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Xiong, Chengjie; Jasielec, Mateusz S.; Xie, Xianyun] Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USA. [Raichle, Marcus E.; Snyder, Abraham Z.; Ances, Beau M.; Bateman, Randall J.; Fagan, Anne M.; Holtzman, David M.; Buckles, Virginia D.; Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cairns, Nigel J.; Moulder, Krista] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Goate, Alison] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Koeppe, Robert A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Mayeux, Richard] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [McDade, Eric] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Brickman, Adam; Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. [Klunk, William] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Ringman, John] Univ Calif Los Angeles, Dept Neurol, Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90024 USA. [Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Los Angeles, CA 90024 USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Saykin, Andrew J.] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN 46202 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Salloway, Stephen] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02903 USA. [Correia, Stephen] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Masters, Colin L.] Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Rowe, Christopher; Villemagne, Victor L.] Austin Hlth, Dept Nucl Med, Heidelberg, Vic 3084, Australia. [Rowe, Christopher; Villemagne, Victor L.] Austin Hlth, Ctr Positron Emiss Tomog, Heidelberg, Vic 3084, Australia. [Martins, Ralph] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Perth, WA 6027, Australia. [Ourselin, Sebastien; Rossor, Martin N.; Fox, Nick C.; Cash, David M.] UCL, Inst Neurol, Dementia Res Ctr, London WC1N 3GB, England. [Weiner, Michael W.] Univ Calif San Francisco, Dept Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. RP Benzinger, TLS (reprint author), Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. EM benzingert@wustl.edu; marc@npg.wustl.edu; morrisj@abraxas.wustl.edu RI Saykin, Andrew/A-1318-2007; Fox, Nick/B-1319-2009; Jack, Clifford/F-2508-2010; OI Saykin, Andrew/0000-0002-1376-8532; Fox, Nick/0000-0002-6660-657X; Jack, Clifford/0000-0001-7916-622X; Klunk, William/0000-0001-5512-0251; Ances, Beau/0000-0003-3862-7397 FU National Institutes of Health(NIH)/National Institute on Aging (NIA) [U19AG032438]; Charles F. and Joanne Knight Alzheimer's Research Initiative, Alzheimer's Research UK; Brain Research Trust; Washington University Institute of Clinical and Translational Sciences grant from the National Center for Advancing Translational Sciences (NCATS) of the NIH [UL1 TR000448] FX We wish to acknowledge the dedication of the participants and their families, without which these studies would not be possible, and all of the participating researchers in the Dominantly Inherited Alzheimer Network (www.dian-info.org/personnel.htm). We also thank Dr. Brian Gordon for his helpful comments on earlier versions of this manuscript. Funding for this research was provided by National Institutes of Health(NIH)/National Institute on Aging (NIA) (U19AG032438). Computations were performed using the facilities of the Washington University Center for High Performance Computing, which were partially provided through National Center for Research Resources (NCRR) 1S10RR022984-01A1. Research reported in this publication was additionally supported by the Charles F. and Joanne Knight Alzheimer's Research Initiative, Alzheimer's Research UK, Brain Research Trust and the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. NR 94 TC 65 Z9 65 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 19 PY 2013 VL 110 IS 47 BP E4502 EP E4509 DI 10.1073/pnas.1317918110 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253PD UT WOS:000327100600015 PM 24194552 ER PT J AU Orzalli, MH Conwell, SE Berrios, C DeCaprio, JA Knipe, DM AF Orzalli, Megan H. Conwell, Sara E. Berrios, Christian DeCaprio, James A. Knipe, David M. TI Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA sensing; intrinsic resistance; host restriction; cellular response ID SIMPLEX-VIRUS TYPE-1; IMMEDIATE-EARLY PROTEINS; GENE-EXPRESSION; VIRAL-DNA; INTRACELLULAR DNA; MAMMALIAN-CELLS; LYTIC INFECTION; IFI16 PROTEIN; ICP0; REPLICATION AB Mammalian cells have evolved mechanisms to silence foreign DNA introduced by viruses or by transfection. Upon herpesviral infection of cells, the viral genome is chromatinized in an attempt by the host cell to restrict expression of the viral genome. HSV ICP0 acts to counter host-intrinsic and innate responses to viral infection. We have found that nuclear interferon (IFN)-inducible protein 16 (IFI16) acts as a restriction factor against ICP0-null herpes simplex virus 1 (HSV-1) to limit viral replication and immediate-early gene expression. IFI16 promoted the addition of heterochromatin marks and the reduction of euchromatin marks on viral chromatin. IFI16 also restricted the expression of plasmid DNAs introduced by transfection but did not restrict SV40 DNA introduced into the cellular nucleus in the form of nudeosomal chromatin by viral infection. These results argue that IFI16 restricts unchromatinized DNA when it enters the cell nucleus by promoting the loading of nucleosomes and the addition of heterochromatin marks. Furthermore, these results indicate that IFI16 provides a broad surveillance role against viral and transfected DNA by promoting restriction of gene expression from the exogenous DNA and inducing innate immune responses. C1 [Orzalli, Megan H.; Conwell, Sara E.; Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [DeCaprio, James A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Orzalli, Megan H.; Conwell, Sara E.; Berrios, Christian; DeCaprio, James A.; Knipe, David M.] Harvard Univ, Sch Med, Program Virol, Boston, MA 02115 USA. [Berrios, Christian; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Knipe, DM (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM david_knipe@hms.harvard.edu FU National Institutes of Health (NIH) [AI063106, AI099081, F31CA177274] FX We thank Connie Cepko (Harvard Medical School) for providing the pEF1 alpha-GFP construct. This research was supported by National Institutes of Health (NIH) Grants AI063106, AI099081 (to D.M.K.), and F31CA177274 (to C.B.). NR 60 TC 49 Z9 50 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 19 PY 2013 VL 110 IS 47 BP E4492 EP E4501 DI 10.1073/pnas.1316194110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253PD UT WOS:000327100600014 PM 24198334 ER PT J AU Vaidya, SA Streeck, H Beckwith, N Ghebremichael, M Pereyra, F Kwon, DS Addo, MM Rychert, J Routy, JP Jessen, H Kelleher, AD Hecht, F Sekaly, RP Carrington, M Walker, BD Allen, TM Rosenberg, ES Altfeld, M AF Vaidya, Sagar A. Streeck, Hendrik Beckwith, Noor Ghebremichael, Musie Pereyra, Florencia Kwon, Douglas S. Addo, Marylyn M. Rychert, Jenna Routy, Jean-Pierre Jessen, Heiko Kelleher, Anthony D. Hecht, Frederick Sekaly, Rafick-Pierre Carrington, Mary Walker, Bruce D. Allen, Todd M. Rosenberg, Eric S. Altfeld, Marcus TI Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection SO RETROVIROLOGY LA English DT Article DE HLA-B*57; HLA-B; Acute HIV-1 infection; Primary HIV-1 infection; Viral load set point; MHC class I ID HLA; DETERMINANTS AB Background: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). Findings: Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n= 171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p< 0.001, n= 135) with nearly 1 log(10) less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p< 0.01) and lower VLSP (p< 0.05). However, this association was dependent on different amino acids at this position for each endpoint. Conclusions: The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function. C1 [Vaidya, Sagar A.; Streeck, Hendrik; Beckwith, Noor; Ghebremichael, Musie; Pereyra, Florencia; Kwon, Douglas S.; Addo, Marylyn M.; Rychert, Jenna; Walker, Bruce D.; Allen, Todd M.; Altfeld, Marcus] MIT, Ragon Inst MGH, Boston, MA USA. [Vaidya, Sagar A.; Streeck, Hendrik; Beckwith, Noor; Ghebremichael, Musie; Pereyra, Florencia; Kwon, Douglas S.; Addo, Marylyn M.; Rychert, Jenna; Walker, Bruce D.; Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vaidya, Sagar A.; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Streeck, Hendrik] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Streeck, Hendrik] Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD USA. [Addo, Marylyn M.] Univ Med Ctr Hamburg Eppendorf, Infect Dis Unit, Hamburg, Germany. [Routy, Jean-Pierre] McGill Univ, Div Hematol, Montreal, PQ, Canada. [Routy, Jean-Pierre] McGill Univ, Chron Viral Illness Serv MUHC, Montreal, PQ, Canada. [Jessen, Heiko] HIV Clin Praxis Jessen, Berlin, Germany. [Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW, Australia. [Hecht, Frederick] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. [Sekaly, Rafick-Pierre] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Carrington, Mary] Leidos Biomed Res Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick Natl Labs Canc Res, Frederick, MD USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Altfeld, Marcus] Heinrich Pette Inst, Hamburg, Germany. RP Altfeld, M (reprint author), MIT, Ragon Inst MGH, Boston, MA USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011; OI Beckwith, Noor/0000-0001-6025-8642 FU Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. NR 14 TC 6 Z9 7 U1 1 U2 5 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 NOV 18 PY 2013 VL 10 AR 139 DI 10.1186/1742-4690-10-139 PG 5 WC Virology SC Virology GA 280QV UT WOS:000329046800002 PM 24245727 ER PT J AU Pascal, LE Ai, JK Masoodi, KZ Wang, YJ Wang, D Eisermann, K Rigatti, LH O'Malley, KJ Ma, HM Wang, XH Dar, JA Parwani, AV Simons, BW Ittman, MM Li, LY Davies, BJ Wang, Z AF Pascal, Laura E. Ai, Junkui Masoodi, Khalid Z. Wang, Yujuan Wang, Dan Eisermann, Kurtis Rigatti, Lora H. O'Malley, Katherine J. Ma, Hei M. Wang, Xinhui Dar, Javid A. Parwani, Anil V. Simons, Brian W. Ittman, Michael M. Li, Luyuan Davies, Benjamin J. Wang, Zhou TI Development of a Reactive Stroma Associated with Prostatic Intraepithelial Neoplasia in EAF2 Deficient Mice SO PLOS ONE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CANCER XENOGRAFTS; TUMOR PROGRESSION; FACTOR EXPRESSION; CRUCIAL ROLE; ANDROGEN; THROMBOSPONDIN-1; ANGIOGENESIS; CARCINOMA; PTEN AB ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/-) mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/-) mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/-) animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors. C1 [Pascal, Laura E.; Ai, Junkui; Masoodi, Khalid Z.; Wang, Yujuan; Wang, Dan; Eisermann, Kurtis; O'Malley, Katherine J.; Ma, Hei M.; Dar, Javid A.; Davies, Benjamin J.; Wang, Zhou] Univ Pittsburgh, Sch Med, Dept Urol, Pittsburgh, PA 15260 USA. [Rigatti, Lora H.] Univ Pittsburgh, Sch Med, Div Lab Anim Resources, Pittsburgh, PA USA. [Wang, Xinhui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Parwani, Anil V.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Simons, Brian W.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Ittman, Michael M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Li, Luyuan] Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China. [Wang, Zhou] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA. [Wang, Zhou] Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Wang, Zhou] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Wang, Z (reprint author), Univ Pittsburgh, Sch Med, Dept Urol, Pittsburgh, PA 15260 USA. EM wangz2@upmc.edu RI Dar, Javid/D-6276-2015; Simons, Brian/G-7352-2015; OI Dar, Javid/0000-0002-4102-6202; Simons, Brian/0000-0003-0644-211X; Masoodi, Khalid/0000-0002-4889-5558 FU National Institutes of Health [R37 DK 51193, R01 CA120386, P50 CA090386, T32 DK007774]; Tippins Foundation; Mellam Foundation; [P30CA047904] FX This work was funded in part by National Institutes of Health grants R37 DK 51193, R01 CA120386, P50 CA090386, and T32 DK007774 and scholarships from the Tippins Foundation (LEP) and the Mellam Foundation (KZM). This project used the UPCI Animal Facility and Tissue and Research Pathology Services (TARPS) and was supported in part by award P30CA047904. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 3 Z9 3 U1 1 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 NOV 18 PY 2013 VL 8 IS 11 AR e79542 DI 10.1371/journal.pone.0079542 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 256KH UT WOS:000327308500074 PM 24260246 ER PT J AU Abdel-Wahab, O Gao, J Adli, M Dey, A Trimarchi, T Chung, YR Kuscu, C Hricik, T Ndiaye-Lobry, D LaFave, LM Koche, R Shih, AH Guryanova, OA Kim, E Li, S Pandey, S Shin, JY Telis, L Liu, JF Bhatt, PK Monette, S Zhao, XY Mason, CE Park, CY Bernstein, BE Aifantis, I Levine, RL AF Abdel-Wahab, Omar Gao, Jie Adli, Mazhar Dey, Anwesha Trimarchi, Thomas Chung, Young Rock Kuscu, Cem Hricik, Todd Ndiaye-Lobry, Delphine LaFave, Lindsay M. Koche, Richard Shih, Alan H. Guryanova, Olga A. Kim, Eunhee Li, Sheng Pandey, Suveg Shin, Joseph Y. Telis, Leon Liu, Jinfeng Bhatt, Parva K. Monette, Sebastien Zhao, Xinyang Mason, Christopher E. Park, Christopher Y. Bernstein, Bradley E. Aifantis, Iannis Levine, Ross L. TI Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELL; CHRONIC MYELOMONOCYTIC LEUKEMIA; BOHRING-OPITZ SYNDROME; TRANSCRIPTION FACTORS; MOLECULAR SIGNATURE; GENE ASXL1; MUTATIONS; DIFFERENTIATION; PU.1 AB Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10-30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis. C1 [Abdel-Wahab, Omar; Chung, Young Rock; Hricik, Todd; LaFave, Lindsay M.; Shih, Alan H.; Guryanova, Olga A.; Kim, Eunhee; Pandey, Suveg; Shin, Joseph Y.; Telis, Leon; Bhatt, Parva K.; Park, Christopher Y.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Abdel-Wahab, Omar; Shih, Alan H.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. [LaFave, Lindsay M.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY 10065 USA. [Park, Christopher Y.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Gao, Jie; Trimarchi, Thomas; Ndiaye-Lobry, Delphine; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Gao, Jie; Trimarchi, Thomas; Ndiaye-Lobry, Delphine; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Adli, Mazhar; Kuscu, Cem] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Koche, Richard; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Koche, Richard; Bernstein, Bradley E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Koche, Richard; Bernstein, Bradley E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dey, Anwesha] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. [Liu, Jinfeng] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA. [Levine, Ross L.] Weill Cornell Med Coll, Grad Sch Med Sci, New York, NY 10065 USA. [Li, Sheng; Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Monette, Sebastien] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Triinst Lab Comparat Pathol, New York, NY 10065 USA. [Monette, Sebastien] Rockefeller Univ, New York, NY 10065 USA. [Zhao, Xinyang] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. EM iannis.aifantis@nyumc.org; leviner@mskcc.org RI Li, Sheng/A-1964-2014; Kim, Eunhee/Q-9162-2016; OI Kim, Eunhee/0000-0001-7143-7769; Liu, Jinfeng/0000-0002-0343-8222; Abdel-Wahab, Omar/0000-0002-3907-6171; Zhao, Xinyang/0000-0001-6677-7072 FU Starr Cancer Consortium; Gabrielle's Angel Fund; National Institutes of Health (NIH) [1R01CA138234-01, 5R01CA173636-01]; Leukemia and Lymphoma Society (LLS) Translational Research Program grant; National Heart, Lung, and Blood Institute [5U01HL100395]; NIH [R01CA133379, R01CA105129, 1R01CA173636, R01CA149655, 5R01CA173636]; LLS Chemotherapy Foundation; William Lawrence Blanche Hughes Foundation; V Foundation for Cancer Research; New York University [T32 CA009161]; NIH K08 Clinical Investigator Award [1K08CA160647-01]; US Department of Defense Postdoctoral Fellow Award in Bone Marrow Failure Research [W81XWH-12-1-0041]; Josie Roberston Investigator Program; Damon Runyon Clinical Investigator Award; Evans Foundation FX This work was supported by a grant from the Starr Cancer Consortium to R.L. Levine and B.E. Bernstein, by grants from Gabrielle's Angel Fund to R.L. Levine, I. Aifantis, and O. Abdel-Wahab, by National Institutes of Health (NIH) grant 1R01CA138234-01 to R.L. Levine and 5R01CA173636-01 to R.L. Levine and I. Aifantis, by a Leukemia and Lymphoma Society (LLS) Translational Research Program grant to R.L. Levine and I. Aifantis, and by National Heart, Lung, and Blood Institute grant 5U01HL100395 to B.E. Bernstein. I. Aifantis is supported by the NIH (grants R01CA133379, R01CA105129, 1R01CA173636, R01CA149655, and 5R01CA173636), the LLS Chemotherapy Foundation, the William Lawrence Blanche Hughes Foundation, and the V Foundation for Cancer Research. J. Gao is supported by the New York University T32 CA009161 (Levy). I. Aifantis and B.E. Bernstein are Howard Hughes Medical Institute Early Career Scientists. O. Abdel-Wahab is supported by an NIH K08 Clinical Investigator Award (1K08CA160647-01), a US Department of Defense Postdoctoral Fellow Award in Bone Marrow Failure Research (W81XWH-12-1-0041), the Josie Roberston Investigator Program, and a Damon Runyon Clinical Investigator Award with support from the Evans Foundation. R.L. Levine is a Scholar of the LLS. NR 55 TC 80 Z9 82 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD NOV 18 PY 2013 VL 210 IS 12 BP 2641 EP 2659 DI 10.1084/jem.20131141 PG 19 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 258GF UT WOS:000327446600012 PM 24218140 ER PT J AU Orkin, SH AF Orkin, Stuart H. TI Genetics and Epigenetics of Fetal Hemoglobin Control SO BLOOD LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-of-Hematology CY DEC 07-10, 2013 CL New Orleans, LA SP Amer Soc Hematol C1 Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA USA. Boston Childrens Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 15 PY 2013 VL 122 IS 21 MA SCI12 PG 1 WC Hematology SC Hematology GA AA9AB UT WOS:000331385000011 ER PT J AU Kelley, JM Tulpule, A Daley, GQ AF Kelley, James M. Tulpule, Asmin Daley, George Q. TI Proteolytic autodigestion Common tissue pathology in Shwachman-Diamond syndrome? SO CELL CYCLE LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS; SBDS C1 [Daley, George Q.] Boston Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol,Broad Inst, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2013 VL 12 IS 22 BP 3457 EP 3458 DI 10.4161/cc.26698 PG 2 WC Cell Biology SC Cell Biology GA 301IO UT WOS:000330526200004 PM 24107623 ER PT J AU Broumand, B Delmonico, FL AF Broumand, Behrooz Delmonico, Francis L. TI Commendable Developments in Deceased Organ Donation and Transplantation in Iran SO TRANSPLANTATION LA English DT Editorial Material C1 [Broumand, Behrooz] Pars Hosp, Tehran 14594, Iran. [Delmonico, Francis L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Broumand, B (reprint author), Pars Hosp, Keshavarz Blvd, Tehran 14594, Iran. EM V4broumand@yahoo.com NR 4 TC 2 Z9 2 U1 0 U2 2 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 NOV 15 PY 2013 VL 96 IS 9 BP 765 EP 766 DI 10.1097/01.tp.0000436099.27866.30 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299HE UT WOS:000330386000001 PM 24162245 ER PT J AU Kang, HW Ozdemir, C Kawano, Y LeClair, KB Vernochet, C Kahn, CR Hagen, SJ Cohen, DE AF Kang, Hye Won Ozdemir, Cafer Kawano, Yuki LeClair, Katherine B. Vernochet, Cecile Kahn, C. Ronald Hagen, Susan J. Cohen, David E. TI Thioesterase Superfamily Member 2/Acyl-CoA Thioesterase 13 (Them2/Acot13) Regulates Adaptive Thermogenesis in Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Energy metabolism; Fatty acid; Fatty acid oxidation; Mitochondrial metabolism; Obesity; Brown adipose tissue; Fatty acyl-CoA ID BROWN ADIPOSE-TISSUE; INSULIN-RESISTANCE; METABOLISM; OXIDATION; PROTECTS; DELETION; OBESITY AB Members of the acyl-CoA thioesterase (Acot) gene family hydrolyze fatty acyl-CoAs, but their biological functions remain incompletely understood. Thioesterase superfamily member 2 (Them2; synonym Acot13) is enriched in oxidative tissues, associated with mitochondria, and relatively specific for long chain fatty acyl-CoA substrates. Using Them2(-/-) mice, we have demonstrated key roles for Them2 in regulating hepatic glucose and lipid metabolism. However, reduced body weights and decreased adiposity in Them2(-/-) mice observed despite increased food consumption were not well explained. To explore a role in thermogenesis, mice were exposed to ambient temperatures ranging from thermoneutrality (30 degrees C) to cold (4 degrees C). In response to short term (24-h) exposures to decreasing ambient temperatures, Them2(-/-) mice exhibited increased adaptive responses in physical activity, food consumption, and energy expenditure when compared with Them2(+/+) mice. By contrast, genotype-dependent differences were not observed in mice that were equilibrated (96 h) at each ambient temperature. In brown adipose tissue, the absence of Them2 was associated with reduced lipid droplets, alterations in the ultrastructure of mitochondria, and increased expression of thermogenic genes. Indicative of a direct regulatory role for Them2 in heat production, cultured primary brown adipocytes from Them2(-/-) mice exhibited increased norepinephrine-mediated triglyceride hydrolysis and increased rates of O-2 consumption, together with elevated expression of thermogenic genes. At least in part by regulating intracellular fatty acid channeling, Them2 functions in brown adipose tissue to suppress adaptive increases in energy expenditure. C1 [Kang, Hye Won; Ozdemir, Cafer; Kawano, Yuki; LeClair, Katherine B.; Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA. [Vernochet, Cecile; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Hagen, Susan J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Cohen, DE (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,HIM 941, Boston, MA 02115 USA. EM dcohen@partners.org FU National Institutes of Health/National Center for Research Resources [S10-RR-023010]; NCI Cancer Center Support Grant, National Institutes of Health [P30 CA06516]; National Institutes of Health [U24 DK76169] FX The use of the Longwood Small Animal Imaging Facility at Beth Israel Deaconess Medical Center (Boston, MA) was supported in part by National Institutes of Health/National Center for Research Resources shared instrumentation Grant S10-RR-023010. The use of the Rodent Histopathology Core Facility of Dana-Farber/Harvard Cancer Center (Boston, MA) was supported in part by an NCI Cancer Center Support Grant, National Institutes of Health Grant P30 CA06516. The use of the Mouse Metabolic Phenotype Center at Yale University School of Medicine (New Haven, CT) was supported in part by National Institutes of Health Grant U24 DK76169. NR 26 TC 8 Z9 9 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 2013 VL 288 IS 46 BP 33376 EP 33386 DI 10.1074/jbc.M113.481408 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277TH UT WOS:000328841700051 PM 24072708 ER PT J AU Quraishi, SA Bittner, EA Christopher, KB Camargo, CA AF Quraishi, Sadeq A. Bittner, Edward A. Christopher, Kenneth B. Camargo, Carlos A., Jr. TI Vitamin D Status and Community-Acquired Pneumonia: Results from the Third National Health and Nutrition Examination Survey SO PLOS ONE LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; LOCALLY WEIGHTED REGRESSION; D SUPPLEMENTATION; ANTIMICROBIAL PEPTIDES; D DEFICIENCY; PULMONARY TUBERCULOSIS; CHRONIC RHINOSINUSITIS; NASAL POLYPS; DOUBLE-BLIND AB Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP). Patients and Methods: We identified 16,975 individuals (>= 17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort. Results: The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18-32) ng/mL. 2.1% [95% confidence interval (CI): 1.9-2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17-2.07] compared to levels >= 30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL. Conclusion: Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP. C1 [Quraishi, Sadeq A.; Bittner, Edward A.; Christopher, Kenneth B.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Quraishi, Sadeq A.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Quraishi, SA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM squraishi@partners.org FU National Institutes of Health (NIH) [5T32GM007592-33, UL1 RR025758, R01 AI093723, U01 AI087881] FX SAQ received support from the National Institutes of Health (NIH) 5T32GM007592-33 and UL1 RR025758. CAC received support from NIH R01 AI093723 and U01 AI087881. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 20 Z9 20 U1 1 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 NOV 15 PY 2013 VL 8 IS 11 AR e81120 DI 10.1371/journal.pone.0081120 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255RX UT WOS:000327258600109 PM 24260547 ER PT J AU Tan, XH Carretero, J Chen, Z Zhang, JS Wang, YX Chen, JC Li, XB Ye, H Tang, CH Cheng, X Hou, N Yang, X Wong, KK AF Tan, Xiaohong Carretero, Julian Chen, Zhao Zhang, Jishuai Wang, Yanxiao Chen, Jicheng Li, Xiubin Ye, Hui Tang, Chuanhao Cheng, Xuan Hou, Ning Yang, Xiao Wong, Kwok-Kin TI Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer SO PLOS ONE LA English DT Article ID NF-KAPPA-B; SERUM-LEVELS; STEM-CELLS; INTERLEUKIN-6 LEVEL; MOUSE MODEL; INFLAMMATION; ACTIVATION; RECEPTOR; CYTOKINES; STAT3 AB Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6(-/-) mice with Kras(G12D) mutant mice, which develop lung tumors after activation of mutant Kras(G12D), to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. Kras(G12D); IL-6(-/-) mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than Kras(G12D) mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated Kras(G12D); p53(flox/flox); IL-6(-/-) mice, which developed lung cancer with a trend for reduced metastases and longer survival than Kras(G12D); p53(flox/flox) mice. Tumors from Kras(G12D); IL-6(-/-) mice showed increased expression of TNF alpha and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3 (pSTAT3) than Kras(G12D) mice; however, these changes were not present between tumors from Kras(G12D); p53(flox/flox); IL-6(-/-) and Kras(G12D); p53(flox/flox) mice. Upregulation of pSTAT3 and phosphorylated AKT (pAKT) were observed in Kras(G12D) tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion. C1 [Tan, Xiaohong; Zhang, Jishuai; Wang, Yanxiao; Chen, Jicheng; Li, Xiubin; Ye, Hui; Cheng, Xuan; Hou, Ning; Yang, Xiao] Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing, Peoples R China. [Tan, Xiaohong; Carretero, Julian; Chen, Zhao; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tan, Xiaohong; Carretero, Julian; Chen, Zhao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yang, Xiao] Shanghai Jiao Tong Univ, E Inst Shanghai Univ, Model Organism Div, Shanghai 200030, Peoples R China. [Tang, Chuanhao] Acad Mil Med Sci, Affiliated Hosp, Dept Lung Canc, Beijing, Peoples R China. [Wong, Kwok-Kin] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Carretero, Julian] Univ Valencia, Fac Med & Odontol, Dept Physiol, Valencia, Spain. RP Yang, X (reprint author), Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing, Peoples R China. EM yangx@nic.bmi.ac.cn; kwong1@partners.org RI Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; wong, kwok kin/0000-0001-6323-235X FU NIH [CA122794, CA140594, CA163896, CA166480, CA154303, SPORE P50CA090578]; United against Lung Cancer; American Lung Association; Susan Spooner Research Fund; Chinese National Key Program on Basic Research [2012CB945100, 2011CB504202]; National Natural Science Foundation of China [31030040] FX This work is supported by the NIH (CA122794, CA140594, CA163896, CA166480, CA154303, and Lung SPORE P50CA090578), United against Lung Cancer, American Lung Association, Susan Spooner Research Fund (KKW), Chinese National Key Program on Basic Research (2012CB945100, 2011CB504202) and National Natural Science Foundation of China (31030040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 10 Z9 10 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 NOV 15 PY 2013 VL 8 IS 11 AR UNSP e80885 DI 10.1371/journal.pone.0080885 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255RX UT WOS:000327258600091 PM 24260500 ER PT J AU Vatansever, F Ferraresi, C de Sousa, MVP Yin, R Rineh, A Sharma, SK Hamblin, MR AF Vatansever, Fatma Ferraresi, Cleber Pires de Sousa, Marcelo Victor Yin, Rui Rineh, Ardeshir Sharma, Sulbha K. Hamblin, Michael R. TI Can biowarfare agents be defeated with light? SO VIRULENCE LA English DT Review DE UV dosimeters; bioterrorism; biowarfare; blue light inactivation; germicidal ultraviolet; microbial cells; photo inactivation; photocatalysis; photocatalytic inactivation; photodynamic therapy; psorales; titanium dioxide; ultraviolet light ID SPORE PHOTOPRODUCT LYASE; ACTIVATED ANTIMICROBIAL AGENT; BACILLUS-ANTHRACIS SPORES; NARROW-SPECTRUM LIGHT; ULTRAVIOLET GERMICIDAL IRRADIATION; STAPHYLOCOCCUS-AUREUS INFECTIONS; TITANIUM-DIOXIDE PHOTOCATALYSTS; TARGETED PHOTODYNAMIC THERAPY; METHICILLIN-RESISTANT STRAINS; BIOLOGICAL WARFARE AGENTS AB Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce killed but metabolically active microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future. C1 [Vatansever, Fatma; Ferraresi, Cleber; Pires de Sousa, Marcelo Victor; Yin, Rui; Rineh, Ardeshir; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vatansever, Fatma; Yin, Rui; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Ferraresi, Cleber] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Fed Sao Carlos, Postgrad Program Biotechnol, Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Sao Paulo, Phys Inst Sao Carlos, Opt Grp, Sao Carlos, SP, Brazil. [Pires de Sousa, Marcelo Victor] Univ Sao Paulo, Lab Radiat Dosimetry & Med Phys, Inst Phys, Sao Paulo, Brazil. