FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Grady, CD Dehlendorf, C Cohen, ED Schwarz, EB Borrero, S AF Grady, Cynthia D. Dehlendorf, Christine Cohen, Elan D. Schwarz, E. Bimla Borrero, Sonya TI Racial and ethnic differences in contraceptive use among women who desire no future children, 2006-2010 National Survey of Family Growth SO CONTRACEPTION LA English DT Article DE Contraception; Disparities; Race/ethnicity; Unwanted pregnancy ID UNITED-STATES; UNINTENDED PREGNANCY; INTENTION; DISPARITIES; PATTERNS; BIRTHS; NONUSE; RISK AB Objective: To evaluate racial/ethnic differences in contraceptive use among women who do not desire future pregnancy. Study Design: We used the 2006-2010 National Survey of Family Growth to examine the associations between race/ethnicity and 1) use of any contraceptive method at last heterosexual intercourse and 2) effectiveness of contraceptive method used among women who stated that they did not desire any (more) children. We conducted multivariable logistic regression to assess the independent effect of race/ethnicity on these outcomes, adjusting for socio-demographic factors, reproductive characteristics, and indicators of healthcare access and utilization. Results: The study sample consisted of 2900 women, aged 15-44 years. The vast majority of women (91.2%) used contraception at last sex, although this varied significantly by race/ethnicity (p<.01). In the fully adjusted model controlling for demographic and reproductive characteristics as well as healthcare access, compared to whites, black women were significantly less likely to use any contraception at last sex (OR: 0.43; 95% CI: 0.27-0.73), while there was no significant difference for Hispanic women (OR: 0.95; 95% CI: 0.52-1.72). Among women who used a method at last sex, the type of contraceptive method varied significantly by race/ethnicity in bivariate analysis (p<.01), although most women (59%) used a highly effective method. In the fully adjusted model, racial/ethnic differences were no longer significant. Conclusions: In this nationally representative cohort of women who report that they do not desire (more) children, black women were significantly less likely than white women to use any contraception at last intercourse; this difference did not appear to be due to differential access to health care. Published by Elsevier Inc. C1 [Grady, Cynthia D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94110 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94110 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Cohen, Elan D.] Univ Pittsburgh, Hlth Care Data Ctr, Res Ctr, Pittsburgh, PA 15213 USA. [Schwarz, E. Bimla] Univ Calif Davis, Sch Med, Div Gen Internal Med, Sacramento, CA 95817 USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Borrero, S (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu FU Eunice Kennedy Shriver National Institute of Child Health & Human Development [1R21HD068736-01A1, K23HD067197]; University of Pittsburgh Clinical Scientist Training Program, (CSTP) [UL1 TL1TR000005] FX This work was supported by Grant Numbers 1R21HD068736-01A1 (S.B.) and K23HD067197 (C.D.) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and from the University of Pittsburgh Clinical Scientist Training Program, (CSTP) UL1 TL1TR000005 (C.G.). NR 45 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD JUL PY 2015 VL 92 IS 1 BP 62 EP 70 DI 10.1016/j.contraception.2015.03.017 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL5IG UT WOS:000356992400010 PM 25863228 ER PT J AU Boynton, GE Raoof, D Niziol, LM Hussain, M Mian, SI AF Boynton, Grace E. Raoof, Duna Niziol, Leslie M. Hussain, Munira Mian, Shahzad I. TI Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation SO CORNEA LA English DT Article DE hematopoietic stem cell transplantation; graft versus host disease; cyclosporine; loteprednol; dry eye ID VERSUS-HOST-DISEASE; PLACEBO-CONTROLLED EVALUATION; BONE-MARROW-TRANSPLANTATION; KERATOCONJUNCTIVITIS SICCA; OCULAR MANIFESTATIONS; CONJUNCTIVITIS; GVHD AB Purpose:To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT).Methods:Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT.Results:There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of DES development in cyclosporine-treated eyes and a 79% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38% rate of disease progression among cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure.Conclusions:Pre-HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5% for the treatment and prophylaxis of DES following HSCT. C1 [Boynton, Grace E.; Raoof, Duna; Niziol, Leslie M.; Hussain, Munira; Mian, Shahzad I.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Raoof, Duna] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Mian, SI (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. EM smian@umich.edu NR 29 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JUL PY 2015 VL 34 IS 7 BP 725 EP 732 DI 10.1097/ICO.0000000000000436 PG 8 WC Ophthalmology SC Ophthalmology GA CL0AO UT WOS:000356601000001 PM 25850708 ER PT J AU Bagwell, CB Hunsberger, BC Herbert, DJ Munson, ME Hill, BL Bray, CM Preffer, FI AF Bagwell, C. Bruce Hunsberger, Benjamin C. Herbert, Donald J. Munson, Mark E. Hill, Beth L. Bray, Chris M. Preffer, Frederic I. TI Probability state modeling theory SO CYTOMETRY PART A LA English DT Article DE high-dimensional modeling; broadened quantile function modeling; cytometry; polychromatic; high-dimensional visualization ID DIMENSIONAL CYTOMETRY DATA; FLOW-CYTOMETRY; VISUALIZATION; CELLS AB As the technology of cytometry matures, there is mounting pressure to address two major issues with data analyses. The first issue is to develop new analysis methods for high-dimensional data that can directly reveal and quantify important characteristics associated with complex cellular biology. The other issue is to replace subjective and inaccurate gating with automated methods that objectively define subpopulations and account for population overlap due to measurement uncertainty. Probability state modeling (PSM) is a technique that addresses both of these issues. The theory and important algorithms associated with PSM are presented along with simple examples and general strategies for autonomous analyses. PSM is leveraged to better understand B-cell ontogeny in bone marrow in a companion Cytometry Part B manuscript. Three short relevant videos are available in the online supporting information for both of these papers. PSM avoids the dimensionality barrier normally associated with high-dimensionality modeling by using broadened quantile functions instead of frequency functions to represent the modulation of cellular epitopes as cells differentiate. Since modeling programs ultimately minimize or maximize one or more objective functions, they are particularly amenable to automation and, therefore, represent a viable alternative to subjective and inaccurate gating approaches. (c) 2015 International Society for Advancement of Cytometry C1 [Bagwell, C. Bruce; Hunsberger, Benjamin C.; Herbert, Donald J.; Munson, Mark E.; Hill, Beth L.; Bray, Chris M.] Ver Software House, Topsham, ME 04086 USA. [Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bagwell, CB (reprint author), Ver Software House, POB 247, Topsham, ME 04086 USA. EM cbb@vsh.com NR 30 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD JUL PY 2015 VL 87A IS 7 SI SI BP 646 EP 660 DI 10.1002/cyto.a.22687 PG 15 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CL3ZK UT WOS:000356891200007 PM 26012929 ER PT J AU Preffer, F AF Preffer, Frederic TI Paired Cytometry Publications - from mathematical theory towards clinical applications SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA. RP Preffer, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL-AUG PY 2015 VL 88 IS 4 BP 211 EP 211 DI 10.1002/cyto.b.21255 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA CL3SD UT WOS:000356869900001 PM 26068944 ER PT J AU Bagwell, CB Hill, BL Wood, BL Wallace, PK Alrazzak, M Kelliher, AS Preffer, FI AF Bagwell, C. Bruce Hill, Beth L. Wood, Brent L. Wallace, Paul K. Alrazzak, Muaz Kelliher, Abigail S. Preffer, Frederic I. TI Human B-cell and progenitor stages as determined by probability state modeling of multidimensional cytometry data SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE bone marrow ontogeny; flow cytometry; human B-cell differentiation; B-cell development; hematopoietic stem cells; bone marrow microenvironment; monoclonal antibodies; high-dimensional modeling; broadened quantile function modeling; flow cytometry; probability state modeling ID HUMAN-BONE-MARROW; FLOW-CYTOMETRY; DEVELOPMENT PATHWAYS; MULTIPLE-MYELOMA; PRECURSORS; DIFFERENTIATION; EXPRESSION; CD19 AB BackgroundHuman progenitor and B-cell development is a highly regulated process characterized by the ordered differential expression of numerous cell-surface and intracytoplasmic antigens. This study investigates the underlying coordination of these modulations by examining a series of normal bone marrow samples with the method of probability state modeling or PSM. ResultsThe study is divided into two sections. The first section examines B-cell stages subsequent to CD19 up-regulation. The second section assesses an earlier differentiation stage before and including CD19 up-regulation. Post-CD19 Antigenic Up-RegulationStatistical analyses of cytometry data derived from sixteen normal bone marrow specimens revealed that B cells have at least three distinct coordinated changes, forming four stages labeled as B1, B2, B3, and B4. At the end of B1; CD34 antigen expression down-regulates with TdT while CD45, CD81, and CD20 slightly up-regulate. At the end of B2, CD45 and CD20 up-regulate. At the end of B3 and beginning of B4; CD10, CD38, and CD81 down-regulate while CD22 and CD44 up-regulate. Pre-CD19 Antigenic Up-RegulationStatistical analysis of ten normal bone marrows revealed that there are at least two measurable coordinated changes with progenitors, forming three stages labeled as P1, P2, and P3. At the end of P1, CD38 up-regulates. At the end of P2; CD19, CD10, CD81, CD22, and CD9 up-regulate while CD44 down-regulates slightly. ConclusionsThese objective results yield a clearer immunophenotypic picture of the underlying cellular mechanisms that are operating in these important developmental processes. Also, unambiguously determined stages define what is meant by normal B-cell development and may serve as a preliminary step for the development of highly sensitive minimum residual disease detection systems. A companion article is simultaneously being published in Cytometry Part A that will explain in further detail the theory behind PSM. Three short relevant videos are available in the online supporting information for both of these papers. (c) 2015 International Clinical Cytometry Society C1 [Bagwell, C. Bruce; Hill, Beth L.] Ver Software House, Topsham, ME USA. [Wood, Brent L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Wood, Brent L.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Wallace, Paul K.; Alrazzak, Muaz] Roswell Pk Canc Inst, Dept Flow & Image Cytometry, Buffalo, NY 14263 USA. [Kelliher, Abigail S.; Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bagwell, CB (reprint author), POB 247, Topsham, ME 04086 USA. EM cbb@vsh.com NR 39 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL-AUG PY 2015 VL 88 IS 4 BP 214 EP 226 DI 10.1002/cyto.b.21243 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA CL3SD UT WOS:000356869900003 PM 25850810 ER PT J AU Vazquez, SE Inlay, MA Serwold, T AF Vazquez, Sara E. Inlay, Matthew A. Serwold, Thomas TI CD201 and CD27 identify hematopoietic stem and progenitor cells across multiple murine strains independently of Kit and Sca-1 SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PROTEIN-C RECEPTOR; BONE-MARROW; NOD MICE; IN-VIVO; EXPRESSION; TRANSPLANTATION; IDENTIFICATION; INTERFERON; ACTIVATION; FREQUENCY AB Identification and isolation of hematopoietic stem cells (HSCs) in mice is most commonly based on the expression of surface molecules Kit and Sca-1 and the absence of markers of mature lineages. However, Sca-1 is absent or weakly expressed in hematopoietic progenitors in many strains, including nonobese diabetic (NOD), BALB/c, C3H, and CBA mice. In addition, both Kit and Sca-1 levels are modulated following bone marrow injury. In these cases, other markers and dye exclusion methods have been employed to identify HSCs, yet there is no antibody-based stain that enables identification of HSCs and early progenitors when Kit and Sca-1 are inadequate. CD201 is a marker that is highly restricted to HSCs and progenitors, and CD27 is expressed at moderate-to-high levels on HSCs. We show here that combining CD201 and CD27 enables highly efficient isolation of long-term HSCs in NOD mice as well as in other strains, including SJL, FVB, AKR, BALB/c, C3H, and CBA. We also find that HSCs appear to maintain expression of CD201 and CD27 after hematopoietic injury when Kit expression is downregulated. These results suggest a widely applicable yet simple alternative for HSC isolation in settings where Kit and Sea-1 expression are insufficient. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Vazquez, Sara E.; Serwold, Thomas] Joslin Diabet Ctr, Dept Immunobiol, Boston, MA 02215 USA. [Vazquez, Sara E.; Serwold, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Inlay, Matthew A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Sue & Bill Gross Stem Cell Res Ctr, Irvine, CA 92717 USA. RP Serwold, T (reprint author), Joslin Diabet Ctr, Dept Immunobiol, Room 468,1 Joslin Pl, Boston, MA 02215 USA. EM thomas.serwold@joslin.harvard.edu FU National Institutes of Health Diabetes Research Center grant [P30DK036836]; Harvard Stem Cell Institute; Peabody Foundation; AM Stewart Trust; Fleisher Family Foundation; Pittsburgh Foundation; Harvard Stem Cell Institute Internship Program FX We thank the Joslin Diabetes Center Flow Cytometry Core, supported by a National Institutes of Health Diabetes Research Center grant (no. P30DK036836) and the Harvard Stem Cell Institute. We thank Joslin Animal Facility for animal care. We also thank Leo Wang for helpful advice and MiJeong Kim and Martin Thelin for comments on the manuscript. This work was supported by grants from the Peabody Foundation, The A&M Stewart Trust, The Fleisher Family Foundation, and the Pittsburgh Foundation (to T Serwold). SE Vazquez received a fellowship from the Harvard Stem Cell Institute Internship Program. NR 34 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2015 VL 43 IS 7 BP 578 EP 585 DI 10.1016/j.exphem.2015.04.001 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CL4ET UT WOS:000356906100009 PM 25892186 ER PT J AU Richardson, PG Laubach, JP Lonial, S Moreau, P Yoon, SS Hungria, VTM Dimopoulos, MA Beksac, M Alsina, M San-Miguel, JF AF Richardson, Paul G. Laubach, Jacob P. Lonial, Sagar Moreau, Philippe Yoon, Sung-Soo Hungria, Vania T. M. Dimopoulos, Meletios A. Beksac, Meral Alsina, Melissa San-Miguel, Jesus F. TI Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE bortezomib; deacetylase inhibitors; multiple myeloma; panobinostat; treatment of relapsed and refractory disease ID HISTONE DEACETYLASES; BORTEZOMIB; COMBINATION; DEXAMETHASONE; LBH589; MULTICENTER; CARFILZOMIB; PROGRESSION; MECHANISM; SURVIVAL AB Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM. C1 [Richardson, Paul G.; Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Moreau, Philippe] Nantes Univ Hosp, Nantes, France. [Yoon, Sung-Soo] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Hungria, Vania T. M.] Santa Casa Misericordia Sao Paulo Hosp, Sao Paulo, Brazil. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Beksac, Meral] Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. [Alsina, Melissa] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [San-Miguel, Jesus F.] Univ Navarra Clin, CIMA, Pamplona, Spain. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU Novartis; Celgene; Millennium; Onyx FX PG Richardson: advisory committees for Novartis, Takeda and Johnson & Johnson; JP Laubach: research funding from Novartis, Celgene, Millennium and Onyx; S Lonial: consultancy for Millennium, Celgene, Novartis, Bristol-Myers Squibb, Onyx and Sanofi; P Moreau: advisory committees for Novartis, Takeda, Janssen, Millennium and Onyx; MA Dimopoulos: honoraria from Novartis, Celgene, Onyx and Janssen; M Beksac: advisory committees for Celgene, Amgen, Novartis, Bristol-Myers Squibb and Millennium; M Alsina: advisory committee for Millennium; JFS-M: member of advisory committee for Janssen, Bristol-Myers Squibb, Merck Sharpe & Dohme, Millennium, Celgene, Novartis and Onyx. S Tanik and W Fazzone provided writing assistance funded by Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 34 TC 12 Z9 13 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JUL PY 2015 VL 15 IS 7 BP 737 EP 748 DI 10.1586/14737140.2015.1047770 PG 12 WC Oncology SC Oncology GA CL3UF UT WOS:000356875400002 PM 26051506 ER PT J AU Hasegawa, K Camargo, CA AF Hasegawa, Kohei Camargo, Carlos A., Jr. TI Airway microbiota and acute respiratory infection in children SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Editorial Material DE acute respiratory infection; bronchiolitis; Haemophilus; immune response; Lactobacillaceae; microbiome; microbiota; Moraxella; pneumonia; probiotics; virus ID PATHOGENIC BACTERIA; BRONCHIOLITIS; COMMUNITIES; PNEUMONIA AB Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e. g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e. g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children. C1 [Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Hasegawa, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. EM khasegawa1@partners.org FU NHLBI NIH HHS [R21 HL129909]; NIAID NIH HHS [U01 AI-67693, U01 AI067693] NR 20 TC 7 Z9 8 U1 0 U2 4 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X EI 1744-8409 J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD JUL PY 2015 VL 11 IS 7 BP 789 EP 792 DI 10.1586/1744666X.2015.1045417 PG 4 WC Immunology SC Immunology GA CL3UM UT WOS:000356876100003 PM 25961472 ER PT J AU DuBrock, HM Channick, RN Krowka, MJ AF DuBrock, Hilary M. Channick, Richard N. Krowka, Michael J. TI What's new in the treatment of portopulmonary hypertension? SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE macitentan; portopulmonary hypertension; pulmonary arterial hypertension; riociguat; treatment; treprostinil ID PULMONARY ARTERIAL-HYPERTENSION; ENDOTHELIN RECEPTOR ANTAGONIST; STAGE LIVER-DISEASE; INTRAVENOUS EPOPROSTENOL PROSTACYCLIN; RANDOMIZED CONTROLLED-TRIAL; 5 INHIBITOR THERAPY; OF-THE-LITERATURE; TERM-FOLLOW-UP; ORAL TREPROSTINIL; TRANSPLANTATION CANDIDATES AB Portopulmonary hypertension (POPH) is a complication of portal hypertension characterized by pulmonary vasoconstriction and vascular remodeling that can lead to right heart failure and death. Differentiation of POPH from other causes of pulmonary hypertension, such as volume overload or a hyperdynamic high flow state, is critical because a diagnosis of POPH has significant implications for liver transplant risk stratification, Model for End Stage Liver Disease exception points, and the use of pulmonary arterial hypertension-(PAH) specific therapy. Currently, there are 12 approved medications for the treatment of PAH in the US, and three of these were approved in 2013. This review will discuss the diagnosis, evaluation and management of POPH and the role of recently approved PAH therapies in the treatment of POPH. C1 [DuBrock, Hilary M.; Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krowka, Michael J.] Mayo Clin, Rochester, MN 55902 USA. RP DuBrock, HM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM hdubrock@mgh.harvard.edu FU Actelion FX MJ Krowka is a member of the steering committee for Portico, a multicenter study for the use of macitenan in portopulmonary hypertension, sponsored by Actelion. RN Channick is a consultant for Actelion pharmaceuticals, Bayer, United Therapeutics, Respira and ZappRx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 73 TC 4 Z9 4 U1 2 U2 13 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD JUL PY 2015 VL 9 IS 7 BP 983 EP 992 DI 10.1586/17474124.2015.1035647 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CL3OO UT WOS:000356859700010 PM 25882070 ER PT J AU Chung, DC AF Chung, Daniel C. TI The Enigma of Carcinoids SO GASTROENTEROLOGY LA English DT Editorial Material ID GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; GENETICS; GENES C1 [Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 704, Boston, MA 02114 USA. EM dchung@partners.org 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2015 VL 149 IS 1 BP 14 EP 15 DI 10.1053/j.gastro.2015.05.029 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CL0DW UT WOS:000356610400009 PM 26021237 ER PT J AU McMeekin, S Dizon, D Barter, J Scambia, G Manzyuk, L Lisyanskaya, A Oaknin, A Ringuette, S Mukhopadhyay, P Rosenberg, J Vergote, I AF McMeekin, Scott Dizon, Don Barter, James Scambia, Giovanni Manzyuk, Lyudmila Lisyanskaya, Alla Oaknin, Ana Ringuette, Sarah Mukhopadhyay, Pralay Rosenberg, Julie Vergote, Ignace TI Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Ixabepilone; Second-line; Advanced; Metastatic; Single-agent; Chemotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; BREAST-CANCER; CARCINOMA; CHEMOTHERAPY; RECURRENT; CISPLATIN; ANTHRACYCLINE; CAPECITABINE; RESISTANT; EFFICACY AB Objective. The purpose of this multicenter, open label, randomized phase III study was to determine whether ixabepilone resulted in improved overall survival (OS) compared with commonly used single-agent chemotherapy (doxorubicin or paclitaxel) in women with locally advanced, recurrent, or metastatic endometrial cancer with at least one failed prior platinum-based chemotherapeutic regimen. Methods. Patients were randomized 1:1 to ixabepilone (40 mg/m(2)), or either paclitaxel (175 mg/m(2)) or doxorubicin (60 mg/m(2)), every 21 days. Patients that had previously received an anthracycline were randomized to ixabepilone or paclitaxel; all other patients were randomized to ixabepilone or doxorubicin. An interim analysis of futility for OS was planned. Results. At the time of database lock, 496 patients were randomized to receive ixabepilone (n = 248) or control (n = 248); nine patients in the control arm were not treated. The interim analysis of futility for OS (219 events) favored the control chemotherapy arm (hazard ratio = 1.3 [95% confidence interval: 1.0-1.7], stratified log rank test P = 0.0397), indicating that the study would not meet its primary objective. The study was discontinued based on the interim OS results. The frequency of adverse events was comparable between the treatment arms. Conclusions. The study did not meet its primary objective of improving OS in the ixabepilone arm compared to the control chemotherapy arm. A favorable risk/benefit ratio was not observed for ixabepilone versus control at the time of the interim analysis. The safety results were consistent with the known safety profiles of ixabepilone and control. (C) 2015 Elsevier Inc. All rights reserved. C1 [McMeekin, Scott] Univ Oklahoma, Stephenson Canc Ctr, Oklahoma City, OK USA. [Dizon, Don] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Med Gynecol Oncol, Boston, MA 02114 USA. [Barter, James] Womens Hlth Specialists, Rockville, MD USA. [Scambia, Giovanni] Policlin Univ A Gemelli, Rome, Italy. [Manzyuk, Lyudmila] Russian Oncol Res Ctr, Moscow, Russia. [Lisyanskaya, Alla] City Clin Oncol Dispensary, St Petersburg, Russia. [Oaknin, Ana] Vall DHebron Univ Hosp, Barcelona, Spain. [Ringuette, Sarah; Mukhopadhyay, Pralay] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Rosenberg, Julie] Bayer HealthCare, Montville, NJ USA. [Vergote, Ignace] Katholieke Univ Leuven, Univ Hosp Leuven, Leuven Canc Inst, Dept Oncol, Leuven, Belgium. RP McMeekin, S (reprint author), Univ Oklahoma, Hlth Sci Ctr, 4502 East 41st St, Tulsa, OK 74135 USA. EM scott-mcmeekin@ouhsc.edu FU Bristol-Myers Squibb FX The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and scientific expertise. They wish to acknowledge Clair Thomas of StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support. NR 18 TC 9 Z9 9 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2015 VL 138 IS 1 BP 18 EP 23 DI 10.1016/j.ygyno.2015.04.026 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL3HN UT WOS:000356841100003 PM 25925990 ER PT J AU Sun, SY Melamed, A Goldstein, DP Bernstein, MR Horowitz, NS Moron, AF Maesta, I Braga, A Berkowitz, RS AF Sun, Sue Yazaki Melamed, Alexander Goldstein, Donald P. Bernstein, Marilyn R. Horowitz, Neil S. Moron, Antonio Fernandes Maesta, Izildinha Braga, Antonio Berkowitz, Ross S. TI Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: Does early diagnosis alter risk for gestational trophoblastic neoplasia? SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Gestational trophoblastic disease; Gestational trophoblastic neoplasia ID PREGNANCY; FEATURES AB Objective. To compare the clinical presentation and incidence of postmolar gestational trophoblastic neoplasia (GTN) among recent (1994-2013) and historical (1988-1993) cases of complete hydatidiform mole (CHM). Methods. This study included two non-concurrent cohorts (1988-1993 versus 1994-2013) of patients from the New England Trophoblastic Disease Center (NETDC). Clinical and pathologic reports of patients diagnosed with CHM between 1994 and 2013 were reviewed. Gestational age at evacuation, features of clinical presentation, human chorionic gonadotropin (hCG) levels, and the rate of progression to GTN were compared. Results. In the current cohort (1994 to 2013) the median gestational age at diagnosis continued to decline compared to our prior cohort (1988-1993) (9 weeks versus 12 weeks). Patients from the current cohort were significantly more likely to be diagnosed prior to the 11th week of gestation (56 versus 41%, p = 0.04). Patients in the current cohort were also significantly less likely to present with vaginal bleeding (46 versus 84%, p < 0.001). Earlier diagnosis of complete mole did not result in a decrease in the rate of postmolar GTN. The frequencies of postmolar GTN in the current (1994-2013) and prior (1988-1993) cohorts were 19 and 23%, respectively. In the current cohort, even diagnosis prior to ten weeks gestation did not decrease the risk of developing GTN. Conclusions. This study indicates that complete mole continues to be diagnosed progressively earlier resulting in a further decrease in some classical presenting symptoms. However, despite earlier detection, the risk of development of postmolar GTN has not been affected. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sun, Sue Yazaki; Moron, Antonio Fernandes] UNIFESP Sao Paulo Fed Univ, Paulista Sch Med, Dept Obstet, Sao Paulo, SP, Brazil. [Melamed, Alexander; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Maesta, Izildinha] UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Botucatu, SP, Brazil. [Melamed, Alexander; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Sun, Sue Yazaki; Moron, Antonio Fernandes] UNIFESP Sao Paulo Fed Univ, Paulista Sch Med, Trophoblast Dis Ctr, Sao Paulo Hosp, Sao Paulo, SP, Brazil. [Maesta, Izildinha] UNESP Sao Paulo State Univ, Botucatu Med Sch, Trophoblast Dis Ctr, Botucatu, SP, Brazil. [Braga, Antonio] Univ Fed Rio de Janeiro, Matern Sch, Trophoblast Dis Ctr, Rio De Janeiro, Brazil. [Braga, Antonio] Univ Fed Fluminense, Antonio Pedro Univ Hosp, Trophoblast Dis Ctr, Rio De Janeiro, Brazil. [Melamed, Alexander; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. [Melamed, Alexander; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Harvard Univ, Sch Med, Boston, MA USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept OBGYN, Div Gynecol Oncol, ASBI, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org OI Melamed, Alexander/0000-0002-0654-0863 FU CNPq - Science Without Borders - Brazil [200756/2014-1]; Dyett Family Trophoblastic Disease Research and Registry Endowment FX This research was supported by a grant from the CNPq 200756/2014-1 - Science Without Borders - Brazil to support the work of Dr. Sue Yazaki Sun and the Donald P. Goldstein, MD Trophoblastic Tumor Registry Endowment and the Dyett Family Trophoblastic Disease Research and Registry Endowment. NR 17 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2015 VL 138 IS 1 BP 46 EP 49 DI 10.1016/j.ygyno.2015.05.002 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL3HN UT WOS:000356841100008 PM 25969351 ER PT J AU Maesta, I Berkowitz, RS Goldstein, DP Bernstein, MR Ramirez, LAC Horowitz, NS AF Maesta, Izildinha Berkowitz, Ross S. Goldstein, Donald P. Bernstein, Marilyn R. Ramirez, Luz Angela C. Horowitz, Neil S. TI Relationship between race and clinical characteristics, extent of disease, and response to chemotherapy in patients with low-risk gestational trophoblastic neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Low-risk gestational trophoblastic neoplasia; Racial disparities; Response to chemotherapy ID FOLINIC ACID; ETHNIC-DIFFERENCES; BREAST-CANCER; PROGNOSTIC-FACTORS; HYDATIDIFORM MOLE; PRIMARY THERAPY; METHOTREXATE; MANAGEMENT; WOMEN; STAGE AB Objective. To evaluate the potential effects of race on clinical characteristics, extent of disease, and response to chemotherapy in women with postmolar low-risk gestational trophoblastic neoplasia (GTN). Methods. This non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained. Results. Of 316 women, 274 (86.7%) were white, 19 (6%) African American, and 23 (7.3%) Asian. African Americans were significantly younger than white and Asian women (p = 0.008). Disease presentation, and extent of disease, including antecedent molar histology, median time to persistence, median hCG level at persistence, rate of D&C at persistence, presence of metastatic disease, and FIGO stage and risk score were similar among races. Need for second line chemotherapy (p = 0.023), and median number of regimens (p = 0.035) were greater in Asian women than in other races. Conclusions. Low-risk GTN was more aggressive in Asian women, who were significantly more likely to need second line chemotherapy and a higher number of chemotherapy regimens to achieve complete remission than women of African American and Asian descent. Further studies involving racial differences related to clinical, biological and environmental characteristics are needed. (C) 2015 Published by Elsevier Inc. C1 [Maesta, Izildinha; Ramirez, Luz Angela C.] UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, BR-18618970 Botucatu, SP, Brazil. [Berkowitz, Ross S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Berkowitz, Ross S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.] Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Maesta, Izildinha] UNESP Sao Paulo State Univ, Botucatu Med Sch, Trophoblast Dis Ctr, BR-18618970 Botucatu, SP, Brazil. [Ramirez, Luz Angela C.] Caldas Univ, Clin Dept, Manizales, Caldas, Colombia. [Berkowitz, Ross S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.] Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. [Berkowitz, Ross S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.] Harvard Univ, Sch Med, Boston, MA USA. RP Maesta, I (reprint author), UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept GYNOB, Ave Prof Montenegro S-N, BR-18618970 Botucatu, SP, Brazil. EM imaesta@fmb.unesp.br FU Dyett Family Trophoblastie Disease Research and Registry Endowment FX The research in this manuscript was supported by the Donald P. Goldstein, MD Trophoblastic Tumor Registry Endowment and the Dyett Family Trophoblastie Disease Research and Registry Endowment. NR 41 TC 3 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2015 VL 138 IS 1 BP 50 EP 54 DI 10.1016/j.ygyno.2015.04.030 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL3HN UT WOS:000356841100009 PM 25933681 ER PT J AU Horowitz, NS Wright, AA AF Horowitz, Neil S. Wright, Alexi A. TI Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Obesity; Chemotherapy; Dosing; Pharmacokinetics; Ovarian cancer; Endometrial cancer ID BODY-SURFACE AREA; EPITHELIAL OVARIAN-CANCER; CELL LUNG-CANCER; MASS INDEX; BREAST-CANCER; ONCOLOGY-GROUP; ADJUVANT CHEMOTHERAPY; CREATININE CLEARANCE; PRIMARY PERITONEAL; COLORECTAL-CANCER AB Objective. To describe the effects of obesity on the pharmacokinetics and dosing of chemotherapies and provide recommendations for chemotherapy management in obese women with gynecologic malignancies. Methods. PubMEd and MEDLINE databases were searched for articles published before June 2014. Only English-language articles were considered. 84 manuscripts were reviewed and 66 were included. Search terms included: obesity, overweight, body mass index, body surface area, glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer, inflammation, and pharmacokinetics. Results. Obese cancer patients have worse clinical outcomes, compared with non-obese patients. This may be because of differences in pharmacokinetics, metabolic dysregulation, or physicians' decisions to reduce chemotherapy dose-intensity during treatment to minimize toxicities. A 2012 American Society of Clinical Oncology Clinical Practice Guideline recommends using actual body weight for chemotherapy dosing in all patients treated with curative intent, irrespective of obesity, to avoid compromising clinical outcomes, including progression free survival (PFS) and overall survival (OS). In women with gynecologic cancers most studies demonstrate no difference in PFS or OS when obese patients receive the same chemotherapy dose intensity as non-obese patients, except perhaps with bevacizumab. Conclusions. Chemotherapy dose-intensity is a critical determinant of cancer outcomes and should be maintained in all patients, irrespective of obesity. Future studies should prospectively examine the impact of obesity on clinical outcomes (adverse events, survival) to improve the care of this growing population of patients who are at risk for inferior clinical outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Horowitz, Neil S.; Wright, Alexi A.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA USA. RP Horowitz, NS (reprint author), Brigham & Womens Hosp, Dept OB GYN, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org FU NCI NIH HHS [K07 CA166210] NR 66 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2015 VL 138 IS 1 BP 201 EP 206 DI 10.1016/j.ygyno.2015.04.002 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL3HN UT WOS:000356841100031 PM 25870918 ER PT J AU Viswanathan, AN Erickson, BA AF Viswanathan, Akila N. Erickson, Beth A. TI Seeing is saving: The benefit of 3D imaging in gynecologic brachytherapy SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Brachytherapy; Cervical cancer; Image-guidance; MRI; CT ID ADVANCED CERVICAL-CANCER; DOSE-RATE BRACHYTHERAPY; GUIDED ADAPTIVE BRACHYTHERAPY; COMBINED INTRACAVITARY/INTERSTITIAL BRACHYTHERAPY; SOCIETY CONSENSUS GUIDELINES; EXTERNAL-BEAM RADIOTHERAPY; LOCALLY ADVANCED-CARCINOMA; MAGNETIC-RESONANCE; INTERSTITIAL BRACHYTHERAPY; COMPUTED-TOMOGRAPHY AB Despite a concerning decline in the use of brachytherapy over the past decade, no other therapy is able to deliver a very high dose of radiation into or near a tumor, with a rapid fall-off of dose to adjacent structures. Compared to traditional X-ray-based brachytherapy that relies on points, the use of CT and MR for 3D planning of gynecologic brachytherapy provides a much more accurate volume-based calculation of dose to an image-defined tumor and to the bladder, rectum, sigmoid, and other pelvic organs at risk (OAR) for radiation complications. The publication of standardized guidelines and an online contouring teaching atlas for performing 3D image-based brachytherapy has created a universal platform for communication and training. This has resulted in a uniform approach to using image-guided brachytherapy for treatment and an internationally accepted format for reporting clinical outcomes. Significant improvements in survival and reductions in toxicity have been reported with the addition of image guidance to increase dose to tumor and decrease dose to the critical OAR. Future improvements in individualizing patient treatments should include a more precise definition of the target. This will allow dose modulation based on the amount of residual disease visualized on images obtained at the time of brachytherapy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Erickson, Beth A.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53266 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu; berickson@mcw.edu FU [NCI R21 167800] FX Dr Viswanathan receives support through NCI R21 167800. Thank you to Barbara Silver for reviewing this manuscript. NR 72 TC 2 Z9 2 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2015 VL 138 IS 1 BP 207 EP 215 DI 10.1016/j.ygyno.2015.02.025 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CL3HN UT WOS:000356841100032 PM 25748646 ER PT J AU Bhatt, AD Goodwin, N Cash, E Bhatt, G Silverman, CL Spanos, WJ Bumpous, JM Potts, K Redman, R Allison, WA Dunlap, NE AF Bhatt, Aashish D. Goodwin, Nicole Cash, Elizabeth Bhatt, Geetika Silverman, Craig L. Spanos, William J. Bumpous, Jeffrey M. Potts, Kevin Redman, Rebecca Allison, Wes A. Dunlap, Neal E. TI Impact of transcutaneous neuromuscular electrical stimulation on dysphagia in patients with head and neck cancer treated with definitive chemoradiation SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE Vital Stim; laryngectomy; dysphagia; radiation; chemotherapy ID QUALITY-OF-LIFE; INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; SWALLOWING DYSFUNCTION; STROKE PATIENTS; CHEMOTHERAPY; CONCURRENT; ASPIRATION; METAANALYSIS; TOXICITY AB BackgroundThe purpose of this study was to investigate the role of transcutaneous neuromuscular electrical stimulation (TNMES) therapy in maintaining swallowing function during chemoradiation for locally advanced head and neck cancer. MethodsWe retrospectively compared 43 consecutive patients with locally advanced head and neck cancer treated with TNMES (treatment group) to 55 control patients. Validated swallowing scale scores were assigned. ResultsAll patients' swallowing scores declined post-chemoradiotherapy. A difference in mean decline in scores for the control group versus the treatment group using the Functional Oral Intake Scale (FOIS) was seen, favoring TNMES intervention (23% vs 7%; p = .015). Age, race, >10 pack-years smoking, diabetes, stage, nodal disease, accelerated fractionation, weight loss, dietary modification, no TNMES, and radiotherapy dose were all significant for poorer scores on the swallowing scales. ConclusionTNMES should be considered an adjunct to dysphagia reduction and possible prevention in patients with locally advanced head and neck cancer. Further studies should be conducted to define the benefit of TNMES intervention. (c) 2015 Wiley Periodicals, Inc. Head Neck 37: 1051-1056, 2015 C1 [Bhatt, Aashish D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Goodwin, Nicole] Univ Louisville, Dept Speech Language Pathol, Louisville, KY 40202 USA. [Cash, Elizabeth; Bumpous, Jeffrey M.; Potts, Kevin] Univ Louisville, Sch Med, Div Otolaryngol HNS, Dept Surg, Louisville, KY 40202 USA. [Bhatt, Geetika] Univ Louisville, Dept Internal Med, Louisville, KY 40202 USA. [Silverman, Craig L.; Spanos, William J.; Dunlap, Neal E.] Univ Louisville, Dept Radiat Oncol, Louisville, KY 40202 USA. [Redman, Rebecca] Univ Louisville, Dept Internal Med, Div Hematol, Louisville, KY 40202 USA. [Allison, Wes A.] Adv ENT & Allergy, Louisville, KY USA. RP Dunlap, NE (reprint author), Univ Louisville, Dept Radiat Oncol, 401 E Chestnut St,580, Louisville, KY 40202 USA. EM nedunl01@louisville.edu NR 26 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 2015 VL 37 IS 7 BP 1051 EP 1056 DI 10.1002/hed.23708 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CL2WH UT WOS:000356807300019 PM 24710791 ER PT J AU Pillarisetti, J Reddy, YM Gunda, S Swarup, V Lee, R Rasekh, A Horton, R Massumi, A Cheng, J Bartus, K Badhwar, N Han, F Atkins, D Bommana, S Earnest, M Nath, J Ferrell, R Bormann, S Dawn, B Di Biase, L Mansour, M Natale, A Lakkireddy, D AF Pillarisetti, Jayasree Reddy, Yeruva Madhu Gunda, Sampath Swarup, Vijay Lee, Randall Rasekh, Abdi Horton, Rodney Massumi, Ali Cheng, Jie Bartus, Krzystzof Badhwar, Nitish Han, Frederick Atkins, Donita Bommana, Sudharani Earnest, Matthew Nath, Jayant Ferrell, Ryan Bormann, Steven Dawn, Buddhadeb Di Biase, Luigi Mansour, Moussa Natale, Andrea Lakkireddy, Dhanunjaya TI Endocardial (Watchman) vs epicardial (Lariat) left atrial appendage exclusion devices: Understanding the differences in the location and type of leaks and their clinical implications SO HEART RHYTHM LA English DT Article DE Watchman device; Lariat; Left atrial appendage; Exclusion; Efficacy; Safety ID STROKE RISK; INITIAL-EXPERIENCE; WARFARIN THERAPY; FIBRILLATION; CLOSURE; ANTICOAGULATION; LIGATION; THROMBUS; OBLITERATION; PREVENTION AB BACKGROUND Watchman and Lariat left atrial appendage (LAA) occlusion devices are associated with LAA leaks postdeployment. OBJECTIVE The purpose of this study was to compare the incidence, characteristics, and clinical significance of these leaks. METHODS We performed a multicenter prospective observational study of all patients who underwent LAA closure. Baseline, procedural, and imaging variables along with LAA occlusion rates at 30-90 days and 1-year postprocedure were compared. RESULTS A total of 478 patients (219 with the Watchman device and 259 with the Lariat device) with successful implants were included. Patients in the Lariat group had a higher CHADS(2) (congestive heart failure, hypertension, age >74 years, diabetes, stroke) score and a larger left atrium and LAA. A total of 79 patients (17%) had a detectable leak at 1 year. More patients in the Watchman group had a leak compared with those in the Lariat group (46 [21%] vs 33 [14%]; P = .019). All the leaks were eccentric (edge effect) in the Watchman group and concentric (gunny sack effect) in the Lariat group. The size of the leak was Larger in the Watchman group than in the Lariat group (3.10 +/- 1.5 mm vs 2.15 +/- 1.3 mm; P = .001). The Watchman group had 1 device embolization requiring surgery and 2 pericardial effusions requiring pericardiocentesis. In the Lariat group, 4 patients had cardiac tamponade requiring urgent surgical repair. Three patients in each group had a cerebrovascular accident and were not associated with device Leaks. CONCLUSION The Lariat device is associated with a lower rate of leaks at 1 year as compared with the Watchman device, with no difference in rates of cerebrovascular accident. There was no correlation between the presence of residual leak and the occurrence of cerebrovascular accident. C1 [Pillarisetti, Jayasree; Reddy, Yeruva Madhu; Atkins, Donita; Bommana, Sudharani; Earnest, Matthew; Nath, Jayant; Ferrell, Ryan; Bormann, Steven; Dawn, Buddhadeb; Lakkireddy, Dhanunjaya] Univ Kansas, Hosp & Med Ctr, Cardiovasc Res Inst, Div Cardiovasc Dis, Kansas City, KS 66196 USA. [Swarup, Vijay] Univ Kansas, Hosp & Med Ctr, Cardiovasc Res Inst, Div Cardiovasc Dis, Kansas City, KS 66196 USA. [Lee, Randall] Univ San Francisco, San Francisco, CA 94117 USA. [Rasekh, Abdi; Massumi, Ali; Cheng, Jie] St Lukes Hosp, Texas Heart Inst, Houston, TX USA. [Horton, Rodney] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Cheng, Jie] Univ Texas Houston, Houston, TX USA. [Bartus, Krzystzof] John Paul II, Krakow, Poland. [Han, Frederick] Univ Utah, Salt Lake City, UT USA. [Di Biase, Luigi; Natale, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lakkireddy, D (reprint author), Univ Kansas, Med Ctr & Hosp, Ctr Excellencein Atrial Fibrillat & EP, Res Div Cardiovasc Dis, 3901 Rainbow Blvd,G-600, Kansas City, KS 66196 USA. EM dlakkireddy@gmail.com OI Di Biase, Luigi/0000-0001-6508-4047 FU SentreHEART FX Dr Lakkireddy has received unrestricted research grant and modest speaker's honorarium from SentreHEART; he has served as a consultant to Estech. Dr Lee is a stakeholder in SentreHEART. Dr Mansour has received modest speaker's honorarium from SentreREART. NR 35 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2015 VL 12 IS 7 BP 1501 EP 1507 DI 10.1016/j.hrthm.2015.03.