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Rineh, Ardeshir] Univ Wollongong, Sch Chem, Wollongong, NSW, Australia. [Sharma, Sulbha K.] Raja Ramanna Ctr Adv Technol, Indore, Madhya Pradesh, India. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Ferraresi, Cleber/B-2458-2014; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875. NR 239 TC 6 Z9 7 U1 4 U2 37 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD NOV 15 PY 2013 VL 4 IS 8 BP 796 EP 825 DI 10.4161/viru.26475 PG 30 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 257XK UT WOS:000327420900018 PM 24067444 ER PT J AU Friedman, DJ Upadhyay, GA Singal, G Orencole, M Moore, SA Parks, KA Heist, EK Singh, JP AF Friedman, Daniel J. Upadhyay, Gaurav A. Singal, Gaurav Orencole, Mary Moore, Stephanie A. Parks, Kimberly A. Heist, E. Kevin Singh, Jagmeet P. TI Usefulness and Consequences of Cardiac Resynchronization Therapy in Dialysis-Dependent Patients With Heart Failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RENAL-FUNCTION; ECHOCARDIOGRAPHY; DEFIBRILLATOR; DYSFUNCTION; EFFICIENCY; MORTALITY; TRIAL AB Cardiac resynchronization therapy (CRT) is often deferred in dialysis-dependent patients with heart failure (HF) because of a perceived lack of benefit and potentially higher risks, although the outcomes associated with CRT in dialysis have not been reported. We therefore studied our center's experience with CRT in dialysis-dependent patients. We constructed a descriptive assessment of these patients (n = 15) and performed a case-control analysis matching for age, gender, bundle branch morphology, diabetes mellitus, cardiomyopathy origin, and beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. Baseline and 6-month echocardiograms were assessed for evidence of reverse remodeling. No periprocedural or long-term complications were observed among dialysis patients. Heterogenous improvement in ejection fraction (+3.1 +/- 9.2%) was noted and 2 patients derived absolute improvements of 8% and 22%, respectively. Dialysis patients demonstrated the following 3-year event rates: HF hospitalization, 31%; all-cause hospitalization, 100%; mortality, 73%; and HF hospitalization or death, 82%. In the case-control analysis, controls demonstrated superior reverse remodeling (+9.2 +/- 9.5% increase in ejection fraction), decreased mortality (73% vs 44%, p = 0.038), and all-cause hospitalizations (76% vs 100%, p = 0.047), with no difference in HF hospitalizations (p = 0.39), compared with dialysis patients. In conclusion, at our center, the dialysis-dependent patients with HF who underwent CRT implantation did so safely and no serious complications were observed. Certain dialysis patients demonstrated compelling improvement after device implantation. Compared with matched controls, dialysis patients were at increased risk for adverse events and worsened echocardiographic outcomes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Friedman, Daniel J.; Singal, Gaurav] Massachusetts Gen Hosp, Dept Med, Corrigan Minehan Heart Ctr, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Upadhyay, Gaurav A.; Orencole, Mary; Heist, E. Kevin; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Corrigan Minehan Heart Ctr, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Moore, Stephanie A.; Parks, Kimberly A.] Massachusetts Gen Hosp, Heart Failure & Transplantat Fellowship, Transplant Ctr, Boston, MA 02114 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Corrigan Minehan Heart Ctr, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. EM jsingh@partners.org OI Friedman, Daniel /0000-0001-5791-1954 FU Biotronik; Sorin; St. Jude Medical; Boston Scientific; Thoratec Inc.; Medtronic; CardioInsight; Thoratec; Biosense Webster FX D.J.F., S.A.M., G.S., and G.A.U. have no disclosures to report. E.K.H. reports receiving honoraria from Biotronik, Boston Scientific, Sorin, and St. Jude Medical; research grants from Biotronik, Sorin, and St. Jude Medical; and consulting fees from Boston Scientific, Sorin, and St. Jude Medical. M.O. reports receiving honoraria from Boston Scientific. K.A.P. reports receiving consulting fees from Thoratec Inc. and honoraria from Biotronik and Sorin. J.P.S. reports receiving research grants from St. Jude Medical, Medtronic, Boston Scientific, and Biotronik; consulting fees from Boston Scientific, Biotronik, St. Jude Medical, Medtronic, CardioInsight, Thoratec, and Biosense Webster; and honoraria from Medtronic, Biotronik, Guidant, St. Jude Medical, and Sorin. NR 25 TC 4 Z9 4 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2013 VL 112 IS 10 BP 1625 EP 1631 DI 10.1016/j.amjcard.2013.07.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 255FH UT WOS:000327224300017 PM 23993121 ER PT J AU Shanmugam, NKN Cherayil, BJ AF Shanmugam, Nanda Kumar N. Cherayil, Bobby J. TI Serum-induced up-regulation of hepcidin expression involves the bone morphogenetic protein signaling pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Iron metabolism; Hepcidin; Hepatocyte; Serum ID HEREDITARY HEMOCHROMATOSIS PROTEIN; IRON-METABOLISM; BMP6; STAT3; LIVER; MICE; HFE AB Hepcidin is a peptide hormone that is secreted by the liver and that functions as the central regulator of systemic iron metabolism in mammal. Its expression is regulated at the transcriptional level by changes in iron status and iron requirements, and by inflammatory cues. There is considerable interest in understanding the mechanisms that influence hepcidin expression because dysregulation of hepcidin production is associated with a number of disease states and can lead to iron overload or iron-restricted anemia. In order to shed light on the factors that alter hepcidin expression, we carried out experiments with HepG2 and HuH7, human hepatoma cell lines that are widely used for this purpose. We found that the addition of heat-inactivated fetal calf serum to these cells resulted in a significant dose- and time-dependent up-regulation of hepcidin expression. Serum also activated signaling events known to be downstream of bone morphogenetic proteins (BMPs), a group of molecules that have been implicated previously in hepcidin regulation. Inhibition of these signals with dorsomorphin significantly suppressed serum-induced hepcidin up-regulation. Our results indicate that a BMP or BMP-like molecule present in serum may play an important role in regulating hepcidin expression. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shanmugam, Nanda Kumar N.; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Cherayil, BJ (reprint author), Mucosal Immunol & Biol Res Ctr, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU National Institute of Allergy and Infectious Diseases [R01 AI489700] FX The authors are grateful to Ms Estela Trebicka for technical assistance, and to Drs. Sunitha Nagrath and Raymond Chung for providing the hepatoma cell lines. This work was supported by Grant number R01 AI489700 from the National Institute of Allergy and Infectious Diseases to N.C. The funding agency had no role in the collection, analysis or interpretation of the data. NR 24 TC 5 Z9 5 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 15 PY 2013 VL 441 IS 2 BP 383 EP 386 DI 10.1016/j.bbrc.2013.10.065 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256DO UT WOS:000327290100019 PM 24157792 ER PT J AU Avan, A Caretti, V Funel, N Galvani, E Maftouh, M Honeywell, RJ Lagerweij, T Van Tellingen, O Campani, D Fuchs, D Verheul, HM Schuurhuis, GJ Boggi, U Peters, GJ Wurdinger, T Giovannetti, E AF Avan, Amir Caretti, Viola Funel, Niccola Galvani, Elena Maftouh, Mina Honeywell, Richard J. Lagerweij, Tonny Van Tellingen, Olaf Campani, Daniela Fuchs, Dieter Verheul, Henk M. Schuurhuis, Gerrit-Jan Boggi, Ugo Peters, Godefridus J. Wurdinger, Thomas Giovannetti, Elisa TI Crizotinib Inhibits Metabolic Inactivation of Gemcitabine in c-Met-driven Pancreatic Carcinoma SO CANCER RESEARCH LA English DT Article ID CANCER STEM-CELLS; HEPATOCYTE GROWTH-FACTOR; LUNG-CANCER; TUMOR-GROWTH; EXPRESSION; METASTASIS; RESISTANCE; RECEPTOR; THERAPY; MODEL AB Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here, we developed four orthotopic mouse models using primary human PDAC cells genetically engineered to express firefly- and Gaussia luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and high-frequency ultrasound. In these models, we conducted detailed histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic characteristics were compared with the originator tumor and primary tumor cells using array-based comparative genomic hybridization, using frozen specimens obtained by laser microdissection. Notably, the orthotopic human xenografts in these models recapitulated the phenotype of human PDACs, including hypovascular and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an increased copy number and overexpression of c-Met in one of the models; we examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In particular, we found that crizotinib decreased tumor dimension, prolonged survival, and increased blood and tissue concentrations of gemcitabine, synergizing with a cytidine deaminase-mediated mechanism of action. Together, these more readily imaged orthotopic PDAC models displayed genetic, histopathologic, and metastatic features similar to their human tumors of origin. Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination of drugs warranting clinical evaluation for PDAC treatment. (C) 2013 AACR. C1 [Avan, Amir; Galvani, Elena; Maftouh, Mina; Honeywell, Richard J.; Verheul, Henk M.; Peters, Godefridus J.; Giovannetti, Elisa] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Schuurhuis, Gerrit-Jan] Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Caretti, Viola; Lagerweij, Tonny; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg & Pediat Oncol Hematol, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Van Tellingen, Olaf] Netherlands Canc Inst, Div Diagnost Oncol, Amsterdam, Netherlands. [Fuchs, Dieter] VisualSonics, Amsterdam, Netherlands. [Caretti, Viola] Stanford Univ, Dept Neurol, Sch Med, Stanford, CA 94305 USA. [Caretti, Viola] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Funel, Niccola; Campani, Daniela] Univ Pisa, Div Surg Pathol, Pisa, Italy. [Boggi, Ugo] Univ Pisa, Div Gen & Transplant Surg, Pisa, Italy. [Wurdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Giovannetti, E (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, CCA Room 1-52,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM e.giovannetti@vumc.nl RI Galvani, Elena/L-3133-2016; OI Lagerweij, Tonny/0000-0003-1043-7452; Giovannetti, Elisa/0000-0002-7565-7504; Funel, Niccola/0000-0002-5028-2363 FU Netherlands Organization for Scientific Research; Veni grant; CCA Foundation; AIRC/Marie Curie International Fellowship; FIRC International Fellowship; PRIN; Istituto Toscano Tumori FX This work was partially supported by grants from Netherlands Organization for Scientific Research, Veni grant (E. Giovannetti), CCA Foundation 2012 (E. Giovannetti, A. Avan, and G.J. Peters), AIRC/Marie Curie International Fellowship (E. Giovannetti), FIRC International Fellowship (E. Galvani), Italian Minister of Research - PRIN-2009 (U. Boggi, N. Funel, and E. Giovannetti), and Istituto Toscano Tumori (U. Boggi, N. Funel, and E. Giovannetti). NR 49 TC 24 Z9 24 U1 0 U2 11 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 NOV 15 PY 2013 VL 73 IS 22 BP 6745 EP 6756 DI 10.1158/0008-5472.CAN-13-0837 PG 12 WC Oncology SC Oncology GA 256NY UT WOS:000327321700020 PM 24085787 ER PT J AU Cho, J Chen, L Sangji, N Okabe, T Yonesaka, K Francis, JM Flavin, RJ Johnson, W Kwon, J Yu, SY Greulich, H Johnson, BE Eck, MJ Janne, PA Wong, KK Meyerson, M AF Cho, Jeonghee Chen, Liang Sangji, Naveen Okabe, Takafumi Yonesaka, Kimio Francis, Joshua M. Flavin, Richard J. Johnson, William Kwon, Jihyun Yu, Soyoung Greulich, Heidi Johnson, Bruce E. Eck, Michael J. Jaenne, Pasi A. Wong, Kwok-Kin Meyerson, Matthew TI Cetuximab Response of Lung Cancer-Derived EGF Receptor Mutants Is Associated with Asymmetric Dimerization SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; METASTATIC COLORECTAL-CANCER; KINASE DOMAIN; TYROSINE KINASE; WILD-TYPE; MUTATIONS; GEFITINIB; ACTIVATION; SENSITIVITY; RESISTANCE AB Kinase domain mutations of the EGF receptor (EGFR) are common oncogenic events in lung adenocarcinoma. Here, we explore the dependency upon asymmetric dimerization of the kinase domain for activation of lung cancer-derived EGFR mutants. We show that whereas wild-type EGFR and the L858R mutant require dimerization for activation and oncogenic transformation, the exon 19 deletion, exon 20 insertion, and L858R/T790M EGFR mutants do not require dimerization. In addition, treatment with the monoclonal antibody, cetuximab, shrinks mouse lung tumors induced by the dimerization-dependent L858R mutant, but exerts only a modest effect on tumors driven by dimerization-independent EGFR mutants. These data imply that different EGFR mutants show differential requirements for dimerization and that disruption of dimerization may be among the antitumor mechanisms of cetuximab. (C) 2013 AACR. C1 [Cho, Jeonghee; Chen, Liang; Sangji, Naveen; Okabe, Takafumi; Yonesaka, Kimio; Francis, Joshua M.; Flavin, Richard J.; Johnson, William; Yu, Soyoung; Greulich, Heidi; Johnson, Bruce E.; Jaenne, Pasi A.; Wong, Kwok-Kin; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yu, Soyoung; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Cho, Jeonghee; Sangji, Naveen; Francis, Joshua M.; Johnson, William; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Okabe, Takafumi; Yonesaka, Kimio; Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Flavin, Richard J.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Greulich, Heidi; Johnson, Bruce E.; Jaenne, Pasi A.; Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Cho, Jeonghee; Kwon, Jihyun] Samsung Med Ctr, Samsung Genome Inst, Seoul 135270, South Korea. [Greulich, Heidi; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jeong.cho@skku.edu; matthew_meyerson@dfci.harvard.edu OI wong, kwok kin/0000-0001-6323-235X FU NCI [R01 CA116020] FX The research was supported in part by NCI R01 CA116020 (M.J. Eck and M. Meyerson). NR 54 TC 19 Z9 19 U1 1 U2 10 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 NOV 15 PY 2013 VL 73 IS 22 BP 6770 EP 6779 DI 10.1158/0008-5472.CAN-13-1145 PG 10 WC Oncology SC Oncology GA 256NY UT WOS:000327321700022 PM 24063894 ER PT J AU Shimamura, T Chen, Z Soucheray, M Carretero, J Kikuchi, E Tchaicha, JH Gao, YD Cheng, KA Cohoon, TJ Qi, J Akbay, E Kimmelman, AC Kung, AL Bradner, JE Wong, KK AF Shimamura, Takeshi Chen, Zhao Soucheray, Margaret Carretero, Julian Kikuchi, Eiki Tchaicha, Jeremy H. Gao, Yandi Cheng, Katherine A. Cohoon, Travis J. Qi, Jun Akbay, Esra Kimmelman, Alec C. Kung, Andrew L. Bradner, James E. Wong, Kwok-Kin TI Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID C-MYC; RAS ONCOGENES; PROTEINS; THERAPY; REVEALS; TARGETS; MICE; LINE AB Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non-small cell lung cancer (NSCLC) with BET inhibition. Experimental Design: We performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cell lines harboring KRAS and/or LKB1 mutations. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. Effects of bromodomain inhibition on transcriptional pathways were explored and validated by expression analysis. Results: Although JQ1 is broadly active in NSCLC cells, activity of JQ1 in mutant KRAS NSCLC is abrogated by concurrent alteration or genetic knockdown of LKB1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1. Conclusion: Bromodomain inhibition comprises a promising therapeutic strategy for KRAS-mutant NSCLC with wild-type LKB1, via inhibition of MYC function. Clinical studies of BET bromodomain inhibitors in aggressive NSCLC will be actively pursued. (C) 2013 AACR. C1 [Shimamura, Takeshi; Soucheray, Margaret; Gao, Yandi] Loyola Univ Chicago, Oncol Res Inst, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL USA. [Chen, Zhao; Kikuchi, Eiki; Tchaicha, Jeremy H.; Cheng, Katherine A.; Cohoon, Travis J.; Qi, Jun; Bradner, James E.; Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Kimmelman, Alec C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Zhao; Kikuchi, Eiki; Tchaicha, Jeremy H.; Cheng, Katherine A.; Cohoon, Travis J.; Akbay, Esra; Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Canc Ctr, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Chen, Zhao; Kikuchi, Eiki; Tchaicha, Jeremy H.; Cheng, Katherine A.; Cohoon, Travis J.; Akbay, Esra; Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA 02115 USA. [Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Chen, Zhao; Kikuchi, Eiki; Tchaicha, Jeremy H.; Akbay, Esra; Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Carretero, Julian] Univ Valencia, Fac Farm, Dept Fisiol, E-46010 Valencia, Spain. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,HIM243, Boston, MA 02215 USA. EM tashimamura@lumc.edu; kwong1@partners.org RI Kikuchi, Eiki/M-9688-2014; Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; Kung, Andrew/0000-0002-9091-488X; wong, kwok kin/0000-0001-6323-235X FU NIH [CA122794, CA140594, CA137181, CA137008, CA147940, CA137008-01, 1U01CA141576, Lung SPORE P50CA090578]; United against Lung Cancer Foundation; American Lung Association; Susan Spooner Research Fund; Damon-Runyon Cancer Research Foundation; Broad Next Generation Award; Smith Family Award; American Cancer Society Illinois Division Basic Sciences [254563] FX This work is supported by the NIH (CA122794, CA140594, CA137181, CA137008, CA147940, CA137008-01, 1U01CA141576, and Lung SPORE P50CA090578), United against Lung Cancer Foundation (to K.-K. Wong), American Lung Association (to K.-K. Wong), Susan Spooner Research Fund (to K.-K. Wong), the Damon-Runyon Cancer Research Foundation, the Broad Next Generation Award, and a Smith Family Award (to J.E. Bradner). This work is also supported by American Cancer Society Illinois Division Basic Sciences Grant #254563 (to T. Shimamura). NR 28 TC 65 Z9 65 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2013 VL 19 IS 22 BP 6183 EP 6192 DI 10.1158/1078-0432.CCR-12-3904 PG 10 WC Oncology SC Oncology GA 256NU UT WOS:000327320900014 PM 24045185 ER PT J AU Axelsson, M Mattsson, N Malmestrom, C Zetterberg, H Lycke, J AF Axelsson, Markus Mattsson, Niklas Malmestrom, Clas Zetterberg, Henrik Lycke, Jan TI The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Multiple sclerosis; Intrathecal IgG; Oligoclonal band (OCB); CXCL13; Mitoxantrone; B-cell ID STEM-CELL TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; DIAGNOSTIC-CRITERIA; PLASMA BLASTS; MS; PROTEIN; TRIAL; PANENCEPHALITIS; ABNORMALITIES AB We investigated the impact of disease duration, clinical course and immunosuppressive therapy on intrathecal IgG synthesis in multiple sclerosis (MS). Cerebrospinal fluid (CSF) was obtained twice, 8-10 years apart, from 20 MS patients and 26 healthy controls, and from 22 MS patients before and after two years of mitoxantrone treatment. The oligoclonal IgG band patterns changed in 15 patients at long-term follow-up, but were only influenced in 4 patients by mitoxantrone therapy. The CSF B-cell-regulating chemokine CXCL13 correlated with intrathecal IgG production suggesting a B-cell-dependence of intrathecal IgG synthesis in MS. (C) 2013 Elsevier B.V. All rights reserved. C1 [Axelsson, Markus; Malmestrom, Clas; Lycke, Jan] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden. [Mattsson, Niklas; Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden. [Mattsson, Niklas] Univ Calif San Francisco, San Francisco VA Med Ctr, CIND, San Francisco, CA 94143 USA. RP Axelsson, M (reprint author), Sahlgrens Univ Hosp, Dept Neurol, Bla Straket 7, S-41345 Gothenburg, Sweden. EM markus.axelsson@vgregion.se RI Malmestrom, Clas/A-8749-2012; OI Malmestrom, Clas/0000-0003-2477-0088; Lycke, Jan/0000-0002-7891-8466 FU Swedish Federal Government (LUA/ALF agreement); Swedish Society of the Neurologically Disabled; Research Foundation of the Multiple Sclerosis Society of Gothenburg; Edit Jacobson Foundation, and Biogen Idec (unconditional grants) FX This study was funded by grants from the Swedish Federal Government (LUA/ALF agreement), the Swedish Society of the Neurologically Disabled, the Research Foundation of the Multiple Sclerosis Society of Gothenburg, the Edit Jacobson Foundation, and Biogen Idec (unconditional grants). NR 49 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV 15 PY 2013 VL 264 IS 1-2 BP 100 EP 105 DI 10.1016/j.jneuroim.2013.09.003 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 260AP UT WOS:000327567700013 PM 24125567 ER PT J AU Wong, IY Bhatia, SN Toner, M AF Wong, Ian Y. Bhatia, Sangeeta N. Toner, Mehmet TI Nanotechnology: emerging tools for biology and medicine SO GENES & DEVELOPMENT LA English DT Review DE Nanoparticle; microfluidics; single cell; biomarker; microneedle; targeted delivery ID CIRCULATING TUMOR-CELLS; RED-BLOOD-CELLS; ON-A-CHIP; DRUG-DELIVERY; MULTIFUNCTIONAL NANOPARTICLES; TISSUE PENETRATION; NANOSCALE SHAPES; LIVING CELLS; FOLDING DNA; IN-VIVO AB Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine. C1 [Wong, Ian Y.] Brown Univ, Sch Engn, Ctr Biomed Engn, Providence, RI 02912 USA. [Wong, Ian Y.] Brown Univ, Inst Mol & Nanoscale Innovat, Providence, RI 02912 USA. [Bhatia, Sangeeta N.] MIT, Inst Med Engn & Sci, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Bhatia, Sangeeta N.] MIT, Cambridge, MA 02139 USA. [Bhatia, Sangeeta N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Bhatia, Sangeeta N.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Toner, Mehmet] Harvard Univ, Sch Med, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med, Charlestown, MA 02129 USA. [Toner, Mehmet] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Wong, IY (reprint author), Brown Univ, Sch Engn, Ctr Biomed Engn, Providence, RI 02912 USA. EM ian_wong@brown.edu; mehmet_toner@hms.harvard.edu RI Wong, Ian/G-1611-2012 OI Wong, Ian/0000-0002-9439-2548 FU Howard Hughes Medical Institute; NCI NIH HHS [U54CA151884, U54 CA151884]; NIBIB NIH HHS [P41 EB002503, P41EB002503] NR 95 TC 18 Z9 18 U1 10 U2 81 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2013 VL 27 IS 22 BP 2397 EP 2408 DI 10.1101/gad.226837.113 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 256NW UT WOS:000327321300001 PM 24240230 ER PT J AU Witzke, C Bhatt, A Inglessis, I AF Witzke, Christian Bhatt, Ami Inglessis, Ignacio TI Percutaneous Embolization of a Giant Collateral Vessel Originating From the Azygos Vein via the Inferior Vena Cava SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE collateral embolization; single ventricle; Fontan ID ANASTOMOSIS; HEART AB We present the case of a 45-year-old man with univentricular heart, small outlet chamber, and L-transposition of the great vessels. As an infant, the patient underwent multiple palliative surgical interventions. He presented with worsening dyspnea and fatigue and was found to have systemic oxygen saturation of 85% on 2 L of oxygen by nasal cannula, whereas he had chronically remained between 90 and 95% throughout most of adulthood. There was no evidence of significant valvular regurgitation or stenosis, nor was there an overt intracardiac shunt by echocardiography. Cardiac CT and cardiac MRI revealed a large serpiginous systemic to pulmonary venovenous collateral located behind the left atrium. The collateral drained into the lower right pulmonary vein as it entered the left atrium. The tributary veins to the giant collateral were determined by these images modalities. The patient underwent a percutaneous embolization of this giant venovenous collateral via a remnant supracardinal vein originating from the infrarenal inferior vena cava using two Amplatzer Vascular Plug II. Immediately after the procedure the patient's oxygen saturation increased to 90% on room air at rest. At 2 months follow-up the patient had a marked clinical improvement with oxygen saturation as high as 95% on room air while walking. Our case illustrates a successful embolization of a giant collateral via an embryological venous remnant connecting the IVC to the azygos system. (c) 2012 Wiley Periodicals, Inc. C1 [Witzke, Christian] Albert Einstein Med Ctr, Dept Cardiovasc Med, Philadelphia, PA 19141 USA. [Bhatt, Ami; Inglessis, Ignacio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Inglessis, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB800, Boston, MA 02114 USA. EM iinglessis@partners.org NR 7 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 15 PY 2013 VL 82 IS 6 BP E798 EP E802 DI 10.1002/ccd.24641 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 246IU UT WOS:000326532300005 PM 22936600 ER PT J AU Lim, SC Friemel, M Marum, JE Tucker, EJ Bruno, DL Riley, LG Christodoulou, J Kirk, EP Boneh, A DeGennaro, CM Springer, M Mootha, VK Rouault, TA Leimkuhler, S Thorburn, DR Compton, AG AF Lim, Sze Chern Friemel, Martin Marum, Justine E. Tucker, Elena J. Bruno, Damien L. Riley, Lisa G. Christodoulou, John Kirk, Edwin P. Boneh, Avihu DeGennaro, Christine M. Springer, Michael Mootha, Vamsi K. Rouault, Tracey A. Leimkuehler, Silke Thorburn, David R. Compton, Alison G. TI Mutations in LYRM4, encoding ironsulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes SO HUMAN MOLECULAR GENETICS LA English DT Article ID IRON-SULFUR CLUSTER; CYTOSOLIC FE/S PROTEINS; MITOCHONDRIAL DISEASE; SCAFFOLD PROTEIN; CYSTEINE DESULFURASE; ESCHERICHIA-COLI; LACTIC-ACIDOSIS; CAUSES MYOPATHY; I DEFICIENCY; 1ST YEAR AB Ironsulfur clusters (ISCs) are important prosthetic groups that define the functions of many proteins. Proteins with ISCs (called ironsulfur or FeS proteins) are present in mitochondria, the cytosol, the endoplasmic reticulum and the nucleus. They participate in various biological pathways including oxidative phosphorylation (OXPHOS), the citric acid cycle, iron homeostasis, heme biosynthesis and DNA repair. Here, we report a homozygous mutation in LYRM4 in two patients with combined OXPHOS deficiency. LYRM4 encodes the ISD11 protein, which forms a complex with, and stabilizes, the sulfur donor NFS1. The homozygous mutation (c.203GT, p.R68L) was identified via massively parallel sequencing of 1000 mitochondrial genes (MitoExome sequencing) in a patient with deficiency of complexes I, II and III in muscle and liver. These three complexes contain ISCs. Sanger sequencing identified the same mutation in his similarly affected cousin, who had a more severe phenotype and died while a neonate. Complex IV was also deficient in her skeletal muscle. Several other FeS proteins were also affected in both patients, including the aconitases and ferrochelatase. Mutant ISD11 only partially complemented for an ISD11 deletion in yeast. Our in vitro studies showed that the l-cysteine desulfurase activity of NFS1 was barely present when co-expressed with mutant ISD11. Our findings are consistent with a defect in the early step of ISC assembly affecting a broad variety of FeS proteins. The differences in biochemical and clinical features between the two patients may relate to limited availability of cysteine in the newborn period and suggest a potential approach to therapy. C1 [Lim, Sze Chern; Marum, Justine E.; Tucker, Elena J.; Bruno, Damien L.; Boneh, Avihu; Thorburn, David R.; Compton, Alison G.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Lim, Sze Chern; Marum, Justine E.; Tucker, Elena J.; Boneh, Avihu; Thorburn, David R.; Compton, Alison G.] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia. [Friemel, Martin; Leimkuehler, Silke] Univ Potsdam, Dept Mol Enzymol, Inst Biochem & Biol, D-14476 Potsdam, Germany. [Bruno, Damien L.; Boneh, Avihu; Thorburn, David R.] Royal Childrens Hosp, Victorian Clin Genet Serv, Parkville, Vic 3052, Australia. [Riley, Lisa G.; Christodoulou, John] Childrens Hosp, Genet Metab Disorders Res Unit, Westmead, NSW 2145, Australia. [Christodoulou, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Christodoulou, John] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia. [Kirk, Edwin P.] Sydney Childrens Hosp, Dept Med Genet, Randwick, NSW 2031, Australia. [DeGennaro, Christine M.; Springer, Michael; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Mootha, Vamsi K.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02141 USA. [Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Compton, AG (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM alison.compton@mcri.edu.au RI Bruno, Damien/C-3665-2013; Christodoulou, John/E-5866-2015; Lim, Sze Chern/I-6763-2013; OI Lim, Sze Chern/0000-0003-0312-9937; Kirk, Edwin/0000-0002-4662-0024; thorburn, david/0000-0002-7725-9470; Compton, Alison/0000-0002-2725-7055; Christodoulou, John/0000-0002-8431-0641 FU NHLBI Lung GO Sequencing Project [HL-102923]; NHLBI WHI Sequencing Project [HL-102924]; NHLBI Broad GO Sequencing Project [HL-102925]; NHLBI Seattle GO Sequencing Project [HL-102926]; NHLBI Heart GO Sequencing Project [HL-103010]; NHLBI Melbourne Research Scholarship; NHLBI Australian National Health and Medical Research Council; NHLBI Victorian Government; NHLBI Eunice Kennedy Shriver National Institute of Child Health and Human Development; NHLBI Deutsche Forschungsgemeinschaft FX The authors thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). This work was supported by a Melbourne Research Scholarship (to S. C. L.), grants and a Principal Research Fellowship from the Australian National Health and Medical Research Council (to D. R. T.), the Victorian Government's Operational Infrastructure Support Program (to D. R. T.) and support from the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (to T. A. R.), and the Deutsche Forschungsgemeinschaft (to S.L.). NR 71 TC 29 Z9 33 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2013 VL 22 IS 22 BP 4460 EP 4473 DI 10.1093/hmg/ddt295 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 248EA UT WOS:000326675300002 PM 23814038 ER PT J AU Pauken, KE Linehan, JL Spanier, JA Sahli, NL Kalekar, LA Binstadt, BA Moon, JJ Mueller, DL Jenkins, MK Fife, BT AF Pauken, Kristen E. Linehan, Jonathan L. Spanier, Justin A. Sahli, Nathanael L. Kalekar, Lokesh A. Binstadt, Bryce A. Moon, James J. Mueller, Daniel L. Jenkins, Marc K. Fife, Brian T. TI Cutting Edge: Type 1 Diabetes Occurs despite Robust Anergy among Endogenous Insulin-Specific CD4 T Cells in NOD Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEPTIDE-MHC COMPLEX; RESPONSE MAGNITUDE; RECOGNIZE; TOLERANCE; FREQUENCY; REGISTER; ALLELES; EPITOPE; MOUSE AB Insulin-specific CD4(+) T cells are required for type 1 diabetes. How these cells are regulated and how tolerance breaks down are poorly understood because of a lack of reagents. Therefore, we used an enrichment method and tetramer reagents to track insulin-specific CD4(+) T cells in diabetes-susceptible NOD and resistant B6 mice expressing I-A(g7). Insulin-specific cells were detected in both strains, but they only became activated, produced IFN-gamma, and infiltrated the pancreas in NOD mice. Unexpectedly, the majority of Ag-experienced cells in NOD mice displayed an anergic phenotype, but this population decreased with age as tolerance was lost. B6 mice expressing I-A(g7) were protected because insulin-specific cells did not become effector or anergic T cells but remained naive. These data suggest that NOD mice promote tolerance through anergy induction, but a small proportion of autoreactive T cells escape anergy to provoke type 1 diabetes. C1 [Pauken, Kristen E.; Linehan, Jonathan L.; Spanier, Justin A.; Sahli, Nathanael L.; Kalekar, Lokesh A.; Binstadt, Bryce A.; Mueller, Daniel L.; Jenkins, Marc K.; Fife, Brian T.] Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA. [Pauken, Kristen E.; Spanier, Justin A.; Sahli, Nathanael L.; Kalekar, Lokesh A.; Mueller, Daniel L.; Fife, Brian T.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Linehan, Jonathan L.; Jenkins, Marc K.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Binstadt, Bryce A.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Moon, James J.] Harvard Univ, Boston, MA 02114 USA. RP Fife, BT (reprint author), Univ Minnesota, 2101 6th St SE,3-144 MBB,Campus Code 2641, Minneapolis, MN 55455 USA. EM bfife@umn.edu RI Binstadt, Bryce/N-1305-2013; Fife, Brian/D-2042-2013; Jenkins, Marc/G-1063-2012 OI Binstadt, Bryce/0000-0003-3127-3856; Fife, Brian/0000-0001-9826-5637; Jenkins, Marc/0000-0001-8009-7655 FU Juvenile Diabetes Research Foundation [22011662]; American Diabetes Association [0709JF21]; National Institutes of Health [P01 AI35296]; Stanwood Johnston Fellowship FX This work was supported by the Juvenile Diabetes Research Foundation (22011662 to B.T.F.), the American Diabetes Association (0709JF21 to B.T.F.), the National Institutes of Health (P01 AI35296 to B.T.F., D.L.M., and M.K.J.), and a Stanwood Johnston Fellowship (to K.E.P.). NR 24 TC 14 Z9 15 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2013 VL 191 IS 10 BP 4913 EP 4917 DI 10.4049/jimmunol.1301927 PG 5 WC Immunology SC Immunology GA 247AK UT WOS:000326584600005 PM 24123682 ER PT J AU Bhowmick, R Maung, NHT Hurley, BP Ghanem, EB Gronert, K McCormick, BA Leong, JM AF Bhowmick, Rudra Maung, Nang H. Tin Hurley, Bryan P. Ghanem, Elsa Bou Gronert, Karsten McCormick, Beth A. Leong, John M. TI Systemic Disease during Streptococcus pneumoniae Acute Lung Infection Requires 12-Lipoxygenase-Dependent Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INVASIVE BACTERIAL PATHOGENS; PULMONARY EPITHELIAL-CELLS; HEPOXILIN A(3); TRANSEPITHELIAL MIGRATION; NEUTROPHIL RECRUITMENT; PNEUMOCOCCAL PNEUMONIA; INTESTINAL EPITHELIA; PHOSPHOLIPASE A(2); GENOME SEQUENCE; EMIGRATION AB Acute pulmonary infection by Streptococcus pneumoniae is characterized by high bacterial numbers in the lung, a robust alveolar influx of polymorphonuclear cells (PMNs), and a risk of systemic spread of the bacterium. We investigated host mediators of S. pneumoniae-induced PMN migration and the role of inflammation in septicemia following pneumococcal lung infection. Hepoxilin A(3) (HXA(3)) is a PMN chemoattractant and a metabolite of the 12-lipoxygenase (12-LOX) pathway. We observed that S. pneumoniae infection induced the production of 12-LOX in cultured pulmonary epithelium and in the lungs of infected mice. Inhibition of the 12-LOX pathway prevented pathogen-induced PMN transepithelial migration in vitro and dramatically reduced lung inflammation upon high-dose pulmonary challenge with S. pneumoniae in vivo, thus implicating HXA(3) in pneumococcus-induced pulmonary inflammation. PMN basolateral-to-apical transmigration in vitro significantly increased apical-to-basolateral transepithelial migration of bacteria. Mice suppressed in the expression of 12-LOX exhibited little or no bacteremia and survived an otherwise lethal pulmonary challenge. Our data suggest that pneumococcal pulmonary inflammation is required for high-level bacteremia and systemic infection, partly by disrupting lung epithelium through 12-LOX-dependent HXA(3) production and subsequent PMN transepithelial migration. C1 [Bhowmick, Rudra; Ghanem, Elsa Bou; Leong, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Maung, Nang H. Tin] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Hurley, Bryan P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Gronert, Karsten] Univ Calif Berkeley, Sch Optometry, Vis Sci Program, Berkeley, CA 94720 USA. [McCormick, Beth A.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. RP Leong, JM (reprint author), Tufts Univ, 136 Harrison Ave, Boston, MA 02111 USA. EM Beth.McCormick@umassmed.edu; John.Leong@tufts.edu FU American Lung Association Senior Research Training Fellowship [RT 194942 N]; National Institutes of Health [EY022208, DK56754, DK33506]; Crohn's and Colitis Association of America; Cystic Fibrosis Foundation; National Institutes of Health/National Institute of Allergy and Infectious Diseases FX This work was supported in part by American Lung Association Senior Research Training Fellowship RT 194942 N (to R.B.) and National Institutes of Health Grant EY022208 (to K.G.). B.A.M. is supported by National Institutes of Health Grants DK56754 and DK33506, as well as the Crohn's and Colitis Association of America. B.P.H. is supported by the Cystic Fibrosis Foundation and National Institutes of Health/National Institute of Allergy and Infectious Diseases. NR 54 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2013 VL 191 IS 10 BP 5115 EP 5123 DI 10.4049/jimmunol.1300522 PG 9 WC Immunology SC Immunology GA 247AK UT WOS:000326584600026 PM 24089193 ER PT J AU Mallampalli, RK Coon, TA Glasser, JR Wang, C Dunn, SR Weathington, NM Zhao, J Zou, CB Zhao, YT Chen, BB AF Mallampalli, Rama K. Coon, Tiffany A. Glasser, Jennifer R. Wang, Claire Dunn, Sarah R. Weathington, Nathaniel M. Zhao, Jing Zou, Chunbin Zhao, Yutong Chen, Bill B. TI Targeting F Box Protein Fbxo3 To Control Cytokine-Driven Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL COLITIS; APAG PROTEIN; MOUSE PAW; SEPSIS; FAMILY; ACTIVATION; EXPRESSION; CORTICOSTEROIDS; UBIQUITINATION; PROLIFERATION AB Cytokine-driven inflammation underlies the pathobiology of a wide array of infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have a vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation of genes encoding proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by mediating the degradation of the TRAF inhibitory protein, Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial-like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and stimulating cytokine secretion. By targeting this ApaG motif, we developed a highly unique, selective genus of small-molecule Fbxo3 inhibitors that by reducing TRAF protein levels, potently inhibited cytokine release from human blood mononuclear cells. The Fbxo3 inhibitors effectively lessened the severity of viral pneumonia, septic shock, colitis, and cytokine-driven inflammation systemically in murine models. Thus, pharmacological targeting of Fbxo3 might be a promising strategy for immune-related disorders characterized by a heightened host inflammatory response. C1 [Mallampalli, Rama K.; Coon, Tiffany A.; Glasser, Jennifer R.; Wang, Claire; Dunn, Sarah R.; Weathington, Nathaniel M.; Zhao, Jing; Zou, Chunbin; Zhao, Yutong; Chen, Bill B.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.; Coon, Tiffany A.; Glasser, Jennifer R.; Wang, Claire; Dunn, Sarah R.; Weathington, Nathaniel M.; Zhao, Jing; Zou, Chunbin; Zhao, Yutong; Chen, Bill B.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15213 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Med Ctr, Montefiore Hosp, Northwest 628,3459 5th Ave, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu; chenb@upmc.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health [R01 HL096376, R01 HL097376, R01 HL098174, R01 HL116472, R01 HL01916]; American Heart Association [12SDG9050005, 12SDG12040330]; U.S. Department of Veterans Affairs FX This work was supported in part by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work also was supported by a Merit Review award from the U.S. Department of Veterans Affairs and National Institutes of Health Grants R01 HL096376, R01 HL097376, and R01 HL098174 (to R.K.M.), R01 HL116472 (to B.B.C.), R01 HL01916 (to Y.Z.), and American Heart Association Awards 12SDG9050005 (to J.Z.) and 12SDG12040330 (to C.Z.). NR 49 TC 19 Z9 19 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2013 VL 191 IS 10 BP 5247 EP 5255 DI 10.4049/jimmunol.1300456 PG 9 WC Immunology SC Immunology GA 247AK UT WOS:000326584600038 PM 24123678 ER PT J AU Morris, PG Iyengar, NM Patil, S Chen, C Abbruzzi, A Lehman, R Steingart, R Oeffinger, KC Lin, N Moy, B Come, SE Winer, EP Norton, L Hudis, CA Dang, CT AF Morris, Patrick G. Iyengar, Neil M. Patil, Sujata Chen, Carol Abbruzzi, Alyson Lehman, Robert Steingart, Richard Oeffinger, Kevin C. Lin, Nancy Moy, Beverley Come, Steven E. Winer, Eric P. Norton, Larry Hudis, Clifford A. Dang, Chau T. TI Long-Term Cardiac Safety and Outcomes of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel and Trastuzumab With and Without Lapatinib in Patients With Early Breast Cancer SO CANCER LA English DT Article DE cardiac safety; dose-dense chemotherapy; early breast cancer; efficacy; lapatinib; trastuzumab ID TRIAL COMPARING DOXORUBICIN; PLUS ADJUVANT CHEMOTHERAPY; HEART-FAILURE; RANDOMIZED-TRIAL; NSABP B-31; OPEN-LABEL; THERAPY; WOMEN; ANTHRACYCLINE; MULTICENTER AB BACKGROUNDThe authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%, respectively. METHODSIn trial A, patients received dd doxorubicin and cyclophosphamide (AC)paclitaxel (T) (each given every 2 weeks) x4 with trastuzumab (H) given x1 year. In trial B, weekly T (weekly x12) was substituted for ddT and lapatinib x1 year was added. Herein, the authors report the longer-term incidence of CHF and distant disease-free survival (DDFS). RESULTSFrom January 2005 to May 2008, 165 patients enrolled (median age, 46 years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]), 17%of whom had previous hypertension. With a median follow-up of 84 months (trial A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%-7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively. CONCLUSIONSLonger follow-up of these 2 studies has demonstrated that ddACTH only or with lapatinib is associated with a low risk of CHF and promising DDFS in patients with early breast cancer. Cancer 2013;119:3943-3951. (c) 2013 American Cancer Society. C1 [Morris, Patrick G.; Iyengar, Neil M.; Abbruzzi, Alyson; Lehman, Robert; Norton, Larry; Hudis, Clifford A.; Dang, Chau T.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10065 USA. [Patil, Sujata] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY 10065 USA. [Chen, Carol; Steingart, Richard] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Lin, Nancy; Winer, Eric P.] Dana Farber Canc Inst, Dept Breast Oncol, Boston, MA 02115 USA. [Moy, Beverley] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Morris, PG (reprint author), Mem Sloan Kettering Canc Ctr, Evelyn H Lauder Breast Ctr, Breast Canc Med Serv, 300 E 66th St, New York, NY 10065 USA. EM morrisp1@mskcc.org OI Norton, Larry/0000-0003-3701-9250 FU Genentech; Amgen; GlaxoSmithKline FX Supported by Genentech, Amgen, and GlaxoSmithKline. NR 38 TC 8 Z9 8 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2013 VL 119 IS 22 BP 3943 EP 3951 DI 10.1002/cncr.28284 PG 9 WC Oncology SC Oncology GA 244VO UT WOS:000326418500011 PM 24037735 ER PT J AU Averbook, BJ Lee, SJ Delman, KA Gow, KW Zager, JS Sondak, VK Messina, JL Sabel, MS Pittelkow, MR Ecker, PM Markovic, SN Swetter, SM Leachman, SA Testori, A Curiel-Lewandrowski, C Go, RS Jukic, DM Kirkwood, JM AF Averbook, Bruce J. Lee, Sandra J. Delman, Keith A. Gow, Kenneth W. Zager, Jonathan S. Sondak, Vernon K. Messina, Jane L. Sabel, Michael S. Pittelkow, Mark R. Ecker, Phillip M. Markovic, Svetomir N. Swetter, Susan M. Leachman, Sancy A. Testori, Alessandro Curiel-Lewandrowski, Clara Go, Ronald S. Jukic, Drazen M. Kirkwood, John M. TI Pediatric Melanoma: Analysis of an International Registry SO CANCER LA English DT Article DE melanoma; pediatric; sentinel lymph node biopsy; mitotic rate; survival ID MALIGNANT-MELANOMA; CHILDHOOD MELANOMA; CUTANEOUS MELANOMA; SINGLE-INSTITUTION; ADULT MELANOMA; YOUNG-ADULTS; CHILDREN; SURVIVAL; ADOLESCENCE; POPULATION AB BACKGROUNDThe management of pediatric melanoma (PM) has largely been extrapolated from adult data. However, the behavior of PM appears to differ from its adult counterparts. Therefore, an international PM registry was created and analyzed. METHODSTwelve institutions contributed deidentified clinicopathologic and outcome data for patients diagnosed with PM from 1953 through 2008. RESULTSOverall survival (OS) data were reported for 365 patients with invasive PM who had adequate follow-up data. The mean age of the patients was 16 years (range 1 year-21 years). The 10-year OS rate, 80.6%, tended to vary by patient age: 100% for those aged birth to 10 years, 69.7% for those aged >10 years to 15 years, and 79.5% for those aged >15 years to 20 years (P=.147). Patients with melanomas measuring 1 mm had a favorable prognosis (10-year OS rate of 97%), whereas survival was lower but similar for patients with melanomas measuring >1 mm to 2 mm, >2 mm to 4 mm, and >4 mm (70%, 78%, and 80%, respectively; P=.0077). Ulceration and lymph node metastasis were found to be correlated with worse survival (P=.022 and P=.017, respectively). The 10-year OS rate was 94.1% for patients with American Joint Committee on Cancer stage I disease, 79.6% for those with stage II disease, and 77.1% for patients with stage III disease (P<.001). CONCLUSIONSTumor thickness, ulceration, lymph node status, and stage were found to be significant predictors of survival in patients with PM, similar to adult melanoma. There is a trend toward increased survival in children aged 10 years versus adolescents aged >10 years. Further analyses are needed to probe for potential biological and behavioral differences in pediatric versus adult melanoma. Cancer 2013;119:4012-4019. (c) 2013 American Cancer Society. C1 [Averbook, Bruce J.] Metrohlth Med Ctr, Dept Surg, Div Surg Oncol, Cleveland, OH 44109 USA. [Lee, Sandra J.] Case Western Reserve Univ, Dept Surg, Cleveland, OH 44106 USA. [Delman, Keith A.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Delman, Keith A.] Emory Univ, Sch Med, Dept Surg, Div Surg Oncol, Atlanta, GA 30322 USA. [Gow, Kenneth W.] Emory Univ, Sch Med, Atlanta, GA USA. [Zager, Jonathan S.; Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Cutaneous Oncol, Tampa, FL 33682 USA. [Zager, Jonathan S.; Sondak, Vernon K.] Univ S Florida, Morsani Coll Med, Dept Oncol Sci, Tampa, FL USA. [Messina, Jane L.] Univ S Florida, Morsani Coll Med, Dept Pathol Cell Biol & Dermatol, Tampa, FL USA. [Messina, Jane L.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Dermatol & Pathol, Tampa, FL 33682 USA. [Sabel, Michael S.] Univ Michigan, Med Ctr, Dept Surg, Div Surg Oncol, Ann Arbor, MI 48109 USA. [Pittelkow, Mark R.; Ecker, Phillip M.] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Markovic, Svetomir N.] Mayo Clin, Div Med Oncol, Rochester, MN USA. [Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Palo Alto, CA 94304 USA. [Swetter, Susan M.] Stanford Canc Inst, Pigmented Cell & Melanoma Program, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Leachman, Sancy A.] Intermt Healthcare, Huntsman Canc Inst, Dept Dermatol, Melanoma & Cutaneous Oncol Program, Salt Lake City, UT USA. [Testori, Alessandro] European Inst Oncol, Melanoma & Soft Tissue Sarcoma Div, Milan, Italy. [Curiel-Lewandrowski, Clara] Univ Arizona, Ctr Canc, Skin Canc Inst, Div Dermatol,Dept Med,Pigmented Les Clin & Multid, Tucson, AZ USA. [Go, Ronald S.] Gundersen Hlth Syst, Ctr Canc & Blood Disorders, La Crosse, WI USA. [Jukic, Drazen M.] Univ Pittsburgh, Med Ctr, Dermatopathol Fellowship Program, Dept Dermatol, Pittsburgh, PA USA. [Jukic, Drazen M.] Univ Pittsburgh, Med Ctr, Dermatopathol Fellowship Program, Dept Pathol, Pittsburgh, PA USA. [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Univ Pittsburgh Sch Med, Dept Med Dermatol & Translat Sci,Melonoma & Skin, Pittsburgh, PA USA. RP Averbook, BJ (reprint author), Metrohlth Med Ctr, Dept Surg, Div Surg Oncol, Canc Care Pavilion,2500 MetroHealth Dr, Cleveland, OH 44109 USA. EM baverbook@metrohealth.org FU Eastern Cooperative Oncology Group (ECOG) [U10 CA014548, U10 CA39229]; MetroHealth Medical Center; AIM at Melanoma; University of Pittsburgh FX Formation of the registry was supported by the Pittsburgh Skin Cancer SPORE P50CA121973, provided by the National Cancer Institute; Eastern Cooperative Oncology Group (ECOG) U10 CA014548 grant to Case Western Reserve University and ECOG U10 CA39229 grant to the University of Pittsburgh; funding from MetroHealth Medical Center; and financial support for editorial assistance from AIM at Melanoma, the University of Pittsburgh, and MetroHealth Medical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or National Institutes of Health. NR 29 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2013 VL 119 IS 22 BP 4012 EP 4019 DI 10.1002/cncr.28289 PG 8 WC Oncology SC Oncology GA 244VO UT WOS:000326418500019 PM 24022819 ER PT J AU Hayes, JH Nakabayashi, M Kantoff, PW AF Hayes, Julia H. Nakabayashi, Mari Kantoff, Philip W. TI Reply to Clinical Predictors of Survival in Men with Castration-Resistant Prostate Cancer Evidence That Gleason Score 6 Cancer Can Evolve to Lethal Disease SO CANCER LA English DT Letter C1 [Hayes, Julia H.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hayes, JH (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2013 VL 119 IS 22 BP 4053 EP 4053 DI 10.1002/cncr.28332 PG 1 WC Oncology SC Oncology GA 244VO UT WOS:000326418500027 PM 24114731 ER PT J AU Deruaz, M Luster, AD AF Deruaz, Maud Luster, Andrew D. TI BLT Humanized Mice as Model to Study HIV Vaginal Transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; humanized mice; mucosal infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE REPRODUCTIVE-TRACT; CD4(+) T-CELLS; GENITAL-TRACT; HETEROSEXUAL TRANSMISSION; ADAPTIVE IMMUNITY; TYPE-1 INFECTION; LANGERHANS CELLS; RHESUS MACAQUES; IN-VIVO AB The majority of human immunodeficiency virus type 1 (HIV-1) infections occur by sexual exposure, and vaginal transmission accounts for more than half of all newly acquired infections. Studies of vaginal transmission of simian immunodeficiency virus to nonhuman primates (NHPs) have suggested an important role for immune cell trafficking in the establishment of infection as well is in the process of viral dissemination. However, NHP models do not permit the study of HIV transmission and dissemination. The improvement of humanized mouse models with robust human immune cell reconstitution of the female genital tract renders these mice susceptible to intravaginal HIV infection. Thus humanized mouse models of HIV vaginal infection will allow the study of the mechanisms involved in HIV transmission and dissemination in vivo. C1 [Deruaz, Maud; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Med Sch, Boston, MA USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, 149 13th St Charlestown, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu FU National Institutes of Health [P01 AI078897]; Swiss National Science foundation [PBGEP3-125895]; Ragon Institute of MGH, MIT, and Harvard FX This work was supported by the National Institutes of Health (grant P01 AI078897); the Swiss National Science foundation (grant PBGEP3-125895); and by a grant from the Ragon Institute of MGH, MIT, and Harvard. NR 50 TC 7 Z9 7 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2013 VL 208 SU 2 BP S131 EP S136 DI 10.1093/infdis/jit318 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 244HM UT WOS:000326378500003 PM 24151319 ER PT J AU Murooka, TT Mempel, TR AF Murooka, Thomas T. Mempel, Thorsten R. TI Intravital Microscopy in BLT-Humanized Mice to Study Cellular Dynamics in HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-1; lymph node; multiphoton intravital microscopy; T-cell trafficking ID MEMORY T-CELLS; VIROLOGICAL SYNAPSES; LYMPH-NODES; DENDRITIC CELLS; NONLYMPHOID TISSUE; PLASMA-MEMBRANE; NATURAL HOSTS; DC-SIGN; MACROPHAGES; MIGRATION AB Humanized mouse models have, over the past few years, seen dramatic improvements, including the colonization of both lymphoid and nonlymphoid tissues with all major immune cell lineages, the development of T cells with human major histocompatibility complex restriction, and the ability to mount functional adaptive immune responses to human pathogens, as documented in some instances. This has greatly increased the range of questions related to the biology of human immunodeficiency virus (HIV) infection that can be usefully addressed through experimental approaches utilizing small animal models. Among these approaches is in vivo imaging, and specifically multiphoton intravital microscopy (MP-IVM), which allows for the investigation of dynamic biological processes at cellular and subcellular resolution in the tissues of live animals. We have recently begun to use MP-IVM in lymph nodes of humanized mice in order to examine HIV infectious spread in vivo at the tissue and cellular level. Here, we provide a short perspective on the close link between the patterns of immune cell migration and the mechanisms of viral dissemination, and summarize the results of our initial studies. C1 [Murooka, Thomas T.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. RP Mempel, TR (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St, Charlestown, MA 02129 USA. EM tmempel@mgh.harvard.edu FU National Institutes of Health (NIH) [P01 AI0178897, R01 AI097052, P30 AI060354]; Mass General Hospital (MGH) Executive Committee on Research (ECOR) Tosteson Postdoctoral Fellowship Award; NIH [T32 AI007387]; Harvard University CFAR [NIH 5P30AI060354-09]; Center for Human Immunology NIH [U19 AI082630] FX This work was supported by the National Institutes of Health (NIH) grants P01 AI0178897, R01 AI097052, and P30 AI060354 (to T. R. M.); and by a Mass General Hospital (MGH) Executive Committee on Research (ECOR) Tosteson Postdoctoral Fellowship Award, NIH training grant T32 AI007387, Harvard University CFAR grant NIH 5P30AI060354-09, and a pilot grant from the Center for Human Immunology NIH U19 AI082630 (to T. T. M.). NR 50 TC 6 Z9 6 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2013 VL 208 SU 2 BP S137 EP S144 DI 10.1093/infdis/jit447 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 244HM UT WOS:000326378500004 PM 24151320 ER PT J AU Seung, E Tager, AM AF Seung, Edward Tager, Andrew M. TI Humoral Immunity in Humanized Mice: A Work in Progress SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE immunology; humanized mice; BLT mice; fetal tissue transplantation; humoral immunity; B cells; antibody ID T-CELL RESPONSES; SEVERE COMBINED IMMUNODEFICIENCY; CYTIDINE DEAMINASE AID; RAG2(-/-)GAMMA(-/-)(C) MICE; MOUSE MODEL; ANTIBODY-RESPONSES; NEW-GENERATION; HIV-INFECTION; SYSTEM MICE; BLT MICE AB Humanized mice historically have not been good models of human humoral immunity induced by either infection or immunization. However, newer versions of humanized mice generated in severely immunodeficient mice with a targeted disruption of the IL2R gamma(c) gene have recently been reported to produce antigen-specific class-switched human antibodies, with some demonstrating neutralizing activities. Here we review the growing ability of humanized mice to support the study of human humoral immune responses, discussing the current and future potential of these models as well as their current limitations. C1 [Seung, Edward; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Med Sch, Boston, MA USA. [Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Pulmonary & Crit Care Unit, Sch Med, Boston, MA USA. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Rm 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU Harvard University Center for AIDS Research (HU CFAR, National Institutes of Health/National Institute of Allergy and Infectious Diseases [NIH/NIAID]) [P30-AI060354]; NIH/NIAID [P01-AI104715]; HU CFAR [NIH/NIAID P30-AI060354]; Ragon Institute Initiative FX This work was supported by a Harvard University Center for AIDS Research (HU CFAR, National Institutes of Health/National Institute of Allergy and Infectious Diseases [NIH/NIAID] P30-AI060354) Scholar Award to E. S.; and by NIH/NIAID P01-AI104715 (Project 2 and Core B), HU CFAR (NIH/NIAID P30-AI060354) Core support, and a Ragon Institute Initiative to A. T. NR 46 TC 14 Z9 14 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2013 VL 208 SU 2 BP S155 EP S159 DI 10.1093/infdis/jit448 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 244HM UT WOS:000326378500007 PM 24151323 ER PT J AU Tager, AM Pensiero, M Allen, TM AF Tager, Andrew M. Pensiero, Michael Allen, Todd M. TI Recent Advances in Humanized Mice: Accelerating the Development of an HIV Vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; humanized mice; vaccine; CD8+T cells; CTL; antibodies ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN IMMUNE-SYSTEM; T-CELL RESPONSES; SCID-HU MOUSE; RHESUS-MONKEYS; INFECTION; MODEL; ACQUISITION; TRIAL; TRANSPLANTATION AB Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research. C1 [Tager, Andrew M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Ctr Immunol & Inflammatory Dis, Cambridge, MA 02138 USA. [Tager, Andrew M.; Allen, Todd M.] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Tager, Andrew M.; Allen, Todd M.] Harvard Univ, Boston, MA 02115 USA. [Pensiero, Michael] NIAID, Vaccine Translat Res Branch, NIH, Bethesda, MD 20892 USA. RP Allen, TM (reprint author), MIT, Ragon Inst MGH, 400 Technol Sq, Cambridge, MA 02139 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011 FU National Institute of Allergy and Infectious Diseases [R01-AI090698, HIVRAD P01-AI104715]; Harvard University Center for AIDS Research [P30-AI060354]; Harvard University Center for AIDS Research; National Institute of Allergy and Infectious Diseases, National Institutes of Health; Ragon Institute of MGH, MIT, and Harvard FX This work was supported by the National Institute of Allergy and Infectious Diseases (grants R01-AI090698 and HIVRAD P01-AI104715 to T. M. A.) and the Harvard University Center for AIDS Research (grant P30-AI060354). Attendance at the Humanized Mouse Meeting was funded by the Harvard University Center for AIDS Research; the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and the Ragon Institute of MGH, MIT, and Harvard. NR 41 TC 10 Z9 10 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2013 VL 208 SU 2 BP S121 EP S124 DI 10.1093/infdis/jit451 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 244HM UT WOS:000326378500001 PM 24151317 ER PT J AU Kawate, T Iwase, N Shimizu, M Stanley, SA Wellington, S Kazyanskaya, E Hung, DT AF Kawate, Tomohiko Iwase, Noriaki Shimizu, Motohisa Stanley, Sarah A. Wellington, Samantha Kazyanskaya, Edward Hung, Deborah T. TI Synthesis and structure-activity relationships of phenyl-substituted coumarins with anti-tubercular activity that target FadD32 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Mycobacterium tuberculosis; Coumarin; Structure-activity relationship (SAR); Inhibitor ID MYCOLIC ACID BIOSYNTHESIS; MYCOBACTERIUM-TUBERCULOSIS; HYDROARYLATION; DERIVATIVES; ACTIVATION; BONDS AB In an effort to develop new and potent agents for therapy against tuberculosis, a high-throughput screen was performed against Mycobacterium tuberculosis strain H37Rv. Two 6-aryl-5,7-dimethyl-4-phenylcoumarin compounds 1a and 1b were found with modest activity. A series of coumarin derivatives were synthesized to improve potency and to investigate the structure-activity relationship of the series. Among them, compounds 1o and 2d showed improved activity with IC90 of 2 mu M and 0.5 mu M, respectively. Further optimization provided compound 3b with better physiochemical properties with IC90 0.4 mu M which had activity in a mouse model of infection. The role of the conformation of the 4- and 6-aryl substituents is also described. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Kawate, Tomohiko; Iwase, Noriaki; Shimizu, Motohisa; Stanley, Sarah A.; Wellington, Samantha; Kazyanskaya, Edward; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Kawate, Tomohiko; Stanley, Sarah A.