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL2II UT WOS:000356766500022 PM 25778430 ER PT J AU Varada, S Mahalingam, M AF Varada, Sowmya Mahalingam, Meera TI Mutation stability in primary and metastatic melanoma: what we know and what we don't SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE Melanoma; Mutations; Stability; BRAF; NRAS ID BRAF-MUTANT MELANOMA; DNA-REPAIR PATHWAYS; ACQUIRED-RESISTANCE; TARGETED THERAPY; DRUG-RESISTANCE; NRAS MUTATIONS; PRIMARY TUMORS; HETEROGENEITY; LANDSCAPE; MEDICINE AB Despite the efficacy and success of targeted therapies, a significant number of patients with melanoma exhibit either intrinsic or acquired resistance to these drugs. Numerous mechanisms for the development of resistance have been postulated, but the precise reason for this is not known. In this review, we examine the incidence of mutations in select genes (BRAF, NRAS, C-KIT, and GNAQ) known to occur in melanoma, specifically in primary tumors and their paired metastases, to understand the significance of intratumoral heterogeneity by assessing how changes in mutation status alters the process of metastatic spread. Our data revealed a small yet consistent degree of discordance of mutations in the MAPK pathway commonly occurring in melanoma indicating that failed targeted therapy may be a consequence of this. C1 [Varada, Sowmya] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Mahalingam, Meera] VA Boston Healthcare Syst, New England Dept Pathol & Lab Med 113, West Roxbury, MA USA. RP Mahalingam, M (reprint author), 609 Albany St,J-301, Boston, MA 02118 USA. EM me@meeramahalingam.com NR 43 TC 4 Z9 4 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 EI 1699-5848 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2015 VL 30 IS 7 BP 763 EP 770 DI 10.14670/HH-11-584 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CL2XN UT WOS:000356811200001 PM 25585249 ER PT J AU Ma, B Khazali, A Wells, A AF Ma, Bo Khazali, Ahmad Wells, Alan TI CXCR3 in carcinoma progression SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE Chemokines; Cancer; CXCR3; CXCR3-A; CXCR3-B ID CHEMOKINE RECEPTOR CXCR3; RENAL-CELL CARCINOMA; METASTATIC BREAST-CANCER; ACTIVATED T-LYMPHOCYTES; LUNG-CANCER; UP-REGULATION; OVARIAN CANCERS; LIGAND-BINDING; MURINE MODEL; LYMPH-NODES AB CXCR3 is a G-protein coupled receptor which binds to ELR-negative CXC chemokines that have been found to impact immune responses, vascular develop, and wound repair. More recently, CXCR3 has been examined in the context of cancer and increased expression in many human tumors has been correlated with poor prognosis in breast, melanoma, colon and renal cancer patients. Three variants of CXCR3 are identified so far (CXCR3-A, CXCR3-B and CXCR3-alt) with the two primary ones, CXCR3-A and CXCR3-B, considered to induce opposite physiological functions. Generally, CXCR3-A, the predominant form in hematopoietic cells, appears to mediate tumor "go" signaling via promoting cell proliferation, survival, chemotaxis, invasion and metastasis; while CXCR3-B, the main form on formed elements including epithelial cells, appears to mediate tumor "stop" signaling via promoting growth suppression, apoptosis and vascular involution. Thus, aberrant expression of the isoforms CXCR3-A and CXCR3-B could affect tumor progression. In this review, we have discussed the profiles of CXCR3 variants and related signaling, as well as the role of CXCR3 variants in cancer. C1 [Wells, Alan] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. EM wellsa@upmc.edu OI Wells, Alan/0000-0002-1637-8150 FU VA Merit Program; DoD CDMRP in Breast and Prostate Cancer; NIH [UH2 TR000496] FX This study was supported by grants from the VA Merit Program and the DoD CDMRP in Breast and Prostate Cancer, and the NIH UH2 TR000496. NR 72 TC 4 Z9 5 U1 1 U2 8 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 EI 1699-5848 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2015 VL 30 IS 7 BP 781 EP 792 DI 10.14670/HH-11-594 PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CL2XN UT WOS:000356811200003 PM 25663474 ER PT J AU Ellenson, LH Young, RH AF Ellenson, Lora Hedrick Young, Robert H. TI A New Historical Feature for the Journal: Eponyms and Entities SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Editorial Material C1 [Ellenson, Lora Hedrick] New York Presbyterian Hosp, Dept Pathol & Lab Med, Weill Cornell Med Coll, New York, NY 10065 USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Ellenson, LH (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 1300 York Ave,F309D, New York, NY 10065 USA. EM lora.ellenson@med.cornell.edu; rhyoung@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2015 VL 34 IS 4 BP 313 EP 313 DI 10.1097/PGP.0000000000000224 PG 1 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA CK9VU UT WOS:000356588400001 PM 26061069 ER PT J AU Rosai, J Young, RH AF Rosai, Juan Young, Robert H. TI Eponyms and Entities Javier Arias-Stella and His Famous Reaction SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Arias-Stella reaction; Javier Arias-Stella; M; D; History of Pathology ID HISTOLOGY; CELL C1 [Rosai, Juan] Ctr Diagnost Italiano, Milan, Italy. [Rosai, Juan] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 24 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2015 VL 34 IS 4 BP 314 EP 322 DI 10.1097/PGP.0000000000000223 PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA CK9VU UT WOS:000356588400002 PM 26061070 ER PT J AU Bennett, JA Sanada, S Selig, MK Hariri, LP Nielsen, GP Oliva, E AF Bennett, Jennifer A. Sanada, Sakiko Selig, Martin K. Hariri, Lida P. Nielsen, Gunnlaugur P. Oliva, Esther TI Giant Cell Tumor of the Uterus: A Report of 3 Cases With a Spectrum of Morphologic Features SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Giant cell tumor; Osteoclast-like giant cells; Uterine carcinoma and; or sarcoma ID UNDIFFERENTIATED PLEOMORPHIC SARCOMA; INFLAMMATORY MYOFIBROBLASTIC TUMOR; MALIGNANT FIBROUS HISTIOCYTOMA; OF-THE-LITERATURE; SOFT-TISSUE; UTERINE LEIOMYOSARCOMA; SMOOTH-MUSCLE; BONE-TUMORS; H-CALDESMON; CYCLIN D1 AB Giant cell tumors, a well-recognized neoplasm of bone, can rarely be found in the uterus. Such tumors are characterized by a dual population of mononuclear and osteoclast-like giant cells that lack epithelial and specific mesenchymal differentiation. In this study, the clinicopathologic features of 3 giant cell tumors of the uterus were reviewed. Immunohistochemistry for CD68, CD163, h-caldesmon, desmin, SMA, AE1/AE3, CD10, ER, PR, cyclin D1, CD1a, CD34, CD30, S100, myogenin/myoglobin, and Ki-67 was performed in all tumors, along with ultrastructural analysis in one. The patients were 47, 57, and 59 yr and the tumors measured 2.5, 7.5, and 16.0 cm. One neoplasm was confined to the endometrium, whereas the other 2 were myometrial. All 3 tumors showed a nodular growth comprised of mononuclear and osteoclast-like giant cells. The endometrial-confined tumor consisted of histologically benign mononuclear cells, whereas the others exhibited marked atypia. Mitotic activity was up to 5/10 HPF in the benign tumor and up to 22/10 HPF in the malignant. No cytologic atypia or mitoses were observed in the giant cells. CD68 and CD10 were strongly and diffusely expressed in both components of 3 and 2 neoplasms, respectively. Cyclin D1 was focal in the mononuclear cells and focal to diffuse in the giant cells. CD163 was diffuse in the mononuclear cells, but absent to focal in the giant cells. Ultrastructural analysis lacked diagnostic features of epithelial or specific mesenchymal differentiation. Both malignant tumors demonstrated an aggressive behavior. In summary, although rare, giant cell tumor of the uterus should be included in the differential diagnosis of benign or malignant tumors containing osteoclast-like giant cells. C1 [Bennett, Jennifer A.; Selig, Martin K.; Hariri, Lida P.; Nielsen, Gunnlaugur P.; Oliva, Esther] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Bennett, Jennifer A.; Selig, Martin K.; Hariri, Lida P.; Nielsen, Gunnlaugur P.; Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sanada, Sakiko] Kurume Univ, Sch Med, Dept Pathol, Fukuoka, Japan. RP Bennett, JA (reprint author), Lahey Hosp & Med Ctr, Dept Pathol, 41 Mall Rd, Burlington, MA 01805 USA. EM Jennifer.A.Bennett@lahey.org NR 66 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2015 VL 34 IS 4 BP 340 EP 350 DI 10.1097/PGP.0000000000000164 PG 11 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA CK9VU UT WOS:000356588400005 PM 25851705 ER PT J AU Bennett, JA Oliva, E Young, RH AF Bennett, Jennifer A. Oliva, Esther Young, Robert H. TI Sclerosing Stromal Tumors With Prominent Luteinization During Pregnancy: A Report of 8 Cases Emphasizing Diagnostic Problems SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Sclerosing stromal tumor; Pregnancy; Lutein cells ID STEROID CELL TUMORS; OF-THE-LITERATURE; CLINICOPATHOLOGICAL ANALYSIS; LEYDIG-CELL; OVARY; INHIBIN; CALRETININ; NEOPLASMS; MARKER; WOMAN AB Ovarian tumors encountered during pregnancy can pose a diagnostic challenge due to an abundance of luteinized cells and other changes. We report 8 sclerosing stromal tumors with massive luteinization discovered in pregnant patients. The tumors ranged from 3.1 to 21 cm (mean=8.8 cm) in size and were typically solid and yellow; the neoplasm was bilateral in 1 case. On microscopic examination, the lutein cells, a feature of sclerosing stromal tumor, had more copious eosinophilic cytoplasm and were more numerous than is usually seen in nonpregnant patients and to varying degrees obscured the typical pseudolobular pattern. This resulted in particular diagnostic difficulty in 3 cases, especially when associated with other changes including irregular shapes of tumor cell nests, edema, and/or myxoid change. However, classic features of these tumors: ectatic vessels and admixed luteinized and nonluteinized cells were still focally evident, allowing for accurate classification. The tumors were cytologically bland and with 1 exception had rare mitoses. As sclerosing stromal tumors have been invariably benign, it is important that they not be confused with other tumors, such as steroid cell tumor, which can occasionally be malignant. C1 [Bennett, Jennifer A.; Oliva, Esther; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Bennett, Jennifer A.; Oliva, Esther; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bennett, JA (reprint author), Lahey Hosp & Med Ctr, Dept Pathol, 41 Mall Rd, Burlington, MA 01805 USA. EM jennifer.a.bennett@lahey.org NR 32 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2015 VL 34 IS 4 BP 357 EP 362 DI 10.1097/PGP.0000000000000163 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA CK9VU UT WOS:000356588400007 PM 25851706 ER PT J AU Pabayo, R Kawachi, I Gilman, SE AF Pabayo, Roman Kawachi, Ichiro Gilman, Stephen E. TI US State-level income inequality and risks of heart attack and coronary risk behaviors: longitudinal findings SO INTERNATIONAL JOURNAL OF PUBLIC HEALTH LA English DT Article DE Income inequality; Coronary heart disease; Social determinants of health; Multilevel modeling; Longitudinal analysis; Population-based study ID STROKE STATISTICS-2013 UPDATE; UNITED-STATES; SOCIOECONOMIC POSITION; HEALTH INEQUALITIES; PHYSICAL-ACTIVITY; SOCIAL COHESION; DISEASE; ASSOCIATION; PREVALENCE; ALCOHOL AB To examine prospectively the association between US state income inequality and incidence of heart attack. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,445). Respondents completed interviews at baseline (2001-2002) and follow-up (2004-2005). Weighted multilevel modeling was used to determine if US state-level income inequality (measured by the Gini coefficient) at baseline was a predictor of heart attack during follow-up, controlling for individual-level and state-level covariates. In comparison to residents of US states in the lowest quartile of income inequality, those living in the second [Adjusted Odds Ratio (AOR) = 1.71, 95 % CI 1.16-2.53)], third (AOR = 1.81, 95 % CI 1.28-2.57), and fourth (AOR = 2.04, 95 % CI 1.26-3.29) quartiles were more likely to have a heart attack. Similar findings were obtained when we excluded those who had a heart attack prior to baseline. This study is one of the first to empirically show the longitudinal relationship between income inequality and coronary heart disease. Living in a state with higher income inequality increases the risk for heart attack among US adults. C1 [Pabayo, Roman] Univ Nevada, Dept Community Hlth Sci, Reno, NV 89557 USA. [Pabayo, Roman; Kawachi, Ichiro; Gilman, Stephen E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pabayo, R (reprint author), Univ Nevada, Dept Community Hlth Sci, Lombardi Bldg 203,MS 0274,1664 North Virginia St, Reno, NV 89557 USA. EM rpabayo@unr.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU NIH [MH087544]; Canadian Institutes of Health Research [234617] FX This work was supported by NIH-grant number MH087544. RP was a Canadian Institutes of Health Research post-doctoral fellowship recipient #234617. NR 50 TC 4 Z9 4 U1 1 U2 9 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1661-8556 EI 1661-8564 J9 INT J PUBLIC HEALTH JI Int. J. Public Health PD JUL PY 2015 VL 60 IS 5 BP 573 EP 588 DI 10.1007/s00038-015-0678-7 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL2WX UT WOS:000356809400007 PM 25981210 ER PT J AU Liggins, JTP Yoo, AJ Mishra, NK Wheeler, HM Straka, M Leslie-Mazwi, TM Chaudhry, ZA Kemp, S Mlynash, M Bammer, R Albers, GW Lansberg, MG AF Liggins, John T. P. Yoo, Albert J. Mishra, Nishant K. Wheeler, Hayley M. Straka, Matus Leslie-Mazwi, Thabele M. Chaudhry, Zeshan A. Kemp, Stephanie Mlynash, Michael Bammer, Roland Albers, Gregory W. Lansberg, Maarten G. CA DEFUSE 2 Investigators TI A score based on age and DWI volume predicts poor outcome following endovascular treatment for acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute care; acute stroke; interventional neuroradiology; thrombolysis ID INFARCT VOLUME; THERAPY; RECANALIZATION; REPERFUSION; DIFFUSION; DEFUSE; TRIAL AB Background and AimsThe Houston Intra-Arterial Therapy score predicts poor functional outcome following endovascular treatment for acute ischemic stroke based on clinical variables. The present study sought to (a) create a predictive scoring system that included a neuroimaging variable and (b) determine if the scoring systems predict the clinical response to reperfusion. MethodsSeparate datasets were used to derive (n=110 from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 study) and validate (n=125 from Massachusetts General Hospital) scoring systems that predict poor functional outcome, defined as a modified Rankin Scale score of 4-6 at 90 days. ResultsAge (P<0001; =0087) and diffusion-weighted imaging volume (P=0023; =0025) were the independent predictors of poor functional outcome. The Stanford Age and Diffusion-Weighted Imaging score was created based on the patient's age (0-3 points) and diffusion-weighted imaging lesion volume (0-1 points). The percentage of patients with a poor functional outcome increased significantly with the number of points on the Stanford Age and Diffusion-Weighted Imaging score (P<001 for trend). The area under the receiver operating characteristic curve for the Stanford Age and Diffusion-Weighted Imaging score was 082 in the derivation dataset. In the validation cohort, the area under the receiver operating characteristic curve was 069 for the Stanford Age and Diffusion-Weighted Imaging score and 066 for the Houston Intra-Arterial Therapy score (P=045 for the difference). Reperfusion, but not the interactions between the prediction scores and reperfusion, were predictors of outcome (P>05). ConclusionsThe Stanford Age and Diffusion-Weighted Imaging and Houston Intra-Arterial Therapy scores can be used to predict poor functional outcome following endovascular therapy with good accuracy. However, these scores do not predict the clinical response to reperfusion. This limits their utility as tools to select patients for acute stroke interventions. C1 [Liggins, John T. P.; Mishra, Nishant K.; Wheeler, Hayley M.; Kemp, Stephanie; Mlynash, Michael; Albers, Gregory W.; Lansberg, Maarten G.] Stanford Univ, Med Ctr, Stanford Stroke Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Straka, Matus; Bammer, Roland] Stanford Univ, Med Ctr, Lucas Magnet Resonance Spect & Imaging Ctr, Dept Radiol, Stanford, CA 94305 USA. [Yoo, Albert J.; Leslie-Mazwi, Thabele M.; Chaudhry, Zeshan A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Liggins, JTP (reprint author), Stanford Univ, Sch Med, Stanford Stroke Ctr, 1215 Welch Rd, Stanford, CA 94305 USA. EM jliggins@stanford.edu OI Mishra, Nishant/0000-0002-9327-3707 FU National Institute for Neurological Disorders and Stroke [R01 NS03932505, K23 NS051372]; Stanford Medical Scholars Fellowship Program FX The study was funded by grants from the National Institute for Neurological Disorders and Stroke (R01 NS03932505 to GWA and K23 NS051372 to MGL) and the Stanford Medical Scholars Fellowship Program. NR 11 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JUL PY 2015 VL 10 IS 5 BP 705 EP 709 DI 10.1111/ijs.12207 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CL1QD UT WOS:000356718000022 PM 24207136 ER PT J AU Wintermark, M Luby, M Bornstein, NM Demchuk, A Fiehler, J Kudo, K Lees, KR Liebeskind, DS Michel, P Nogueira, RG Parsons, MW Sasaki, M Wardlaw, JM Wu, O Zhang, WW Zhu, GM Warach, SJ AF Wintermark, Max Luby, Marie Bornstein, Natan M. Demchuk, Andrew Fiehler, Jens Kudo, Kohsuke Lees, Kennedy R. Liebeskind, David S. Michel, Patrik Nogueira, Raul G. Parsons, Mark W. Sasaki, Makoto Wardlaw, Joanna M. Wu, Ona Zhang, Weiwei Zhu, Guangming Warach, Steven J. TI International survey of acute Stroke imaging used to make revascularization treatment decisions SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE CT; MRI; penumbra; perfusion imaging; stroke; vascular imaging ID ACUTE ISCHEMIC-STROKE; ENDOVASCULAR TREATMENT; TRIAL AB BackgroundTo assess the differences across continental regions in terms of stroke imaging obtained for making acute revascularization therapy decisions, and to identify obstacles to participating in randomized trials involving multimodal imaging. MethodsSTroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and the above mentioned societies. ResultsWe received responses from 223 centers (2 from Africa, 38 from Asia, 10 from Australia, 101 from Europe, 4 from Middle East, 55 from North America, 13 from South America). In combination, the sites surveyed administered acute revascularization therapy to a total of 25326 acute stroke patients in 2012. Seventy-three percent of these patients received intravenous (IV) tissue plasminogen activator (tPA), and 27%, endovascular therapy. Vascular imaging was routinely obtained in 79% (152/193) of sites for endovascular therapy decisions, and also as part of standard IV tPA treatment decisions at 46% (92/198) of sites. Modality, availability and use of acute vascular and perfusion imaging before revascularization varied substantially between geographical areas. The main obstacles to participate in randomized trials involving multimodal imaging included: mainly insufficient research support and staff (50%, 79/158) and infrequent use of multimodal imaging (27%, 43/158) . ConclusionThere were significant variations among sites and geographical areas in terms of stroke imaging work-up used tomake decisions both for intravenous and endovascular revascularization. Clinical trials using advanced imaging as a selection tool for acute revascularization therapy should address the need for additional resources and technical support, and take into consideration the lack of routine use of such techniques in trial planning. C1 [Wintermark, Max] Stanford Univ, Dept Radiol, Neuroradiol, Palo Alto, CA 94304 USA. [Luby, Marie] NINDS, NIH, Bethesda, MD 20892 USA. [Luby, Marie; Warach, Steven J.] UT Southwestern Med Ctr, Dept Neurol & Neurotherapeut, Seton UT Southwestern Clin Res Inst Austin, Austin, TX USA. [Bornstein, Natan M.] Tel Aviv Univ, Sackler Fac Med, Dept Neurol, Elias Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Demchuk, Andrew] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Demchuk, Andrew] Univ Calgary, Hotchkiss Brain Inst, Dept Radiol, Calgary, AB, Canada. [Fiehler, Jens] Univ Med Ctr Hamburg Eppendorf, Dept Neuroradiol, Hamburg, Germany. [Kudo, Kohsuke] Hokkaido Univ Hosp, Dept Diagnost Radiol, Sapporo, Hokkaido 060, Japan. [Lees, Kennedy R.] Univ Glasgow, Western Infirm, Univ Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. [Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, Stroke Ctr, Los Angeles, CA 90024 USA. [Michel, Patrik] Univ Lausanne, CHU Vaudois, Lausanne, Switzerland. [Nogueira, Raul G.] Emory Univ, Sch Med, Marcus Stroke & Neurosci Ctr, Atlanta, GA USA. [Parsons, Mark W.] Univ Newcastle, Dept Neurol, John Hunter Hosp, Med Res Inst, Newcastle, NSW 2300, Australia. [Sasaki, Makoto] Iwate Med Univ, Inst Biomed Sci, Yahaba, Iwate, Japan. [Wardlaw, Joanna M.] Univ Edinburgh, Ctr Clin Brain Sci, Brain Res Imaging Ctr, Div Neuroimaging Sci, Edinburgh, Midlothian, Scotland. [Wu, Ona] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Wu, Ona] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Weiwei; Zhu, Guangming] Beijing PLA, Mil Gen Hosp, Dept Neurol, Beijing, Peoples R China. RP Wintermark, M (reprint author), UVA Dept Radiol, Neuroradiol Div, Radiol Neurol Neurosurg & Biomed Engn, Box 800170, Charlottesville, VA 22908 USA. EM Max.Wintermark@gmail.com RI Michel, Patrik/Q-2275-2016; OI Michel, Patrik/0000-0003-4954-7579; Wintermark, Max/0000-0002-6726-3951 FU Intramural NIH HHS [Z99 NS999999] NR 7 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JUL PY 2015 VL 10 IS 5 BP 759 EP 762 DI 10.1111/ijs.12491 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CL1QD UT WOS:000356718000030 PM 25833105 ER PT J AU Menendez, ME Neuhaus, V Ring, D AF Menendez, Mariano E. Neuhaus, Valentin Ring, David TI Inpatient mortality after orthopaedic surgery SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Mortality; Charlson; Elixhauser; Orthopaedic surgery; Risk adjustment; Outcome; Prediction ID IN-HOSPITAL MORTALITY; CHARLSON COMORBIDITY INDEX; SIMPLE-RISK-SCORE; ADMINISTRATIVE DATA; PERIOPERATIVE MORTALITY; KNEE ARTHROPLASTY; HIP-FRACTURES; UNITED-STATES; ADJUSTMENT; VALIDATION AB Purpose Adequate comorbidity risk adjustment is central for reliable outcome prediction and provider performance evaluation. The two most commonly employed risk-adjustment methods in orthopaedic surgery were not originally validated in this patient population. We sought (1) to develop a single numeric comorbidity score for predicting inpatient mortality in patients undergoing orthopaedic surgery by combining and reweighting the conditions included in the Charlson and Elixhauser measures, and to compare its predictive performance to each of the separate component scores. We also (2) evaluated the new score separately for spine surgery, adult reconstruction, hip fracture, and musculoskeletal oncology admissions. Methods Data from the National Hospital Discharge Survey for the years 1990 through 2007 were obtained. A comorbidity score for predicting inpatient mortality was developed by combining conditions from the Charlson and Elixhauser measures. Weights were derived from a random sample of 80 % of the cohort (n = 26,454,972), and the predictive ability of the new score was internally validated on the remaining 20 % (n = 6,739,169). Performance of scores was assessed and compared using the area under the receiver operating characteristic curve (AUC) derived from multivariable logistic regression models. Results The new combined comorbidity score (AUC = 0.858, 95 % CI 0.856-0.859) performed 58 % better than the Charlson score (AUC = 0.794, 95 % CI 0.792-0.796) and 12 % better than the Elixhauser score (AUC = 0.845, 95 % CI 0.844-0.847). Of the seven conditions that received the highest weights in the new combined score, only three of them were included in both the Charlson and the Elixhauser indices. The new combined score achieved higher discriminatory power for all orthopaedic admission subgroups. Conclusion A single numeric comorbidity score combining conditions from the Charlson and Elixhauser models provided better discrimination of inpatient mortality than either of its constituent scores. Future research should test this score in other populations and data settings. C1 [Menendez, Mariano E.; Neuhaus, Valentin; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM memenendez@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 53 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD JUL PY 2015 VL 39 IS 7 BP 1307 EP 1314 DI 10.1007/s00264-015-2702-1 PG 8 WC Orthopedics SC Orthopedics GA CL2XB UT WOS:000356809900009 PM 25711395 ER PT J AU O'Sullivan, NA Kobayashi, S Ranka, MP Zaleski, KL Yaremchuk, MJ Bonassar, LJ Randolph, MA AF O'Sullivan, Niamh A. Kobayashi, Shinji Ranka, Mitun P. Zaleski, Katherine L. Yaremchuk, Michael J. Bonassar, Lawrence J. Randolph, Mark A. TI Adhesion and integration of tissue engineered cartilage to porous polyethylene for composite ear reconstruction SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE cartilage tissue engineering; integrative repair; biomechanical analysis; adhesion; porous polyethylene; tissue engineered ear ID DIFFERENT CHONDROCYTES; BIOMECHANICAL ANALYSIS; SUBCUTANEOUS IMPLANTS; SHAPED CARTILAGE; NECK-SURGERY; IN-VITRO; MODEL; POLYMER; REPAIR; CONSTRUCT AB The objective of this study was to assess the ability of tissue engineered cartilage to adhere to and integrate with porous polyethylene (PPE) in vivo and to evaluate the biomechanical integrity of the bond formed at the interface. Porcine auricular, articular, and costal chondrocytes were suspended in fibrin gel polymer and placed between discs of PPE to form tri-layer constructs. Controls consisted of fibroblasts suspended in gel or gel alone between the discs. Constructs were implanted into nude mice for 6, 12, and 18 weeks. Upon harvest, specimens were evaluated for neocartilage formation and integration into the PPE, using histological, dimensional (mass, thickness, diameter), and biomechanical (adhesion strength, interfacial stiffness, failure energy and failure strain) analyses. Neotissue was formed in all experimental constructs, consisting mostly of neocartilage integrating with discs of PPE. Control samples contained only fibrous tissue. Biomechanical analyses demonstrated that adhesion strength, interfacial stiffness, and failure energy were all significantly higher in the chondrocyte-seeded samples than in fibroblast-seeded controls, with the exception of costal constructs at 12 weeks, which were not significantly greater than controls. In general, failure strains did not vary between groups. In conclusion, porous polyethylene supported the growth of neocartilage that formed mechanically functional bonds with the PPE. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 983-991, 2015. C1 [O'Sullivan, Niamh A.; Kobayashi, Shinji; Ranka, Mitun P.; Zaleski, Katherine L.; Yaremchuk, Michael J.; Randolph, Mark A.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Bonassar, Lawrence J.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Bonassar, Lawrence J.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. [Randolph, Mark A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. EM marandolph@mgh.harvard.edu RI Bonassar, Lawrence/C-2103-2016; Randolph, Mark/A-4406-2009 OI Bonassar, Lawrence/0000-0003-1094-6433; NR 36 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD JUL PY 2015 VL 103 IS 5 BP 983 EP 991 DI 10.1002/jbm.b.33269 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CL0ZO UT WOS:000356671800004 PM 25196223 ER PT J AU Ominsky, MS Libanati, C Niu, QT Boyce, RW Kostenuik, PJ Wagman, RB Baron, R Dempster, DW AF Ominsky, Michael S. Libanati, Cesar Niu, Qing-Tian Boyce, Rogely W. Kostenuik, Paul J. Wagman, Rachel B. Baron, Roland Dempster, David W. TI Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ANTIRESORPTIVES; BONE HISTOMORPHOMETRY; BONE MODELING AND REMODELING; OSTEOPOROSIS; PRECLINICAL STUDIES ID HUMAN RANKL ANTIBODY; POSTMENOPAUSAL WOMEN; STRUCTURAL ADAPTATIONS; COMPUTED-TOMOGRAPHY; TURNOVER MARKERS; ZOLEDRONIC ACID; TRABECULAR BONE; OSTEOPOROSIS; STRENGTH; ALENDRONATE AB Denosumab (DMAb) administration to postmenopausal women with osteoporosis is associated with continued bone mineral density (BMD) increases and low fracture incidence through 8 years, despite persistently reduced bone turnover markers and limited fluorochrome labeling in iliac crest bone biopsies. BMD increases were hypothesized to result from additional accrual of bone matrix via modeling-based bone formationa hypothesis that was tested by examining fluorochrome labeling patterns in sections from ovariectomized (OVX) cynomolgus monkeys (cynos) treated with DMAb for 16 months. Mature OVX or Sham cynos were treated monthly with vehicle for 16 months, whereas other OVX cynos received monthly 25 or 50mg/kg DMAb. DMAb groups exhibited very low serum bone resorption and formation biomarkers and near-absent fluorochrome labeling in proximal femur cancellous bone. Despite these reductions, femoral neck dual-energy X-ray absorptiometry (DXA) BMD continued to rise in DMAb-treated cynos, from a 4.6% increase at month 6 to 9.8% above baseline at month 16. Further examination of cortical bone in the proximal femur demonstrated consistent and prominent labeling on the superior endocortex and the inferior periosteal surface, typically containing multiple superimposed labels from month 6 to 16 over smooth cement lines, consistent with continuous modeling-based bone formation. These findings were evident in all groups. Quantitative analysis at another modeling site, the ninth rib, demonstrated that DMAb did not alter the surface extent of modeling-based labels, or the cortical area bound by them, relative to OVX controls, while significantly reducing remodeling-based bone formation and eroded surface. This conservation of modeling-based formation occurred concomitantly with increased femoral neck strength and, when coupled with a reduction in remodeling-based bone loss, is likely to contribute to increases in bone mass with DMAb treatment. Thus, this study provides preclinical evidence for a potential mechanism that could contribute to the clinical observations of continued BMD increases and low fracture rates with long-term DMAb administration. (c) 2015 American Society for Bone and Mineral Research. C1 [Ominsky, Michael S.; Niu, Qing-Tian; Kostenuik, Paul J.] Amgen Inc, Metabol Disorders, Thousand Oaks, CA 91320 USA. [Libanati, Cesar; Wagman, Rachel B.] Amgen Inc, Clin Dev, Thousand Oaks, CA 91320 USA. [Boyce, Rogely W.] Amgen Inc, Comparat Biol & Safety Sci, Thousand Oaks, CA 91320 USA. [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Dempster, David W.] Columbia Univ, Coll Physicians & Surg, Clin Pathol & Cell Biol, New York, NY USA. [Dempster, David W.] New York State Dept Hlth, Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. RP Ominsky, MS (reprint author), One Amgen Ctr Dr,MS 29-M-B, Newbury Pk, CA 91320 USA. EM mominsky@amgen.com NR 38 TC 18 Z9 18 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2015 VL 30 IS 7 BP 1280 EP 1289 DI 10.1002/jbmr.2480 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL1PL UT WOS:000356715900015 PM 25684625 ER PT J AU Ang, JWJ Khanna, A Walcott, BP Kahle, KT Eskandar, EN AF Ang, Jensen W. J. Khanna, Arjun Walcott, Brian P. Kahle, Kristopher T. Eskandar, Emad N. TI Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Lymphoma; Skull base; Trigeminal neuralgia ID PRIMARY CNS LYMPHOMA; MIMICKING; BRAIN; BASE AB We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel's cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Khanna, Arjun; Walcott, Brian P.; Kahle, Kristopher T.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ang, Jensen W. J.] Univ Edinburgh, Coll Med & Vet Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Khanna, Arjun; Walcott, Brian P.; Kahle, Kristopher T.; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,WACC 745, Boston, MA 02115 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 16 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUL PY 2015 VL 22 IS 7 BP 1188 EP 1190 DI 10.1016/j.jocn.2015.01.018 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CK9KE UT WOS:000356558200024 PM 25865026 ER PT J AU Walker, RJ Lynch, CP Williams, JS Voronca, D Egede, LE AF Walker, Rebekah J. Lynch, Cheryl P. Williams, Joni Strom Voronca, Delia Egede, Leonard E. TI Meaning of illness and quality of life in patients with type 2 diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Meaning of illness; Diabetes; Quality of life; Physical health; Mental health ID QUESTIONNAIRE; RELIABILITY; VALIDITY; SCALE AB Background: Investigations into personal factors influencing quality of life are important for those developing strategies to support patients with diabetes. This study aimed to investigate the influence of meaning of illness on quality of life in patients with type 2 diabetes. Methods: Veterans from primary care clinics in the southeastern United States completed a questionnaire including questions from the validated 5-scale Meaning of Illness Questionnaire (MIQ). Unadjusted and adjusted linear regression models investigated the physical and mental components of quality of life with the 5 MIQ factors. Results: The sample comprised 302 Black and White veterans. The physical component of quality of life (PCS) was positively associated with type of stress/attitude of harm (beta = 2.43, CI: 0.94 to 3.93) and challenge/motivation/hope (beta = 3.02, CI: 0.40 to 5.64) after adjustment, whereas the mental component of quality of life (MCS) was positively associated with the degree of stress/change in commitment (beta = 2.58, CI: 0.78 to 438), and negatively associated with challenge/motivation/hope (beta = -2.55, CI: -4.99 to -0.11). Conclusion: Attitudes of challenge, motivation and hope had opposite effects on mental and physical components of quality of life in this sample of veterans. Additionally, whereas, the type of stress and attitude towards harm or loss was associated with the physical component, the degree of stress and change in commitments was associated with the mental component This suggests addressing the meaning of an illness may be complex but is an important consideration in improving both physical and mental components of quality of life in patients with type 2 diabetes. Published by Elsevier Inc. C1 [Walker, Rebekah J.; Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, HEROIC, Charleston, SC USA. [Walker, Rebekah J.; Lynch, Cheryl P.; Williams, Joni Strom; Voronca, Delia; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Williams, Joni Strom; Voronca, Delia; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Hlth Equ & Rural Outreach Innovat Ctr, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU VHA Health Services Research and Development (HSRD) program [TRP 04-038] FX This study was supported by grant #TRP 04-038 (PI: Leonard Egede) funded by the VHA Health Services Research and Development (HSR&D) program. NR 19 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL PY 2015 VL 29 IS 5 BP 665 EP 669 DI 10.1016/j.jdiacomp.2015.04.006 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL4EW UT WOS:000356906400010 PM 25934437 ER PT J AU Lerner-Ellis, J Wang, M White, S Lebo, MS AF Lerner-Ellis, Jordan Wang, Marina White, Shana Lebo, Matthew S. TI Canadian Open Genetics Repository (COGR): a unified clinical genomics database as a community resource for standardising and sharing genetic interpretations SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SEQUENCE AB Background The Canadian Open Genetics Repository is a collaborative effort for the collection, storage, sharing and robust analysis of variants reported by medical diagnostics laboratories across Canada. As clinical laboratories adopt modern genomics technologies, the need for this type of collaborative framework is increasingly important. Methods A survey to assess existing protocols for variant classification and reporting was delivered to clinical genetics laboratories across Canada. Based on feedback from this survey, a variant assessment tool was made available to all laboratories. Each participating laboratory was provided with an instance of GeneInsight, a software featuring versioning and approval processes for variant assessments and interpretations and allowing for variant data to be shared between instances. Guidelines were established for sharing data among clinical laboratories and in the final outreach phase, data will be made readily available to patient advocacy groups for general use. Results The survey demonstrated the need for improved standardisation and data sharing across the country. A variant assessment template was made available to the community to aid with standardisation. Instances of the GeneInsight tool were provided to clinical diagnostic laboratories across Canada for the purpose of uploading, transferring, accessing and sharing variant data. Conclusions As an ongoing endeavour and a permanent resource, the Canadian Open Genetics Repository aims to serve as a focal point for the collaboration of Canadian laboratories with other countries in the development of tools that take full advantage of laboratory data in diagnosing, managing and treating genetic diseases. C1 [Lerner-Ellis, Jordan] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada. [Lerner-Ellis, Jordan] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Lerner-Ellis, Jordan] Ontario Inst Canc Res, Toronto, ON, Canada. [Wang, Marina] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [White, Shana; Lebo, Matthew S.] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA USA. [White, Shana] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lebo, Matthew S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lebo, Matthew S.] Harvard Univ, Sch Med, Boston, MA USA. RP Lerner-Ellis, J (reprint author), Univ Toronto, Lab Med & Pathobiol, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM jlerner-ellis@mtsinai.on.ca RI Campeau, Philippe/J-8614-2015; Karsan, Aly/K-2067-2015; Hegele, Robert/G-3301-2011; Scherer, Stephen /B-3785-2013; Charames, George/J-2328-2016; Lerner-Ellis, Jordan/J-5559-2016; OI Lebo, Matthew/0000-0002-9733-5207; Campeau, Philippe/0000-0001-9713-7107; Scherer, Stephen /0000-0002-8326-1999; Charames, George/0000-0002-5937-9276; Wintle, Richard/0000-0003-1987-1095; Nelson, Tanya/0000-0001-5344-3516 FU Government of Canada through Genome Canada; Ontario Genomics Institute [OGI-070] FX This work was funded by the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-070). NR 14 TC 4 Z9 4 U1 1 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD JUL PY 2015 VL 52 IS 7 BP 438 EP 445 DI 10.1136/jmedgenet-2014-102933 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CL3PH UT WOS:000356861900002 PM 25904639 ER PT J AU Thoonen, R Ernande, L Cheng, J Nagasaka, Y Yao, V Miranda-Bezerra, A Chen, C Chao, W Panagia, M Sosnovik, DE Puppala, D Armoundas, AA Hindle, A Bloch, KD Buys, ES Scherrer-Crosbie, M AF Thoonen, Robrecht Ernande, Laura Cheng, Juan Nagasaka, Yasuko Yao, Vincent Miranda-Bezerra, Alexandre Chen, Chan Chao, Wei Panagia, Marcello Sosnovik, David E. Puppala, Dheeraj Armoundas, Antonis A. Hindle, Allyson Bloch, Kenneth D. Buys, Emmanuel S. Scherrer-Crosbie, Marielle TI Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Brown adipose tissue; Uncoupling protein 1; Isoproterenol; Cardioprotection; Heart failure ID STREPTOZOTOCIN-DIABETIC RATS; MYOCARDIAL-ISCHEMIA; PRESSURE-OVERLOAD; GLUCOSE-HOMEOSTASIS; INSULIN SENSITIVITY; UNCOUPLING PROTEIN; MICE; FAT; ISOPROTERENOL; REPERFUSION AB Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Panagia, Marcello; Sosnovik, David E.; Puppala, Dheeraj; Armoundas, Antonis A.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ernande, Laura] Hop Henri Mondor, AP HP, Fac Med Creteil, DHU Ageing Thorax Vessels Blood,Inserm Unit Team, F-94010 Creteil, France. [Cheng, Juan] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Ultrasound, Shanghai 200030, Peoples R China. [Nagasaka, Yasuko; Chen, Chan; Chao, Wei; Hindle, Allyson; Bloch, Kenneth D.; Buys, Emmanuel S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Pain, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU SPARK award from the Massachusetts General Hospital; French Federation of Cardiology; [R21-DK092909] FX This work was supported by grant R21-DK092909 and a SPARK award from the Massachusetts General Hospital (both to M.S-C.) and a training grant from the French Federation of Cardiology (to L.E.) NR 54 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2015 VL 84 BP 202 EP 211 DI 10.1016/j.yjmcc.2015.05.002 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CL3GU UT WOS:000356839200025 PM 25968336 ER PT J AU Ponte, PR Nicholas, PK AF Ponte, Patricia Reid Nicholas, Patrice K. TI Addressing the Confusion Related to DNS, DNSc, and DSN Degrees, With Lessons for the Nursing Profession SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Doctor of Nursing Practice (DNP); Doctor of Nursing Science (DNS; DNSc); Doctor of Philosophy (PhD); Doctor of Science in Nursing (DSN); doctoral education; nursing education; nursing research ID UNITED-STATES AB PurposeThis article examines the evolution of Doctor of Nursing Science (DNS or DNSc) and Doctor of Science in Nursing (DSN) degrees, including their emergence as research-intensive doctoral degrees in the 1960s, efforts to distinguish the degrees from the Doctor of Philosophy (PhD) and Doctor of Nursing Practice (DNP) degrees, the recent decline in program numbers, and implications for degree holders. ApproachThe article reviews the U.S. history of doctoral education in nursing, research examining similarities and differences between the PhD and DNS, DNSc, or DSN degrees, and how the DNS, DNSc, or DSN degree differs from DNP programs. The article also examines the confusion regarding the focus of the DNS, DNSc, or DSN degree among nurses, patients, and potential funders; and describes actions taken by universities to address the confusion, with examples provided by academic deans, nurse leaders, and nurse researchers. FindingsLongstanding confusion about the research merits of the DNS, DNSc, or DSN degree, and the growing prominence of the similarly-titled DNP degree, has created confusion about the focus of DNS, DNSc, or DSN programs and the capabilities of degree holders. Many universities have addressed this confusion by converting their DNS, DNSc, and DSN programs to a PhD or retroactively converting degrees to a PhD. Other universities have chosen not to pursue this route. ConclusionsThe DNS, DNSc, or DSN experience highlights the importance of clarifying and standardizing the purpose and goals of nursing education programs and the repercussions for degree holders when such clarity is lacking. The international academic nursing communities have consistently pursued one doctoral-level nursing degree and therefore have not shared this challenging landscape in nursing education. Clinical RelevanceFindings and recommendations presented in this article have implications for schools of nursing and professional groups that oversee the development of educational programs and pathways for nurses. C1 [Ponte, Patricia Reid] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Dana Farber Canc Inst, Dana Farber Canc Ctr, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Dana Farber Canc Inst, Oncol Nursing Serv, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Dana Farber Canc Inst, Clin Serv, Boston, MA 02215 USA. [Nicholas, Patrice K.] Brigham & Womens Hosp, Global Hlth & Acad Partnerships, Boston, MA 02215 USA. [Nicholas, Patrice K.] MGH Inst Hlth Profess, Sch Nursing, Div Global Hlth Equ, Boston, MA USA. [Nicholas, Patrice K.] MGH Inst Hlth Profess, Sch Nursing, Ctr Nursing Excellence, Boston, MA USA. [Nicholas, Patrice K.] MGH Inst Hlth Profess, Sch Nursing, Boston, MA USA. RP Ponte, PR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave D1632A, Boston, MA 02215 USA. EM pat_reid_ponte@dfci.harvard.edu NR 18 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD JUL PY 2015 VL 47 IS 4 BP 347 EP 353 DI 10.1111/jnu.12148 PG 7 WC Nursing SC Nursing GA CL5QV UT WOS:000357015800009 ER PT J AU Briggs, A Raja, AS Joyce, MF Yule, SJ Jiang, W Lipsitz, SR Havens, JM AF Briggs, Alexandra Raja, All S. Joyce, Maurice F. Yule, Steven J. Jiang, Wei Lipsitz, Stuart R. Havens, Joaquim M. TI The Role of Nontechnical Skills in Simulated Trauma Resuscitation SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE trauma team training; nontechnical skills; trauma simulation ID TEAMWORK TRAINING IMPROVES; CARE; PERFORMANCE; MULTIDISCIPLINARY; RELIABILITY; MANAGEMENT; SURGEONS AB OBJECTIVE: Trauma team training provides instruction on crisis management through debriefing and discussion of teamwork and leadership skills during simulated trauma scenarios. The effects of team leader's nontechnical skills (NTSs) on technical performance have not been thoroughly studied. We hypothesized that team's and team leader's NTSs correlate with technical performance of clinical tasks. DESIGN: Retrospective cohort study. SETTING: Brigham and Women's Hospital, STRATUS Center for Surgical Simulation PARTICIPANTS: A total of 20 teams composed of surgical residents, emergency medicine residents, emergency department nurses, and emergency services assistants underwent 2 separate, high-fidelity, simulated trauma scenarios. Each trauma scenario was recorded on video for analysis and divided into 4 consecutive sections. For each section, 2 raters used the Non-Technical Skills for Surgeons framework to assess NTSs of the team. To evaluate the entire team's NTS, 2 additional raters used the Modified Non-Technical Skills Scale for Trauma system. Clinical performance measures including adherence to guidelines and time to perform critical tasks were measured independently. RESULTS: NTSs performance by both teams and team leaders in all NTS categories decreased from the beginning to the end of the scenario (all p < 0.05). There was significant correlation between team's and team leader's cognitive skills and critical task performance, with correlation coefficients between 0.351 and 0.478 (p < 0.05). The NTS performance of the team leader highly correlated with that of the entire team, with correlation coefficients between 0.602 and 0.785 (p < 0.001). CONCLUSIONS: The NTSs of trauma teams and team leaders deteriorate as clinical scenarios progress, and the performance of team leaders and teams is highly correlated. Cognitive NTS scores correlate with critical task performance. Increased attention to NTSs during trauma team training may lead to sustained performance throughout trauma scenarios. Decision making and situation awareness skills are critical for both team leaders and teams and should be specifically addressed to improve performance. (J Surg 72:732-739. (C) 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) C1 [Briggs, Alexandra; Yule, Steven J.; Havens, Joaquim M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raja, All S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Joyce, Maurice F.; Yule, Steven J.] Brigham & Womens Hosp, STRATUS Ctr Med Simulat, Boston, MA 02115 USA. [Jiang, Wei; Lipsitz, Stuart R.; Havens, Joaquim M.