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kawate, Tomohiko; Stanley, Sarah A.; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat, Boston, MA 02114 USA. [Kawate, Tomohiko; Stanley, Sarah A.; Wellington, Samantha; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Hung, DT (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM hung@molbio.mgh.harvard.edu NR 22 TC 19 Z9 20 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2013 VL 23 IS 22 BP 6052 EP 6059 DI 10.1016/j.bmcl.2013.09.035 PG 8 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 235YU UT WOS:000325760300004 PM 24103299 ER PT J AU Gunderson, LL Moughan, J Ajani, JA Pedersen, JE Winter, KA Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, CG AF Gunderson, Leonard L. Moughan, Jennifer Ajani, Jaffer A. Pedersen, John E. Winter, Kathryn A. Benson, Al B., III Thomas, Charles R., Jr. Mayer, Robert J. Haddock, Michael G. Rich, Tyvin A. Willett, Christopher G. TI Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADIATION-THERAPY; RANDOMIZED-TRIAL; POOLED ANALYSIS; RECTAL-CANCER; MITOMYCIN-C; RADIOTHERAPY; CHEMORADIATION; 5-FLUOROURACIL; CHEMOTHERAPY; OUTCOMES AB Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the logerank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. (C) 2013 Elsevier Inc. C1 [Gunderson, Leonard L.] Mayo Clin, Ctr Canc, Scottsdale, AZ USA. [Moughan, Jennifer; Winter, Kathryn A.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pedersen, John E.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddock, Michael G.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Rich, Tyvin A.] Univ Virginia, Charlottesville, VA USA. [Willett, Christopher G.] Duke Univ, Durham, NC USA. RP Gunderson, LL (reprint author), 9723 E Peak View Rd, Scottsdale, AZ 85262 USA. EM gunderson.leonard@mayo.edu FU National Institutes of Health National Cancer Institute [U10 CA37422]; RTOG [U10 CA21661] FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG) and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Institutes of Health National Cancer Institute. The manuscript's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH National Cancer Institute. NR 26 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2013 VL 87 IS 4 BP 638 EP 645 DI 10.1016/j.ijrobp.2013.07.035 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 235ZS UT WOS:000325763300011 PM 24035327 ER PT J AU Sadek, BT Shenouda, MN Raad, RFA Niemierko, A Keruakous, AR Goldberg, SI Taghian, AG AF Sadek, Betro T. Shenouda, Mina N. Raad, Rita F. Abi Niemierko, Andrzej Keruakous, Amany R. Goldberg, Saveli I. Taghian, Alphonse G. TI Risk of Local Failure in Breast Cancer Patients With Lobular Carcinoma In Situ at the Final Surgical Margins: Is Re-excision Necessary? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID CONSERVING THERAPY; CONSERVATIVE SURGERY; ADJUVANT BREAST; BOWEL PROJECT; RECURRENCE; INSITU; RADIATION; COMPONENT; NEOPLASIA; IMPACT AB Purpose: To compare the outcome of patients with invasive breast cancer both with and without lobular carcinoma in situ (LCIS)-positive/close surgical margins after breast-conserving treatment. Methods and Materials: We retrospectively studied 2358 patients with T1-T2 invasive breast cancer treated with lumpectomy and radiation therapy from January 1980 to December 2009. Median age was 57 years (range, 24-91 years). There were 82 patients (3.5%) with positive/close LCIS margins (<0.2 cm) and 2232 patients (95.7%) with negative margins. A total of 1789 patients (76%) had negative lymph nodes. Patients who received neoadjuvant chemotherapy were excluded. A total of 1783 patients (76%) received adjuvant systemic therapy. Multivariable analysis (MVA) was performed using Cox's proportional hazards model. Results: The 5-year cumulative incidence of locoregional recurrence (LRR) was 3.2%(95% confidence interval [CI] 2.5%-4.1%) for the 2232 patients with LCIS-negative surgical margins (median follow-up 104months) and 2.8%(95% CI 0.7%-10.8%) for the 82 patients with LCIS-positive/close surgical margins (median follow-up 90 months). This was not statistically significant (P=.5). On MVA, LCIS-positive margins after the final surgery were not associated with increased risk of LRR (hazard ratio [HR] 3.4, 95% CI 0.5-24.5, P=.2). Statistically significant prognostic variables on Cox's MVA for risk of LRR included systemic therapy (HR 0.5, 95% CI 0.33-0.75, P=.001), number of positive lymph nodes (HR 1.11, 95% CI 1.05-1.18, P=.001), menopausal status (HR 0.96, 95% CI 0.95-0.98, P=.001), and histopathologic grade (grade 3 vs grade 1/2) (HR 2.6, 95% CI 1.4-4.7, P=.003). Conclusion: Our results suggest that the presence of LCIS at the surgical margin after lumpectomy does not increase the risk of LRR or the final outcome. These findings suggest that re-excision or mastectomy in patients with LCIS-positive/close final surgical margins is unnecessary. (C) 2013 Elsevier Inc. C1 [Sadek, Betro T.; Shenouda, Mina N.; Raad, Rita F. Abi; Niemierko, Andrzej; Keruakous, Amany R.; Goldberg, Saveli I.; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Niemierko, Andrzej; Goldberg, Saveli I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stat Sect, Boston, MA USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3 Bldg,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 18 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2013 VL 87 IS 4 BP 726 EP 730 DI 10.1016/j.ijrobp.2013.08.012 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 235ZS UT WOS:000325763300024 PM 24064317 ER PT J AU Keator, DB Helmer, K Steffener, J Turner, JA Van Erp, TGM Gadde, S Ashish, N Burns, GA Nichols, BN AF Keator, D. B. Helmer, K. Steffener, J. Turner, J. A. Van Erp, T. G. M. Gadde, S. Ashish, N. Burns, G. A. Nichols, B. N. TI Towards structured sharing of raw and derived neuroimaging data across existing resources SO NEUROIMAGE LA English DT Review DE XCEDE; Provenance; Data model; Neuroimaging; Database; Web services ID DISCOVERY SCIENCE; BRAIN-FUNCTION; NEUROSCIENCE; INTEGRATION; PROVENANCE; KNOWLEDGE; MRI AB Data sharing efforts increasingly contribute to the acceleration of scientific discovery. Neuroimaging data is accumulating in distributed domain-specific databases and there is currently no integrated access mechanism nor an accepted format for the critically important meta-data that is necessary for making use of the combined, available neuroimaging data. In this manuscript, we present work from the Derived Data Working Group, an open-access group sponsored by the Biomedical Informatics Research Network (BIRN) and the International Neuroimaging Coordinating Facility (INCF) focused on practical tools for distributed access to neuroimaging data. The working group develops models and tools facilitating the structured interchange of neuroimaging meta-data and is making progress towards a unified set of tools for such data and meta-data exchange. We report on the key components required for integrated access to raw and derived neuroimaging data as well as associated meta-data and provenance across neuroimaging resources. The components include (1) a structured terminology that provides semantic context to data, (2) a formal data model for neuroimaging with robust tracking of data provenance, (3) a web service-based application programming interface (API) that provides a consistent mechanism to access and query the data model, and (4) a provenance library that can be used for the extraction of provenance data by image analysts and imaging software developers. We believe that the framework and set of tools outlined in this manuscript have great potential for solving many of the issues the neuroimaging community faces when sharing raw and derived neuroimaging data across the various existing database systems for the purpose of accelerating scientific discovery. Published by Elsevier Inc. C1 [Keator, D. B.; Van Erp, T. G. M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. [Keator, D. B.] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92617 USA. [Helmer, K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Helmer, K.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Steffener, J.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY 10027 USA. [Turner, J. A.] Mind Res Network, Albuquerque, NM USA. [Gadde, S.] Duke Univ, Brain Imaging & Anal Ctr, Durham, NC 27706 USA. [Ashish, N.] Univ Calif Irvine, Calif Inst Telecommun & Informat Technol CalIT2, Irvine, CA 92617 USA. [Burns, G. A.] Univ So Calif, Inst Informat Sci, Los Angeles, CA 90089 USA. [Nichols, B. N.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA. [Nichols, B. N.] Univ Washington, Dept Radiol, Integrated Brain Imaging Ctr, Seattle, WA 98195 USA. RP Keator, DB (reprint author), Univ Calif Irvine, Brain Imaging Ctr, Irvine Hall Rm 163 Zot 3960, Irvine, CA 92617 USA. EM dbkeator@uci.edu RI Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Burns, Gully/0000-0003-1493-865X; Nichols, Nolan/0000-0003-1099-3328 FU Function Biomedical Informatics Research Network [NIH 1 U24 U24 RR021992]; BIRN Coordinating Center [NIH 1 U24 RR025736-01]; International Neuroinformatics Coordinating Facility; National Academies Keck Futures Initiative; [RC4 NS073008-01] FX This work was supported by the Function Biomedical Informatics Research Network (NIH 1 U24 U24 RR021992) and the BIRN Coordinating Center (https://www.bimcommunity.org; NIH 1 U24 RR025736-01). The International Neuroinformatics Coordinating Facility provided financial support for some of the work reported in this article. This work was further supported by RC4 NS073008-01 (PI: Grabowski, co-author Nichols, B.N.) and the National Academies Keck Futures Initiative (PI: Grabowski, co-author Nichols, B.N.). NR 47 TC 18 Z9 18 U1 1 U2 30 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 NOV 15 PY 2013 VL 82 BP 647 EP 661 DI 10.1016/j.neuroimage.2013.05.094 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 220FQ UT WOS:000324568400061 PM 23727024 ER PT J AU Barnes, JA Abramson, JS Scott, JA Sohani, AR AF Barnes, Jeffrey A. Abramson, Jeremy S. Scott, James A. Sohani, Aliyah R. TI Case 35-2013: A 77-Year-Old Man with Confusion and Malaise SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID B-CELL LYMPHOMA; BURKITTS-LYMPHOMA; CLINICAL PRESENTATION; PLUS RITUXIMAB; ADULT BURKITT; CODOX-M/IVAC; T-CELL; FEATURES; REARRANGEMENTS; PROGNOSIS C1 [Barnes, Jeffrey A.; Abramson, Jeremy S.] Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02114 USA. [Scott, James A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Barnes, Jeffrey A.; Abramson, Jeremy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Scott, James A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Barnes, JA (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02114 USA. NR 26 TC 0 Z9 0 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 14 PY 2013 VL 369 IS 20 BP 1946 EP 1957 DI 10.1056/NEJMcpc1209274 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 300MP UT WOS:000330468300012 PM 24224628 ER PT J AU Bronte, V Pittet, MJ AF Bronte, Vincenzo Pittet, Mikael J. TI The Spleen in Local and Systemic Regulation of Immunity SO IMMUNITY LA English DT Review ID SPLENIC MARGINAL ZONE; HEMATOPOIETIC STEM-CELLS; TUMOR-ASSOCIATED MACROPHAGES; CD8(+) T-CELLS; DENDRITIC CELLS; IN-VIVO; B-CELLS; MYELOID CELLS; EXTRAMEDULLARY HEMATOPOIESIS; ATHEROSCLEROTIC LESIONS AB The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity. C1 [Bronte, Vincenzo] Verona Univ Hosp, I-37134 Verona, Italy. [Bronte, Vincenzo] Dept Pathol, I-37134 Verona, Italy. [Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bronte, V (reprint author), Verona Univ Hosp, I-37134 Verona, Italy. EM vincenzo.bronte@univr.it; mpittet@mgh.harvard.edu RI Bronte, Vincenzo/K-7902-2016 OI Bronte, Vincenzo/0000-0002-3741-5141 FU Italian Ministry of Education, University and Research (FIRB project) [RBAP11T3WB_003]; Fondazione Cariverona; Italian Association for Cancer Research (AIRC) [IG10400, 12182, AGIMM 100005, 6599]; US National Institutes of Health (NIH) [R01-AI084880, P50-CA086355, N01-HV08235]; project Verona Nanomedicine Initiative FX The work of V. B. is supported in part by Italian Ministry of Education, University and Research (FIRB project RBAP11T3WB_003), Fondazione Cariverona, project Verona Nanomedicine Initiative, and Italian Association for Cancer Research (AIRC, Grants IG10400, 12182, AGIMM 100005, and 6599). The work of M.J.P. is supported in part by US National Institutes of Health (NIH) grants R01-AI084880, P50-CA086355, and N01-HV08235. NR 118 TC 67 Z9 67 U1 3 U2 35 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 NOV 14 PY 2013 VL 39 IS 5 BP 806 EP 818 DI 10.1016/j.immuni.2013.10.010 PG 13 WC Immunology SC Immunology GA AA2UV UT WOS:000330950600005 PM 24238338 ER PT J AU Fried, LF Emanuele, N Zhang, JH Brophy, M Conner, TA Duckworth, W Leehey, DJ McCullough, PA O'Connor, T Palevsky, PM Reilly, RF Seliger, SL Warren, SR Watnick, S Peduzzi, P Guarino, P AF Fried, Linda F. Emanuele, Nicholas Zhang, Jane H. Brophy, Mary Conner, Todd A. Duckworth, William Leehey, David J. McCullough, Peter A. O'Connor, Theresa Palevsky, Paul M. Reilly, Robert F. Seliger, Stephen L. Warren, Stuart R. Watnick, Suzanne Peduzzi, Peter Guarino, Peter CA VA NEPHRON-D Investigators TI Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONVERTING ENZYME-INHIBITOR; CHRONIC KIDNEY-DISEASE; RENAL OUTCOMES; HIGH-RISK; PROTEINURIA; TRIAL; TELMISARTAN; RAMIPRIL; THERAPY; BLOCKER AB Background Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of = 30 ml per minute per 1.73 m(2) if the initial estimated GFR was = 60 ml per minute per 1.73 m(2) or a decline of >= 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P = 0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = 0.10) decreased with time (P = 0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P = 0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. C1 [Fried, Linda F.; Palevsky, Paul M.] Vet Affairs VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fried, Linda F.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Emanuele, Nicholas; Leehey, David J.] Hines VA Hosp, Hines, IL USA. [Emanuele, Nicholas; Leehey, David J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Zhang, Jane H.; O'Connor, Theresa; Peduzzi, Peter; Guarino, Peter] VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Peduzzi, Peter] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Brophy, Mary] VA Boston Healthcare Syst, Boston, MA USA. [Brophy, Mary] Boston Univ, Sch Med, Boston, MA 02118 USA. [Conner, Todd A.; Warren, Stuart R.] VA Cooperat Studies Program Res Pharm, Albuquerque, NM USA. [Conner, Todd A.; Warren, Stuart R.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Duckworth, William] Arizona State Univ, Carl T Hayden VA Med Ctr, Tempe, AZ USA. [Duckworth, William] Univ Arizona, Phoenix, AZ USA. [McCullough, Peter A.] St John Providence Hlth Syst, Warren, MI USA. [McCullough, Peter A.] St Johns Hosp, Detroit, MI USA. [McCullough, Peter A.] Med Ctr, Detroit, MI USA. [McCullough, Peter A.] St John Oakland Macomb Ctr, Warren, MI USA. [McCullough, Peter A.] St John Oakland Macomb Ctr, Madison Hts, MI USA. [McCullough, Peter A.] Providence Hosp, Southfield, MI 48037 USA. [McCullough, Peter A.] Med Ctr, Southfield, MI USA. [McCullough, Peter A.] Providence Hosp, Novi, MI USA. [McCullough, Peter A.] Med Ctr, Novi, MI USA. [Reilly, Robert F.] VA North Texas Healthcare Syst, Dallas, TX USA. [Reilly, Robert F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Seliger, Stephen L.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Watnick, Suzanne] Portland VA Med Ctr & Oregon Hlth, Portland, OR 97239 USA. [Watnick, Suzanne] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM linda.fried@va.gov OI Palevsky, Paul/0000-0002-7334-5400 FU Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development FX Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217. NR 21 TC 258 Z9 270 U1 8 U2 42 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 NOV 14 PY 2013 VL 369 IS 20 BP 1892 EP 1903 DI 10.1056/NEJMoa1303154 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 300MP UT WOS:000330468300008 PM 24206457 ER PT J AU Khalili, H Ananthakrishnan, AN Konijeti, GG Liao, XM Higuchi, LM Fuchs, CS Spiegelman, D Richter, JM Korzenik, JR Chan, AT AF Khalili, Hamed Ananthakrishnan, Ashwin N. Konijeti, Gauree G. Liao, Xiaomei Higuchi, Leslie M. Fuchs, Charles S. Spiegelman, Donna Richter, James M. Korzenik, Joshua R. Chan, Andrew T. TI Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID CROHNS-DISEASE; ULCERATIVE-COLITIS; OLMSTED COUNTY; US WOMEN; PREVALENCE; MINNESOTA; VALIDITY; REPRODUCIBILITY; MORTALITY; SURVIVAL AB Objective To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease. Design Prospective cohort study. Setting Nurses' Health Study and Nurses' Health Study II. Participants 194 711 women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses' Health Study and 1989 in the Nurses' Health Study II and followed up through 2010. Main outcome measure Incident ulcerative colitis and Crohn's disease. Results During 3 421 972 person years of follow-up, we documented 284 cases of Crohn's disease and 363 cases of ulcerative colitis. The risk of Crohn's disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn's disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn's disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn's disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn's disease (all P for interaction >0.35). Conclusion In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn's disease but not of ulcerative colitis. C1 [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liao, Xiaomei; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Higuchi, Leslie M.] Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA USA. [Korzenik, Joshua R.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM achan@partners.org FU National Institute of Health [R01 CA137178, R01 CA050385, P01 CA87969, P30 DK043351, K23 DK099681, K08 DK064256, K24 098311, K23 DK091742]; American Gastroenterological Association; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681, K08 DK064256] FX This study was funded by National Institute of Health grants: R01 CA137178, R01 CA050385, P01 CA87969, P30 DK043351, K23 DK099681, K08 DK064256, K24 098311, and K23 DK091742. ATC is a Damon Runyon Cancer Research Foundation clinical investigator. HK is supported by a career development award from the American Gastroenterological Association and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). LMH is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK064256). ANA is a member of the scientific advisory board for Prometheus and Janssen. JMR is a consultant for policy analysis. ATC has served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pfizer, and Pozen. NR 31 TC 27 Z9 27 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD NOV 14 PY 2013 VL 347 AR f6633 DI 10.1136/bmj.f6633 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 254HF UT WOS:000327155000002 PM 24231178 ER PT J AU Tata, PR Mou, HM Pardo-Saganta, A Zhao, R Prabhu, M Law, BM Vinarsky, V Cho, JL Breton, S Sahay, A Medoff, BD Rajagopal, J AF Tata, Purushothama Rao Mou, Hongmei Pardo-Saganta, Ana Zhao, Rui Prabhu, Mythili Law, Brandon M. Vinarsky, Vladimir Cho, Josalyn L. Breton, Sylvie Sahay, Amar Medoff, Benjamin D. Rajagopal, Jayaraj TI Dedifferentiation of committed epithelial cells into stem cells in vivo SO NATURE LA English DT Article ID MOUSE DIGIT TIP; PROGENITOR CELLS; LUNG DEVELOPMENT; PROSTATE-CANCER; TRANSGENIC MICE; REGENERATION; ORIGIN; AIRWAY; MAINTENANCE; EXPRESSION AB Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. Here we present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts in repairing epithelial injury. Single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. By contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate is inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer. C1 [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Sahay, Amar; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Cho, Josalyn L.; Medoff, Benjamin D.; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Sahay, Amar; Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cho, Josalyn L.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02214 USA. [Breton, Sylvie] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02214 USA. [Breton, Sylvie] Harvard Univ, Sch Med, Boston, MA 02214 USA. [Sahay, Amar] Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM jrajagopal@partners.org RI Zhao, Rui/J-7110-2014 FU Harvard Stem Cell Institute Seed Grant; National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty [5P30HL101287-02]; Harvard Stem Cell Institute (HSCI) Junior Investigator Grant FX The work in this manuscript was supported by a Harvard Stem Cell Institute Seed Grant and a National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty (P30) award (5P30HL101287-02) and a Harvard Stem Cell Institute (HSCI) Junior Investigator Grant to J.R. J.R. is a New York Stem Cell Foundation-Robertson Investigator. We wish to extend our thanks to W. Anderson, Y. Dor, Q. Zhou, A. Brack, J. Galloway and all members of the Rajagopal laboratory for their constructive criticism. We thank the members of the HSCI flow cytometry core facility for help with cell sorting. NR 35 TC 164 Z9 166 U1 6 U2 101 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 14 PY 2013 VL 503 IS 7475 BP 218 EP + DI 10.1038/nature12777 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250YX UT WOS:000326894200042 PM 24196716 ER PT J AU Haim, H Salas, I McGee, K Eichelberger, N Winter, E Pacheco, B Sodroski, J AF Haim, Hillel Salas, Ignacio McGee, Kathleen Eichelberger, Noah Winter, Elizabeth Pacheco, Beatriz Sodroski, Joseph TI Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus Neutralization Efficiency SO CELL HOST & MICROBE LA English DT Article ID ENVELOPE GLYCOPROTEIN; TYPE-1 NEUTRALIZATION; HIV-1 NEUTRALIZATION; STRUCTURAL BASIS; PRIMARY ISOLATE; VARIABLE LOOPS; GP120; BINDING; SENSITIVITY; MECHANISM AB Efforts to prevent human immunodeficiency virus type 1 (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies. C1 [Haim, Hillel; Salas, Ignacio; McGee, Kathleen; Pacheco, Beatriz; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02215 USA. [Haim, Hillel; Eichelberger, Noah; Winter, Elizabeth] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA. [Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp MIT & Harvard M, Boston, MA 02129 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02215 USA. EM joseph_sodroski@dfci.harvard.edu FU NRSA Postdoctoral Training Program in AIDS Research [NIH T32 AI007386]; National Institutes of Health [AI24755, AI67854, AI060354]; International AIDS Vaccine Initiative FX We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for help with the manuscript preparation. H. H. was supported by an NRSA Postdoctoral Training Program in AIDS Research (NIH T32 AI007386). The National Institutes of Health (AI24755, AI67854, and CFAR Award AI060354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper supported this research. NR 33 TC 15 Z9 15 U1 0 U2 2 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 NOV 13 PY 2013 VL 14 IS 5 BP 547 EP 558 DI 10.1016/j.chom.2013.10.006 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AA1JT UT WOS:000330853200009 PM 24237700 ER PT J AU Ashizawa, T Figueroa, KP Perlman, SL Gomez, CM Wilmot, GR Schmahmann, JD Ying, SH Zesiewicz, TA Paulson, HL Shakkottai, VG Bushara, KO Kuo, SH Geschwind, MD Xia, GB Mazzoni, P Krischer, JP Cuthbertson, D Holbert, AR Ferguson, JH Pulst, SM Subramony, SH AF Ashizawa, Tetsuo Figueroa, Karla P. Perlman, Susan L. Gomez, Christopher M. Wilmot, George R. Schmahmann, Jeremy D. Ying, Sarah H. Zesiewicz, Theresa A. Paulson, Henry L. Shakkottai, Vikram G. Bushara, Khalaf O. Kuo, Sheng-Han Geschwind, Michael D. Xia, Guangbin Mazzoni, Pietro Krischer, Jeffrey P. Cuthbertson, David Holbert, Amy Roberts Ferguson, John H. Pulst, Stefan M. Subramony, S. H. TI Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article DE Spinocerebellar ataxia; Natural history; SARA; Progression rate ID DOMINANT CEREBELLAR ATAXIAS; NATURAL-HISTORY; SCALE AB Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods: To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean +/- SE: 1.61 +/- 0.41) than in SCA2 (0.71 +/- 0.31), SCA3 (0.65 +/- 0.24) and SCA6 (0.87 +/- 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. C1 [Ashizawa, Tetsuo; Xia, Guangbin; Subramony, S. H.] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA. [Ashizawa, Tetsuo; Xia, Guangbin; Subramony, S. H.] Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA. [Figueroa, Karla P.; Pulst, Stefan M.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Perlman, Susan L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Gomez, Christopher M.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Wilmot, George R.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ying, Sarah H.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Ying, Sarah H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Ying, Sarah H.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Zesiewicz, Theresa A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Paulson, Henry L.; Shakkottai, Vikram G.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Bushara, Khalaf O.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Kuo, Sheng-Han; Mazzoni, Pietro] Columbia Univ, Dept Neurol, New York, NY USA. [Geschwind, Michael D.] UCSF, Dept Neurol, San Francisco, CA USA. [Krischer, Jeffrey P.; Cuthbertson, David; Holbert, Amy Roberts] Univ S Florida, Data Management Coordinating Ctr, Tampa, FL USA. [Ferguson, John H.] NIH, ORDR NCATS, Bethesda, MD 20892 USA. RP Ashizawa, T (reprint author), Univ Florida, Dept Neurol, 1149 S Newell Dr,L3-100, Gainesville, FL 32611 USA. EM ashizawa@ufl.edu FU NIH [NS068897] FX This study was supported by NIH grant NS068897 to TA. We thank local support groups and the National Ataxia Foundation Chapters. We also thank following clinical research coordinators: Bettye Robinson and Rebecca McMurray (Emory University), Elizabeth Sullivan (University of Michigan), J McMore (Massachusetts General Hospital), Brian Jung (Johns Hopkins University), Vicky Staszak (University of Chicago), Sharone Trifkin, Tarshia Nulliah and Maria Casado (UCLA), Gigi Satris (UCSF), Diane Hutter (University of Minnesota), Jessica Shaw and Kelly Sullivan (University of South Florida), and Rebecca Beaulier and Phuong Deleyroll (University of Florida). NR 18 TC 16 Z9 18 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD NOV 13 PY 2013 VL 8 AR 177 DI 10.1186/1750-1172-8-177 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 286KE UT WOS:000329466700002 PM 24225362 ER PT J AU Chitnis, T Guttmann, CR Zaitsev, A Musallam, A Weinstock-Guttman, B Yeh, A Rodriguez, M Ness, J Gorman, MP Healy, BC Kuntz, N Chabas, D Strober, JB Waubant, E Krupp, L Pelletier, D Erickson, B Bergsland, N Zivadinov, R AF Chitnis, Tanuja Guttmann, Charles R. Zaitsev, Alexander Musallam, Alexander Weinstock-Guttman, Bianca Yeh, Ann Rodriguez, Moses Ness, Jayne Gorman, Mark P. Healy, Brian C. Kuntz, Nancy Chabas, Dorothee Strober, Jonathan B. Waubant, Emmanuelle Krupp, Lauren Pelletier, Daniel Erickson, Bradley Bergsland, Niels Zivadinov, Robert CA US Network Pediat MS Ctr Excellenc TI Quantitative MRI analysis in children with multiple sclerosis: a multicenter feasibility pilot study SO BMC NEUROLOGY LA English DT Article ID PSYCHOSOCIAL FEATURES; UNITED-STATES; JUVENILE MS; CHILDHOOD; ONSET; METHYLPREDNISOLONE; ADOLESCENTS; DISABILITY; PHENOTYPE AB Background: Pediatric multiple sclerosis (MS) is a rare disorder with significant consequences. Quantitative MRI measurements may provide significant insights, however multicenter collaborative studies are needed given the small numbers of subjects. The goal of this study is to demonstrate feasibility and evaluate lesion volume (LV) characteristics in a multicenter cohort of children with MS. Methods: A common MRI-scanning guideline was implemented at six member sites of the U. S. Network of Pediatric MS Centers of Excellence. We included in this study the first ten scans performed at each site on patients meeting the following inclusion criteria: pediatric RRMS within 3 years of disease onset, examination within 1 month of MRI and no steroids 1 month prior to MRI. We quantified T2 number, T2-LV and individual lesion size in a total of 53 MRIs passing quality control procedures and assessed gadolinium-enhancing lesion number and LV in 55 scans. We studied MRI measures according to demographic features including age, race, ethnicity and disability scores, controlling for disease duration and treatment duration using negative binomial regression and linear regression. Results: The mean number of T2 lesions was 24.30 +/- 19.68 (range: 1-113) and mean gadolinium-enhancing lesion count was 1.85 +/- 5.84, (range: 0-32). Individual lesion size ranged from 14.31 to 55750.60 mm(3). Non-white subjects had higher T2-LV (unadjusted p(T2-LV) = 0.028; adjusted p(T2-LV) = 0.044), and maximal individual T2-LV (unadjusted p(Max) = 0.007; adjusted p(Max) = 0.011) than white patients. We also found a trend toward larger mean lesion size in males than females (p = 0.07). Conclusion: Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS. C1 [Chitnis, Tanuja; Musallam, Alexander; Gorman, Mark P.] Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Guttmann, Charles R.; Zaitsev, Alexander] Brigham & Womens Hosp, Ctr Neurol Imaging, Boston, MA 02115 USA. [Weinstock-Guttman, Bianca; Yeh, Ann] SUNY Buffalo, Jacobs Neurol Inst, Pediat MS Ctr, Buffalo, NY 14260 USA. [Rodriguez, Moses] Dept Neurol & Immunol, Rochester, MN USA. [Erickson, Bradley] Mayo Clin, Dept Radiol, Rochester, MN USA. [Ness, Jayne] Univ Alabama Birmingham, Dept Pediat Neurol, Birmingham, AL USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Chabas, Dorothee; Strober, Jonathan B.; Waubant, Emmanuelle; Pelletier, Daniel] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Krupp, Lauren] SUNY Stony Brook, Dept Neurol, Stony Brook, NY USA. [Bergsland, Niels; Zivadinov, Robert] SUNY Buffalo, Jacobs Neurol Inst, Buffalo Neuroimaging Anal Ctr, Buffalo, NY 14260 USA. [Kuntz, Nancy] Mayo Clin, Dept Pediat, Rochester, MN USA. RP Chitnis, T (reprint author), Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM tchitnis@rics.bwh.harvard.edu OI Rodriguez, Moses/0000-0001-6328-6497; Bergsland, Niels/0000-0002-7792-0433 FU National Multiple Sclerosis Society - Regional Pediatric Multiple Sclerosis Centers of Excellence FX This work was supported by a grant from the National Multiple Sclerosis Society - Regional Pediatric Multiple Sclerosis Centers of Excellence to MGH (TC), UCSF (EW), UAB (JN), SUNY Stonybrook (LK), SUNY Buffalo (AY, BWG) and Mayo Clinic (MR). NR 23 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 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD NOV 13 PY 2013 VL 13 AR 173 DI 10.1186/1471-2377-13-173 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 280WM UT WOS:000329061500001 PM 24225378 ER PT J AU Govindasamy, D Kranzer, K van Schaik, N Noubary, F Wood, R Walensky, RP Freedberg, KA Bassett, IV Bekker, LG AF Govindasamy, Darshini Kranzer, Katharina van Schaik, Nienke Noubary, Farzad Wood, Robin Walensky, Rochelle P. Freedberg, Kenneth A. Bassett, Ingrid V. Bekker, Linda-Gail TI Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa SO PLOS ONE LA English DT Article ID SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY; RISK-FACTORS; HYPERTENSION; COMMUNITY; SERVICES; ACCESS; DETERMINANTS; POPULATION; STRATEGIES AB Background: HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives: To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods: A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results: Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI:1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion: Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. C1 [Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Wood, Robin; Bekker, Linda-Gail] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Kranzer, Katharina] London Sch Hyg & Trop Med, Dept Clin Res, Fac Infect & Trop Dis, London WC1, England. [Noubary, Farzad; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Wood, Robin; Bekker, Linda-Gail] Univ Cape Town, Fac Hlth Sci, Dept Med, ZA-7925 Cape Town, South Africa. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Harvard Univ, Ctr AIDS Res CFAR, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Govindasamy, D (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. EM gdarsh@gmail.com RI Kranzer, Katharina/O-8845-2014; OI Kranzer, Katharina/0000-0001-5691-7270; Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [3R01AI058736, K24 AI062476]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; Presidents Emergency Plan for AIDS Relief (PEPFAR); Claflin Distinguished Scholar Award; PEPFAR through the Anova Health Institute; United States Agency for International Development program; Agence Francaise de Developpement FX This work was supported in part by: the National Institute of Allergy and Infectious Disease: 3R01AI058736, K24 AI062476; the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Mental Health: R01 MH090326, R01 MH073445, the Presidents Emergency Plan for AIDS Relief (PEPFAR); and the Claflin Distinguished Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The mobile testing unit is partially funded by PEPFAR through the Anova Health Institute and the United States Agency for International Development program and received further funding through the Agence Francaise de Developpement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 18 Z9 18 U1 2 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 NOV 13 PY 2013 VL 8 IS 11 AR e80017 DI 10.1371/journal.pone.0080017 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255QK UT WOS:000327254700171 PM 24236170 ER PT J AU Harel, NY Yigitkanli, K Fu, YG Cafferty, WBJ Strittmatter, SM AF Harel, Noam Y. Yigitkanli, Kazim Fu, Yiguang Cafferty, William B. J. Strittmatter, Stephen M. TI Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion SO BRAIN RESEARCH LA English DT Article DE Spinal cord injury; Corticospinal tract; Pyramidotomy; Exercise rehabilitation; Reticulospinal ID SPINAL-CORD-INJURY; RETICULAR-FORMATION; AXONAL GROWTH; MOTOR SYSTEMS; RECOVERY; TRACT; PLASTICITY; CONNECTIONS; PRIMATE; NEURONS AB In the context of injury to the corticospinal tract (CST), brainstem-origin circuits may provide an alternative system of descending motor influence. However, subcortical circuits are largely under subconscious control. To improve volitional control over spared fibers after CST injury, we hypothesized that a combination of physical exercises simultaneously stimulating cortical and brainstem pathways above the injury would strengthen corticobulbar connections through Hebbian-like mechanisms. We sought to test this hypothesis in mice with unilateral CST lesions. Ten days after pyramidotomy, mice were randomized to four training groups: (1) postural exercises designed to stimulate brainstem pathways (BS); (2) distal limb-grip exercises preferentially stimulating CST pathways (CST); (3) simultaneous multimodal exercises (BS+CST); or (4) no training (NT). Behavioral and anatomical outcomes were assessed after 20 training sessions over 4 weeks. Mice in the BS+CST training group showed a trend toward greater improvements in skilled limb performance than mice in the other groups. There were no consistent differences between training groups in gait kinematics. Anatomically, multimodal BS+CST training neither increased corticobulbar fiber density of the lesioned CST rostral to the lesion nor collateral sprouting of the unlesioned CST caudal to the lesion. Further studies should incorporate electrophysiological assessment to gauge changes in synaptic strength of direct and indirect pathways between the cortex and spinal cord in response to multimodal exercises. Published by Elsevier B.V. C1 [Harel, Noam Y.; Yigitkanli, Kazim; Fu, Yiguang; Cafferty, William B. J.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Harel, Noam Y.; Yigitkanli, Kazim; Fu, Yiguang; Cafferty, William B. J.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06520 USA. RP Harel, NY (reprint author), James J Peters Vet Affairs Med Ctr, 130 West Kingsbridge Rd,7A-13G, Bronx, NY 10468 USA. EM noam.harel@mssm.edu; kazim.yigitkanli@yale.edu; yiguang.fu@yale.edu; william.cafferty@yale.edu; stephen.strittmatter@yale.edu OI Strittmatter, Stephen/0000-0001-8188-3092 FU NINDS; Falk Medical Research Trust; Christopher and Dana Reeve Foundation; Wings for Life Foundation FX This work was funded by grants to S.M.S. from the NINDS, the Falk Medical Research Trust, the Christopher and Dana Reeve Foundation, and the Wings for Life Foundation, and a career development award to N.Y.H. from the NINDS. We also appreciate the help of Christopher Cardozo and Lauren Collier. NR 37 TC 4 Z9 4 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 13 PY 2013 VL 1538 BP 17 EP 25 DI 10.1016/j.brainres.2013.07.012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 266FU UT WOS:000328009600002 PM 24055330 ER PT J AU Birkbak, NJ Kochupurakkal, B Izarzugaza, JMG Eklund, AC Li, Y Liu, J Szallasi, Z Matulonis, UA Richardson, AL Iglehart, JD Wang, ZC AF Birkbak, Nicolai Juul Kochupurakkal, Bose Izarzugaza, Jose M. G. Eklund, Aron C. Li, Yang Liu, Joyce Szallasi, Zoltan Matulonis, Ursula A. Richardson, Andrea L. Iglehart, J. Dirk Wang, Zhigang C. TI Tumor Mutation Burden Forecasts Outcome in Ovarian Cancer with BRCA1 or BRCA2 Mutations SO PLOS ONE LA English DT Article ID HOMOLOGOUS RECOMBINATION; BREAST-CANCER; COPY NUMBERS; DNA-REPAIR; SENSITIVITY; ASSOCIATION; SURVIVAL; ARRAYS; CELLS; WOMEN AB Background: Increased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA repair and is associated with treatment outcome in ovarian cancer. Methods and Results: The total number of synonymous and non-synonymous exome mutations (Nmut), and the presence of germline or somatic mutation in BRCA1 or BRCA2 (mBRCA) were extracted from whole-exome sequences of high-grade serous ovarian cancers from The Cancer Genome Atlas (TCGA). Cox regression and Kaplan-Meier methods were used to correlate Nmut with chemotherapy response and outcome. Higher Nmut correlated with a better response to chemotherapy after surgery. In patients with mBRCA-associated cancer, low Nmut was associated with shorter progression-free survival (PFS) and overall survival (OS), independent of other prognostic factors in multivariate analysis. Patients with mBRCA-associated cancers and a high Nmut had remarkably favorable PFS and OS. The association with survival was similar in cancers with either BRCA1 or BRCA2 mutations. In cancers with wild-type BRCA, tumor Nmut was associated with treatment response in patients with no residual disease after surgery. Conclusions: Tumor Nmut was associated with treatment response and with both PFS and OS in patients with high-grade serous ovarian cancer carrying BRCA1 or BRCA2 mutations. In the TCGA cohort, low Nmut predicted resistance to chemotherapy, and for shorter PFS and OS, while high Nmut forecasts a remarkably favorable outcome in mBRCA-associated ovarian cancer. Our observations suggest that the total mutation burden coupled with BRCA1 or BRCA2 mutations in ovarian cancer is a genomic marker of prognosis and predictor of treatment response. This marker may reflect the degree of deficiency in BRCA-mediated pathways, or the extent of compensation for the deficiency by alternative mechanisms. C1 [Birkbak, Nicolai Juul; Kochupurakkal, Bose; Li, Yang; Iglehart, J. Dirk; Wang, Zhigang C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Birkbak, Nicolai Juul; Izarzugaza, Jose M. G.; Eklund, Aron C.; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Liu, Joyce; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Childrens Hosp Informat Program Harvard Massachus, Sch Med, Boston, MA USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Iglehart, J. Dirk; Wang, Zhigang C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Iglehart, JD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM JIGLEHART@PARTNERS.ORG; zhigang_wang@dfci.harvard.edu RI Izarzugaza, Jose /N-4503-2014; OI Izarzugaza, Jose /0000-0003-1754-5122; Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001 FU Breast Cancer Research Foundation; Villum Kann Rasmussen Foundation FX This work was supported by the funding granted from the Breast Cancer Research Foundation to ALR, JDI, UAM, ZS, and ZCW. NUB was funded by The Villum Kann Rasmussen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 24 Z9 25 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 NOV 12 PY 2013 VL 8 IS 11 AR e80023 DI 10.1371/journal.pone.0080023 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255PK UT WOS:000327252100126 PM 24265793 ER PT J AU Kim, E Yang, KS Weissleder, R AF Kim, Eunha Yang, Katherine S. Weissleder, Ralph TI Bioorthogonal Small Molecule Imaging Agents Allow Single-Cell Imaging of MET SO PLOS ONE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; C-MET; IN-VIVO; KINASE INHIBITORS; MET/HGF RECEPTOR; TYROSINE KINASE; CANCER-CELLS; EXPRESSION; DISCOVERY; POLYPHARMACOLOGY AB The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that has emerged as an important cancer target. Consequently, a number of different inhibitors varying in specificity are currently in clinical development. However, to date, it has been difficult to visualize MET expression, intracellular drug distribution and small molecule MET inhibition. Using a bioorthogonal approach, we have developed two companion imaging drugs based on both mono- and polypharmacological MET inhibitors. We show exquisite drug and target co-localization that can be visualized at single-cell resolution. The developed agents may be useful chemical biology tools to investigate single-cell pharmacokinetics and pharmacodynamics of MET inhibitors. C1 [Kim, Eunha; Yang, Katherine S.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Kim, Eunha/G-1242-2013 OI Kim, Eunha/0000-0002-0766-696X FU National Institutes of Health/National Cancer Institute [P50 CA086355, R01 CA164448, T32 CA79443] FX This work was supported by grants P50 CA086355, R01 CA164448, T32 CA79443 from the National Institutes of Health/National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 5 Z9 5 U1 1 U2 11 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 NOV 12 PY 2013 VL 8 IS 11 AR UNSP e81275 DI 10.1371/journal.pone.0081275 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255PK UT WOS:000327252100179 PM 24265843 ER PT J AU Thukkani, AK Bhatt, DL AF Thukkani, Arun K. Bhatt, Deepak L. TI Renal Denervation Therapy for Hypertension SO CIRCULATION LA English DT Article DE hypertension; hypertension, renal ID RANDOMIZED CONTROLLED-TRIAL; RESISTANT HYPERTENSION; SYMPATHETIC DENERVATION; BLOOD-PRESSURE; ARTERIAL-HYPERTENSION; PILOT; PROGNOSIS; PREVENTS; FAILURE; SAFETY C1 [Thukkani, Arun K.; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), 75 Francis St, Boston, MA 02115 USA. EM DLBHATTMD@post.harvard.edu NR 32 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 12 PY 2013 VL 128 IS 20 BP 2251 EP 2254 DI 10.1161/CIRCULATIONAHA.113.004660 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 251GG UT WOS:000326915200018 PM 24218440 ER PT J AU Swirski, FK Nahrendorf, M AF Swirski, Filip K. Nahrendorf, Matthias TI Macrophage-Stem Cell Crosstalk After Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE inflammation; macrophage; mesenchymal stroma cell; myocardial infarction; remodeling ID MONOCYTE SUBSETS; HEART-FAILURE; REPAIR AB Myocardial infarcts are wounds inflicted by ischemic injury of the heart muscle. As in any other wound, a sufficient healing process after acute injury is prerequisite to the recovery and integrity of the organ's function. If infarct healing derails, fibrosis may be insufficient or too widespread, either endangering the left ventricle's geometry or increasing its stiffness, especially if fibrosis occurs in the remote myocardium. The imminent threat of insufficient healing is a weak scar that may rupture, often a deadly complication. More frequently, the weak infarct scar acutely maintains the ventricle's integrity but expands over time, thus causing chronic post-myocardial infarction (MI) remodeling and heart failure. Macrophages are centrally involved in wound healing, including healing of the heart (1). These cells are also part of the causal pathology leading to ischemia of the heart because macrophages destabilize atherosclerotic plaques, rendering them prone to rupture (1). C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swirski, FK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu FU NHLBI NIH HHS [R01HL114477, R01HL095612, R01HL095629, R01HL096576] NR 16 TC 6 Z9 6 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 12 PY 2013 VL 62 IS 20 BP 1902 EP 1904 DI 10.1016/j.jacc.2013.07.058 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 246XI UT WOS:000326574400014 PM 23973700 ER PT J AU Portal, D Zhou, HF Zhao, B Kharchenko, PV Lowry, E Wong, L Quackenbush, J Holloway, D Jiang, SZ Lu, Y Kieff, E AF Portal, Daniel Zhou, Hufeng Zhao, Bo Kharchenko, Peter V. Lowry, Elizabeth Wong, Limsoon Quackenbush, John Holloway, Dustin Jiang, Sizun Lu, Yong Kieff, Elliott TI Epstein-Barr virus nuclear antigen leader protein localizes to promoters and enhancers with cell transcription factors and EBNA2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome-wide ChIP-seq analysis; gene expression ID NUCLEAR-PROTEIN-2 ACIDIC DOMAIN; SIGNAL-BINDING-PROTEIN; HUMAN B-LYMPHOCYTES; GENE-EXPRESSION; CYCLIN D2; DNA-DAMAGE; CTCF; LP; TRANSFORMATION; COHESIN AB Epstein-Barr virus (EBV) nuclear antigens EBNALP (LP) and EBNA2 (E2) are coexpressed in EBV-infected B lymphocytes and are critical for lymphoblastoid cell line outgrowth. LP removes NCOR and RBPJ repressive complexes from promoters, enhancers, and matrix-associated deacetylase bodies, whereas E2 activates transcription from distal enhancers. LP ChIP-seq analyses identified 19,224 LP sites of which similar to 50% were +/- 2 kb of a transcriptional start site. LP sites were enriched for B-cell transcription factors (TFs), YY1, SP1, PAX5, BATF, IRF4, ETS1, RAD21, PU.1, CTCF, RBPJ, ZNF143, SMC3, NF kappa B, TBLR, and EBF. E2 sites were also highly enriched for LP-associated cell TFs and were more highly occupied by RBPJ and EBF. LP sites were highly marked by H3K4me3, H3K27ac, H2Az, H3K9ac, RNAPII, and P300, indicative of activated transcription. LP sites were 29% colocalized with E2 (LP/E2). LP/E2 sites were more similar to LP than to E2 sites in associated cell TFs, RNAPII, P300, and histone H3K4me3, H3K9ac, H3K27ac, and H2Az occupancy, and were more highly transcribed than LP or E2 sites. Gene affected by CTCF and LP cooccupancy were more highly expressed than genes affected by CTCF alone. LP was at myc enhancers and promoters and of MYC regulated ccnd2, 23 med complex components, and MYC regulated cell survival genes, igf2r and bcl2. These data implicate LP and associated TFs and DNA looping factors CTCF, RAD21, SMC3, and YY1/INO80 chromatin-remodeling complexes in repressor depletion and gene activation necessary for lymphoblastoid cell line growth and survival. C1 [Portal, Daniel; Zhou, Hufeng; Zhao, Bo; Lowry, Elizabeth; Jiang, Sizun; Kieff, Elliott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Portal, Daniel; Zhou, Hufeng; Zhao, Bo; Lowry, Elizabeth; Jiang, Sizun; Kieff, Elliott] Harvard Univ, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Zhou, Hufeng; Wong, Limsoon] Natl Univ Singapore, Sch Comp, Singapore 117417, Singapore. [Kharchenko, Peter V.; Jiang, Sizun] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Quackenbush, John; Holloway, Dustin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lu, Yong] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Kieff, E (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM ekieff@rics.bwh.harvard.edu RI Wong, Limsoon/E-5033-2010; Zhou, Hufeng/M-1307-2014 OI Wong, Limsoon/0000-0003-1241-5441; Zhou, Hufeng/0000-0001-9382-5674 FU National Cancer Institute of the National Institutes of Health of the US Public Health Service [R01CA131354, R01CA170023, R01CA047006] FX This research was supported by Grants R01CA131354, R01CA170023, and R01CA047006 from the National Cancer Institute of the National Institutes of Health of the US Public Health Service. NR 59 TC 23 Z9 24 U1 0 U2 12 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 NOV 12 PY 2013 VL 110 IS 46 BP 18537 EP 18542 DI 10.1073/pnas.1317608110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DQ UT WOS:000326830900057 PM 24167291 ER PT J AU Stylianopoulos, T Jain, RK AF Stylianopoulos, Triantafyllos Jain, Rakesh K. TI Combining two strategies to improve perfusion and drug delivery in solid tumors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tumor microenvironment; vessel decompression; vessel permeability; mechanical forces; mathematical modeling ID ENDOTHELIAL GROWTH-FACTOR; ANTI-ANGIOGENIC THERAPY; PHASE-III TRIAL; BLOOD-VESSELS; PANCREATIC-CANCER; BREAST-CANCER; VASCULAR NORMALIZATION; ANTIANGIOGENIC THERAPY; DUCTAL ADENOCARCINOMA; GLIOBLASTOMA PATIENTS AB Blood perfusion in tumors can be significantly lower than that in the surrounding normal tissue owing to the leakiness and/or compression of tumor blood vessels. Impaired perfusion reduces oxygen supply and results in a hypoxic microenvironment. Hypoxia promotes tumor progression and immunosuppression, and enhances the invasive and metastatic potential of cancer cells. Furthermore, poor perfusion lowers the delivery of systemically administered drugs. Therapeutic strategies to improve perfusion include reduction in vascular permeability by vascular normalization and vascular decompression by alleviating physical forces (solid stress) inside tumors. Both strategies have shown promise, but guidelines on how to use these strategies optimally are lacking. To this end, we developed a mathematical model to guide the optimal use of these strategies. The model accounts for vascular, transvascular, and interstitial fluid and drug transport as well as the diameter and permeability of tumor vessels. Model simulations reveal an optimal perfusion region when vessels are uncompressed, but not very leaky. Within this region, intratumoral distribution of drugs is optimized, particularly for drugs 10 nm in diameter or smaller and of low binding affinity. Therefore, treatments should modify vessel diameter and/or permeability such that perfusion is optimal. Vascular normalization is more effective for hyperpermeable but largely uncompressed vessels (e. g., glioblastomas), whereas solid stress alleviation is more beneficial for compressed but less-permeable vessels (e. g., pancreatic ductal adenocarcinomas). In the case of tumors with hyperpermeable and compressed vessels (e. g., subset of mammary carcinomas), the two strategies need to be combined for improved treatment outcomes. C1 [Stylianopoulos, Triantafyllos] Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU National Cancer Institute [P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706]; Federal Share Income Grant [T32-CA073479]; Department of Defense Breast Cancer Research Innovator Award [W81XWH-10-1-0016]; European Commission [FP7-PIRG08-GA-2010-276894, ERC-2013-StG-336839] FX We thank J. Baish, V. Chauhan, D. Duda, K. Emblem, D. Fukumura, E. Gerstner, S. Goel, L. Munn, T. Padera, and M. Datta. This work was supported by National Cancer Institute Grants P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, and R01-CA098706; Federal Share Income Grant T32-CA073479; Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R. K. J.); and European Commission Grants FP7-PIRG08-GA-2010-276894 and ERC-2013-StG-336839 (to T.S.). NR 67 TC 89 Z9 90 U1 11 U2 61 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 NOV 12 PY 2013 VL 110 IS 46 BP 18632 EP 18637 DI 10.1073/pnas.1318415110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DQ UT WOS:000326830900073 PM 24167277 ER PT J AU Xu, XY Xie, K Zhang, XQ Pridgen, EM Park, GY Cui, DS Shi, JJ Wu, J Kantoff, PW Lippard, SJ Langer, R Walker, GC Farokhzad, OC AF Xu, Xiaoyang Xie, Kun Zhang, Xue-Qing Pridgen, Eric M. Park, Ga Young Cui, Danica S. Shi, Jinjun Wu, Jun Kantoff, Philip W. Lippard, Stephen J. Langer, Robert Walker, Graham C. Farokhzad, Omid C. TI Enhancing tumor cell response to chemotherapy through nanoparticle-mediated codelivery of siRNA and cisplatin prodrug SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE siRNA delivery; chemosensitivity; combination therapy ID DRUG-RESISTANT; INTERFERING RNA; CO-DELIVERY; POL-ZETA; IN-VIVO; DNA; CHEMORESISTANCE; THERAPY; NANOTECHNOLOGY; COMPLEXES AB Cisplatin and other DNA-damaging chemotherapeutics are widely used to treat a broad spectrum of malignancies. However, their application is limited by both intrinsic and acquired chemoresistance. Most mutations that result from DNA damage are the consequence of error-prone translesion DNA synthesis, which could be responsible for the acquired resistance against DNA-damaging agents. Recent studies have shown that the suppression of crucial gene products (e. g., REV1, REV3L) involved in the error-prone translesion DNA synthesis pathway can sensitize intrinsically resistant tumors to chemotherapy and reduce the frequency of acquired drug resistance of relapsed tumors. In this context, combining conventional DNA-damaging chemotherapy with siRNA-based therapeutics represents a promising strategy for treating patients with malignancies. To this end, we developed a versatile nanoparticle (NP) platform to deliver a cisplatin prodrug and REV1/REV3L-specific siRNAs simultaneously to the same tumor cells. NPs are formulated through self-assembly of a biodegradable poly(lactide-coglycolide)-b-poly(ethylene glycol) diblock copolymer and a self-synthesized cationic lipid. We demonstrated the potency of the siRNA-containing NPs to knock down target genes efficiently both in vitro and in vivo. The therapeutic efficacy of NPs containing both cisplatin prodrug and REV1/REV3L-specific siRNAs was further investigated in vitro and in vivo. Quantitative real-time PCR results showed that the NPs exhibited a significant and sustained suppression of both genes in tumors for up to 3 d after a single dose. Administering these NPs revealed a synergistic effect on tumor inhibition in a human Lymph Node Carcinoma of the Prostate xenograft mouse model that was strikingly more effective than platinum monotherapy. C1 [Xu, Xiaoyang; Zhang, Xue-Qing; Cui, Danica S.; Shi, Jinjun; Wu, Jun; Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Lab Nanomed & Biomat, Sch Med, Boston, MA 02115 USA. [Xu, Xiaoyang; Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Xie, Kun; Walker, Graham C.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Pridgen, Eric M.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Park, Ga Young; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Kantoff, Philip W.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Farokhzad, OC (reprint author), Harvard Univ, Brigham & Womens Hosp, Lab Nanomed & Biomat, Sch Med, Boston, MA 02115 USA. EM gwalker@mit.edu; ofarokhzad@zeus.bwh.harvard.edu OI /0000-0001-7243-8261 FU David Koch-Prostate Cancer Foundation Award in Nanotherapeutics; Centers of Cancer Nanotechnology Excellence; National Institutes of Health (NIH) [CA151884]; National Institutes of Environmental Health Sciences [ES015818]; NIH National Research Service Award [1F32CA168163-01]; National Cancer Institute [K99CA160350] FX We thank Dr. Akin Akinc (Alnylam Pharmaceuticals, Inc.) and Prof. Daniel G. Anderson (Massachusetts Institute of Technology) for providing Dual-Luc HeLa cells. G. C. W. is an American Cancer Society Professor. This work was supported by the David Koch-Prostate Cancer Foundation Award in Nanotherapeutics, the Centers of Cancer Nanotechnology Excellence, and the National Institutes of Health (NIH) (Grant CA151884). This work was also supported by National Institutes of Environmental Health Sciences Grant ES015818 (to G. C. W.). X. X. acknowledges postdoctoral support from an NIH National Research Service Award (Grant 1F32CA168163-01). J.S. received financial support from National Cancer Institute Grant K99CA160350. NR 32 TC 91 Z9 91 U1 16 U2 149 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 NOV 12 PY 2013 VL 110 IS 46 BP 18638 EP 18643 DI 10.1073/pnas.1303958110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DQ UT WOS:000326830900074 PM 24167294 ER PT J AU Lam, TI Brennan-Minnella, AM Won, SJ Shen, YG Hefner, C Shi, YJ Sun, DD Swanson, RA AF Lam, Tina I. Brennan-Minnella, Angela M. Won, Seok Joon Shen, Yiguo Hefner, Colleen Shi, Yejie Sun, Dandan Swanson, Raymond A. TI Intracellular pH reduction prevents excitotoxic and ischemic neuronal death by inhibiting NADPH oxidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NOX2; acidosis; Hv1; cariporide ID DEPENDENT SUPEROXIDE-PRODUCTION; NMDA RECEPTOR ACTIVATION; FOCAL CEREBRAL-ISCHEMIA; HIPPOCAMPAL-NEURONS; GLUTAMATE NEUROTOXICITY; NERVOUS-SYSTEM; NITRIC-OXIDE; CELL-DEATH; IN-VIVO; BRAIN AB Sustained activation of N-methyl-d-aspartate (NMDA) -type glutamate receptors leads to excitotoxic neuronal death in stroke, brain trauma, and neurodegenerative disorders. Superoxide production by NADPH oxidase is a requisite event in the process leading from NMDA receptor activation to excitotoxic death. NADPH oxidase generates intracellular H+ along with extracellular superoxide, and the intracellular H+ must be released or neutralized to permit continued NADPH oxidase function. In cultured neurons, NMDA-induced superoxide production and neuronal death were prevented by intracellular acidification by as little as 0.2 pH units, induced by either lowered medium pH or by inhibiting Na+/H+ exchange. In mouse brain, superoxide production induced by NMDA injections or ischemia-reperfusion was likewise prevented by inhibiting Na+/H+ exchange and by reduced expression of the Na+/H+ exchanger-1 (NHE1). Neuronal intracellular pH and neuronal Na+/H+ exchange are thus potent regulators of excitotoxic superoxide production. These findings identify a mechanism by which cell metabolism can influence coupling between NMDA receptor activation and superoxide production. C1 [Lam, Tina I.; Brennan-Minnella, Angela M.; Won, Seok Joon; Shen, Yiguo; Hefner, Colleen; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Lam, Tina I.; Brennan-Minnella, Angela M.; Won, Seok Joon; Shen, Yiguo; Hefner, Colleen; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA. [Shi, Yejie; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU Department of Veterans Affairs; National Institutes of Health [NS081149, R01NS48216, R01NS38118] FX We thank Dr. Stephen Massa for helpful discussions. This work was supported by the Department of Veterans Affairs (R.A.S.) and by National Institutes of Health Grants NS081149 (to R.A.S.), R01NS48216 (to D.S.), and R01NS38118 (to D.S.). NR 46 TC 16 Z9 16 U1 2 U2 12 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 NOV 12 PY 2013 VL 110 IS 46 BP E4362 EP E4368 DI 10.1073/pnas.1313029110 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DQ UT WOS:000326830900015 PM 24163350 ER PT J AU Steinman, MA Auerbach, AD AF Steinman, Michael A. Auerbach, Andrew D. TI Managing Chronic Disease in Hospitalized Patients SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ELDERLY-PATIENTS; DISCHARGE; ADHERENCE; COHORT C1 [Steinman, Michael A.; Auerbach, Andrew D.