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Havens, JM (reprint author), Brigham & Womens Hosp, Div Trauma Burn & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA. EM jhavens@partners.org RI JIANG, WEI /F-3930-2015 NR 12 TC 6 Z9 6 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JUL-AUG PY 2015 VL 72 IS 4 BP 732 EP 739 DI 10.1016/j.jsurg.2015.01.020 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA CL3HT UT WOS:000356841700027 PM 25817012 ER PT J AU Tapias, LF Lanuti, M AF Tapias, Luis F. Lanuti, Michael TI Better Prognostic Models May Result in Improved Patient Selection for Adjuvant Therapies After Complete Resection of Solitary Fibrous Tumors of the Pleura SO JOURNAL OF THORACIC ONCOLOGY LA English DT Letter ID SCORING SYSTEM; RECURRENCE C1 [Tapias, Luis F.; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2015 VL 10 IS 7 BP E61 EP E61 DI 10.1097/JTO.0000000000000556 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CL4SM UT WOS:000356944400003 PM 26134235 ER PT J AU Scali, S Patel, V Neal, D Bertges, D Ho, K Jorgensen, JE Cronenwett, J Beck, A AF Scali, Salvatore Patel, Virendra Neal, Daniel Bertges, Daniel Ho, Karen Jorgensen, Jens-Eldrup Cronenwett, Jack Beck, Adam TI Preoperative beta-blockers do not improve cardiac outcomes after major elective vascular surgery and may be harmful SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; RANDOMIZED-CONTROLLED-TRIAL; ASSOCIATION TASK-FORCE; ABDOMINAL AORTIC-ANEURYSM; NONCARDIAC SURGERY; PRACTICE GUIDELINES; AMERICAN-COLLEGE; MYOCARDIAL-INFARCTION; FOCUSED UPDATE; RISK PATIENTS AB Objective: Routine initiation beta-blocker medications before vascular surgery is controversial due to conflicting data. The purpose of this analysis was to determine whether prophylactic use of beta-blockers before major elective vascular surgery decreased postoperative cardiac events or mortality. Methods: The Society for Vascular Surgery Vascular Quality Initiative (SVS-VQI) data set was used to perform a retrospective cohort analysis of infrainguinal lower extremity bypass (LEB), aortofemoral bypass (AFB), and open abdominal aortic aneurysm(AAA) repair patients. Chronic (>30 days preoperatively) beta-blocker patients were excluded, and comparisons were made between preoperative (0-30 day) and no beta-blocker groups. Patients were risk stratified using a novel prediction tool derived specifically from the SVS-VQI data set. Propensity-matched pairs and interprocedural specific risk stratification comparisons were performed. End points included in-hospital major adverse cardiac events (MACEs), including myocardial infarction (MI; defined as new ST or T wave electrocardiographic changes, troponin elevation, or documentation by echocardiogram or other imaging modality), dysrhythmia, and congestive heart failure, and 30-day mortality. Results: The study analyzed 13,291 patients (LEB, 68% [n = 9047]; AFB, 11% [n = 1474]; and open AAA, 21% [n = 2770]); of these, 67.7% (n = 8999) were receiving beta-blockers at time of their index procedure. Specifically, 13.2% (n = 1753) were identified to have been started on a preoperative beta-blocker, 54.5% (n = 7426) were on chronic beta-blockers, and 32.3% (n = 4286) were on no preoperative beta-blockers. Among the three procedures, patients had significant demographic and comorbidity differences and thus were not combined. A 1: 1 propensity-matched pairs analysis (1459 pairs) revealed higher rates of postoperative MI with preoperative beta-blockers (preoperative beta-blocker relative risk, 1.65; 95% confidence interval, 1.02-2.68; P = .05 vs no beta-blocker), with no difference in dysrhythmia, congestive heart failure, or 30-day mortality. When stratified into low-risk, medium-risk, and high-risk groups within each procedure, all groups of preoperative beta-blocker patients had no difference or higher rates of MACEs and 30-day mortality, with the exception of high-risk open AAA patients, who had a lower rate of MI (odds ratio, 0.35; 95% confidence interval, 011-0.87; P = .04). Conclusions: Exclusive of high-risk open AAA patients, preoperative beta-blockers did not decrease rates of MACEs or mortality after LEB, AFB, or open AAA. Importantly, exposure to prophylactic preoperative beta-blockers increased the rates of some adverse events in several subgroups. Given these data, the SVS-VQI cannot support routine initiation of preoperative beta-blockers before major elective vascular surgery in most patients. C1 [Scali, Salvatore; Neal, Daniel; Beck, Adam] Univ Florida, Div Vasc Surg & Endovasc Therapy, Gainesville, FL 32610 USA. [Patel, Virendra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. [Bertges, Daniel] Univ Vermont, Div Vasc Surg, Burlington, VT USA. [Ho, Karen] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. [Jorgensen, Jens-Eldrup] Maine Med Ctr, Vasc Ctr, Portland, ME 04102 USA. [Cronenwett, Jack] Darmouth Hitchcock Med Ctr, Heart & Vasc Ctr, Lebanon, NH USA. RP Scali, S (reprint author), Univ Florida, Sch Med, Div Vasc Surg & Endovasc Therapy, 1600 SW Archer Rd,Ste NG 45, Gainesville, FL 32610 USA. EM salvatore.scali@surgery.ufl.edu FU National Institutes of Health [NIH-NHLBI 5K23HL115673-02]; Society for Vascular Surgery Foundation Mentored Patient-Oriented Research Award FX This work was supported in part by funding from the National Institutes of Health (NIH-NHLBI 5K23HL115673-02) and the Society for Vascular Surgery Foundation Mentored Patient-Oriented Research Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the Society for Vascular Surgery Foundation. NR 35 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2015 VL 62 IS 1 BP 166 EP U337 DI 10.1016/j.jvs.2015.01.053 PG 13 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CL3FR UT WOS:000356836300023 PM 26115922 ER PT J AU Drewry, J Sen, B Wingate, M Bronstein, J Foster, EM Kotelchuck, M AF Drewry, Jonathan Sen, Bisakha Wingate, Martha Bronstein, Janet Foster, E. Michael Kotelchuck, Milton TI The Impact of the State Children's Health Insurance Program's Unborn Child Ruling Expansions on Foreign-Born Latina Prenatal Care and Birth Outcomes, 2000-2007 SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Prenatal care; Foreign-born Latina; Differences-in-differences; Unborn child ruling; Immigrant health; Birth outcomes ID HISPANIC WOMEN; WELFARE-REFORM; WEIGHT; RISK; IMMIGRANTS; ADEQUACY; DELIVERY AB The 2002 "unborn child ruling" resulted in State Children's Health Insurance Program (SCHIP) expansion for states to cover prenatal care for low-income women without health insurance. Foreign-born Latinas who do not qualify for Medicaid coverage theoretically should have benefited most from the policy ruling given their documented low rates of prenatal care utilization. This study compares prenatal care utilization and subsequent birth outcomes among foreign-born Latinas in six states that used the unborn child ruling to expand coverage to those in ten states that did not implement the expansion. This policy analysis examines cross-sectional pooled US natality data from the pre-enactment years (2000-2003) versus post-enactment years (2004-2007) to estimate the effect of the UCR on prenatal care utilization and birth outcome measures for foreign-born Latinas. Then using a difference-in-difference estimator, we assessed these differences across time for states that did or did not enact the unborn child ruling. Analyses were then replicated on a high-risk subset of the population (single foreign-born Latinas with lower levels of education). The SCHIP unborn child ruling policy expansion increased PNCU over time in the six enacting states. Foreign-born Latinas in expansion enacting states experienced increases in prenatal care utilization though only the high-risk subset were statistically significant. Birth outcomes did not change. The SCHIP unborn child ruling policy was associated with enhanced PNC for a subset of high-risk foreign-born Latinas. C1 [Drewry, Jonathan] Pan Amer Hlth Org, Lima, Peru. [Sen, Bisakha; Wingate, Martha; Bronstein, Janet; Foster, E. Michael] UAB Sch Publ Hlth, Hlth Care Org & Policy, Birmingham, AL USA. [Kotelchuck, Milton] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Maternal Child Hlth Ctr,Ctr Child & Adolescent Hl, Boston, MA USA. RP Drewry, J (reprint author), Pan Amer Hlth Org, Lima, Peru. EM jdelpaso45@gmail.com; bsen@uab.edu; mslay@uab.edu; jbronste@uab.edu; MKOTELCHUCK@mgh.harvard.edu NR 51 TC 2 Z9 2 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JUL PY 2015 VL 19 IS 7 BP 1464 EP 1471 DI 10.1007/s10995-014-1650-5 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL0DM UT WOS:000356609300005 PM 25476607 ER PT J AU Wallace, ML Iyengar, S Bramoweth, AD Frank, E Germain, A AF Wallace, Meredith L. Iyengar, Satish Bramoweth, Adam D. Frank, Ellen Germain, Anne TI Clarifying Heterogeneity of Daytime and Nighttime Symptoms of Posttraumatic Stress in Combat Veterans With Insomnia SO MILITARY PSYCHOLOGY LA English DT Article DE chronic insomnia; clustering; personalized medicine; PTSD; sleep ID SLEEP QUALITY INDEX; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; ADMINISTERED PTSD SCALE; MENTAL-HEALTH PROBLEMS; PSYCHOMETRIC PROPERTIES; BEHAVIORAL THERAPY; PROLONGED EXPOSURE; MILITARY VETERANS; DISORDER AB Daytime and nighttime symptoms of posttraumatic stress disorder (PTSD) are common among combat veterans and military service members. However, there is a great deal of heterogeneity in how symptoms are expressed. Clarifying the heterogeneity of daytime and nighttime PTSD symptoms through exploratory clustering may generate hypotheses regarding ways to optimally match evidence-based treatments to PTSD symptom profiles. We used mixture modeling to reveal clusters based on 6 daytime and nighttime symptoms of 154 combat veterans with insomnia and varying levels of PTSD symptoms. Three clusters with increasing symptom severity were identified (n1 = 50, n2 = 70, n3 = 34). These results suggest that, among veterans with insomnia, PTSD symptoms tend to exist on a continuum of severity, rather than as a categorical PTSD diagnosis. Hypotheses regarding possible targeted treatment strategies for veterans within each identified cluster, as well as ways to generalize these methods to other groups within the military, are discussed. C1 [Wallace, Meredith L.; Frank, Ellen; Germain, Anne] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Iyengar, Satish] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. [Bramoweth, Adam D.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Wallace, ML (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM lotzmj@upmc.edu FU VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), VA Pittsburgh Healthcare System; [K01 MH096944]; [PR054093]; [PT073961]; [MH080696]; [MH083035]; [Log11293006] FX Drs. Wallace, Iyengar, Bramoweth, and Germain have no conflicts of interest. Dr. Frank has the following conflicts of interest: (a) American Psychiatric Press, Editorial Consultant; (b) Psychiatric Assessments Inc, Stockholder; (c) American Psychological Association Press and Guilford Press, Royalties; (d) Servier International, Advisory Board. The contents of this article do not represent the views of the Department of the Veterans Affairs of the United States Government. This research was supported by Grants K01 MH096944 (PI: Wallace) and PR054093, PT073961, MH080696, MH083035, and Log11293006 (PI: Germain). Dr. Bramoweth is supported by funds from the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC, Director: D. Oslin; Pittsburgh Site Director: G. Haas), VA Pittsburgh Healthcare System. NR 60 TC 1 Z9 1 U1 3 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0899-5605 EI 1532-7876 J9 MIL PSYCHOL JI Milit. Psychol. PD JUL PY 2015 VL 27 IS 4 BP 212 EP 222 DI 10.1037/mil0000077 PG 11 WC Psychology, Multidisciplinary SC Psychology GA CL5BS UT WOS:000356975400002 PM 26457001 ER PT J AU Zhao, Y Olonisakin, TF Xiong, Z Hulver, M Sayeed, S Yu, MT Gregory, AD Kochman, EJ Chen, BB Mallampalli, RK Sun, M Silverstein, RL Stolz, DB Shapiro, SD Ray, A Ray, P Lee, JS AF Zhao, Y. Olonisakin, T. F. Xiong, Z. Hulver, M. Sayeed, S. Yu, M. T. Gregory, A. D. Kochman, E. J. Chen, B. B. Mallampalli, R. K. Sun, M. Silverstein, R. L. Stolz, D. B. Shapiro, S. D. Ray, A. Ray, P. Lee, J. S. TI Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; BINDING COMPETITIVE INHIBITOR; IMPAIRED HOST-DEFENSE; ACUTE LUNG INJURY; CATHEPSIN-G; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; ELASTASE; CELLS; ACTIVATION AB Neutrophil elastase (NE) and cathepsin G (CG) contribute to intracellular microbial killing but, if left unchecked and released extracellularly, promote tissue damage. Conversely, mechanisms that constrain neutrophil serine protease activity protect against tissue damage but may have the untoward effect of disabling the microbial killing arsenal. The host elaborates thrombospondin-1 (TSP-1), a matricellular protein released during inflammation, but its role during neutrophil activation following microbial pathogen challenge remains uncertain. Mice deficient in TSP-1 (thbs1(-/-)) showed enhanced lung bacterial clearance, reduced splenic dissemination, and increased survival compared with wildtype (WT) controls during intrapulmonary Klebsiella pneumoniae infection. More effective pathogen containment was associated with reduced burden of inflammation in thbs1(-/-) mouse lungs compared with WT controls. Lung NE activity was increased in thbs1(-/-) mice following K. pneumoniae challenge, and thbs1(-/-) neutrophils showed enhanced intracellular microbial killing that was abrogated with recombinant TSP-1 administration or WT serum. Thbs1(-/-) neutrophils exhibited enhanced NE and CG enzymatic activity, and a peptide corresponding to amino-acid residues 793-801 within the type-III repeat domain of TSP-1 bridled neutrophil proteolytic function and microbial killing in vitro. Thus, TSP-1 restrains proteolytic action during neutrophilic inflammation elicited by K. pneumoniae, providing a mechanism that may regulate the microbial killing arsenal. C1 [Zhao, Y.; Olonisakin, T. F.; Xiong, Z.; Hulver, M.; Sayeed, S.; Yu, M. T.; Gregory, A. D.; Kochman, E. J.; Chen, B. B.; Mallampalli, R. K.; Shapiro, S. D.; Ray, A.; Ray, P.; Lee, J. S.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA. [Mallampalli, R. K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. [Sun, M.; Stolz, D. B.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Sun, M.; Stolz, D. B.] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA USA. [Silverstein, R. L.] Blood Ctr SE Wisconsin Inc, Dept Med, Med Coll Wisconsin, Milwaukee, WI 53233 USA. [Silverstein, R. L.] Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53233 USA. [Lee, J. S.] Univ Pittsburgh, Dept Med, Vasc Med Inst, Pittsburgh, PA USA. RP Lee, JS (reprint author), Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA. EM leejs3@upmc.edu FU Flight Attendant Medical Research Institute; Pilot Project Program in Hemostasis and Vascular Biology (University of Pittsburgh CTSI) [UL1 RR024153, UL1 TR000005]; Vascular Medicine Institute; Hemophilia Center of Western Pennsylvania; Institute for Transfusion Medicine; Merit Review Award from the US Department of Veterans Affairs; [R01 HL086884]; [P01 HL114453] FX Funding sources include R01 HL086884 (J.S.L.), Flight Attendant Medical Research Institute (J.S.L.), Pilot Project Program in Hemostasis and Vascular Biology through UL1 RR024153 and UL1 TR000005 (University of Pittsburgh CTSI), the Vascular Medicine Institute, the Hemophilia Center of Western Pennsylvania, Institute for Transfusion Medicine (J.S.L.), P01 HL114453 (R.K.M., P.R.), and a Merit Review Award from the US Department of Veterans Affairs (R.K.M.). NR 51 TC 6 Z9 6 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JUL PY 2015 VL 8 IS 4 BP 896 EP 905 DI 10.1038/mi.2014.120 PG 10 WC Immunology SC Immunology GA CL3QP UT WOS:000356865700018 PM 25492474 ER PT J AU Kim, YH Choi, SH D'Avanzo, C Hebisch, M Sliwinski, C Bylykbashi, E Washicosky, KJ Klee, JB Brustle, O Tanzi, RE Kim, DY AF Kim, Young Hye Choi, Se Hoon D'Avanzo, Carla Hebisch, Matthias Sliwinski, Christopher Bylykbashi, Enjana Washicosky, Kevin J. Klee, Justin B. Bruestle, Oliver Tanzi, Rudolph E. Kim, Doo Yeon TI A 3D human neural cell culture system for modeling Alzheimer's disease SO NATURE PROTOCOLS LA English DT Article ID PLURIPOTENT STEM-CELLS; INTRACELLULAR A-BETA; IPSC-DERIVED NEURONS; LINE RENCELL VM; PROGENITOR CELLS; DIFFERENTIATION; BRAIN; RESPONSIVENESS; EXPRESSION; CHALLENGES AB Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer's disease (AD), because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel 3D culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of amyloid-beta (A beta) and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCNPCNPCs) with familial AD mutations, the differentiation of the hNPCNPCNPCs in a 3D matrix and the analysis of AD pathogenesis. The 3D culture generation takes 1-2 d. The aggregation of A beta is observed after 6 weeks of differentiation, followed by robust tau pathology after 10-14 weeks. C1 [Kim, Young Hye; Choi, Se Hoon; D'Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Tanzi, Rudolph E.; Kim, Doo Yeon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis,Genet & Aging, Charlestown, MA 02129 USA. [Kim, Young Hye] Korea Basic Sci Inst, Biomed Om Grp, Cheongju, Chungbuk, South Korea. [Hebisch, Matthias; Bruestle, Oliver] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, Bonn, Germany. [Hebisch, Matthias; Bruestle, Oliver] Hertie Fdn, Bonn, Germany. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis,Genet & Aging, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu; dkim@helix.mgh.harvard.edu FU Cure Alzheimer's Fund; US National Institutes of Health (NIH) [1RF1AG048080-01, 5P01AG15379, 2R01AG014713, 5R37MH060009]; German Federal Ministry for Education and Research BioPharma-NeuroAllianz [0315608A]; EU SCRTox [HEALTH-F5-2010-266753]; Bio & Medical Technology Development Program of the National Research Foundation - Korean government; NIH/National Institute of Neurological Disorders and Stroke [P30NS04776] FX This work is supported by grants from the Cure Alzheimer's Fund to D.Y.K. and R.E.T., from the US National Institutes of Health (NIH) 1RF1AG048080-01 (D.Y.K. and R.E.T.), 5P01AG15379 (D.Y.K. and R.E.T.), 2R01AG014713 (D.Y.K.) and 5R37MH060009 (R.E.T.), from the German Federal Ministry for Education and Research BioPharma-NeuroAllianz 0315608A (O.B.), from EU SCR&Tox HEALTH-F5-2010-266753 (O.B.), and from Bio & Medical Technology Development Program of the National Research Foundation (funded by the Korean government) (Y.H.K.). We appreciate B.T. Hyman, O. Berezovska, D.M. Kovacs (MGH), J. Hardy (NIH) and P. Davies (Albert Einstein College of Medicine) for providing cDNAs and antibodies. We also acknowledge B.A. Tannos at MGH Viral Vector Core (supported by NIH/National Institute of Neurological Disorders and Stroke P30NS04776), M. Waring at Ragon Institute's Imaging Core facility (part of the Harvard Center for AIDS Research Immunology Core), and M.L. McKee and D. Capen at MGH Microscopy Core of the Center for Systems Biology for providing the detailed protocols and for revising the manuscript. NR 44 TC 16 Z9 17 U1 4 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD JUL PY 2015 VL 10 IS 7 BP 985 EP 1006 DI 10.1038/nprot.2015.065 PG 22 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CL3QZ UT WOS:000356866700004 PM 26068894 ER PT J AU Scherzer, R Shlipak, MG AF Scherzer, Rebecca Shlipak, Michael G. TI Individual assessment of CKD risk in HIV-positive patients SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID KIDNEY-DISEASE RISK; TENOFOVIR; INFECTION AB Despite reductions in morbidity and mortality owing to widespread use of highly effective antiretroviral therapy (ART), HIV-positive patients remain at high risk of chronic kidney disease (CKD) and end-stage renal disease. A new report provides a HIV-specific CKD risk score to balance the potential benefits and harms of nephrotoxic ART. C1 [Scherzer, Rebecca; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU NIAID NIH HHS [R01 AI098472] NR 10 TC 2 Z9 2 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 EI 1759-507X J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD JUL PY 2015 VL 11 IS 7 BP 392 EP 393 DI 10.1038/nrneph.2015.75 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CL2UT UT WOS:000356801900003 PM 25963593 ER PT J AU Chen, PP Lin, SC Junk, AK Radhakrishnan, S Singh, K Chen, TC AF Chen, Philip P. Lin, Shan C. Junk, Anna K. Radhakrishnan, Sunita Singh, Kuldev Chen, Teresa C. TI The Effect of Phacoemulsification on Intraocular Pressure in Glaucoma Patients A Report by the American Academy of Ophthalmology SO OPHTHALMOLOGY LA English DT Article ID ANGLE-CLOSURE GLAUCOMA; CLEAR CORNEAL PHACOEMULSIFICATION; CATARACT-EXTRACTION; LENS IMPLANTATION; COMBINED PHACOTRABECULECTOMY; TRABECULAR ASPIRATION; PERIPHERAL-IRIDOTOMY; CLINICAL-OUTCOMES; RANDOMIZED-TRIAL; EYES AB Objective: To examine effects of phacoemulsification on longer-term intraocular pressure (IOP) in patients with medically treated primary open-angle glaucoma (POAG; including normal-tension glaucoma), pseudoexfoliation glaucoma (PXG), or primary angle-closure glaucoma (PACG), without prior or concurrent incisional glaucoma surgery. Methods: PubMed and Cochrane database searches, last conducted in December 2014, yielded 541 unique citations. Panel members reviewed titles and abstracts and selected 86 for further review. The panel reviewed these articles and identified 32 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on standardized grading adopted by the American Academy of Ophthalmology. One, 15, and 16 studies were rated as providing level I, II, and III evidence, respectively. Results: All follow-up, IOP, and medication data listed are weighted means. In general, the studies reported on patients using few glaucoma medications (1.5-1.9 before surgery among the different diagnoses). For POAG, 9 studies (total, 461 patients; follow-up, 17 months) showed that phacoemulsification reduced IOP by 13% and glaucoma medications by 12%. For PXG, 5 studies (total, 132 patients; follow-up, 34 months) showed phacoemulsification reduced IOP by 20% and glaucoma medications by 35%. For chronic PACG, 12 studies (total, 495 patients; follow-up, 16 months) showed phacoemulsification reduced IOP by 30% and glaucoma medications by 58%. Patients with acute PACG (4 studies; total, 119 patients; follow-up, 24 months) had a 71% reduction from presenting IOP and rarely required long-term glaucoma medications when phacoemulsification was performed soon after medical reduction of IOP. Trabeculectomy after phacoemulsification was uncommon; the median rate reported within 6 to 24 months of follow-up in patients with controlled POAG, PXG, or PACG was 0% and was 7% in patients with uncontrolled chronic PACG. Conclusions: Phacoemulsification typically results in small, moderate, and marked reductions of IOP and medications for patients with POAG, PXG, and PACG, respectively, and using 1 to 2 medications before surgery. Trabeculectomy within 6 to 24 months after phacoemulsification is rare in such patients. However, reports on its effects in eyes with advanced disease or poor IOP control before surgery are few, particularly for POAG and PXG. (C) 2015 by the American Academy of Ophthalmology. C1 [Chen, Philip P.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. [Lin, Shan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Junk, Anna K.] Univ Miami, Miami Vet Affairs Med Ctr, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL USA. [Radhakrishnan, Sunita] Glaucoma Res & Educ Grp, Glaucoma Ctr San Francisco, San Francisco, CA USA. [Singh, Kuldev] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Chen, PP (reprint author), Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. FU American Academy of Ophthalmology FX Funded without commercial support by the American Academy of Ophthalmology. NR 38 TC 15 Z9 15 U1 0 U2 5 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 JUL PY 2015 VL 122 IS 7 BP 1294 EP 1307 DI 10.1016/j.ophtha.2015.03.021 PG 14 WC Ophthalmology SC Ophthalmology GA CL0HI UT WOS:000356621700012 PM 25943711 ER PT J AU Witkin, AJ Shah, AR Engstrom, RE Kron-Gray, MM Baumal, CR Johnson, MW Witkin, DI Leung, J Albini, TA Moshfeghi, AA Batlle, IR Sobrin, L Eliott, D AF Witkin, Andre J. Shah, Anjali R. Engstrom, Robert E. Kron-Gray, Michelle M. Baumal, Caroline R. Johnson, Mark W. Witkin, Deborah I. Leung, John Albini, Thomas A. Moshfeghi, Andrew A. Batlle, Ivan R. Sobrin, Lucia Eliott, Dean TI Postoperative Hemorrhagic Occlusive Retinal Vasculitis Expanding the Clinical Spectrum and Possible Association with Vancomycin SO OPHTHALMOLOGY LA English DT Article ID CATARACT EXTRACTION ENDOPHTHALMITIS; INTRACAMERAL ANTIBIOTICS; SURGERY; PROPHYLAXIS; TOXICITY; GENTAMICIN; DIAGNOSIS; PURPURA; CHOICE AB Purpose: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. Design: Retrospective case series. Subjects: Eleven eyes of 6 patients from 6 different institutions. Methods: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. Main Outcome Measures: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. Results: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. Conclusions: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma. (C) 2015 by the American Academy of Ophthalmology. C1 [Witkin, Andre J.; Baumal, Caroline R.; Witkin, Deborah I.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Boston, MA 02111 USA. [Shah, Anjali R.; Kron-Gray, Michelle M.; Johnson, Mark W.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Engstrom, Robert E.] Valley Retina Associates, Encino, CA USA. [Leung, John] Tufts Med Ctr, Div Allergy, Boston, MA 02111 USA. [Albini, Thomas A.; Moshfeghi, Andrew A.] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. [Batlle, Ivan R.] Retina Associates PA, Shawnee Mission, KS USA. [Sobrin, Lucia; Eliott, Dean] Harvard Univ, Sch Med, Retina Serv, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Witkin, AJ (reprint author), Tufts Med Ctr, Dept Ophthalmol, 800 Washington St,Box 450, Boston, MA 02111 USA. EM ajwitkin@gmail.com OI Albini, Thomas/0000-0003-2199-9047 FU Research to Prevent Blindness, Inc, New York, New York FX Supported by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York, to the New England Eye Center. The sponsor had no role in the design or conduct of this research. NR 28 TC 25 Z9 25 U1 1 U2 3 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 JUL PY 2015 VL 122 IS 7 BP 1438 EP 1451 DI 10.1016/j.ophtha.2015.03.016 PG 14 WC Ophthalmology SC Ophthalmology GA CL0HI UT WOS:000356621700025 PM 25886796 ER PT J AU Amparo, F Schaumberg, DA Dana, R AF Amparo, Francisco Schaumberg, Debra A. Dana, Reza TI Comparison of Two Questionnaires for Dry Eye Symptom Assessment The Ocular Surface Disease Index and the Symptom Assessment in Dry Eye SO OPHTHALMOLOGY LA English DT Article ID EPIDEMIOLOGY; VALIDATION; DIAGNOSIS AB Purpose: The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12-item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency-and severity-based visual analog scale. Design: Clinic-based evaluation of a diagnostic test. Participants: A total of 114 patients with DED. Methods: Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate DED-related symptoms. The correlations between both questionnaires' scores were evaluated using the Spearman coefficient, and their clinical differences were assessed using Bland-Altman analysis. Main Outcome Measures: Baseline and follow-up visit OSDI and SANDE dry eye symptom scores. Results: At the baseline visit, the OSDI and SANDE questionnaire scores were significantly correlated (R = 0.64; P < 0.001). Moreover, a significant correlation was found between changes in the OSDI and SANDE scores from baseline to follow-up visits (R = 0.47; P < 0.001). A Bland-Altman analysis, after score normalization, revealed a difference (bias) of less than 2 centesimal units between the scores of the 2 questionnaires. Conclusions: Data collected from the SANDE questionnaire showed a significant correlation and negligible score differences with those from the OSDI, suggesting that the SANDE visual analog scale-based questionnaire has the potential to provide clinicians with a short, quick, and reliable measure for DED symptoms. (C) 2015 by the American Academy of Ophthalmology. C1 [Amparo, Francisco; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Cornea Serv,Massachusetts Eye & Ear Infirm, Boston, MA USA. [Schaumberg, Debra A.] Univ Utah, Sch Med, John A Moran Eye Ctr, Moran Ctr Translat Med, Salt Lake City, UT USA. [Schaumberg, Debra A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Eye Institute, National Institutes of Health [K24-EY019098]; Research to Prevent Blindness FX Supported by the National Eye Institute, National Institutes of Health (grant no: K24-EY019098) and Research to Prevent Blindness. The funding organizations had no role in the design or conduct of this research. NR 16 TC 6 Z9 6 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 JUL PY 2015 VL 122 IS 7 BP 1498 EP 1503 DI 10.1016/j.ophtha.2015.02.037 PG 6 WC Ophthalmology SC Ophthalmology GA CL0HI UT WOS:000356621700031 PM 25863420 ER PT J AU Pace-Schott, EF Germain, A Milad, MR AF Pace-Schott, Edward F. Germain, Anne Milad, Mohammed R. TI Effects of Sleep on Memory for Conditioned Fear and Fear Extinction SO PSYCHOLOGICAL BULLETIN LA English DT Article DE sleep; fear conditioning; extinction; memory; habituation; anxiety ID POSTTRAUMATIC-STRESS-DISORDER; EYE-MOVEMENT SLEEP; MEDIAL PREFRONTAL CORTEX; SLOW-WAVE SLEEP; CORTICOTROPIN-RELEASING-FACTOR; OBSESSIVE-COMPULSIVE DISORDER; SOCIAL ANXIETY DISORDER; ANTERIOR CINGULATE CORTEX; REM-SLEEP; EXPOSURE THERAPY AB Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. C1 [Pace-Schott, Edward F.; Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Pace-Schott, Edward F.; Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Germain, Anne] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Pace-Schott, EF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, CNY 149 13th St Room 2624, Charlestown, MA 02129 USA. EM epace-schott@mgh.harvard.edu FU [MH090357]; [USAMRAA Log11293006]; [MH097965] FX Research supported by MH090357, USAMRAA Log11293006, MH097965. We thank Marie-France Marin, Lisa Maeng, and Kara Cover for helpful comments. NR 268 TC 13 Z9 13 U1 10 U2 50 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 EI 1939-1455 J9 PSYCHOL BULL JI Psychol. Bull. PD JUL PY 2015 VL 141 IS 4 BP 835 EP 857 DI 10.1037/bul0000014 PG 23 WC Psychology; Psychology, Multidisciplinary SC Psychology GA CL5BG UT WOS:000356974100006 PM 25894546 ER PT J AU Vachha, BA Schaefer, PW AF Vachha, Behroze A. Schaefer, Pamela W. TI Imaging Patterns and Management Algorithms in Acute Stroke An Update for the Emergency Radiologist SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Stroke; Infarct; MR imaging; MRA; Perfusion; Diffusion; CT angiography; CT perfusion ID ACUTE ISCHEMIC-STROKE; CEREBRAL-BLOOD-FLOW; DIGITAL-SUBTRACTION-ANGIOGRAPHY; CAROTID-ARTERY STENOSIS; SPIRAL CT ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; MR-ANGIOGRAPHY; INTRAVENOUS THROMBOLYSIS; SYMPTOM ONSET; INFARCT CORE AB Neuroimaging plays a key role in the initial work-up of patients with symptoms of acute stroke. Understanding the advantages and limitations of available CT and MR imaging techniques and how to use them optimally in the emergency setting is crucial for accurately making the diagnosis of acute stroke and for rapidly determining appropriate treatment. C1 [Vachha, Behroze A.; Schaefer, Pamela W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM pschaefer@mgh.harvard.edu NR 122 TC 4 Z9 4 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2015 VL 53 IS 4 BP 801 EP + DI 10.1016/j.rcl.2015.02.012 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5GF UT WOS:000356987100012 PM 26046512 ER PT J AU Fink, KR Benjert, JL AF Fink, Kathleen R. Benjert, Jayson L. TI Imaging of Nontraumatic Neuroradiology Emergencies SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Subarachnoid hemorrhage; Vasogenic edema; Hydrocephalus; Neurologic abnormalities ID RADIOLOGIC-PATHOLOGICAL CORRELATION; CEREBRAL VASOCONSTRICTION SYNDROME; ENCEPHALOPATHY SYNDROME PRES; OF-THE-LITERATURE; SUBARACHNOID HEMORRHAGE; PERIMESENCEPHALIC HEMORRHAGE; INTRACEREBRAL HEMORRHAGE; CT ANGIOGRAPHY; BRAIN-ABSCESS; AMYLOID ANGIOPATHY AB Imaging of acute neurologic disease in the emergency department can be challenging because of the wide range of possible causes and the overlapping imaging appearance of many of these entities on nonenhanced computed tomography (CT). The key to formulating a succinct, pertinent differential diagnosis includes characterizing the pattern of abnormalities on CT and identifying key features that suggest a particular diagnosis. This article divides neurologic emergencies into 5 scenarios based on the CT findings, including subarachnoid hemorrhage, intraparenchymal hemorrhage, vasogenic edema without and with underlying mass lesion, and acute hydrocephalus. Specific common or important diagnoses in each category are discussed. C1 [Fink, Kathleen R.] Univ Washington, Dept Radiol, Seattle, WA 98104 USA. [Benjert, Jayson L.] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. RP Fink, KR (reprint author), Univ Washington, Dept Radiol, Box 359728,325 9th Ave, Seattle, WA 98104 USA. EM ktozer@u.washington.edu NR 59 TC 1 Z9 1 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2015 VL 53 IS 4 BP 871 EP + DI 10.1016/j.rcl.2015.02.004 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5GF UT WOS:000356987100015 PM 26046515 ER PT J AU Xian, Y O'Brien, EC Fonarow, GC Olson, DM Schwamm, LH Lindholm, B Maisch, L Lytle, BL Greiner, MA Wu, JJ Peterson, ED Pencina, MJ Hernandez, AF AF Xian, Ying O'Brien, Emily C. Fonarow, Gregg C. Olson, DaiWai M. Schwamm, Lee H. Lindholm, Brianna Maisch, Lesley Lytle, Barbara L. Greiner, Melissa A. Wu, Jingjing Peterson, Eric D. Pencina, Michael J. Hernandez, Adrian F. TI Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research: Implementing the patient-driven research paradigm to aid decision making in stroke care SO AMERICAN HEART JOURNAL LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; NONRHEUMATIC ATRIAL-FIBRILLATION; AMERICAN-HEART-ASSOCIATION; GUIDELINES-STROKE; POSTSTROKE DEPRESSION; PATIENTS PERSPECTIVE; UNCERTAINTY LIFE; PREVENTION; WARFARIN; PROFESSIONALS AB Background Stroke is common and costly, annually depriving the lives and well-being of 800,000 Americans. Despite demonstrated efficacy in clinical trials, questions remain about the safety and clinical effectiveness of various treatment options given patient characteristics, conditions, preferences, and their desired outcomes. Methods and results The Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient-Centered Outcomes Research Institute-sponsored project designed to help patients, physicians, and other stakeholders make informed decisions regarding stroke care and improve outcomes through patient-centered comparative effectiveness research. The primary outcomes identified and prioritized by stroke patients are "home time" (time spent alive and outside a hospital) and major adverse cardiovascular events. With inputs from stroke patients themselves, a series of comparative safety and effectiveness analyses will be performed across 3 prioritized therapeutic areas identified as important by stroke survivors: oral anticoagulants, statin therapy, and antidepressants. We obtained data from Get With the Guidelines-Stroke linked with Medicare claims and follow-up telephone interviews. Our combined retrospective and prospective research strategy allows the evaluation of the safety and effectiveness of various treatment options and patient-centered longitudinal outcomes. To ensure the rapid translation of findings into clinical practice, results will be disseminated to stroke survivors, caregivers, and health care providers through traditional and social media, including an online decision aid tool. Conclusions PROSPER is a patient-centered outcome research study guided by patients, caregivers, and the broader health care community. By addressing knowledge gaps in treatment uncertainties through comparative effectiveness research, PROSPER has the potential to improve decision making in stroke care and patient outcomes reflecting individual patient preferences, needs, and values. C1 [Xian, Ying; O'Brien, Emily C.; Lytle, Barbara L.; Greiner, Melissa A.; Wu, Jingjing; Peterson, Eric D.; Pencina, Michael J.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC 27705 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Olson, DaiWai M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Xian, Y (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM ying.xian@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Patient-Centered Outcomes Research Institute [CE-1304] FX This work was supported by an award (CE-1304) from the Patient-Centered Outcomes Research Institute. NR 47 TC 7 Z9 7 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUL PY 2015 VL 170 IS 1 BP 36 EP U66 DI 10.1016/j.ahj.2015.04.008 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK7YJ UT WOS:000356452700005 PM 26093862 ER PT J AU Pokorney, SD Simon, DN Thomas, L Fonarow, GC Kowey, PR Chang, P Singer, DE Ansell, J Blanco, RG Gersh, B Mahaffey, KW Hylek, EM Go, AS Piccini, JP Peterson, ED AF Pokorney, Sean D. Simon, DaJuanicia N. Thomas, Laine Fonarow, Gregg C. Kowey, Peter R. Chang, Paul Singer, Daniel E. Ansell, Jack Blanco, Rosalia G. Gersh, Bernard Mahaffey, Kenneth W. Hylek, Elaine M. Go, Alan S. Piccini, Jonathan P. Peterson, Eric D. CA ORBIT-AF Investigators TI Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry SO AMERICAN HEART JOURNAL LA English DT Article ID NORMALIZED RATIO CONTROL; ORAL ANTICOAGULATION; STROKE PREVENTION; UNITED-STATES; QUALITY; OUTCOMES; EFFICACY; RISK; INTENSITY; ALGORITHM AB Background Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice. Methods Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR. Results Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65%+/- 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) (P < .0001). Conclusions Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range. C1 [Pokorney, Sean D.; Piccini, Jonathan P.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Pokorney, Sean D.; Simon, DaJuanicia N.; Thomas, Laine; Blanco, Rosalia G.; Piccini, Jonathan P.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Kowey, Peter R.] Lankenau Inst Med Res, Wynnewood, PA USA. [Chang, Paul] Janssen Sci Affairs, Raritan, NJ USA. [Singer, Daniel E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ansell, Jack] Lenox Hill Hosp, New York, NY USA. [Gersh, Bernard] Mayo Clin, Rochester, MN USA. [Mahaffey, Kenneth W.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Hylek, Elaine M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. RP Peterson, ED (reprint author), Duke Univ, Med Ctr, Div Cardiol, DUMC 3236, Durham, NC 27710 USA. EM eric.peterson@duke.edu FU Astra Zeneca; Janssen Pharmaceuticals; Boehringer Ingelheim; Bristol-Myers Squibb; Johnson Johnson; Portola; Merck; Sanofi; Daiichi Sankyo; Bayer Healthcare; Pfizer; CSL Behring; Medtronic; Baxter Healthcare Corporation; InspireMD; Johnson & Johnson/Janssen Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc; Boston Scientific Corporation; Johnson & Johnson Pharmaceutical Research Development; Forest Laboratories, Inc; Medtronic, Inc; Eli Lilly Company; Janssen Pharmaceuticals, Inc; American Heart Association; Genentech Inc FX D.N.H., L.T., R.G.B., and A.S.G. report no disclosures. S.D.P. reports modest educational grant support from Astra Zeneca and modest advisory board to Janssen Pharmaceuticals. G.C.F. reports modest consultant/advisory board support from Janssen Pharmaceuticals. P.R.K. reports modest consultant/advisory board support from Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Portola, Merck, Sanofi, and Daiichi Sankyo. P.C. reports significant employment with Johnson & Johnson. D.E.S. reports significant consulting fees from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and CSL Behring; significant research grant from Johnson & Johnson. J.A. reports modest consultant/advisory board: Boehringer Ingelheim, Alere, Bristol-Myers Squibb, Pfizer, Janssen, and Daiichi. B.G. reports modest Data and Safety Monitoring Board/advisory board support from Medtronic, Baxter Healthcare Corporation, InspireMD, Cardiovascular Research Foundation, PPD Development, LP, Boston Scientific, and St. Jude. K.W.M. financial disclosures before August 1, 2013, can be viewed at https://www.dcri.org/aboutus/conflict-of-interest/Mahaffey-COI_2011-2013 . pdf; disclosures after August 1, 2013, can be viewed at http://med.stanford.edu/profiles/kenneth_mahaffey. E.M.H. reports modest honoraria from Boehringer Ingelheim and Bayer and modest consultant/advisory board from Daiichi Sankyo, Ortho-McNeil-Janssen, Johnson & Johnson, Boehringer Ingelheim, Bristol-Myers Squibb, Roche, and Pfizer. J.P.P. reports significant research grant support from Johnson & Johnson/Janssen Pharmaceuticals; significant other research support from Bayer HealthCare Pharmaceuticals Inc (formerly Berlex Labs), Boston Scientific Corporation, Johnson & Johnson Pharmaceutical Research & Development; modest Consultant/Advisory Board support from Forest Laboratories, Inc and Medtronic, Inc; and significant Consultant/Advisory Board support from Johnson & Johnson/Janssen Pharmaceuticals. E.D.P. reports significant research grant support from Eli Lilly & Company, Janssen Pharmaceuticals, Inc, and the American Heart Association; modest consultant/advisory board support from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc, Pfizer, and Genentech Inc. NR 28 TC 22 Z9 23 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUL PY 2015 VL 170 IS 1 BP 141 EP U194 DI 10.1016/j.ahj.2015.03.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK7YJ UT WOS:000356452700018 PM 26093875 ER PT J AU Wang, SA Hasserjian, RP AF Wang, Sa A. Hasserjian, Robert P. TI Acute Erythroleukemias, Acute Megakaryoblastic Leukemias, and Reactive Mimics SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE Acute erythroid leukemia; Pure erythroid leukemia; Megaloblastic anemia; Acute megakaryoblastic leukemia; Transient abnormal myelopoiesis; Down syndrome ID ACUTE MYELOID-LEUKEMIA; TRANSIENT MYELOPROLIFERATIVE DISORDER; WORLD-HEALTH-ORGANIZATION; ACUTE ERYTHROID LEUKEMIA; ACUTE MEGAKARYOCYTIC LEUKEMIA; DOWN-SYNDROME; MYELODYSPLASTIC SYNDROMES; BONE-MARROW; NATURAL-HISTORY; CLASSIFICATION AB Objectives: At the 2013 Society for Hematopathology/European Association for Hematopathology Workshop, 36 cases were submitted to the session that covered acute erythroid leukemia (AEL), acute megakaryoblastic leukemia (AMKL), and reactive mimics. Methods: Cases were reviewed by the session chairs and workshop panel to reach a consensus diagnosis. Results: For acute erythroleukemia, erythroid/myeloid type, discussion acknowledged overlapping features between AEL and myelodysplastic syndromes. Cases submitted as pure erythroid leukemia had distinctive morphology and immunophenotype, complex karyotypes, and aggressive clinical behavior, illustrating certain diagnostic features not currently captured by the current World Health Organization (WHO) definition. In Down syndrome, there were striking similarities between transient abnormal myelopoiesis and AMKL. Most cases of AMKL in adults would be classified as acute myeloid leukemia with myelodysplasia-related changes according to the WHO classification, but this approach deemphasizes their unique clinical, morphologic, and immunophenotypic features. Conclusions: The broad spectrum of cases illustrated the difficulties and complex issues involved in establishing a diagnosis of these entities and the need for better disease definitions. C1 [Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, SA (reprint author), Dept Hematopathol, 1515 Holcombe Blvd,Unit 72, Houston, TX 77030 USA. EM Swang5@mdanderson.org; RHasserjian@mgh.harvard.edu NR 55 TC 6 Z9 7 U1 1 U2 5 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 2015 VL 144 IS 1 BP 44 EP 60 DI 10.1309/AJCPRKYAT6EZQHC7 PG 17 WC Pathology SC Pathology GA CL2DH UT WOS:000356753300005 PM 26071461 ER PT J AU Wormser, GP Villafuerte, P Nolan, SM Wang, GQ Lerner, RG Saetre, KL Maria, MH Branda, JA AF Wormser, Gary P. Villafuerte, Patrick Nolan, Sheila M. Wang, Guiqing Lerner, Robert G. Saetre, Kirsten L. Maria, Mazen H. Branda, John A. TI Neutropenia in Congenital and Adult Babesiosis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Babesia; Babesiosis; Diagnosis; Neutropenia ID PLASMODIUM-FALCIPARUM MALARIA; CLINICAL-MANIFESTATIONS; UNITED-STATES; TRANSMISSION; COUNTS AB Objectives: Anemia and thrombocytopenia are expected hematologic abnormalities in patients with acute babesiosis, whereas neutropenia (defined as an absolute neutrophil count of <= 1,800 neutrophils/mu L for adults and <1,200 neutrophils/mu L for infants) is not usually considered a feature of this infection. We studied the frequency with which neutropenia occurs in congenital and adult cases of babesiosis. Methods: The frequency of neutropenia in cases of congenital babesiosis was determined based on a literature review and on the findings in an unreported case. The frequency of neutropenia in adult patients was assessed based on a review of the medical records of 51 patients who were diagnosed with babesiosis between 2010 and 2013 at two medical centers in the Northeastern United States. Results: Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia. Conclusions: Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection. C1 [Wormser, Gary P.; Villafuerte, Patrick] New York Med Coll, Div Adult Infect Dis, Valhalla, NY 10595 USA. [Nolan, Sheila M.] New York Med Coll, Div Pediat Infect Dis, Valhalla, NY 10595 USA. [Lerner, Robert G.] New York Med Coll, Div Hematol, Valhalla, NY 10595 USA. [Saetre, Kirsten L.; Maria, Mazen H.] New York Med Coll, Div Gen Pediat, Valhalla, NY 10595 USA. [Wang, Guiqing] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, John A.] Harvard Univ, Sch Med, Boston, MA USA. RP Wormser, GP (reprint author), New York Med Coll, Div Infect Dis, 40 Sunshine Cottage Rd, Valhalla, NY 10595 USA. EM gwormser@nymc.edu FU Immunetics; Rarecyte; bioMerieux SA; Institute for Systems Biology; Alere; DiaSorin FX Dr Wormser reports receiving research grants from Immunetics, Rarecyte, bioMerieux SA, and the Institute for Systems Biology. He owns equity in Abbott, has been an expert witness in a malpractice case involving babesiosis, 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 was a consultant to Baxter for Lyme disease vaccine development. Dr Branda reports receiving research grants from Immunetics, bioMerieux SA, Alere, and DiaSorin and was a consultant to AdvanDx. NR 13 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 2015 VL 144 IS 1 BP 94 EP 96 DI 10.1309/AJCP2PHH4HBVHZFS PG 3 WC Pathology SC Pathology GA CL2DH UT WOS:000356753300010 PM 26071466 ER PT J AU Cohen, AR Caruso, P Duhaime, AC Klig, JE AF Cohen, Ari R. Caruso, Paul Duhaime, Ann-Christine Klig, Jean E. TI Feasibility of "rapid" magnetic resonance imaging in pediatric acute head injury SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; HYDROCEPHALUS; CT AB Objective: The objective was to determine the feasibility of "rapid" magnetic resonance imaging (rMRI) versus noncontrast computed tomography (NCCT) for pediatric patients with possible traumatic brain injury and to compare the populations receiving imaging in an urban tertiary care emergency department ED. Methods: We retrospectively reviewed the electronic medical records of ED patients younger than 19 years with possible traumatic brain injury over 4 years who received an rMRI and then age-matched with NCCT patients. Data collection