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,POB 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NHLBI NIH HHS [K24 HL098372]; NIA NIH HHS [1K23-AG030999, K23 AG030999] NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 11 PY 2013 VL 173 IS 20 BP 1857 EP 1858 DI 10.1001/jamainternmed.2013.9511 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 302FD UT WOS:000330586600001 PM 23921959 ER PT J AU Rosenthal, MB Friedberg, MW Singer, SJ Eastman, D Li, ZH Schneider, EC AF Rosenthal, Meredith B. Friedberg, Mark W. Singer, Sara J. Eastman, Diana Li, Zhonghe Schneider, Eric C. TI Effect of a Multipayer Patient-Centered Medical Home on Health Care Utilization and Quality The Rhode Island Chronic Care Sustainability Initiative Pilot Program SO JAMA INTERNAL MEDICINE LA English DT Article AB IMPORTANCE The patient-centered medical home is advocated to reduce health care costs and improve the quality of care. OBJECTIVE To evaluate the effects of the pilot program of a multipayer patient-centered medical home on health care utilization and quality. DESIGN An interrupted time series design with propensity score-matched comparison practices, including multipayer claims data from 2 years before (October 1, 2006-September 30, 2008) and 2 years after (October 1, 2008-September 30, 2010) the launch of the pilot program. Uptake of the intervention was measured with audit data from the National Committee for Quality Assurance patient-centered medical home recognition process. SETTING Five independent primary care practices and 3 private insurers in the Rhode Island Chronic Care Sustainability Initiative. PARTICIPANTS Patients in 5 pilot and 34 comparison practices. INTERVENTIONS Financial support, care managers, and technical assistance for quality improvement and practice transformation. MAIN OUTCOMES AND MEASURES Hospital admissions, emergency department visits, and 6 process measures of quality of care (3 for diabetes mellitus and 3 for colon, breast, and cervical cancer screening). RESULTS The mean National Committee for Quality Assurance recognition scores of the pilot practices increased from 42 to 90 points of a possible 100 points. The pilot and comparison practices had statistically indistinguishable baseline patient characteristics and practice patterns, except for higher numbers of attributed member months per year in the pilot practices (31 130 per practice vs 14 779, P = .01) and lower rates of cervical cancer screening in the comparison practices. Although estimates of the emergency department visits and inpatient admissions of patients in the pilot practices trended toward lower utilization, the only significant difference was a lower rate of ambulatory care sensitive emergency department visits in the pilot practices. The Chronic Care Sustainability Initiative pilot program was associated with a reduction in ambulatory care-sensitive emergency department visits of approximately 0.8 per 1000 member months or approximately 11.6% compared with the baseline rate of 6.9 for emergency department visits per 1000 member months (P = .002). No significant improvements were found in any of the quality measures. CONCLUSION AND RELEVANCE After 2 years, a pilot program of a patient-centered medical home was associated with substantial improvements in medical home recognition scores and a significant reduction in ambulatory care sensitive emergency department visits. Although not achieving significance, there were downward trends in emergency department visits and inpatient admissions. C1 [Rosenthal, Meredith B.; Singer, Sara J.; Eastman, Diana; Li, Zhonghe; Schneider, Eric C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Friedberg, Mark W.; Schneider, Eric C.] RAND Corp, Boston, MA USA. [Singer, Sara J.; Schneider, Eric C.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Friedberg, Mark W.; Singer, Sara J.; Schneider, Eric C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Morgan Inst Hlth Policy, Boston, MA 02114 USA. RP Rosenthal, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM meredith_rosenthal@harvard.edu OI Rosenthal, Meredith/0000-0003-3410-0184; Schneider, Eric/0000-0002-1132-5084 FU Commonwealth Fund, New York, New York FX This study was supported by The Commonwealth Fund, New York, New York. NR 17 TC 48 Z9 48 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 11 PY 2013 VL 173 IS 20 BP 1907 EP 1913 DI 10.1001/jamainternmed.2013.10063 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 302FD UT WOS:000330586600013 PM 24018613 ER PT J AU Singh, H Thomas, EJ AF Singh, Hardeep Thomas, Eric J. TI Origins of Diagnostic Error Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID PRIMARY-CARE C1 [Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Med Sch Houston, Mem Hermann Ctr Healthcare Qual & Safety, Div Gen Med,Dept Med, Houston, TX USA. RP Singh, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 11 PY 2013 VL 173 IS 20 BP 1926 EP 1927 DI 10.1001/jamainternmed.2013.9717 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 302FD UT WOS:000330586600021 PM 24217378 ER PT J AU Messina, S Vargas-Lowy, D Musallam, A Healy, BC Kivisakk, P Gandhi, R Bove, R Gholipour, T Khoury, S Weiner, HL Chitnis, T AF Messina, Silvia Vargas-Lowy, David Musallam, Alexander Healy, Brian C. Kivisakk, Pia Gandhi, Roopali Bove, Riley Gholipour, Taha Khoury, Samia Weiner, Howard L. Chitnis, Tanuja TI Increased leptin and A-FABP levels in relapsing and progressive forms of MS SO BMC NEUROLOGY LA English DT Article DE 41. Multiple sclerosis; 132. Autoimmune disease; 175. Neuroendocrinology ID PEDIATRIC MULTIPLE-SCLEROSIS; ACID-BINDING PROTEINS; BODY-MASS INDEX; AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-BETA; OBESITY; MACROPHAGES; EXPRESSION; DISORDERS; RESPONSES AB Background: Leptin and adipocyte-fatty acid binding protein (A-FABP) are produced by white adipose tissue and may play a role in chronic inflammation in Multiple Sclerosis (MS). To assess leptin and A-FABP in relapsing and progressive forms of MS. Methods: Adipokine levels were measured in untreated adult relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and Healthy control (HC). Pediatric-onset MS (POMS) and pediatric healthy controls (PHC) were also assessed. Leptin and A-FABP levels were measured in serum by ELISA. Groups were compared using linear mixed-effects model. Results: Excluding two patients with Body Mass Index (BMI) > 50, a significant difference in leptin level was found between RRMS and HC controlling for age (p = 0.007), SPMS and HC controlling for age alone (p = 0.002), or age and BMI (p = 0.007). A-FABP levels were higher in SPMS than HC (p = 0.007), controlling for age and BMI. Differences in A-FABP levels between POMS and PHC was observed after controlling for age (p = 0.019), but not when BMI was added to the model (p = 0.081). Conclusion: Leptin and A-FABP levels are highest in SPMS compared to HC, suggesting a role in pathogenesis of this disease subtype. A-FABP levels are increased in POMS patients and may play a role in the early stages of disease. C1 [Messina, Silvia; Musallam, Alexander; Healy, Brian C.; Bove, Riley; Gholipour, Taha; Khoury, Samia; Weiner, Howard L.; Chitnis, Tanuja] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. [Messina, Silvia] Univ Catania, Sect Neurosci, Dept GF Ingrassia, Catania, Italy. [Vargas-Lowy, David; Kivisakk, Pia; Gandhi, Roopali; Khoury, Samia; Chitnis, Tanuja] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat MS Ctr, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 75 Francis St, Boston, MA 02115 USA. EM tchitnis@partners.org OI khoury, samia/0000-0003-3198-6063 FU National Multiple Sclerosis Society [TC-RG-4256A4/2]; Novartis; Merck Serono; Merck-Serono FX Supported by the National Multiple Sclerosis Society (TC-RG-4256A4/2). We thank the BWH Phenogenetic project for providing healthy control subjects for this study.; Dr. Messina has received funding from Novartis for travel to a medical conference. Dr. Healy has received research support from Merck Serono. Mr. Musallam reports no disclosures. Dr. Bove reports no disclosures. Dr. Kivisakk has received grant support from Merck-Serono. Dr. Gandhi has received research support from Merck-Serono and Novartis. Dr. Gholipour has received research support from Merck-Serono. Dr. Khoury has served as a consultant for Epivax and Novartis. Dr. Weiner has served as a consultant for Teva Neurosciences, Novartis, Biogen and EMD-Serono, and hs received grant support from Merck-Serono for unrelated activities. Dr. Chitnis has served as a consultant for Biogen-Idec, Sanofi Aventis, Novartis, EMD-Serono, and Teva Neurosciences, and has received grant support from Merck-Serono for unrelated activities. NR 37 TC 5 Z9 5 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD NOV 11 PY 2013 VL 13 AR 172 DI 10.1186/1471-2377-13-172 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 280WJ UT WOS:000329061200004 PM 24215402 ER PT J AU Wasson, NJ Varley, CD Schwab, P Fu, RW Winthrop, KL AF Wasson, Ngoc J. Varley, Cara D. Schwab, Pascal Fu, Rongwei Winthrop, Kevin L. TI "Serious skin & soft tissue infections in rheumatoid arthritis patients taking anti-tumor necrosis factor alpha drugs: a nested case-control study" SO BMC INFECTIOUS DISEASES LA English DT Article DE Infectious skin diseases; Tumor necrosis factor-alpha; Anti-TNF therapy; Arthritis; Rheumatoid ID BACTERIAL-INFECTIONS; OPPORTUNISTIC INFECTIONS; RISK; THERAPY; ANTAGONISTS; EPIDEMIOLOGY; BIOLOGICS; DATABASES; DISEASES AB Background: Anti-tumor necrosis factor alpha (anti-TNF) drugs are very effective for the treatment of rheumatoid arthritis but may increase the risk of serious bacterial infections. We assessed the association between the risk of serious skin and soft tissue infections (SSSTI) and the use of these agents in rheumatoid arthritis patients (RA). Methods: We conducted a nested case-control study among rheumatoid arthritis patients in the Veterans Integrated Service Network 20 from 2000-2008. We identified rheumatoid arthritis patients with SSSTI, matched them to three sets of RA controls and used conditional logistic regression to compare the risk of SSSTI between patients treated and those not treated with an anti-TNF drug, after adjusting for known confounders and important covariates. Limited by the design, we could not assess (absolute) risk but only relative risk in terms of association. Results: Among the 97 cases and 291 controls, 90 percent were male, 62 percent white, with a mean age of 63 years. Twenty percent received anti-TNF drugs during the study period. Thirty-nine percent of cases and 15 percent of controls died, (OR 3.5, 95% CI: 2.033, 6.11, p < 0.01). Diabetes mellitus (37%), kidney disease (16%) and a history of skin infections (27%) were common among cases. Based on conditional logistic regression, anti-TNF use was not significantly associated with skin and soft tissue infections (OR 1.1, 95% CI: 0.61-2.03, p = 0.92). However, patients with diabetes mellitus (OR 2.5, 95% CI: 1.53-4.13, p = 0.01) or a prior history of skin infection (OR 5.7, 95% CI: 2.87-11.43, p < 0.01) were more likely to have skin and soft tissue infections. Conclusion: Use of anti-TNF therapy among RA patients was not associated with an increased risk of SSSTI, but patients with diabetes mellitus and those with a history of prior skin infection were significantly more likely to have SSSTI and mortality was higher among cases than controls in this veteran cohort. C1 [Wasson, Ngoc J.; Varley, Cara D.; Schwab, Pascal; Fu, Rongwei; Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Schwab, Pascal] Portland VA Med Ctr, Portland, OR USA. RP Wasson, NJ (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. EM wassonn@ohsu.edu FU NCATS NIH HHS [UL1 TR000128] NR 28 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD NOV 11 PY 2013 VL 13 AR 533 DI 10.1186/1471-2334-13-533 PG 7 WC Infectious Diseases SC Infectious Diseases GA 278QW UT WOS:000328905800001 PM 24498926 ER PT J AU Harriff, MJ Burgdorf, S Kurts, C Wiertz, EJHJ Lewinsohn, DA Lewinsohn, DM AF Harriff, Melanie J. Burgdorf, Sven Kurts, Christian Wiertz, Emmanuel J. H. J. Lewinsohn, Deborah A. Lewinsohn, David M. TI TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I SO PLOS ONE LA English DT Article ID CROSS-PRESENTATION; INFECTED MACROPHAGES; DENDRITIC CELLS; T-CELLS; EXOGENOUS ANTIGENS; PATHWAY; TRAFFICKING; COMPARTMENT; ORGANELLES; MOLECULES AB Processing and presentation of antigen on MHC-I class I molecules serves to present peptides derived from cytosolic proteins to CD8(+) T cells. Infection with bacteria that remain in phagosomal compartments, such as Mycobacterium tuberculosis (Mtb), provides a challenge to this immune recognition as bacterial proteins are segregated from the cytosol. Previously we identified the Mtb phagosome itself as an organelle capable of loading MHC Class I molecules with Mtb antigens. Here, we find that the TAP transporter, responsible for importing peptides into the ER for loading in Class I molecules, is both present and functional in Mtb phagosomes. Furthermore, we describe a novel peptide reagent, representing the N-terminal domain of the bovine herpes virus UL49.5 protein, which is capable of specifically inhibiting the lumenal face of TAP. Together, these results provide insight into the mechanism by which peptides from intra-phagosomal pathogens are loaded onto Class I molecules. C1 [Harriff, Melanie J.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. [Harriff, Melanie J.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland, OR 97201 USA. [Burgdorf, Sven] Univ Bonn, Life & Med Sci LIMES Inst, Bonn, Germany. [Burgdorf, Sven; Kurts, Christian] Univ Bonn, IMMEI, Bonn, Germany. [Wiertz, Emmanuel J. H. J.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Wiertz, Emmanuel J. H. J.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Lewinsohn, Deborah A.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Harriff, MJ (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM harriffm@ohsu.edu; lewinsod@ohsu.edu; lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU National Institutes of Health [R01AI048090, T32HL083808]; Veterans Affairs Hospitals Merit Review Grant; Portland Veterans Affairs Medical Center; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [S10-RR023432]; Oregon Health & Sciences University MMI Imaging Core FX This research was supported by National Institutes of Health Grants R01AI048090 and T32HL083808, a Veterans Affairs Hospitals Merit Review Grant, and the Portland Veterans Affairs Medical Center. The microscopy in this publication was made possible in part by Grant Number S10-RR023432 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the Oregon Health & Sciences University MMI Imaging Core. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 1 Z9 1 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 NOV 11 PY 2013 VL 8 IS 11 AR e79571 DI 10.1371/journal.pone.0079571 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EG UT WOS:000327221600135 PM 24244525 ER PT J AU Liu, ML Idkowiak-Baldys, J Roddy, PL Baldys, A Raymond, J Clarke, CJ Hannun, YA AF Liu, Mengling Idkowiak-Baldys, Jolanta Roddy, Patrick L. Baldys, Aleksander Raymond, John Clarke, Christopher J. Hannun, Yusuf A. TI Sustained Activation of Protein Kinase C Induces Delayed Phosphorylation and Regulates the Fate of Epidermal Growth Factor Receptor SO PLOS ONE LA English DT Article ID BREAST-CANCER CELLS; PHOSPHOLIPASE-D; RECYCLING ENDOSOMES; COUPLED RECEPTORS; ANGIOTENSIN-II; SEQUESTRATION; DEGRADATION; PATHWAY; INTERNALIZATION; ENDOCYTOSIS AB It is well established that acute activation of members of the protein kinase C (PKC) family induced by activation of cellular receptors can transduce extracellular stimuli to intracellular signaling. However, the functions of sustained activation of PKC are not well studied. We have previously shown that sustained activation of classical PKC isoforms over 15-60 min induced the formation of the pericentrion, a subset of recycling endosomes that are sequestered perinuclearly in a PKC- and phospholipase D (PLD)-dependent manner. In this study, we investigated the role of this process in the phosphorylation of EGFR on threonine 654 (Thr-654) and in the regulation of intracellular trafficking and fate of epidermal growth factor receptor (EGFR). Sustained stimulation of the angiotensin II receptor induced translocation of the EGFR to the pericentrion, which in turn prevents full access of EGF to the EGFR. These effects required PKC and PLD activities, and direct stimulation of PKC with phorbol esters was sufficient to reproduce these effects. Furthermore, activation of PKC induced delayed phosphorylation of EGFR on Thr-654 that coincided with the formation of the pericentrion and which was dependent on PLD and endocytosis of EGFR. Thus, Thr-654 phosphorylation required the formation of the pericentrion. On the other hand, using a T654A mutant of EGFR, we find that the phosphorylation on Thr-654 was not required for translocation of EGFR to the pericentrion but was required for protection of EGFR from degradation in response to EGF. Taken together, these results demonstrate a novel role for the pericentrion in the regulation of EGFR phosphorylation, which in turn is important for the fates of EGFR. C1 [Liu, Mengling; Clarke, Christopher J.; Hannun, Yusuf A.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Liu, Mengling; Clarke, Christopher J.; Hannun, Yusuf A.] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA. [Liu, Mengling; Idkowiak-Baldys, Jolanta; Roddy, Patrick L.; Clarke, Christopher J.; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Baldys, Aleksander] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Baldys, Aleksander] Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. [Baldys, Aleksander] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Raymond, John] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Hannun, YA (reprint author), SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. EM yusuf.hannun@sbumed.org FU NIH [HL43707]; Department of Veterans Affairs Merit Award [1I01BX000182]; American Heart Association Mid-Atlantic Affiliate [0725358U] FX NIH grant HL43707; Department of Veterans Affairs Merit Award 1I01BX000182; American Heart Association Mid-Atlantic Affiliate grant 0725358U. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 1 Z9 1 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 NOV 11 PY 2013 VL 8 IS 11 AR e80721 DI 10.1371/journal.pone.0080721 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EG UT WOS:000327221600215 PM 24244711 ER PT J AU Xia, ZQ Secor, E Chibnik, LB Bove, RM Cheng, SC Chitnis, T Cagan, A Gainer, VS Chen, PJ Liao, KP Shaw, SY Ananthakrishnan, AN Szolovits, P Weiner, HL Karlson, EW Murphy, SN Savova, GK Cai, TX Churchill, SE Plenge, RM Kohane, IS De Jager, PL AF Xia, Zongqi Secor, Elizabeth Chibnik, Lori B. Bove, Riley M. Cheng, Suchun Chitnis, Tanuja Cagan, Andrew Gainer, Vivian S. Chen, Pei J. Liao, Katherine P. Shaw, Stanley Y. Ananthakrishnan, Ashwin N. Szolovits, Peter Weiner, Howard L. Karlson, Elizabeth W. Murphy, Shawn N. Savova, Guergana K. Cai, Tianxi Churchill, Susanne E. Plenge, Robert M. Kohane, Isaac S. De Jager, Philip L. TI Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records SO PLOS ONE LA English DT Article ID RHEUMATOID-ARTHRITIS; MEDICAL-RECORDS; INTEGRATING BIOLOGY; DISCOVERY RESEARCH; BRAIN ATROPHY; WHITE-MATTER; DISABILITY; INFORMATICS; ENTERPRISE; BEDSIDE AB Objective: To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods: In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results: The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R-2 = 0.38 +/- 0.05, and that between EHR-derived and true BPF has a mean R-2 = 0.22 +/- 0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56x10(-12)). Conclusion: Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders. C1 [Xia, Zongqi; Secor, Elizabeth; Chibnik, Lori B.; Bove, Riley M.; Chitnis, Tanuja; Weiner, Howard L.; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Xia, Zongqi; Chibnik, Lori B.; Bove, Riley M.; Chitnis, Tanuja; Liao, Katherine P.; Shaw, Stanley Y.; Ananthakrishnan, Ashwin N.; Weiner, Howard L.; Karlson, Elizabeth W.; Murphy, Shawn N.; Savova, Guergana K.; Plenge, Robert M.; Kohane, Isaac S.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA. [Xia, Zongqi; Chibnik, Lori B.; Bove, Riley M.; Plenge, Robert M.; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Cheng, Suchun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Cagan, Andrew; Gainer, Vivian S.; Murphy, Shawn N.] Partners HealthCare, Res Comp & Informat Serv, Charlestown, MA USA. [Chen, Pei J.; Savova, Guergana K.; Kohane, Isaac S.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Liao, Katherine P.; Karlson, Elizabeth W.; Plenge, Robert M.; Kohane, Isaac S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Szolovits, Peter] MIT, Comp Sci Lab, Cambridge, MA 02139 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Charlestown, MA USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Churchill, Susanne E.] Partners HealthCare, Natl Ctr Biomed Comp I2b2, Boston, MA USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu OI Szolovits, Peter/0000-0001-8411-6403 FU National Institutes of Health Office of the Director, National Library of Medicine and the National Institute of General Medical Sciences [NIH U54-LM008748]; National Multiple Sclerosis Society; American Academy of Neurology; NIH [K08-NS079493, K08 AR 060257, K23 DK097142]; Harold and Duval Bowen Fund FX The study was supported by NIH U54-LM008748 from the National Institutes of Health Office of the Director, National Library of Medicine and the National Institute of General Medical Sciences. ZX was a recipient of the Clinician Scientist Development Award from the National Multiple Sclerosis Society and the American Academy of Neurology and is supported by NIH K08-NS079493. KPL is supported by NIH K08 AR 060257 and the Harold and Duval Bowen Fund. ANA is supported by NIH K23 DK097142. PLD is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 16 Z9 16 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 NOV 11 PY 2013 VL 8 IS 11 AR e78927 DI 10.1371/journal.pone.0078927 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255EG UT WOS:000327221600080 PM 24244385 ER PT J AU Zhang, H Alberich-Jorda, M Amabile, G Yang, H Staber, PB DiRuscio, A Welner, RS Ebralidze, A Zhang, JY Levantini, E Lefebvre, V Valk, PJM Delwel, R Hoogenkamp, M Nerlov, C Cammenga, J Saez, B Scadden, DT Bonifer, C Ye, M Tenen, DG AF Zhang, Hong Alberich-Jorda, Meritxell Amabile, Giovanni Yang, Henry Staber, Philipp B. DiRuscio, Annalisa Welner, Robert S. Ebralidze, Alexander Zhang, Junyan Levantini, Elena Lefebvre, Veronique Valk, Peter J. M. Delwel, Ruud Hoogenkamp, Maarten Nerlov, Claus Cammenga, Jorg Saez, Borja Scadden, David T. Bonifer, Constanze Ye, Min Tenen, Daniel G. TI Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia SO CANCER CELL LA English DT Article ID BINDING-PROTEIN-ALPHA; INITIATING CELLS; STEM-CELLS; SELF-RENEWAL; TGF-BETA; MUTATIONS; DIFFERENTIATION; TRANSFORMATION; EXPRESSION; GRANULOPOIESIS AB Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype. C1 [Zhang, Hong; Alberich-Jorda, Meritxell; Amabile, Giovanni; Staber, Philipp B.; DiRuscio, Annalisa; Welner, Robert S.; Ebralidze, Alexander; Zhang, Junyan; Levantini, Elena; Saez, Borja; Scadden, David T.; Ye, Min; Tenen, Daniel G.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02215 USA. [Zhang, Hong; Alberich-Jorda, Meritxell; Amabile, Giovanni; Staber, Philipp B.; DiRuscio, Annalisa; Welner, Robert S.; Ebralidze, Alexander; Zhang, Junyan; Levantini, Elena; Ye, Min] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Alberich-Jorda, Meritxell] Acad Sci Czech Republic, Inst Mol Genet, Prague 14220, Czech Republic. [Yang, Henry; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore. [Staber, Philipp B.] Med Univ Vienna, Comprehens Canc Ctr Vienna, Div Hematol & Hemostaseol, A-1090 Vienna, Austria. [Levantini, Elena] CNR, Inst Biomed Technol, I-56124 Pisa, Italy. [Lefebvre, Veronique] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Orthopaed & Rheumatol Res Ctr, Cleveland, OH 44195 USA. [Valk, Peter J. M.; Delwel, Ruud] Erasmus Univ, Med Ctr, NL-3015 GE Rotterdam, Netherlands. [Hoogenkamp, Maarten; Bonifer, Constanze] Univ Birmingham, Inst Biomed Res, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England. [Nerlov, Claus] Univ Oxford, Weatherall Inst Mol Med, MRC, Mol Hematol Unit, Oxford OX3 9DS, England. [Cammenga, Jorg] Lund Univ, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden. [Cammenga, Jorg] Lund Univ, Dept Hematol, S-22184 Lund, Sweden. [Saez, Borja; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. RP Ye, M (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02215 USA. EM mye@bidmc.harvard.edu; csidgt@nus.edu.sg RI Alberich Jorda, Meritxell/G-3137-2014 FU National Institutes of Health [HL 56745, CA118316, NIH/NIAMS R01 AR54153]; Harvard Stem Cell Institute [DP-0086-10-00]; Navrat grant from the Czech Ministry of Youth, Health and Sports [LK21307]; Collegio Ghislieri fellowship; Austrian Research Foundation; European Union; Societa' Italiana di Ematologia Sperimentale borsa di studio; Jose Carreras Leukemia Foundation [FIJC F11/01]; FAMRI CIA; Leukaemia Lymphoma Research FX This study was supported by National Institutes of Health grants HL 56745 and CA118316 and Harvard Stem Cell Institute grant DP-0086-10-00. M.A. was supported by Navrat grant LK21307 from the Czech Ministry of Youth, Health and Sports. G.A. was supported by a Collegio Ghislieri fellowship. P.S. was supported by the Austrian Research Foundation and European Union. A.D.R. was supported by the Societa' Italiana di Ematologia Sperimentale borsa di studio "Dr. Tito Bastianello." R.S.W. was supported by the Jose Carreras Leukemia Foundation (FIJC F11/01). E.L. was supported by FAMRI CIA. V.L. was supported by National Institutes of Health grant NIH/NIAMS R01 AR54153. C.B. and M.H. were supported by grants from Leukaemia Lymphoma Research. We thank all members of the Tenen laboratory and Kristian Reckzeh for helpful discussions, the Harvard Stem Cell Institute/Beth Israel Deaconess Medical Center Flow Cytometry Core for their expertise, Angie Tan Lay Keng and Lee Ming Hui from the NUS-Duke genomic facility in Singapore for their expertise in microarray analysis, and Archibald Perkins and Joseph R. Nevins for providing us with experimental reagents. NR 35 TC 34 Z9 34 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD NOV 11 PY 2013 VL 24 IS 5 BP 575 EP 588 DI 10.1016/j.ccr.2013.09.018 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 252LB UT WOS:000327005100006 PM 24183681 ER PT J AU Konry, T Golberg, A Yarmush, M AF Konry, Tania Golberg, Alexander Yarmush, Martin TI Live single cell functional phenotyping in droplet nano-liter reactors SO SCIENTIFIC REPORTS LA English DT Article ID DENDRITIC CELLS; T-CELLS; IMMUNOLOGICAL SYNAPSE; GENETIC NOISE; GM-CSF; SECRETION; CYTOKINE; IL-6; LPS AB While single cell heterogeneity is present in all biological systems, most studies cannot address it due to technical limitations. Here we describe a nano-liter droplet microfluidic-based approach for stimulation and monitoring of surfaceand secreted markers of live single immune dendritic cells (DCs) as well as monitoring the live T cell/ DC interaction. This nano-liter in vivo simulating microenvironment allows delivering various stimuli reagents to each cell and appropriate gas exchanges which are necessary to ensure functionality and viability of encapsulated cells. Labeling bioassay and microsphere sensors were integrated into nano-liter reaction volume of the droplet to monitor live single cell surface markers and secretion analysis in the time-dependent fashion. Thus live cell stimulation, secretion and surface monitoring can be obtained simultaneously in distinct microenvironment, which previously was possible using complicated and multi-step in vitro and in vivo live-cell microscopy, together with immunological studies of the outcome secretion of cellular function. C1 [Konry, Tania] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Golberg, Alexander; Yarmush, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Golberg, Alexander; Yarmush, Martin] Shriners Burn Inst, Boston, MA 02114 USA. RP Konry, T (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, 140 Fenway,Room 156,360 Huntington Ave, Boston, MA 02115 USA. EM tkonry@neu.edu OI Golberg, Alexander/0000-0001-8782-8879 FU MGH Fund for Medical Discovery; NIH/.NCI [R21 [RM11-014]] FX AG acknowledges MGH Fund for Medical Discovery for the ECOR postdoctoral fellowship award. TK acknowledges NIH/.NCI funds R21 [RM11-014] Exceptional Innovative Tools and Technologies for Single Cell Analysis. We acknowledge Nir Hacohen, Arnon Arazi, Raktima Raychowdhury from Broad Institute of MIT and Harvard for cells in this study. NR 27 TC 15 Z9 15 U1 1 U2 36 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 NOV 11 PY 2013 VL 3 AR 3179 DI 10.1038/srep03179 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248VB UT WOS:000326731700006 PM 24212247 ER PT J AU Shih, YCT Ganz, PA Aberle, D Abernethy, A Bekelman, J Brawley, O Goodwin, JS Hu, JC Schrag, D Temel, JS Schnipper, L AF Shih, Ya-Chen Tina Ganz, Patricia A. Aberle, Denise Abernethy, Amy Bekelman, Justin Brawley, Otis Goodwin, James S. Hu, Jim C. Schrag, Deborah Temel, Jennifer S. Schnipper, Lowell TI Delivering High-Quality and Affordable Care Throughout the Cancer Care Continuum SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EARLY PALLIATIVE CARE; CELL LUNG-CANCER; SERVICES TASK-FORCE; OF-LIFE CARE; BREAST-CANCER; RADICAL PROSTATECTOMY; SCREENING MAMMOGRAPHY; INSURANCE STATUS; RADIATION-THERAPY; HEALTH-INSURANCE AB The national cost of cancer care is projected to reach $173 billion by 2020, increasing from $125 billion in 2010. This steep upward cost trajectory has placed enormous an financial burden on patients, their families, and society as a whole and raised major concern about the ability of the health care system to provide and sustain high-quality cancer care. To better understand the cost drivers of cancer care and explore approaches that will mitigate the problem, the National Cancer Policy Forum of the Institute of Medicine held a workshop entitled "Delivering Affordable Cancer Care in the 21st Century" in October 2012. Workshop participants included bioethicists, health economists, primary care physicians, and medical, surgical, and radiation oncologists, from both academic and community settings. All speakers expressed a sense of urgency about the affordability of cancer care resulting from the future demographic trend as well as the high cost of emerging cancer therapies and rapid diffusion of new technologies in the absence to evidence indicating improved outcomes for patients. This article is our summary of presentations at the workshop that highlighted the overuse and underuse of screening, treatments, and technologies throughout the cancer care continuum in oncology practice in the United States. (C) 2013 by American Society of Clinical Oncology C1 [Shih, Ya-Chen Tina] Univ Chicago, Chicago, IL 60637 USA. [Ganz, Patricia A.; Aberle, Denise; Hu, Jim C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Abernethy, Amy] Duke Univ, Durham, NC USA. [Bekelman, Justin] Univ Penn, Philadelphia, PA 19104 USA. [Brawley, Otis] Amer Canc Soc, Atlanta, GA 30329 USA. [Goodwin, James S.] Univ Texas, Galveston, TX USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA USA. [Temel, Jennifer S.; Schnipper, Lowell] Harvard Univ, Sch Med, Boston, MA USA. RP Shih, YCT (reprint author), Univ Chicago, Dept Med, Sect Hosp Med, 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM tinashih@uchicago.edu OI Aberle, Denise/0000-0002-8858-3401 FU National Cancer Institute [K07CA16316] FX Supported in part by National Cancer Institute Grant No. K07CA16316 (J.B.). NR 57 TC 29 Z9 30 U1 2 U2 6 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 NOV 10 PY 2013 VL 31 IS 32 BP 4151 EP + DI 10.1200/JCO.2013.51.0651 PG 8 WC Oncology SC Oncology GA 301LG UT WOS:000330533200019 PM 24127450 ER PT J AU Lawson, KA Teteak, CJ Zou, JH Hacquebord, J Ghatan, A Zielinska-Kwiatkowska, A Fernandes, RJ Chansky, HA Yang, L AF Lawson, Kevin A. Teteak, Colin J. Zou, Junhui Hacquebord, Jacques Ghatan, Andrew Zielinska-Kwiatkowska, Anna Fernandes, Russell J. Chansky, Howard A. Yang, Liu TI Mesenchyme-specific Knockout of ESET Histone Methyltransferase Causes Ectopic Hypertrophy and Terminal Differentiation of Articular Chondrocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Arthritis; Articular cartilage; Cartilage biology; Chondrocytes; Differentiation; Epigenetics; Gene Knockout; Histone methylation ID CELL NUCLEAR ANTIGEN; ALKALINE-PHOSPHATASE; OSTEOARTHRITIC CARTILAGE; DNA FRAGMENTATION; GROWTH-PLATE; MOUSE LIMB; EXPRESSION; JOINT; APOPTOSIS; GENE AB The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis. C1 [Lawson, Kevin A.; Teteak, Colin J.; Zou, Junhui; Hacquebord, Jacques; Ghatan, Andrew; Zielinska-Kwiatkowska, Anna; Fernandes, Russell J.; Chansky, Howard A.; Yang, Liu] Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98108 USA. [Chansky, Howard A.; Yang, Liu] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Program, Seattle, WA 98108 USA. RP Yang, L (reprint author), Univ Washington, Dept Orthoped & Sports Med, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. EM lyang@u.washington.edu FU National Institutes of Health [RO1 AR051455, RO1 AR057025]; Merit Review Award from the United States Department of Veterans Affairs, Office of Research and Development Biomedical Laboratory Research Program FX This work was supported in part by National Institutes of Health Grant RO1 AR051455 (to L. Y.). This work was also supported by a Merit Review Award from the United States Department of Veterans Affairs, Office of Research and Development Biomedical Laboratory Research Program (to H. A. C.).; Supported by National Institutes of Health Grant RO1 AR057025. NR 28 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 2013 VL 288 IS 45 BP 32119 EP 32125 DI 10.1074/jbc.M113.473827 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 275MQ UT WOS:000328681700002 PM 24056368 ER PT J AU Yu, YM Schurpf, T Springer, TA AF Yu, Yamei Schuerpf, Thomas Springer, Timothy A. TI How Natalizumab Binds and Antagonizes alpha(4) Integrins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Adhesion; Cell Surface; Crystal Structure; Immunology; Integrins; Structure ID CELL-ADHESION MOLECULE-1; RELAPSING MULTIPLE-SCLEROSIS; AMINO-ACID-RESIDUES; LIGAND-BINDING; ANGSTROM RESOLUTION; COST-EFFECTIVENESS; CRYSTAL-STRUCTURE; AFFINITY; RECEPTOR; VCAM-1 AB Natalizumab antibody to (4)-integrins is used in therapy of multiple sclerosis and Crohn's disease. A crystal structure of the Fab bound to an (4) integrin -propeller and thigh domain fragment shows that natalizumab recognizes human-mouse differences on the circumference of the -propeller domain. The epitope is adjacent to but outside of a ligand-binding groove formed at the interface with the -subunit I domain and shows no difference in structure when bound to Fab. Competition between Fab and the ligand vascular cell adhesion molecule (VCAM) for binding to cell surface (41) shows noncompetitive antagonism. In agreement, VCAM docking models suggest that binding of domain 1 of VCAM to (4)-integrins is unimpeded by the Fab, and that bound Fab requires a change in orientation between domains 1 and 2 of VCAM for binding to (41). Mapping of species-specific differences onto (41) and (47) shows that their ligand-binding sites are highly conserved. Skewing away from these conserved regions of the epitopes recognized by current therapeutic function-blocking antibodies has resulted in previously unanticipated mechanisms of action. C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu FU National Institutes of Health [HL-103526] FX This work was supported, in whole or in part, by National Institutes of Health inhibitors than was originally envisioned. Grant HL-103526. NR 51 TC 13 Z9 13 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 2013 VL 288 IS 45 BP 32314 EP 32325 DI 10.1074/jbc.M113.501668 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 275MQ UT WOS:000328681700018 PM 24047894 ER PT J AU Yang, P Huang, X Shen, J Wang, CS Dang, XQ Mankin, H Duan, ZF Wang, KZ AF Yang, Pei Huang, Xin Shen, Jacson Wang, Chunsheng Dang, Xiaoqian Mankin, Henry Duan, Zhenfeng Wang, Kunzheng TI Development of a new pre-vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nano-hydroxyapatide-polyamide 66 scaffold SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Adipose-derived stem cells; Tissue engineering; Angiogenesis; Scaffolds; Prefabrication ID HUMAN ADIPOSE-TISSUE; ENDOTHELIAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; IN-VIVO; BONE-GRAFTS; PHOSPHATE CERAMICS; INTERNAL STRUCTURE; SKIN FLAPS; ANGIOGENESIS; PREFABRICATION AB Background: Development of a pre-vascularized tissue-engineered construct with intrinsic vascular system for cell growth and tissue formation still faces many difficulties due to the complexity of the vascular network of natural bone tissue. The present study was to design and form a new vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nHA-PA 66 scaffold. Methods: rADSCs were pre-differentiated to endothelial cells (rADSCs-Endo) and then incorporated in nHA-PA 66 scaffolds in vitro. Subsequently, in vivo experiments were carried out according to the following groups: Group A (rADSCs-Endo/nHA-PA 66 scaffold with arteriovenous vascular bundle), Group B (rADSCs/nHA-PA 66 scaffold with arteriovenous vascular bundle); Group C (nHA-PA66 scaffold with arteriovenous vascular bundle), Group D (nHA-PA 66 scaffold only). The vessel density and vessel diameter were measured based on histological and immunohistochemical evaluation, furthermore, the VEGF-C, FGF-2 and BMP-2 protein expressions were also evaluated by western blot analysis. Results: The results of in vivo experiments showed that the vessel density and vessel diameter in group A were significantly higher than the other three groups. Between Group B and C, no statistical difference was observed at each time point. In accordance with the results, there were dramatically higher expressions of VEGF-C and FGF-2 protein in Group A than that of Group B, C and D at 2 or 4 weeks. Statistical differences were not observed in VEGF-C and FGF-2 expression between Group B and C. BMP-2 was not expressed in any group at each time point. Conclusions: Compared with muscular wrapping method, arteriovenous vascular bundle implantation could promote vascularization of the scaffold; and the angiogenesis of the scaffold was significantly accelerated when pre-differentiated rADSCs (endothelial differentiation) were added. These positive results implicate the combination of pre-differentiated rADSCs (endothelial differentiation) and arteriovenous vascular bundle may achieve rapidly angiogenesis of biomaterial scaffold. C1 [Yang, Pei; Wang, Chunsheng; Dang, Xiaoqian; Wang, Kunzheng] Xi An Jiao Tong Univ, Dept Orthopaed, Affiliated Hosp 2, Coll Med, Xian 710004, Shaanxi, Peoples R China. [Huang, Xin] Xi An Jiao Tong Univ, Key Lab Environm & Genes Related Dis, Affiliated Hosp 1, Dept Cardiol,Med Coll,Ion Channel Dis Lab,Educ Mi, Xian 710061, Shaanxi, Peoples R China. [Shen, Jacson] Wellesley Coll, Dept Biol Chem, Wellesley, MA 02481 USA. [Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Mankin, Henry; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA USA. [Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Wang, KZ (reprint author), Xi An Jiao Tong Univ, Dept Orthopaed, Affiliated Hosp 2, Coll Med, 157 Xiwu Rd, Xian 710004, Shaanxi, Peoples R China. EM kunzhengwang@126.com FU National Natural Science Foundation of China [81000809]; Natural Science Foundation of Shaanxi Province [2010JQ4009] FX The study was supported by the National Natural Science Foundation of China (No. 81000809) and Natural Science Foundation of Shaanxi Province (2010JQ4009). We thank Prof. Zongchang He of the Foreign Language Department Xi'an Jiaotong University for the help in preparing the manuscript. NR 59 TC 8 Z9 9 U1 2 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD NOV 8 PY 2013 VL 14 AR 318 DI 10.1186/1471-2474-14-318 PG 14 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 266WJ UT WOS:000328054300001 PM 24209783 ER PT J AU Berger, AH Chen, M Morotti, A Janas, JA Niki, M Bronson, RT Taylor, BS Ladanyi, M Van Aelst, L Politi, K Varmus, HE Pandolfi, PP AF Berger, Alice H. Chen, Ming Morotti, Alessandro Janas, Justyna A. Niki, Masaru Bronson, Roderick T. Taylor, Barry S. Ladanyi, Marc Van Aelst, Linda Politi, Katerina Varmus, Harold E. Pandolfi, Pier Paolo TI DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; RECEPTOR GENE-MUTATIONS; PTB DOMAIN; GEFITINIB; CANCER; RECRUITMENT; RESISTANCE; ERLOTINIB; RAS; ATTENUATION AB Somatic mutations in the EGFR proto-oncogene occur in similar to 15% of human lung adenocarcinomas and the importance of EGFR mutations for the initiation and maintenance of lung cancer is well established from mouse models and cancer therapy trials in human lung cancer patients. Recently, we identified DOK2 as a lung adenocarcinoma tumor suppressor gene. Here we show that genomic loss of DOK2 is associated with EGFR mutations in human lung adenocarcinoma, and we hypothesized that loss of DOK2 might therefore cooperate with EGFR mutations to promote lung tumorigenesis. We tested this hypothesis using genetically engineered mouse models and find that loss of Dok2 in the mouse accelerates lung tumorigenesis initiated by oncogenic EGFR, but not that initiated by mutated Kras. Moreover, we find that DOK2 participates in a negative feedback loop that opposes mutated EGFR; EGFR mutation leads to recruitment of DOK2 to EGFR and DOK2-mediated inhibition of downstream activation of RAS. These data identify DOK2 as a tumor suppressor in EGFR-mutant lung adenocarcinoma. C1 [Berger, Alice H.; Chen, Ming; Morotti, Alessandro; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Dept Med,Med Sch,Canc Genet Program, Boston, MA 02215 USA. [Berger, Alice H.; Chen, Ming; Morotti, Alessandro; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Dept Pathol,Med Sch,Canc Genet Program, Boston, MA 02215 USA. [Politi, Katerina; Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Janas, Justyna A.; Van Aelst, Linda] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Niki, Masaru] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Bronson, Roderick T.] Dana Farber Harvard Canc Ctr, Rodent Histopathol Core, Boston, MA USA. [Taylor, Barry S.] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA. [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Dept Med,Med Sch,Canc Genet Program, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu OI Morotti, Alessandro/0000-0002-8407-2903 FU National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA-129243, CA-142787, CA-120247, CA-131488] FX This work was supported by National Cancer Institute (NCI)/National Institutes of Health (NIH) grants CA-129243 (to ML), CA-142787 (to PPP), CA-120247 (to HV and KP), and CA-131488 (to KP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 1 Z9 1 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 NOV 8 PY 2013 VL 8 IS 11 AR e79526 DI 10.1371/journal.pone.0079526 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255CG UT WOS:000327216200070 PM 24255704 ER PT J AU Guo, LQ Chen, HX Li, YS Zhou, QX Sui, Y AF Guo, Liqiong Chen, Hongxiang Li, Yongsheng Zhou, Qixing Sui, Yang TI An Aquaporin 3-Notch1 Axis in Keratinocyte Differentiation and Inflammation SO PLOS ONE LA English DT Article ID HYDROGEN-PEROXIDE UPTAKE; NOTCH SIGNALING PATHWAY; CELL-MIGRATION; GENE DISRUPTION; WATER CHANNELS; RETINOIC ACID; HUMAN SKIN; EPIDERMAL-KERATINOCYTES; MICE; EXPRESSION AB Aquaporin 3 (AQP3) is an aquaglyceroporin which transports water, glycerol and small solutes across the plasma membrane. Its functions are not limited to fluid transport but also involve the regulation of cell proliferation, migration, skin hydration, wound healing and tumorigenesis. While AQP3 has been reported to play an important role in keratinocyte proliferation, its role in differentiation remains controversial. Our study demonstrated that the expression of AQP3 was regulated during differentiation and that it participated in keratinocyte differentiation control. We further revealed that AQP3 was a transcriptional target of Notch signaling, a critical pathway regulating keratinocyte differentiation and tumor suppression, and it regulated differentiation through a reciprocal negative feedback loop with Notch1. When the expression level of AQP3 was elevated, impaired barrier integrity and increased pro-inflammatory cytokine production ensued, mimicking the pathological conditions in Notch deficient mice and in atopic dermatitis. Dysregulation of AQP3 and Notch receptors has been reported in several skin diseases, including skin cancer. Our discovery of the novel AQP3-Notch1 axis may provide insight into epidermal homeostasis control and possible translational applications, including its potential use as a biomarker for molecular diagnosis in environmental studies. C1 [Guo, Liqiong; Zhou, Qixing] Nankai Univ, Key Lab Pollut Proc & Environm Criteria, Coll Environm Sci & Engn, Tianjin 300071, Peoples R China. [Chen, Hongxiang] Huazhong Univ Sci & Technol, Dept Dermatol, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China. [Chen, Hongxiang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA USA. [Li, Yongsheng] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Harvard Inst Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Li, Yongsheng] Harvard Univ, Sch Med, Boston, MA USA. [Sui, Yang] Wuhan Univ, Dept Bioinformat, Int Sch Software, Wuhan 430072, Hubei, Peoples R China. RP Zhou, QX (reprint author), Nankai Univ, Key Lab Pollut Proc & Environm Criteria, Coll Environm Sci & Engn, Tianjin 300071, Peoples R China. EM zhouqx@nankai.edu.cn; suiyang@iss.whu.edu.cn FU China Ministry of Science and Technology [2011CB503802]; National Natural Science Foundation of China [21037002, 81171495, 81271765] FX This work was supported by grants from China Ministry of Science and Technology (2011CB503802 to QXZ), National Natural Science Foundation of China as a key project (grant No. 21037002 to QXZ) and National Natural Science Foundation of China Grants (grant No. 81171495 and 81271765 to HXC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 8 Z9 9 U1 2 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 NOV 8 PY 2013 VL 8 IS 11 AR e80179 DI 10.1371/journal.pone.0080179 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255CG UT WOS:000327216200108 PM 24260356 ER PT J AU Tinzl, M Chen, BS Chen, SY Semenas, J Abrahamsson, PA Dizeyi, N AF Tinzl, Martina Chen, Binshen Chen, Shao-Yong Semenas, Julius Abrahamsson, Per-Anders Dizeyi, Nishtman TI Interaction between c-jun and Androgen Receptor Determines the Outcome of Taxane Therapy in Castration Resistant Prostate Cancer SO PLOS ONE LA English DT Article ID TRANSCRIPTION FACTORS; CELL-PROLIFERATION; CYTOTOXIC INSULT; DOCETAXEL; MITOXANTRONE; PREDNISONE; TRANSFORMATION; EXPRESSION; APOPTOSIS; COMPLEX AB Taxane based chemotherapy is the standard of care treatment in castration resistant prostate cancer (CRPC). There is convincing evidence that taxane therapy affects androgen receptor (AR) but the exact mechanisms have to be further elucidated. Our studies identified c-jun as a crucial key player which interacts with AR and thus determines the outcome of the taxane therapy given. Docetaxel (Doc) and paclitaxel (Pac) agents showed different effects on LNCaP and LNb4 evidenced by alteration in the protein and mRNA levels of c-jun, AR and PSA. Docetaxel-induced phophorylation of c-jun occurred before JNK phosphorylation which suggests that c-jun phosphorylation is independent of JNK pathways in prostate cancer cells. A xenograft study showed that mice treated with Pac and bicalutamide showed worse outcome supporting our hypothesis that upregulation of c-jun might act as a potent antiapoptotic factor. We observed in our in vitro studies an inverse regulation of PSA- and AR-mRNA levels in Doc treated LNb4 cells. This was also seen for kallikrein 2 (KLK 2) which followed the same pattern. Given the fact that response to taxane therapy is measured by PSA decrease we have to consider that this might not reflect the true activity of AR in CRPC patients. C1 [Tinzl, Martina; Chen, Binshen; Abrahamsson, Per-Anders; Dizeyi, Nishtman] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Chen, Shao-Yong] Harvard Univ, Sch Med, BIDMC, Dept Hematol Oncol, Boston, MA USA. [Semenas, Julius] Lund Univ, Dept Lab Med, Malmo, Sweden. RP Dizeyi, N (reprint author), Lund Univ, Dept Clin Sci, Malmo, Sweden. EM nishtman.dizeyi@med.lu.se FU Sandbergs private funding; Percy Falk Foundation; Malmo cancer funding FX This project is funded by Sandbergs private funding, Percy Falk Foundation and Malmo cancer funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 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 NOV 8 PY 2013 VL 8 IS 11 AR e79573 DI 10.1371/journal.pone.0079573 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255CG UT WOS:000327216200076 PM 24260253 ER PT J AU Doulatov, S Daley, GQ AF Doulatov, Sergei Daley, George Q. TI A Stem Cell Perspective on Cellular Engineering SO SCIENCE LA English DT Editorial Material ID HEMATOPOIETIC PROGENITORS; DIFFERENTIATION CULTURES; FIBROBLASTS C1 [Doulatov, Sergei] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Broad Inst, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Doulatov, S (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 12 TC 14 Z9 14 U1 0 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 8 PY 2013 VL 342 IS 6159 BP 700 EP 702 DI 10.1126/science.1238363 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247UK UT WOS:000326647600028 PM 24202165 ER PT J AU Silberstein, LE Lin, CP AF Silberstein, Leslie E. Lin, Charles P. TI A New Image of the Hematopoietic Stem Cell Vascular Niche SO CELL STEM CELL LA English DT Editorial Material ID BONE-MARROW AB The microenvironment within the bone marrow that maintains hematopoietic stem cell (HSC) quiescence is the subject of intense study. In a recent Nature paper, Kunisaki et al. combine imaging techniques and computational modeling to define a novel arteriolar niche for quiescent HSCs within the bone marrow. C1 [Silberstein, Leslie E.] Boston Childrens Hosp, Dept Lab Med, Div Transfus Med, Boston, MA 02115 USA. [Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lin, CP (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM charles_lin@hms.harvard.edu FU NHLBI NIH HHS [P01 HL095489] NR 9 TC 6 Z9 6 U1 0 U2 4 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 NOV 7 PY 2013 VL 13 IS 5 BP 514 EP 516 DI 10.1016/j.stem.2013.10.012 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VX UT WOS:000329571500005 PM 24209758 ER PT J AU Cortese, S Comencini, E Vincenzi, B Speranza, M Angriman, M AF Cortese, Samuele Comencini, Erika Vincenzi, Brenda Speranza, Mario Angriman, Marco TI Attention-deficit/hyperactivity disorder and impairment in executive functions: a barrier to weight loss in individuals with obesity? SO BMC PSYCHIATRY LA English DT Article DE ADHD; Executive functions; Obesity; Treatment resistance ID DEFICIT HYPERACTIVITY DISORDER; CHILDREN; ADHD; METAANALYSIS; ASSOCIATION; ADOLESCENTS; PREVALENCE; SYMPTOMS; ADULTS; COMORBIDITY AB Background: An increasing body of research points to a significant association of obesity to Attention-Deficit/ Hyperactivity Disorder (ADHD) and deficits in executive functions. There is also preliminary evidence suggesting that children with ADHD may be at risk of obesity in adulthood. Discussion: In this article, we discuss the evidence showing that ADHD and/or deficits in executive functions are a barrier to a successful weight control in individuals enrolled in weight loss programs. Impairing symptoms of ADHD or deficits in executive functions may foster dysregulated eating behaviors, such as binge eating, emotionally-induced eating or eating in the absence of hunger, which, in turn, may contribute to unsuccessful weight loss. ADHD-related behaviors or neurocognitive impairment may also hamper a regular and structured physical activity. There is initial research showing that treatment of comorbid ADHD and executive functions training significantly improve the outcome of obesity in individuals with comorbid ADHD or impairment in executive functions. Summary: Preliminary evidence suggests that comorbid ADHD and deficits in executive functions are a barrier to a successful weight loss in individuals involved in obesity treatment programs. If further methodologically sound evidence confirms this relationship, screening and effectively managing comorbid ADHD and/or executive functions deficits in individuals with obesity might have the potential to reduce not only the burden of ADHD but also the obesity epidemics. C1 [Cortese, Samuele; Comencini, Erika] Univ Verona, Child Neuropsychiat Unit, GB Rossi Hosp, Dept Life Sci & Reprod, I-37100 Verona, Italy. [Cortese, Samuele] NYU Langone Med Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, Ctr Child Study, New York, NY USA. [Vincenzi, Brenda] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Speranza, Mario] Univ Versailles St Quentin En Yvelines, EA4047, Versailles, France. [Speranza, Mario] Versailles Gen Hosp, Le Chesnay, France. [Angriman, Marco] Cent Hosp Bolzano, Child Neurol & Neurorehabil Unit, Dept Pediat, Bolzano, Italy. [Cortese, Samuele] Osped GB Rossi, Unita Autonoma Neuropsichiatria Infantile, I-37134 Verona, Italy. RP Cortese, S (reprint author), Univ Verona, Child Neuropsychiat Unit, GB Rossi Hosp, Dept Life Sci & Reprod, I-37100 Verona, Italy. EM samuele.cortese@gmail.com FU European Commission [PIOF-253103] FX Dr. Cortese was supported by a "Marie Curie" grant for Career Development, International Outgoing Fellowship, PIOF-253103 from the European Commission. NR 47 TC 11 Z9 11 U1 2 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD NOV 7 PY 2013 VL 13 AR 286 DI 10.1186/1471-244X-13-286 PG 7 WC Psychiatry SC Psychiatry GA 281XK UT WOS:000329134100003 PM 24200119 ER PT J AU Swanson, DM Blacker, D AlChawa, T Ludwig, KU Mangold, E Lange, C AF Swanson, David M. Blacker, Deborah AlChawa, Taofik Ludwig, Kerstin U. Mangold, Elisabeth Lange, Christoph TI Properties of permutation-based gene tests and controlling type 1 error using a summary statistic based gene test SO BMC GENETICS LA English DT Article DE Dimension reduction; Eigenvector; Gene-based testing; Permutation tests ID ASSOCIATION TEST; VARIABLES AB Background: The advent of genome-wide association studies has led to many novel disease-SNP associations, opening the door to focused study on their biological underpinnings. Because of the importance of analyzing these associations, numerous statistical methods have been devoted to them. However, fewer methods have attempted to associate entire genes or genomic regions with outcomes, which is potentially more useful knowledge from a biological perspective and those methods currently implemented are often permutation-based. Results: One property of some permutation-based tests is that their power varies as a function of whether significant markers are in regions of linkage disequilibrium (LD) or not, which we show from a theoretical perspective. We therefore develop two methods for quantifying the degree of association between a genomic region and outcome, both of whose power does not vary as a function of LD structure. One method uses dimension reduction to "filter" redundant information when significant LD exists in the region, while the other, called the summary-statistic test, controls for LD by scaling marker Z-statistics using knowledge of the correlation matrix of markers. An advantage of this latter test is that it does not require the original data, but only their Z-statistics from univariate regressions and an estimate of the correlation structure of markers, and we show how to modify the test to protect the type 1 error rate when the correlation structure of markers is misspecified. We apply these methods to sequence data of oral cleft and compare our results to previously proposed gene tests, in particular permutation-based ones. We evaluate the versatility of the modification of the summary-statistic test since the specification of correlation structure between markers can be inaccurate. Conclusion: We find a significant association in the sequence data between the 8q24 region and oral cleft using our dimension reduction approach and a borderline significant association using the summary-statistic based approach. We also implement the summary-statistic test using Z-statistics from an already-published GWAS of Chronic Obstructive Pulmonary Disorder (COPD) and correlation structure obtained from HapMap. We experiment with the modification of this test because the correlation structure is assumed imperfectly known. C1 [Swanson, David M.; Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA. [AlChawa, Taofik; Ludwig, Kerstin U.; Mangold, Elisabeth] Univ Bonn, Inst Human Genet, Bonn, Germany. [Ludwig, Kerstin U.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Lange, Christoph] Univ Bonn, German Ctr Neurodegenerat Dis, Inst Genom Math, Bonn, Germany. RP Swanson, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM dms866@mail.harvard.edu FU National Institutes of Health [T32 NS048005] FX This work was supported by the National Institutes of Health [Training Grant T32 NS048005]. NR 16 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD NOV 7 PY 2013 VL 14 AR 108 DI 10.1186/1471-2156-14-108 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 272UA UT WOS:000328485500001 PM 24199751 ER PT J AU Rozenberg, JM Bhattacharya, P Chatterjee, R Glass, K Vinson, C AF Rozenberg, Julian M. Bhattacharya, Paramita Chatterjee, Raghunath Glass, Kimberly Vinson, Charles TI Combinatorial Recruitment of CREB, C/EBP beta and c-Jun Determines Activation of Promoters upon Keratinocyte Differentiation SO PLOS ONE LA English DT Article ID ELEMENT-BINDING PROTEIN; INVOLUCRIN GENE PROMOTER; GENOME-WIDE ANALYSIS; TRANSCRIPTION FACTORS; IN-VITRO; CHROMATIN ACCESSIBILITY; MEDIATED TRANSCRIPTION; SKIN TUMORIGENESIS; CELL-SURVIVAL; ONCOGENIC RAS AB Background: Transcription factors CREB, C/EBP beta and Jun regulate genes involved in keratinocyte proliferation and differentiation. We questioned if specific combinations of CREB, C/EBP beta and c-Jun bound to promoters correlate with RNA polymerase II binding, mRNA transcript levels and methylation of promoters in proliferating and differentiating keratinocytes. Results: Induction of mRNA and RNA polymerase II by differentiation is highest when promoters are bound by C/EBP beta alone, C/EBP beta together with c-Jun, or by CREB, C/EBP beta and c-Jun, although in this case CREB binds with low affinity. In contrast, RNA polymerase II binding and mRNA levels change the least upon differentiation when promoters are bound by CREB either alone or in combination with C/EBP beta or c-Jun. Notably, promoters bound by CREB have relatively high levels of RNA polymerase II binding irrespective of differentiation. Inhibition of C/EBP beta or c-Jun preferentially represses mRNA when gene promoters are bound by corresponding transcription factors and not CREB. Methylated promoters have relatively low CREB binding and, accordingly, those which are bound by C/EBP beta are induced by differentiation irrespective of CREB. Composite "Half and Half'' consensus motifs and co localizing consensus DNA binding motifs are overrepresented in promoters bound by the combination of corresponding transcription factors. Conclusion: Correlational and functional data describes combinatorial mechanisms regulating the activation of promoters. Colocalization of C/EBP beta and c-Jun on promoters without strong CREB binding determines high probability of activation upon keratinocyte differentiation. C1 [Rozenberg, Julian M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Bhattacharya, Paramita] Saha Inst Nucl Phys, Crystallog & Mol Biol Div, Kolkata, W Bengal, India. [Chatterjee, Raghunath] Indian Stat Inst, Div Biol Sci, Human Genet Unit, Kolkata, India. [Glass, Kimberly] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Vinson, Charles] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, Bethesda, MD 20892 USA. EM vinsonc@dc37a.nci.nih.gov FU National Institutes of Health, Bethesda, Maryland USA; NIH FX This study was performed and funded by the National Institutes of Health, Bethesda, Maryland USA. The source of funding was intramural budget of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 5 Z9 5 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 NOV 7 PY 2013 VL 8 IS 11 AR e78179 DI 10.1371/journal.pone.0078179 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 254KD UT WOS:000327162900009 PM 24244291 ER PT J AU Hildick-Smith, GJ Cooney, JD Garone, C Kremer, LS Haack, TB Thon, JN Miyata, N Lieber, DS Calvo, SE Akman, HO Yien, YY Huston, NC Branco, DS Shah, DI Freedman, ML Koehler, CM Italiano, JE Merkenschlager, A Beblo, S Strom, TM Meitinger, T Freisinger, P Donati, MA Prokisch, H Mootha, VK DiMauro, S Paw, BH AF Hildick-Smith, Gordon J. Cooney, Jeffrey D. Garone, Caterina Kremer, Laura S. Haack, Tobias B. Thon, Jonathan N. Miyata, Non Lieber, Daniel S. Calvo, Sarah E. Akman, H. Orhan Yien, Yvette Y. Huston, Nicholas C. Branco, Diana S. Shah, Dhvanit I. Freedman, Matthew L. Koehler, Carla M. Italiano, Joseph E., Jr. Merkenschlager, Andreas Beblo, Skadi Strom, Tim M. Meitinger, Thomas Freisinger, Peter Donati, M. Alice Prokisch, Holger Mootha, Vamsi K. DiMauro, Salvatore Paw, Barry H. TI Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID WHOLE-GENOME; DISORDERS; MUTATIONS; DISEASE; PROTEIN; GENE; IDENTIFICATION; DEFICIENCY; CONSORTIUM; COBALAMIN AB We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated-the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia. C1 [Hildick-Smith, Gordon J.; Cooney, Jeffrey D.; Thon, Jonathan N.; Yien, Yvette Y.; Huston, Nicholas C.; Branco, Diana S.; Shah, Dhvanit I.; Italiano, Joseph E., Jr.; Paw, Barry H.