and analysis included demographic and clinical variables, ED length of stay (LOS), and follow-up outcomes. Results: The final cohort had 45 rMRIs and 45 NCCTs. The mean age was 2.7 years, 63% were male, and 65% sustained a fall. Age, sex, and injury mechanism were similar. Time parameters were longer for rMRI patients: ED arrival to completion of imaging (172 vs 93 minutes, P < .001) and ED LOS (266 vs 225 minutes, P = .008). The NCCT group had higher-acuity patients with higher pediatric intensive care unit admission rates (33% vs 7%, P = .002). No patients returned to the ED within 72 hours. Follow-up was available on 78% patients. No clinically significant intracranial injuries were missed. Conclusions: Rapid MRI may be a viable imaging modality for moderate-risk pediatric head injury. Although rMRI took longer to obtain during this pilot study, scan time was only 3 to 4 minutes; and LOS was only 41 minutes longer. Further integration of rMRI in patient care should decrease time variation. Future study of rMRI reliability and satisfaction is needed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cohen, Ari R.; Klig, Jean E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Caruso, Paul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Cohen, AR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM Acohen7@partners.org NR 13 TC 7 Z9 7 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 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2015 VL 33 IS 7 BP 887 EP 890 DI 10.1016/j.ajem.2015.03.052 PG 4 WC Emergency Medicine SC Emergency Medicine GA CL0BG UT WOS:000356602900005 PM 25912791 ER PT J AU Edla, S Reisner, AT Liu, JB Convertino, VA Carter, R Reifman, J AF Edla, Shwetha Reisner, Andrew T. Liu, Jianbo Convertino, Victor A. Carter, Robert, III Reifman, Jaques TI In reply to "Utility of shock index calculation in hemorrhagic trauma" SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID VITAL SIGNS C1 [Edla, Shwetha; Liu, Jianbo; Reifman, Jaques] US Army Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Biotechnol High Performance Comp Software Applica, Dept Def, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Convertino, Victor A.; Carter, Robert, III] US Army Inst Surg Res, Ft Sam Houston, TX 78234 USA. RP Reifman, J (reprint author), US Army Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Biotechnol High Performance Comp Software Applica, Dept Def,ATTN MCMR TT, 504 Scott St, Ft Detrick, MD 21702 USA. EM jaques.reifman.civ@mail.mil NR 5 TC 1 Z9 1 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2015 VL 33 IS 7 BP 978 EP 979 DI 10.1016/j.ajem.2015.04.002 PG 4 WC Emergency Medicine SC Emergency Medicine GA CL0BG UT WOS:000356602900031 PM 25913084 ER PT J AU Hoenig, MP AF Hoenig, Melanie P. TI Share Your Passion for Nephrology: Ten Tips to Invigorate Attending Rounds and Precepting Sessions SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Nephrology education; mentoring; precepting; nephrology workforce; teaching strategies; medical student; resident; attending rounds; inpatient ward ID METABOLIC-ACIDOSIS; RENAL-FAILURE; URINE; DIAGNOSIS; SODIUM; WATER AB Although there have been mounting concerns over the decline in applicants to nephrology training programs, strategies to entice students and trainees to pursue a career in nephrology are lacking. Furthermore, the complex factors that contribute to career decisions and the lag between a positive interaction and a decision to pursue nephrology make such strategies difficult to assess. Nevertheless, it is still important to continue efforts to mentor and inspire. This article offers 10 strategies to help nephrologists share passion for nephrology in the clinical arena. These include the excitement of the dialysis unit, ethical dilemmas, pearls for the bedside, and questions "on the fly." (C) 2015 by the National Kidney Foundation, Inc. C1 [Hoenig, Melanie P.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Hoenig, Melanie P.] Harvard Univ, Sch Med, Boston, MA USA. RP Hoenig, MP (reprint author), Beth Israel Deaconess Med Ctr Clin, Dept Med, Div Renal, Fa 8-185 Pilgrim Rd, Boston, MA 02215 USA. EM mhoenig@bidmc.harvard.edu NR 35 TC 2 Z9 2 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2015 VL 66 IS 1 BP 28 EP 32 DI 10.1053/j.ajkd.2015.03.027 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CL1UO UT WOS:000356730600009 PM 26003473 ER PT J AU Nigwekar, SU Kroshinsky, D Nazarian, RM Goverman, J Malhotra, R Jackson, VA Kamdar, MM Steele, DJR Thadhani, RI AF Nigwekar, Sagar U. Kroshinsky, Daniela Nazarian, Rosalynn M. Goverman, Jeremy Malhotra, Rajeev Jackson, Vicki Ann Kamdar, Mihir M. Steele, David J. R. Thadhani, Ravi I. TI Calciphylaxis: Risk Factors, Diagnosis, and Treatment SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Calcific uremic arteriolopathy; calciphylaxis; risk factors; sodium thiosulfate; warfarin; review ID CALCIFIC UREMIC ARTERIOLOPATHY; STAGE RENAL-DISEASE; INTRAPERITONEAL SODIUM THIOSULFATE; TISSUE-PLASMINOGEN ACTIVATOR; HYPERBARIC-OXYGEN THERAPY; OF-THE-LITERATURE; VASCULAR CALCIFICATION; PROXIMAL CALCIPHYLAXIS; HEMODIALYSIS-PATIENT; SKIN NECROSIS AB Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in patients with chronic kidney failure treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal kidney function. In this review, we discuss the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and nonuremic calciphylaxis. High-quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence and poorly understood pathogenesis and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by a multidisciplinary team for patients with calciphylaxis. (C) 2015 by the National Kidney Foundation, Inc. C1 [Nigwekar, Sagar U.; Steele, David J. R.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Burn Serv, Boston, MA 02114 USA. [Malhotra, Rajeev] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Jackson, Vicki Ann; Kamdar, Mihir M.] Massachusetts Gen Hosp, Palliat Care Div, Boston, MA 02114 USA. RP Nigwekar, SU (reprint author), 165 Cambridge St,Ste 302, Boston, MA 02114 USA. EM snigwekar@mgh.harvard.edu OI Malhotra, Rajeev/0000-0003-0120-4630 FU Sanofi-Aventis; Abbott Laboratories FX Dr Nigwekar reports receiving lecture honoraria from Sanofi-Aventis and is a prior recipient of Nephrology Fellowship Award from Sanofi-Aventis. Dr Thadhani is a consultant to Fresenius Medical Care, North America and has received a research grant from Abbott Laboratories. The remaining authors declare that they have no relevant financial interests. NR 135 TC 41 Z9 41 U1 6 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2015 VL 66 IS 1 BP 133 EP 146 DI 10.1053/j.ajkd.2015.01.034 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA CL1UO UT WOS:000356730600023 PM 25960299 ER PT J AU Hoo, GWS Lin, HK Junaid, I Klaustermeyer, WB AF Hoo, Guy W. Soo Lin, Henry K. Junaid, Imran Klaustermeyer, William B. TI Angiotensin-converting Enzyme Inhibitor Angioedema Requiring Admission to an Intensive Care Unit SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Angioedema; Angiotensin-converting enzyme inhibitor; Respiratory failure ID EMERGENCY-DEPARTMENT; CLINICAL-EXPERIENCE; RISK; HOSPITALIZATIONS; STATES; DRUGS AB OBJECTIVE: The purpose of this study was to review consecutive cases of angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive care unit. METHODS: Fifty subjects with ACE-inhibitor angioedema admitted from 1998-2011 were reviewed. RESULTS: All 50 subjects were men, 62.8 +/- 8.4 years of age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%) required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year. Logistic regression identified dyspnea and tongue involvement with the need for ventilatory support (P < .01). Hypercapnia (PaCO2 +/- 45.2 +/- 6.7; P < 0.046) also identified patients needing ventilatory support. CONCLUSIONS: Ventilatory support was provided for about one-third of those with ACE inhibitorassociated angioedema. Angioedema can occur even after extended use. Dyspnea and tongue involvement identified patients requiring ventilatory support. Published by Elsevier Inc. C1 [Hoo, Guy W. Soo] Univ Calif Los Angeles, Pulm & Crit Care Sect, Los Angeles, CA USA. [Lin, Henry K.; Junaid, Imran; Klaustermeyer, William B.] Univ Calif Los Angeles, Allergy & Immunol Sect, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lin, Henry K.; Junaid, Imran; Klaustermeyer, William B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hoo, GWS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Pulm & Crit Care Sect, 11301 Wilshire Blvd W111Q, Los Angeles, CA 90073 USA. EM guy.soohoo@va.gov NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2015 VL 128 IS 7 BP 785 EP 789 DI 10.1016/j.amjmed.2015.02.006 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CK6WS UT WOS:000356370000036 ER PT J AU Kelly, JF Wakeman, SE Saitz, R AF Kelly, John F. Wakeman, Sarah E. Saitz, Richard TI Neither Abusiveness with Patients nor Naivety with Drugs Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Kelly, John F.; Wakeman, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Saitz, Richard] Boston Univ, Med Ctr, Boston, MA USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2015 VL 128 IS 7 BP E29 EP E29 DI 10.1016/j.amjmed.2015.03.003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CK6WS UT WOS:000356370000015 ER PT J AU Hernandez, RA Hevelone, ND Lopez, L Finlayson, SRG Chittenden, E Cooper, Z AF Hernandez, Roland A. Hevelone, Nathanael D. Lopez, Lenny Finlayson, Samuel R. G. Chittenden, Eva Cooper, Zara TI Racial variation in the use of life-sustaining treatments among patients who die after major elective surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE End-of-life care; Life-sustaining treatment; Quality of death; Racial disparities ID INTENSIVE-CARE-UNIT; QUALITY-OF-LIFE; MEDICARE BENEFICIARIES; ETHNIC-DIFFERENCES; MENTAL-HEALTH; END; DEATH; PREFERENCES; ATTITUDES; CANCER AB BACKGROUND: Although various studies have documented increased life-sustaining treatments among racial minorities in medical patients, whether similar disparities exist in surgical patients is unknown. METHODS: A retrospective cohort study using the Nationwide Inpatient Sample (2006 to 2011) examining patients older than 39 years who died after elective colectomy was performed. Primary predictor variable was race, and main outcome was the use of life-sustaining treatment. RESULTS: In univariate analysis, significant differences existed in use of cardiopulmonary resuscitation (CPR; black, 35.9%; Hispanic, 29.0%; other, 24.5%; white, 11.7%; P = .002) and reintubation (Hispanic, 75.0%; other, 69.0%; black, 52.3%; white, 45.2%; P = .01). In multivariate analysis, black (odds ratio [OR], 3.67; P = .01) and Hispanic (OR, 4.21; P = .03) patients were more likely to have undergone CPR, and Hispanic patients (OR, 4.24; P = .01) were more likely to have been reintubated (reference: white). CONCLUSIONS: Blacks and Hispanics had increased odds of experiencing CPR, and Hispanics were more likely to have been reintubated before death after a major elective operation. These variations may imply worse quality of death and increased associated costs. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hernandez, Roland A.; Hevelone, Nathanael D.; Cooper, Zara] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hernandez, Roland A.] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02115 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. [Lopez, Lenny] Brigham & Womens Hosp, Boston, MA 02115 USA. [Finlayson, Samuel R. G.] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA. [Chittenden, Eva] Massachusetts Gen Hosp, Div Pain & Palliat Med, Boston, MA 02114 USA. [Cooper, Zara] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, Boston, MA 02115 USA. RP Cooper, Z (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM zcooper@partners.org OI Hernandez, Roland/0000-0002-8258-3339 FU Loan Repayment Grant National Institute on Minority Health and Health Disparities,; Klarman Family Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK098280-01] FX Zara Cooper was supported by a Loan Repayment Grant National Institute on Minority Health and Health Disparities, and a grant from the Klarman Family Foundation. Dr. Lopez thanks the RWJ Foundation Harold Amos Faculty Development Program and National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK098280-01). Dr. Cooper had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 29 TC 6 Z9 6 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2015 VL 210 IS 1 BP 52 EP 58 DI 10.1016/j.amjsurg.2014.08.025 PG 7 WC Surgery SC Surgery GA CK4YR UT WOS:000356229800009 PM 25465749 ER PT J AU Tang, R Coopey, SB Specht, MC Lei, L Gadd, MA Hughes, KS Brachtel, EF Smith, BL AF Tang, Rong Coopey, Suzanne B. Specht, Michelle C. Lei, Lan Gadd, Michele A. Hughes, Kevin S. Brachtel, Elena F. Smith, Barbara L. TI Lumpectomy specimen margins are not reliable in predicting residual disease in breast conserving surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast cancer; Lumpectomy margins; Shaved cavity margins; Residual disease ID CARCINOMA IN-SITU; RE-EXCISION RATES; 20-YEAR FOLLOW-UP; TUMOR BURDEN; SURGICAL MARGINS; LOCAL RECURRENCE; CANCER PATIENTS; MASTECTOMY; CONSERVATION; IRRADIATION AB BACKGROUND: In breast conserving surgery, the concordance between lumpectomy margin (LM) status and the status of the corresponding lumpectomy cavity remains uncertain. METHODS: We analyzed pathology reports of lumpectomies from 2004 to 2006. We included those which contained both ink-directed LM and complete (>= 4) separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a surrogate for lumpectomy cavity status, to determine the predictive value of LM for residual disease. RESULTS: Pathology from 1,201 pairs of LM and SCM from 242 patients was compared. LM status predicted corresponding lumpectomy cavity status with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and 81.4% negative predictive value, giving an overall accuracy of 64.9%. CONCLUSIONS: Oriented LMs are not reliable for predicting lumpectomy cavity status, and therefore not reliable for directing re-excision. Taking complete, oriented SCMs at the time of lumpectomy may improve accuracy compared with traditional LM assessment. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tang, Rong; Coopey, Suzanne B.; Specht, Michelle C.; Lei, Lan; Gadd, Michele A.; Hughes, Kevin S.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Tang, Rong] Cent S Univ, Affiliated Tumor Hosp, Hunan Prov Tumor Hosp, Xiangya Med Sch,Div Breast Surg, Changsha 410013, Hunan, Peoples R China. [Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 36 TC 2 Z9 2 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2015 VL 210 IS 1 BP 93 EP 98 DI 10.1016/j.amjsurg.2014.09.029 PG 6 WC Surgery SC Surgery GA CK4YR UT WOS:000356229800015 PM 25613784 ER PT J AU Fishman, JA Thomson, AW AF Fishman, J. A. Thomson, A. W. TI Clinical Implications of Basic Science Discoveries: Immune Homeostasis and the Microbiome-Dietary and Therapeutic Modulation and Implications for Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review ID SEGMENTED FILAMENTOUS BACTERIA; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; ALLOGRAFT ACCEPTANCE; INFECTION PREVENTS; COMMENSAL BACTERIA; RETINOIC ACID; GUT MICROBES; TOLERANCE; ECOLOGY AB Links between the human microbiome and the innate and adaptive immune systems and their impact on autoimmune and inflammatory diseases are only beginning to be recognized. Characterization of the complex human microbial community is facilitated by culture-independent nucleic acid sequencing tools and bioinformatics systems. Specific organisms and microbial antigens are linked with initiation of innate immune responses that, depending on the context, may be associated with tolerogenic or effector immune responses. Further complexity is introduced by preclinical data that demonstrate the impacts of dietary manipulation on the prevention of genetically determined, systemic autoimmune disorders and on gastrointestinal microbiota. Investigation of interactions of complex microbial populations with the human immune system may provide new targets for clinical management in allotransplantation. C1 [Fishman, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Thomson, A. W.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jfishman@mgh.harvard.edu NR 49 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2015 VL 15 IS 7 BP 1755 EP 1758 DI 10.1111/ajt.13236 PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA CK8NF UT WOS:000356494300011 PM 25810247 ER PT J AU Streblow, DN Hwee, YK Kreklywich, CN Andoh, T Denton, M Smith, P Hart, E Broekel, R Pallett, C Rogers, K Streblow, AD Chuop, M Perry, A Slifka, M Messaoudi, I Orloff, SL AF Streblow, D. N. Hwee, Y. K. Kreklywich, C. N. Andoh, T. Denton, M. Smith, P. Hart, E. Broekel, R. Pallett, C. Rogers, K. Streblow, A. D. Chuop, M. Perry, A. Slifka, M. Messaoudi, I. Orloff, S. L. TI Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naive Recipients of Infected Donor Allograft Hearts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; TRANSPLANT VASCULAR SCLEROSIS; CELL IMMUNE RECONSTITUTION; GLYCOPROTEIN-B VACCINE; CD8(+) T-CELLS; SMALL-BOWEL; PREEMPTIVE THERAPY; CARDIAC ALLOGRAFTS; VIRUS-VACCINE; RESPONSES AB Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in solid organ transplants; however, the mechanisms involved are unclear. We determined the efficacy of a CMV vaccine in preventing CMV-accelerated rat cardiac allograft rejection in naive recipients of CMV+ donor hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic cardiac transplantation into CMV-naive or H2O2-inactivated RCMV-vaccinated Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59, whereas vaccinated recipients exhibited a significantly prolonged time to rejection-POD97, similar to recipients of uninfected donor hearts (POD108). Although all of the donor hearts were preinfected, the vaccinated recipients had lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls. Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into naive recipients demonstrate that both T-cell and B-cell arms of the adaptive immune response provide protection against CMV-accelerated rejection. Similar findings were obtained when testing three different adjuvants in passive transfer experiments. We have determined that the timing of the vaccine prior to transplantation and the specific adjuvant play critical roles in mediating anti-viral responses and promoting graft survival. CMV vaccination prior to transplantation may effectively increase graft survival. C1 [Streblow, D. N.; Perry, A.; Slifka, M.; Orloff, S. L.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Streblow, D. N.; Kreklywich, C. N.; Denton, M.; Smith, P.; Hart, E.; Broekel, R.; Pallett, C.; Rogers, K.; Streblow, A. D.; Chuop, M.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Hwee, Y. K.; Kreklywich, C. N.; Andoh, T.; Orloff, S. L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. [Andoh, T.; Orloff, S. L.] Portland VA Med Ctr, Portland, OR USA. [Slifka, M.] Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR USA. [Messaoudi, I.] Univ Calif Riverside, Sch Med, Div Biomed Sci, Riverside, CA 92521 USA. RP Streblow, DN (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. EM streblow@ohsu.edu FU National Institutes of Health [HL083194, HL 66238-01] FX This work was supported by research grants from the National Institutes of Health to D.N.S. (HL083194) and S.L.O. (HL 66238-01). NR 44 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2015 VL 15 IS 7 BP 1805 EP 1816 DI 10.1111/ajt.13188 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA CK8NF UT WOS:000356494300016 PM 25766876 ER PT J AU Adler, JT Dong, N Markmann, JF Schoenfeld, D Yeh, H AF Adler, J. T. Dong, N. Markmann, J. F. Schoenfeld, D. Yeh, H. TI Role of Patient Factors and Practice Patterns in Determining Access to Liver Waitlist SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID DEATH CERTIFICATES; UNITED-STATES; TRANSPLANTATION; RISK; MORTALITY; SURVIVAL; FAILURE; CANCER AB Geographic variability in access to care is a persistent challenge in transplantation. Little is known about how patients with end-stage liver disease are chosen for referral, evaluation and listing. Utilizing death certificate data from the Centers for Disease Control and Prevention from 2002 to 2009, estimated liver demand (ELD) was measured by aggregating annual deaths from liver disease and liver transplants performed in each donor service area (DSA). In DSAs with higher ELD, more patients per capita were listed for transplantation (p<0.001). In addition, listing rates per ELD varied fivefold across DSAs, with more patients per ELD being transplanted in DSAs with higher listing rates (p<0.001). After adjusting for liver donor risk index and MELD at transplant, there was no association between listing rate and posttransplant survival (HR 1.002, p=0.77). In addition, DSAs with lower listing rates were more likely to export organs (p<0.001) of lower liver donor risk index (p<0.001). Listing sicker patients was associated with increased access to the waitlist and transplantation and more efficient organ utilization, but had minimal effect on posttransplant outcomes after adjusting for the resulting organ shortage. C1 [Adler, J. T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Adler, J. T.; Dong, N.; Markmann, J. F.; Yeh, H.] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Markmann, J. F.; Yeh, H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schoenfeld, D.