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Hildick-Smith, Gordon J.; Cooney, Jeffrey D.; Thon, Jonathan N.; Yien, Yvette Y.; Huston, Nicholas C.; Branco, Diana S.; Shah, Dhvanit I.; Freedman, Matthew L.; Italiano, Joseph E., Jr.; Paw, Barry H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Garone, Caterina; Akman, H. Orhan; DiMauro, Salvatore] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Kremer, Laura S.; Haack, Tobias B.; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80333 Munich, Germany. [Kremer, Laura S.; Haack, Tobias B.; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Miyata, Non; Koehler, Carla M.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Merkenschlager, Andreas] Univ Leipzig, Univ Hosp Children & Adolescents, Dept Neuropediat, D-04103 Leipzig, Germany. [Beblo, Skadi] Univ Leipzig, Univ Hosp Children & Adolescents, Dept Inborn Metab Dis, D-04103 Leipzig, Germany. [Freisinger, Peter] Kinderklin Klinikum Reutlingen, Dept Pediat, D-72764 Reutlingen, Germany. [Donati, M. Alice] Meyer Children Hosp, Unit Metab & Muscular Dis, I-50132 Florence, Italy. [Paw, Barry H.] Boston Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Paw, Barry H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Paw, BH (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu RI Prokisch, Holger/N-8964-2013; Meitinger, Thomas/O-1318-2015; OI Garone, Caterina/0000-0003-4928-1037 FU American Heart Association; American Society of Hematology; Cooley's Anemia Foundation; March of Dimes Foundation [6-FY09-289]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; GENOMIT; Marriott Mitochondrial Disorders Clinical Research Fund; MEET; MitoNET; National Institutes of Health [K01 DK085217, T32 HL007574, F32 DK098866, R01 GM61721, R01 GM097136, P01 HD032062, R01 DK070838, P01 HL032262] FX We are indebted to the individuals described in our study and families for their participation. We thank members of our respective labs (Caiyong Chen and Jacky Chung) and Samuel E. Lux IV, H. Franklin Bunn, David G. Nathan, and Ellis J. Neufeld for critical feedback on the manuscript. We thank Leonard Zon for the Tg(globin-LCR:eGFP) transgenic line, Karin Hoffmeister for the use of the fluorescence-activated cell sorting machine, Caiyong Chen for protein technical advice, Ramiro Massol for confocal microscopy imaging, and Christian Lawrence and his team for the zebrafish husbandry. Fluorescence confocal microscopy was performed at the Harvard Digestive Disease Center Imaging Facility (Boston Children's Hospital). This work was supported by grants from the American Heart Association (J.D.C.), the American Society of Hematology (G.J.H.-S., J.D.C.), Cooley's Anemia Foundation (D.I.S.), the March of Dimes Foundation (6-FY09-289, B.H.P.), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (D.S.B.), GENOMIT (H.P.), the Marriott Mitochondrial Disorders Clinical Research Fund (V.K.M., S.D.), MEET (H.P.), MitoNET (H.P.), and the National Institutes of Health (K01 DK085217, D.I.S.; T32 HL007574 and F32 DK098866, Y.Y.Y.; R01 GM61721, C.M.K.; R01 GM097136, V.K.M.; P01 HD032062, S.D.M.; R01 DK070838 and P01 HL032262, B.H.P.). NR 43 TC 6 Z9 8 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 7 PY 2013 VL 93 IS 5 BP 906 EP 914 DI 10.1016/j.ajhg.2013.09.011 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 252HU UT WOS:000326996600011 PM 24119684 ER PT J AU Wissemann, WT Hill-Burns, EM Zabetian, CP Factor, SA Patsopouos, N Hoglund, B Holcomb, C Donahue, RJ Thomson, G Erlich, H Payami, H AF Wissemann, William T. Hill-Burns, Erin M. Zabetian, Cyrus P. Factor, Stewart A. Patsopouos, Nikolaos Hoglund, Bryan Holcomb, Cherie Donahue, Ryan J. Thomson, Glenys Erlich, Henry Payami, Haydeh TI Association of Parkinson Disease with Structural and Regulatory Variants in the HLA Region SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID WHOLE-GENOME ASSOCIATION; GENE-EXPRESSION; C EXPRESSION; HIV CONTROL; POPULATION; SUSCEPTIBILITY; ALLELES; LOCUS; SNP AB Historically, association of disease with the major histocompatibility complex (HLA) genes has been tested with HLA alleles that encode antigen-binding affinity. The association with Parkinson disease (PD), however, was discovered with noncoding SNPs in a genome-wide association study (GWAS). We show here that several HLA-region SNPs that have since been associated with PD form two blocks tagged by rs3129882 (p = 9 x 10(-11)) and by rs9268515 and/or rs2395163 (p = 3 x 10-11). We investigated whether these SNP-associations were driven by HLA-alleles at adjacent loci. We imputed class I and class II HLA-alleles for 2000 PD cases and 1986 controls from the NeuroGenetics Research Consortium GWAS and sequenced a subset of 194 cases and 204 controls. We were therefore able to assess accuracy of two imputation algorithms against next-generation-sequencing while taking advantage of the larger imputed data sets for disease study. Additionally, we imputed HLA alleles for 843 cases and 856 controls from another GWAS for replication. PD risk was positively associated with the B*07:02_C*07:02 DRB5*01_DRB1*15:01_DQA1*01:02_DQB1*06:02 haplotype and negatively associated with the C*03:04, DRB1*04:04 and DQA1*03:01 alleles. The risk haplotype and DQA1*03:01 lost significance when conditioned on the SNPs, but C*03:04 (OR = 0.72, p = 8 x 10(-6)) and DRB1*04:04 (OR = 0.65, p = 4 x 10(-5)) remained significant. Similarly, rs3129882 and the closely linked rs9268515 and rs2395163 remained significant irrespective of HLA alleles. rs3129882 and rs2395163 are expression quantitative trait loci (eQTLs) for HLA-DR and HLA-DQ (9 x 10(-5) >= P-eQTL, 2 x 10(-79)), suggesting that HLA gene expression might influence PD. Our data suggest that PD is associated with both structural and regulatory elements in HLA. Furthermore, our study demonstrates that noncoding SNPs in the HLA region can be associated with disease irrespective of HLA alleles, and that observed associations with HLA alleles can sometimes be secondary to a noncoding variant. C1 [Wissemann, William T.; Hill-Burns, Erin M.; Donahue, Ryan J.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12208 USA. [Zabetian, Cyrus P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Patsopouos, Nikolaos] Brigham & Womens Hosp, Inst Neurosci, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Patsopouos, Nikolaos] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Patsopouos, Nikolaos] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Hoglund, Bryan; Holcomb, Cherie] Roche Mol Syst, Dept Human Genet, Pleasanton, CA 94588 USA. [Thomson, Glenys] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Erlich, Henry] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Payami, Haydeh] SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12208 USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306 FU National Institute of Neurological Disorders and Stroke (NINDS) [R01NS36960]; Global Genetic Consortium Grant from the Michael J. Fox Foundation for Parkinson's Disease Research; Department of Veterans Affairs [1I01BX000531]; National Institutes of Aging [P30AG08017]; Office of Research Development; Clinical Sciences Research & Development Service; Department of Veteran Affairs; Close to the Cure Foundation; National Institutes of Health [HHSN272201200028C]; NINDS FX We thank the research participants. We thank Tatiana Foroud and Richard Myers for making their datasets available for replication. The project was supported by award number R01NS36960 from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by a Global Genetic Consortium Grant from the Michael J. Fox Foundation for Parkinson's Disease Research, a Merit Review Award from the Department of Veterans Affairs (1I01BX000531), the National Institutes of Aging (P30AG08017), the Office of Research & Development, the Clinical Sciences Research & Development Service, the Department of Veteran Affairs, Close to the Cure Foundation, and National Institutes of Health contract HHSN272201200028C. Funding for PROGENI and GenePD studies, which generated the data used for replication, was provided by NINDS, and the GWAS data were obtained from the NINDS database at dbGaP accession number phs000126.v1.p1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 31 TC 23 Z9 23 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 7 PY 2013 VL 93 IS 5 BP 984 EP 993 DI 10.1016/j.ajhg.2013.10.009 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 252HU UT WOS:000326996600019 PM 24183452 ER PT J AU Shyh-Chang, N Zhu, H de Soysa, TY Shinoda, G Seligson, MT Tsanov, KM Nguyen, L Asara, JM Cantley, LC Daley, GQ AF Shyh-Chang, Ng Zhu, Hao de Soysa, T. Yvanka Shinoda, Gen Seligson, Marc T. Tsanov, Kaloyan M. Liem Nguyen Asara, John M. Cantley, Lewis C. Daley, George Q. TI Lin28 Enhances Tissue Repair by Reprogramming Cellular Metabolism SO CELL LA English DT Article ID GENOME-WIDE ASSOCIATION; GLUCOSE-METABOLISM; TAIL REGENERATION; MEMBRANE VOLTAGE; GROWTH; LIN-28; CELLS; MICE; MICRORNA; EXPRESSION AB Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. C1 [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Shyh-Chang, Ng; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA. [Zhu, Hao] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Zhu, Hao; Liem Nguyen] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA. [Zhu, Hao; Liem Nguyen] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Internal Med, Dallas, TX 75390 USA. [Cantley, Lewis C.] Cornell Weill Med Coll, Dept Med, New York, NY 10065 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Cantley, Lewis/D-1800-2014; Zhu, Hao/L-5114-2013; OI Cantley, Lewis/0000-0002-1298-7653; Zhu, Hao/0000-0002-8417-9698; Shyh-Chang, Ng/0000-0003-3138-9525 FU A*STAR National Science Scholarship; Graduate Training in Cancer Research Grant; American Cancer Society Postdoctoral Fellowship; NIH; CPRIT; Herchel Smith Graduate Fellowship; Ellison Medical Foundation FX We thank John Powers, Costas Lyssiotis, Charles Kaufman, Jessica Lehoczky, and Clifford Tabin for invaluable feedback and discussions; Jin Zhang and the lab of Marcia Haigis for help with the Seahorse Analyzer; Min Yuan and Susanne Breitkopf for help with metabolomics; Samar Shah and Akiko Yabuuchi for help with the mouse work; Asher Bomer for help with the scratch assays; James Thornton for help with northern blots; and Roderick Bronson and the Harvard Medical School Rodent Histopathology Core for mouse tissue pathology. This work was supported by an A*STAR National Science Scholarship to N.S.-C., a Graduate Training in Cancer Research Grant, an American Cancer Society Postdoctoral Fellowship, an NIH K08 grant, and a CPRIT award to H.Z.; a Herchel Smith Graduate Fellowship to K. M. T.; and a grant from the Ellison Medical Foundation to G. Q. D. G. Q. D. is an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. NR 57 TC 97 Z9 103 U1 8 U2 106 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 7 PY 2013 VL 155 IS 4 BP 778 EP 792 DI 10.1016/j.cell.2013.09.059 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251MW UT WOS:000326934300009 PM 24209617 ER PT J AU Emerling, BM Hurov, JB Poulogiannis, G Tsukazawa, KS Choo-Wing, R Wulf, GM Bell, EL Shim, HS Lamia, KA Rameh, LE Bellinger, G Sasaki, AT Asara, JM Yuan, X Bullock, A DeNicola, GM Song, JX Brown, V Signoretti, S Cantley, LC AF Emerling, Brooke M. Hurov, Jonathan B. Poulogiannis, George Tsukazawa, Kazumi S. Choo-Wing, Rayman Wulf, Gerburg M. Bell, Eric L. Shim, Hye-Seok Lamia, Katja A. Rameh, Lucia E. Bellinger, Gary Sasaki, Atsuo T. Asara, John M. Yuan, Xin Bullock, Andrea DeNicola, Gina M. Song, Jiaxi Brown, Victoria Signoretti, Sabina Cantley, Lewis C. TI Depletion of a Putatively Druggable Class of Phosphatidylinositol Kinases Inhibits Growth of p53-Null Tumors SO CELL LA English DT Article ID INOSITOL POLYPHOSPHATE 4-PHOSPHATASE; METASTATIC BREAST-CANCER; SUBSTRATE-SPECIFICITY; SENESCENCE; SUPPRESSOR; PTDINS5P; MICE; ACTIVATION; PATHWAY; SYSTEM AB Here, we show that a subset of breast cancers express high levels of the type 2 phosphatidylinositol-5-phosphate 4-kinases alpha and/or beta (PI5P4K alpha and beta) and provide evidence that these kinases are essential for growth in the absence of p53. Knocking down PI5P4K alpha and beta in a breast cancer cell line bearing an amplification of the gene encoding PI5P4K beta and deficient for p53 impaired growth on plastic and in xenografts. This growth phenotype was accompanied by enhanced levels of reactive oxygen species (ROS) leading to senescence. Mice with homozygous deletion of both TP53 and PIP4K2B were not viable, indicating a synthetic lethality for loss of these two genes. Importantly however, PIP4K2A(-/-), PIP4K2B(+/-), and TP53(-/-) mice were viable and had a dramatic reduction in tumor formation compared to TP53(-/-) littermates. These results indicate that inhibitors of PI5P4Ks could be effective in preventing or treating cancers with mutations in TP53. C1 [Emerling, Brooke M.; Poulogiannis, George; Tsukazawa, Kazumi S.; Choo-Wing, Rayman; Shim, Hye-Seok; DeNicola, Gina M.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Emerling, Brooke M.; Poulogiannis, George; Tsukazawa, Kazumi S.; Choo-Wing, Rayman; Wulf, Gerburg M.; Shim, Hye-Seok; Asara, John M.; Yuan, Xin; Bullock, Andrea; DeNicola, Gina M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Emerling, Brooke M.; Choo-Wing, Rayman; Bellinger, Gary; Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Hurov, Jonathan B.] Agios Pharmaceut, Cambridge, MA 02139 USA. [Bell, Eric L.] MIT, Dept Biol, Paul F Glenn Lab, Cambridge, MA 02139 USA. [Lamia, Katja A.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Rameh, Lucia E.] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA. [Sasaki, Atsuo T.] Univ Cincinnati, Coll Med, UC Neurosci Inst, Dept Internal Med,Brain Tumor Ctr, Cincinnati, OH 45267 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Song, Jiaxi; Brown, Victoria; Signoretti, Sabina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Song, Jiaxi; Brown, Victoria; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lcantley@med.cornell.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIH [R01 GM041890]; DF/HCC Career Development Award; Stand Up to Cancer Dream Team Translational Research Grant; Entertainment Industry Foundation [SU2C-AACR-DT0209]; NIH DK [R01-63219] FX We thank Rodrick Bronson and the entire HMS Rodent Histopathology Core for technical help with the mouse histopathology and discussions concerning the project. Also, we would like to thank Jared Johnson for cloning expertise and the Nikon Imaging Center at Harvard Medical School for help with light microscopy. This work was supported by NIH grant R01 GM041890 to L. C. C., DF/HCC Career Development Award to B. M. E., and by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). G. P. is a Pfizer Fellow of the Life Sciences Research Foundation. NIH DK R01-63219 supports L.E.R. NR 34 TC 40 Z9 41 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 7 PY 2013 VL 155 IS 4 BP 844 EP 857 DI 10.1016/j.cell.2013.09.057 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251MW UT WOS:000326934300014 PM 24209622 ER PT J AU Xu, C Tabebordbar, M Iovino, S Ciarlo, C Liu, JX Castiglioni, A Price, E Liu, M Barton, ER Kahn, CR Wagers, AJ Zon, LI AF Xu, Cong Tabebordbar, Mohammadsharif Iovino, Salvatore Ciarlo, Christie Liu, Jingxia Castiglioni, Alessandra Price, Emily Liu, Min Barton, Elisabeth R. Kahn, C. Ronald Wagers, Amy J. Zon, Leonard I. TI A Zebrafish Embryo Culture System Defines Factors that Promote Vertebrate Myogenesis across Species SO CELL LA English DT Article ID MUSCLE STEM-CELLS; SKELETAL-MUSCLE; SATELLITE CELLS; ADENYLATE-CYCLASE; SELF-RENEWAL; CYCLIC-AMP; REGENERATION; EXPRESSION; PATHWAY; PROGENITORS AB Ex vivo expansion of satellite cells and directed differentiation of pluripotent cells to mature skeletal muscle have proved difficult challenges for regenerative biology. Using a zebrafish embryo culture system with reporters of early and late skeletal muscle differentiation, we examined the influence of 2,400 chemicals on myogenesis and identified six that expanded muscle progenitors, including three GSK3 beta inhibitors, two calpain inhibitors, and one adenylyl cyclase activator, forskolin. Forskolin also enhanced proliferation of mouse satellite cells in culture and maintained their ability to engraft muscle in vivo. A combination of bFGF, forskolin, and the GSK3 beta inhibitor BIO induced skeletal muscle differentiation in human induced pluripotent stem cells (iPSCs) and produced engraftable myogenic progenitors that contributed to muscle repair in vivo. In summary, these studies reveal functionally conserved pathways regulating myogenesis across species and identify chemical compounds that expand mouse satellite cells and differentiate human iPSCs into engraftable muscle. C1 [Xu, Cong; Ciarlo, Christie; Liu, Jingxia; Price, Emily; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Cong; Ciarlo, Christie; Liu, Jingxia; Price, Emily; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Xu, Cong; Tabebordbar, Mohammadsharif; Ciarlo, Christie; Liu, Jingxia; Castiglioni, Alessandra; Price, Emily; Wagers, Amy J.; Zon, Leonard I.] Harvard Stem Cell Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Xu, Cong; Tabebordbar, Mohammadsharif; Iovino, Salvatore; Ciarlo, Christie; Liu, Jingxia; Price, Emily; Kahn, C. Ronald; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tabebordbar, Mohammadsharif; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Iovino, Salvatore; Castiglioni, Alessandra; Kahn, C. Ronald; Wagers, Amy J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Castiglioni, Alessandra] Univ Vita Salute San Raffaele, I-20132 Milan, Italy. [Liu, Min] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barton, Elisabeth R.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Iovino, Salvatore; Wagers, Amy J.] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. RP Wagers, AJ (reprint author), Harvard Stem Cell Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM amy_wagers@harvard.edu; zon@enders.tch.harvard.edu FU NIH [P30DK036836, DP2OD004345, UO1HL100402, DK31036]; HHMI; NIH NIDDK [R24DK092760-03, 5P30 DK49216-19]; NIH NCI [5R01CA103846-10]; NIH NHLBI [5U01HL10001-05]; Novo Nordisk Diabetes Center in Copenhagen; Paul D. Wellstone Muscular Dystrophy Research Center [U54 AR052646]; Harvard Stem Cell Institute FX We thank T. Schlaeger for helpful discussions; W. Yee of hESC Core Facility at Children's Hospital Boston for screening support; K. Zhu for mouse satellite cell differentiation data analysis; E. Durand for cAMP assay assistance; J. LaVecchio, S. Ionescu, A. Wakabayashi, and G. Buruzula of Joslin's HSCI/DERC Flow Cytometry Core (NIH award P30DK036836); and the HSCRB/HSCI Flow Cytometry Core at Harvard for excellent flow cytometry support. We thank C. Cahill of Joslin's electron microscopy core for help with EM and immune-gold assays, and we thank C. Cowan and L. Daheron of the HSCI iPSC Core Facility for assistance with human iPSC generation. This work was supported by HHMI, NIH NIDDK R24DK092760-03, NIH NIDDK 5P30 DK49216-19, NIH NCI 5R01CA103846-10, and NIH NHLBI 5U01HL10001-05 to L.I.Z.; NIH DP2OD004345 and UO1HL100402 to A. J. W.; NIH DK31036 to C. R. K.; the Novo Nordisk Diabetes Center in Copenhagen to C. R. K.; the Paul D. Wellstone Muscular Dystrophy Research Center (U54 AR052646 to E. R. B.); and the Harvard Stem Cell Institute to A. J. W. A. J. W is an Early Career Scientist of the Howard Hughes Medical Institute. L.I.Z. is an Investigator of the Howard Hughes Medical Institute, a founder and stockholder of Fate, Inc., and a scientific advisor for Stemgent. NR 50 TC 51 Z9 53 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 7 PY 2013 VL 155 IS 4 BP 909 EP 921 DI 10.1016/j.cell.2013.10.023 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251MW UT WOS:000326934300019 PM 24209627 ER PT J AU Davoli, T Xu, AW Mengwasser, KE Sack, LM Yoon, JC Park, PJ Elledge, SJ AF Davoli, Teresa Xu, Andrew Wei Mengwasser, Kristen E. Sack, Laura M. Yoon, John C. Park, Peter J. Elledge, Stephen J. TI Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns and Shape the Cancer Genome SO CELL LA English DT Article ID COPY-NUMBER ALTERATION; DNA-DAMAGE RESPONSE; HUMAN BREAST; MUTATIONS; REVEALS; GENES; LANDSCAPES; GENERATION; RESOURCE AB Aneuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. Here, we develop Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing >8,200 tumor-normal pairs, we provide statistical evidence suggesting that many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and potency of TSGs (STOP genes), OGs, and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. C1 [Davoli, Teresa; Mengwasser, Kristen E.; Sack, Laura M.; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. [Davoli, Teresa; Xu, Andrew Wei; Mengwasser, Kristen E.; Sack, Laura M.; Yoon, John C.; Park, Peter J.; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Yoon, John C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Xu, Andrew Wei; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu FU DOD Breast Cancer Innovator Award; NIH [U54LM008748, K08DK081612] FX We thank Simon Forbes and Michael Stratton (Wellcome Trust Sanger Institute, UK) for the data from the Cosmic dataset (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/), Eric Wooten for help on data extraction, and Chad Creighton and Kim Rathmell for allowing access to their unpublished data on KICH SCNAs. We also thank Andrew Futreal, Semin Lee, David Livingston, David Page, Mary-Claire King, Jim Lupski, Rameen Beroukhim, Matt Meyerson, Atanas Kamburov, and Paul Edwards for helpful advice and Bert Vogelstein, Judith Glaven, and members of the Elledge lab for helpful comments on the manuscript. This work was funded by a DOD Breast Cancer Innovator Award and NIH grant to S.J.E., U54LM008748 to P.J.P., and K08DK081612 to J.C.Y. S.J.E. is an investigator with the Howard Hughes Medical Institute. We apologize to our colleagues whose papers we could not cite due to space limitations. NR 37 TC 145 Z9 147 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 7 PY 2013 VL 155 IS 4 BP 948 EP 962 DI 10.1016/j.cell.2013.10.011 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251MW UT WOS:000326934300022 PM 24183448 ER PT J AU Boer, IH Thadhani, R AF de Boer, Ian H. Thadhani, Ravi TI Vitamin D Deficiency: Consequence or Cause of CKD? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; SUBTOTALLY NEPHRECTOMIZED RATS; RANDOMIZED CONTROLLED-TRIAL; SERUM 25-HYDROXYVITAMIN D; 1,25-DIHYDROXYVITAMIN D-3; DIABETIC-NEPHROPATHY; BIOLOGICAL ACTIVITY; 1,25-DIHYDROXYCHOLECALCIFEROL; METABOLISM; GLOMERULOSCLEROSIS C1 [de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol & Kidney Res Inst, Seattle, WA 98104 USA. [de Boer, Ian H.] Univ Washington, Dept Epidemiol, Div Nephrol & Kidney Res Inst, Seattle, WA 98104 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Boer, IH (reprint author), Univ Washington, Dept Med, Div Nephrol & Kidney Res Inst, Box 359606,325 Ninth Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu NR 26 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV 7 PY 2013 VL 8 IS 11 BP 1844 EP 1846 DI 10.2215/CJN.09480913 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 250FR UT WOS:000326836400002 ER PT J AU Kalim, S Tamez, H Wenger, J Ankers, E Trottier, CA Deferio, JJ Berg, AH Karumanchi, SA Thadhani, RI AF Kalim, Sahir Tamez, Hector Wenger, Julia Ankers, Elizabeth Trottier, Caitlin A. Deferio, Joseph J. Berg, Anders H. Karumanchi, S. Ananth Thadhani, Ravi I. TI Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HEMODIALYSIS-PATIENTS; PROTEIN CARBAMYLATION; HEMOGLOBIN CARBAMYLATION; ENDOTHELIAL-CELLS; DIALYSIS PATIENTS; PLASMA-PROTEIN; RENAL-FAILURE; UREMIA; INFLAMMATION AB Background and objectivesThe mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.Design, setting, participants, & measurementsIn a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.ResultsThe median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).ConclusionCarbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index. C1 [Kalim, Sahir; Tamez, Hector; Wenger, Julia; Ankers, Elizabeth; Trottier, Caitlin A.; Deferio, Joseph J.; Thadhani, Ravi I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Boston, MA USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. RP Kalim, S (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM skalim@partners.org FU National Institutes of Health [2T32DK007540-26, K24 DK094872] FX S.K. is supported by National Institutes of Health Grant 2T32DK007540-26, and R. I. T. is supported by National Institutes of Health Grant K24 DK094872. NR 41 TC 14 Z9 15 U1 0 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV 7 PY 2013 VL 8 IS 11 BP 1927 EP 1934 DI 10.2215/CJN.04310413 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 250FR UT WOS:000326836400014 PM 23970130 ER PT J AU Whitman, CB Shreay, S Gitlin, M van Oijen, MGH Spiegel, BMR AF Whitman, Cynthia B. Shreay, Sanatan Gitlin, Matthew van Oijen, Martijn G. H. Spiegel, Brennan M. R. TI Clinical Factors and the Decision to Transfuse Chronic Dialysis Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; ERYTHROPOIESIS-STIMULATING AGENTS; INCIDENT HEMODIALYSIS-PATIENTS; CONJOINT-ANALYSIS APPLICATIONS; STANDARDIZED PATIENTS; HEMATOCRIT VALUES; CHART ABSTRACTION; EPOETIN-ALPHA; ANEMIA; PREFERENCES AB Background and objectivesRed blood cell transfusion was previously the principle therapy for anemia in CKD but became less prevalent after the introduction of erythropoiesis-stimulating agents. This study used adaptive choice-based conjoint analysis to identify preferences and predictors of transfusion decision-making in CKD.Design, setting, participants, & measurementsA computerized adaptive choice-based conjoint survey was administered between June and August of 2012 to nephrologists, internists, and hospitalists listed in the American Medical Association Masterfile. The survey quantified the relative importance of 10 patient attributes, including hemoglobin levels, age, occult blood in stool, severity of illness, eligibility for transplant, iron indices, erythropoiesis-stimulating agents, cardiovascular disease, and functional status. Triggers of transfusions in common dialysis scenarios were studied, and based on adaptive choice-based conjoint-derived preferences, relative importance by performing multivariable regression to identify predictors of transfusion preferences was assessed.ResultsA total of 350 providers completed the survey (n=305 nephrologists; mean age=46 years; 21% women). Of 10 attributes assessed, absolute hemoglobin level was the most important driver of transfusions, accounting for 29% of decision-making, followed by functional status (16%) and cardiovascular comorbidities (12%); 92% of providers transfused when hemoglobin was 7.5 g/dl, independent of other factors. In multivariable regression, Veterans Administration providers were more likely to transfuse at 8.0 g/dl (odds ratio, 5.9; 95% confidence interval, 1.9 to 18.4). Although transplant eligibility explained only 5% of decision-making, nephrologists were five times more likely to value it as important compared with non-nephrologists (odds ratio, 5.2; 95% confidence interval, 2.4 to11.1).ConclusionsAdaptive choice-based conjoint analysis was useful in predicting influences on transfusion decisions. Hemoglobin level, functional status, and cardiovascular comorbidities most strongly influenced transfusion decision-making, but preference variations were observed among subgroups. C1 [Whitman, Cynthia B.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. [Whitman, Cynthia B.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, Vet Adm Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Shreay, Sanatan; Gitlin, Matthew] Amgen Inc, Global Hlth Econ, Thousand Oaks, CA 91320 USA. [van Oijen, Martijn G. H.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. [van Oijen, Martijn G. H.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Amgen, Inc. FX This study was supported by a research grant from Amgen, Inc. The opinions and assertions contained herein are the sole views of the authors and not to be construed as official or reflecting the views of the Department of Veterans Affairs. NR 46 TC 8 Z9 8 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV 7 PY 2013 VL 8 IS 11 BP 1942 EP 1951 DI 10.2215/CJN.00160113 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 250FR UT WOS:000326836400016 PM 23929931 ER EF