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Yeh, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. EM hyeh@partners.org OI Adler, Joel/0000-0001-8190-3444 FU Harvard Catalyst (National Center for Research Resources); Harvard Catalyst (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR00170-05]; Harvard University; NIH [K08-DK094965]; Center for Surgery and Public Health at Brigham and Women's Hospital FX J.T.A. is funded by the Arthur Tracy Cabot fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital. This work was conducted with support from Harvard Catalyst (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR00170-05, and financial contributions from Harvard University and its affiliated academic healthcare centers) (DAS) and NIH K08-DK094965 (HY). NR 18 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2015 VL 15 IS 7 BP 1836 EP 1842 DI 10.1111/ajt.13301 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA CK8NF UT WOS:000356494300019 PM 25931200 ER PT J AU Bao, Y Curhan, G Merriman, T Plenge, R Kraft, P Choi, HK AF Bao, Ying Curhan, Gary Merriman, Tony Plenge, Robert Kraft, Peter Choi, Hyon K. TI Lack of gene-diuretic interactions on the risk of incident gout: the Nurses' Health Study and Health Professionals Follow-up Study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID GENOME-WIDE ASSOCIATION; COFFEE CONSUMPTION; MEN; HYPERTENSION; VARIANTS; DISEASE; COHORT AB Background Diuretic-induced gout might occur only among those with a genetic predisposition to hyperuricaemia, as suggested by a recent study with 108 self-reported gout cases. Methods We examined the role of urate genes on the risk of diuretic-induced incident gout in 6850 women from the Nurses' Health Study (NHS) and in 4223 men from the Health Professionals Follow-up Study (HPFS). Two published genetic risk scores (GRSs) were calculated using urate-associated single-nucleotide polymorphisms for 8 (GRS8) and 29 genes (GRS29). Results Our analyses included 727 and 354 confirmed incident gout cases in HPFS and NHS, respectively. The multivariate relative risk (RR) for diuretic use was 2.20 and 1.69 among those with GRS8 < and >= the median (p for interaction=0.27). The corresponding RRs using GRS29 were 2.19 and 1.88 (p for interaction=0.40). The lack of interaction persisted in NHS (all p values >0.20) and in our analyses limited to those with hypertension in both cohorts. SLC22A11 (OAT4) showed a significant interaction only among women but in the opposite direction to the recent study. Conclusions In these large prospective studies, individuals with a genetic predisposition for hyperuricaemia are not at a higher risk of developing diuretic-induced gout than those without. C1 [Bao, Ying; Curhan, Gary; Choi, Hyon K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02114 USA. [Curhan, Gary; Plenge, Robert] Harvard Univ, Sch Med, Brigham & Womens Hosp, Renal Div,Dept Med, Boston, MA 02114 USA. [Merriman, Tony] Univ Otago, Dunedin, New Zealand. [Kraft, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02114 USA. [Choi, Hyon K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. RP Choi, HK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM hchoi@partners.org OI Merriman, Tony/0000-0003-0844-8726 FU National Institutes of Health [R01AR056291, R01AR065944, UM1CA167552, P01CA87969] FX This research was supported by grants R01AR056291, R01AR065944, UM1CA167552 and P01CA87969 from the National Institutes of Health. NR 20 TC 7 Z9 7 U1 1 U2 4 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 JUL PY 2015 VL 74 IS 7 BP 1394 EP 1398 DI 10.1136/annrheumdis-2014-206534 PG 5 WC Rheumatology SC Rheumatology GA CK2EZ UT WOS:000356024700011 PM 25667207 ER PT J AU Zhang, Y Vasheghani, F Li, YH Blati, M Simeone, K Fahmi, H Lussier, B Roughley, P Lagares, D Pelletier, JP Martel-Pelletier, J Kapoor, M AF Zhang, Yue Vasheghani, Faezeh Li, Ying-hua Blati, Meryem Simeone, Kayla Fahmi, Hassan Lussier, Bertrand Roughley, Peter Lagares, David Pelletier, Jean-Pierre Martel-Pelletier, Johanne Kapoor, Mohit TI Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; LIFE-SPAN; MOUSE; RAPAMYCIN; MODEL; AMPK; KINASE; GROWTH; ULK1 AB Objectives Mammalian target of rapamycin (mTOR) (a serine/threonine protein kinase) is a major repressor of autophagy, a cell survival mechanism. The specific in vivo mechanism of mTOR signalling in OA pathophysiology is not fully characterised. We determined the expression of mTOR and known autophagy genes in human OA cartilage as well as mouse and dog models of experimental OA. We created cartilage-specific mTOR knockout (KO) mice to determine the specific role of mTOR in OA pathophysiology and autophagy signalling in vivo. Methods Inducible cartilage-specific mTOR KO mice were generated and subjected to mouse model of OA. Human OA chondrocytes were treated with rapamycin and transfected with Unc-51-like kinase 1 (ULK1) siRNA to determine mTOR signalling. Results mTOR is overexpressed in human OA cartilage as well as mouse and dog experimental OA. Upregulation of mTOR expression co-relates with increased chondrocyte apoptosis and reduced expression of key autophagy genes during OA. Subsequently, we show for the first time that cartilage-specific ablation of mTOR results in increased autophagy signalling and a significant protection from destabilisation of medial meniscus (DMM)-induced OA associated with a significant reduction in the articular cartilage degradation, apoptosis and synovial fibrosis. Furthermore, we show that regulation of ULK1/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway by mTOR may in part be responsible for regulating autophagy signalling and the balance between catabolic and anabolic factors in the articular cartilage. Conclusions This study provides a direct evidence of the role of mTOR and its downstream modulation of autophagy in articular cartilage homeostasis. C1 [Zhang, Yue; Vasheghani, Faezeh; Li, Ying-hua; Blati, Meryem; Simeone, Kayla; Fahmi, Hassan; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Kapoor, Mohit] Univ Montreal Res Ctr CRCHUM, Osteoarthrit Res Unit, Montreal, PQ, Canada. [Lussier, Bertrand] Univ Montreal, Dept Clin Sci, Fac Vet Med, Montreal, PQ, Canada. [Roughley, Peter] McGill Univ, Shriners Hosp, Genet Unit, Montreal, PQ, Canada. [Lagares, David] Harvard Univ, Pulm & Crit Care Unit, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Lagares, David] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Dept Med,Med Sch, Cambridge, MA 02138 USA. [Kapoor, Mohit] Toronto Western Hosp, Div Genet & Dev, Toronto Western Res Inst, UHN, Toronto, ON M5T 2S8, Canada. RP Kapoor, M (reprint author), Toronto Western Hosp, Div Genet & Dev, Toronto Western Res Inst, UHN, 60 Leonard Ave, Toronto, ON M5T 2S8, Canada. EM mkapoor@uhnresearch.ca FU Dr Mohit Kapoor's Canadian Institutes of Health Research [MOP126016]; European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO); Amgen FX This work was supported by Dr Mohit Kapoor's Canadian Institutes of Health Research Operating Grant MOP126016. Y Z is a recipient of Young Investigator Fellowship from The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and Amgen. NR 30 TC 36 Z9 37 U1 6 U2 17 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 JUL PY 2015 VL 74 IS 7 BP 1432 EP 1440 DI 10.1136/annrheumdis-2013-204599 PG 9 WC Rheumatology SC Rheumatology GA CK2EZ UT WOS:000356024700016 PM 24651621 ER PT J AU McGuire, JF Piacentini, J Scahill, L Woods, DW Villarreal, R Wilhelm, S Walkup, JT Peterson, AL AF McGuire, Joseph F. Piacentini, John Scahill, Lawrence Woods, Douglas W. Villarreal, Robert Wilhelm, Sabine Walkup, John T. Peterson, Alan L. TI Bothersome tics in patients with chronic tic disorders: Characteristics and individualized treatment response to behavior therapy SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Tourette's disorder; Behavior therapy; Habit reversal training; Comprehensive behavioral intervention for tics; Treatment outcome; Individualized treatment response ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; SYNDROME IMPACT SURVEY; TOURETTE SYNDROME; PREMONITORY URGES; ANXIETY DISORDERS; HABIT-REVERSAL; SUPPORTIVE PSYCHOTHERAPY; NEGATIVE REINFORCEMENT; SEVERITY-SCALE AB This report examined the most frequently reported bothersome tics among individuals with chronic tic disorders and evaluated the improvement and remission of tics and their associated characteristics. Youths and adults (N = 240) were randomly assigned to receive the comprehensive behavioral intervention for tics (CBIT) or psychoeducation and supportive therapy (PST). At baseline, motor tics and tics with an urge were rated as more bothersome relative to vocal tics and tics without premonitory urges. The five most common bothersome tics included eye blinking, head jerks, sniffing, throat clearing, and other complex motor tics. While CBIT outperformed PST across tic type and urge presence, tics preceded by premonitory urges at baseline had higher severity at posttreatment across treatment condition. Six individual tic types had lower severity at posttreatment following CBIT relative to PST. Baseline urge presence was associated with tic remission for CBIT but not PST. Specific bothersome tics were more likely to remit with CBIT relative to PST. Findings suggest that individual tics respond and remit differently to CBIT relative to PST, with implications highlighting the negative reinforcement hypothesis in tic symptom maintenance. Clinicaltrials.gov identifiers: NCT00218777; NCT00231985. Published by Elsevier Ltd. C1 [McGuire, Joseph F.; Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Scahill, Lawrence] Emory Univ, Marcus Ctr, Sch Med, Atlanta, GA 30329 USA. [Woods, Douglas W.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Villarreal, Robert; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Walkup, John T.] Cornell Univ, Weil Cornell Med Coll, New York, NY 10065 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Peterson, Alan L.] Univ Texas San Antonio, San Antonio, TX 78249 USA. RP Peterson, AL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7550 IH 10 West,Suite 1325, San Antonio, TX 78229 USA. EM jfmcguire@mednet.ucla.edu; jpiacentini@mednet.ucla.edu; lawrence.scahill@emory.edu; dowoods@tamu.edu; villarrear10@uthscsa.edu; swilhelm@mgh.harvard.edu; jtw9001@med.cornell.edu; petersona3@uthscsa.edu FU National Institute of Mental Health [R01MH070802, 5R01MH069877, R01MH069874, RO1MH069875] FX This research was supported by the following National Institute of Mental Health grants: R01MH070802 (Dr. Piacentini) with subcontracts to Drs. Woods, Scahill, Wilhelm, Peterson, and Walkup; 5R01MH069877 (Dr. Wilhelm), R01MH069874 (Dr. Scahill), and RO1MH069875 (Dr. Peterson), with subcontracts to Drs. Piacentini and Woods. Dr. Walkup served as a consult on these three grants. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health. NR 51 TC 4 Z9 4 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2015 VL 70 BP 56 EP 63 DI 10.1016/j.brat.2015.05.006 PG 8 WC Psychology, Clinical SC Psychology GA CK9HW UT WOS:000356552200007 PM 25988365 ER PT J AU Safdar, N Perencevich, E AF Safdar, Nasia Perencevich, Eli TI Crossing the quality chasm for Clostridium difficile infection prevention SO BMJ QUALITY & SAFETY LA English DT Editorial Material ID CARE; HOSPITALS C1 [Safdar, Nasia] Univ Wisconsin, Dept Med, Sch Med, Infect Dis Sect,William S Middleton Mem Vet Hosp, Madison, WI USA. [Perencevich, Eli] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Perencevich, Eli] Iowa City VA Healthcare Syst, Iowa City, IA USA. RP Safdar, N (reprint author), Univ Wisconsin Hosp & Clin, 1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU AHRQ HHS [R03 HS023791, R03HS023791, R18 HS024039] NR 17 TC 1 Z9 1 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2015 VL 24 IS 7 BP 409 EP 411 DI 10.1136/bmjqs-2015-004344 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CK9EI UT WOS:000356543000001 PM 25979001 ER PT J AU Sacks, GD Shannon, EM Dawes, AJ Rollo, JC Nguyen, DK Russell, MM Ko, CY Maggard-Gibbons, MA AF Sacks, Greg D. Shannon, Evan M. Dawes, Aaron J. Rollo, Johnathon C. Nguyen, David K. Russell, Marcia M. Ko, Clifford Y. Maggard-Gibbons, Melinda A. TI Teamwork, communication and safety climate: a systematic review of interventions to improve surgical culture SO BMJ QUALITY & SAFETY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; OPERATING-ROOM BRIEFINGS; INTERRUPTED TIME-SERIES; PATIENT SAFETY; TRAINING-PROGRAM; CHECKLIST; THEATER; PERFORMANCE; SURGERY; CARE AB Objectives To define the target domains of culture-improvement interventions, to assess the impact of these interventions on surgical culture and to determine whether culture improvements lead to better patient outcomes and improved healthcare efficiency. Background Healthcare systems are investing considerable resources in improving workplace culture. It remains unclear whether these interventions, when aimed at surgical care, are successful and whether they are associated with changes in patient outcomes. Methods PubMed, Cochrane, Web of Science and Scopus databases were searched from January 1980 to January 2015. We included studies on interventions that aimed to improve surgical culture, defined as the interpersonal, social and organisational factors that affect the healthcare environment and patient care. The quality of studies was assessed using an adapted tool to focus the review on higher-quality studies. Due to study heterogeneity, findings were narratively reviewed. Findings The 47 studies meeting inclusion criteria (4 randomised trials and 10 moderate-quality observational studies) reported on interventions that targeted three domains of culture: teamwork (n=28), communication (n=26) and safety climate (n=19); several targeted more than one domain. All moderate-quality studies showed improvements in at least one of these domains. Two studies also demonstrated improvements in patient outcomes, such as reduced postoperative complications and even reduced postoperative mortality (absolute risk reduction 1.7%). Two studies reported improvements in healthcare efficiency, including fewer operating room delays. These findings were supported by similar results from low-quality studies. Conclusions The literature provides promising evidence for various strategies to improve surgical culture, although these approaches differ in terms of the interventions employed as well as the techniques used to measure culture. Nevertheless, culture improvement appears to be associated with other positive effects, including better patient outcomes and enhanced healthcare efficiency. C1 [Sacks, Greg D.; Dawes, Aaron J.; Rollo, Johnathon C.; Nguyen, David K.; Russell, Marcia M.; Ko, Clifford Y.; Maggard-Gibbons, Melinda A.] Univ Calif Los Angeles, David Geffen Sch Med, Surg, Los Angeles, CA 90095 USA. [Shannon, Evan M.] UCSF Sch Med, San Francisco, CA USA. [Russell, Marcia M.; Ko, Clifford Y.; Maggard-Gibbons, Melinda A.] VA Greater Los Angeles Healthcare Syst, Gen Surg, Los Angeles, CA USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Surg, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 NR 73 TC 10 Z9 10 U1 3 U2 29 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2015 VL 24 IS 7 BP 458 EP 467 DI 10.1136/bmjqs-2014-003764 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CK9EI UT WOS:000356543000012 PM 26002946 ER PT J AU Brown, LC Petersen, IA Haddock, MG Bakkum-Gamez, JN Lee, LJ Cimbak, NC Berkowitz, RS Viswanathan, AN AF Brown, Lindsay C. Petersen, Ivy A. Haddock, Michael G. Bakkum-Gamez, Jamie N. Lee, Larissa J. Cimbak, Nicole C. Berkowitz, Ross S. Viswanathan, Akila N. TI Vaginal brachytherapy for early-stage carcinosarcoma of the uterus SO BRACHYTHERAPY LA English DT Article DE Carcinosarcoma; Radiation therapy; Uterine cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; MIXED MULLERIAN TUMORS; PHASE-III TRIAL; CELL ENDOMETRIAL CANCER; UTERINE CARCINOSARCOMA; METAPLASTIC CARCINOMAS; RADIOTHERAPY; IFOSFAMIDE; SARCOMAS; THERAPY AB OBJECTIVE: Uterine caicinosarcoma (CS) is an aggressive malignancy and the optimal adjuvant treatment is not well-established. We report outcomes with vaginal brachytherapy (VB) for women with early-stage CS. METHODS AND MATERIALS: A multi-institutional retrospective study of Stage CS treated with hysterectomy, surgical staging, and adjuvant high-dose-rate VB without external-beam pelvic radiotherapy was performed. Rates of vaginal control, pelvic control, locoregional control, disease-free survival, and overall survival were determined using the Kaplan-Meier method. RESULTS: 33 patients were identified. Prescribed VB dose was 21 Gy in three fractions (n = 15 [45%]) or 24 Gy in six fractions (n = 18 [55%]). Eighteen patients (55%) received chemotherapy. Median followup was 2.0 years. Twenty-seven patients (82%) underwent pelvic lymphadenectomy, 5 (15%) had nodal sampling, and 1 (3%) had no lymph node assessment. Relapse occurred in 11 patients (33%), all of whom had lymph node evaluation. Locoregional relapse was a component of failure in 6 patients (18%), of whom 3 (9%) failed in the pelvis alone. Three patients (9%) had simultaneous distant and locoregional relapse (two vaginal, one pelvic). Five additional patients (15%) had distant relapse. Six of the 11 patients (55%) with disease recurrence received chemotherapy. Two-year vaginal control and pelvic control were 94% and 87%. Two-year locoregional control, disease-free survival, and overall survival were 81%, 66%, and 79%. CONCLUSIONS: Despite having early-stage disease and treatment with VB, patients in this series had relatively high rates of local and distant relapse. Patients who undergo lymphadenectomy and VB remain at risk for relapse. Novel treatment strategies are needed. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Brown, Lindsay C.; Petersen, Ivy A.; Haddock, Michael G.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Bakkum-Gamez, Jamie N.] Mayo Clin, Dept Gynecol Oncol, Rochester, MN USA. [Lee, Larissa J.; Cimbak, Nicole C.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Dana Farber Canc Inst, Div Gynecol Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 28 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JUL-AUG PY 2015 VL 14 IS 4 BP 433 EP 439 DI 10.1016/j.brachy.2015.02.194 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CK9JH UT WOS:000356555900002 PM 25890795 ER PT J AU Damato, AL Lee, LJ Bhagwat, MS Buzurovic, I Cormack, RA Finucane, S Hansen, JL O'Farrell, DA Offiong, A Randall, U Friesen, S Viswanathan, AN AF Damato, Antonio L. Lee, Larissa J. Bhagwat, Mandar S. Buzurovic, Ivan Cormack, Robert A. Finucane, Susan Hansen, Jorgen L. O'Farrell, Desmond A. Offiong, Alecia Randall, Una Friesen, Scott Viswanathan, Akila N. TI Redesign of process map to increase efficiency: Reducing procedure time in cervical cancer brachytherapy SO BRACHYTHERAPY LA English DT Article DE Brachytherapy; Efficiency; Process maps; Workflow ID DOSE-RATE BRACHYTHERAPY; SOCIETY CONSENSUS GUIDELINES; QUALITY MANAGEMENT PROGRAM; LOCALLY ADVANCED-CARCINOMA; GYNECOLOGIC BRACHYTHERAPY; AMERICAN BRACHYTHERAPY; ADAPTIVE BRACHYTHERAPY; COMPUTED-TOMOGRAPHY; VOLUME PARAMETERS; CLINICAL-OUTCOMES AB PURPOSE: To increase intraprocedural efficiency in the use of clinical resources and to decrease planning time for cervical cancer brachytherapy treatments through redesign of the procedure's process map. METHODS AND MATERIALS: A multidisciplinary team identified all tasks and associated resources involved in cervical cancer brachytherapy in our institution and arranged them in a process map. A redesign of the treatment planning component of the process map was conducted with the goal of minimizing planning time. Planning time was measured on 20 consecutive insertions, of which 10 were performed with standard procedures and 10 with the redesigned process map, and results were compared. Statistical significance (p < 0.05) was measured with a two-tailed t test. RESULTS: Twelve tasks involved in cervical cancer brachytherapy treatments were identified. The process map showed that in standard procedures, the treatment planning tasks were performed sequentially. The process map was redesigned to specify that contouring and some planning tasks are performed concomitantly. Some quality assurance tasks were reorganized to minimize adverse effects of a possible error on procedure time. Test dry runs followed by live implementation confirmed the applicability of the new process map to clinical conditions. A 29% reduction in planning time (p < 0.01) was observed with the introduction of the redesigned process map. CONCLUSIONS: A process map for cervical cancer brachytherapy was generated. The treatment planning component of the process map was redesigned, resulting in a 29% decrease in planning time and a streamlining of the quality assurance process. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Damato, Antonio L.; Lee, Larissa J.; Bhagwat, Mandar S.; Buzurovic, Ivan; Cormack, Robert A.; Finucane, Susan; Hansen, Jorgen L.; O'Farrell, Desmond A.; Offiong, Alecia; Randall, Una; Friesen, Scott; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Damato, AL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM adamato@lroc.harvard.edu RI Buzurovic, Ivan/C-8036-2011 OI Buzurovic, Ivan/0000-0001-9632-3434 FU National Institutes of Health [R21 CA167800] FX This work was partially funded by the National Institutes of Health R21 CA167800 (Principal Investigator: ANV). NR 38 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JUL-AUG PY 2015 VL 14 IS 4 BP 471 EP 480 DI 10.1016/j.brachy.2014.11.016 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CK9JH UT WOS:000356555900007 PM 25572438 ER PT J AU Muralidhar, V Mahal, BA Ziehr, DR Chen, YW Nezolosky, MD Viswanathan, VB Beard, CJ Devlin, PM Martin, NE Orio, PF Nguyen, PL AF Muralidhar, Vinayak Mahal, Brandon A. Ziehr, David R. Chen, Yu-Wei Nezolosky, Michelle D. Viswanathan, Vidya B. Beard, Clair J. Devlin, Phillip M. Martin, Neil E. Orio, Peter F., III Nguyen, Paul L. TI Shifting brachytherapy monotherapy case mix toward intermediate-risk prostate cancer SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Intermediate-risk prostate cancer; Prostate brachytherapy ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; CARCINOMA; OUTCOMES; SURGERY; TRENDS AB PURPOSE: The relative use of brachytherapy (BT) for prostate cancer has declined in recent years. In this setting, we sought to determine whether the case mix of BT monotherapy treated men has changed over time in terms of risk group composition. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was used to identify 30,939 patients diagnosed with prostate adenocarcinoma between 2004 and 2011 who received BT monotherapy. The case mix of BT monotherapy patients was calculated by patient risk group and year of diagnosis. RESULTS: Between 2004 and 2011, the use of BT monotherapy declined overall. The relative percentage of men undergoing BT with low-risk disease declined by 4.5%, whereas the relative percentage of patients with intermediate-risk disease increased by 4.7%. Non-white patients and those from poorer counties did not show shifts in the risk group makeup of BT monotherapy patients, whereas white patients and those from wealthier counties did. CONCLUSIONS: Although fewer patients with prostate cancer are undergoing BT monotherapy, men with intermediate-risk disease comprised a significantly larger portion of the BT case mix in 2011 compared with 2004. Future research efforts by brachytherapists should be directed toward improving BT technique, optimizing radiation doses, and obtaining long-term followup data for patients with intermediate-risk prostate cancer. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Mahal, Brandon A.; Ziehr, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Wei] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA USA. [Nezolosky, Michelle D.; Viswanathan, Vidya B.; Beard, Clair J.; Devlin, Phillip M.; Martin, Neil E.; Orio, Peter F., III; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nezolosky, Michelle D.; Viswanathan, Vidya B.; Beard, Clair J.; Devlin, Phillip M.; Martin, Neil E.; Orio, Peter F., III; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Health Sciences and Technology IDEA2 Program - Peter C. Farrell (1967) Fund; Prostate Cancer Foundation; Fitz's Cancer Warriors; Scott Forbes and Gina Ventre Fund FX This work was supported by grants from the Health Sciences and Technology IDEA2 Program supported by the Peter C. Farrell (1967) Fund, The Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, and The Scott Forbes and Gina Ventre Fund. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JUL-AUG PY 2015 VL 14 IS 4 BP 511 EP 516 DI 10.1016/j.brachy.2015.03.004 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CK9JH UT WOS:000356555900012 PM 25887342 ER PT J AU Gutchess, AH Sokal, R Coleman, JA Gotthilf, G Grewal, L Rosa, N AF Gutchess, Angela H. Sokal, Rebecca Coleman, Jennifer A. Gotthilf, Gina Grewal, Lauren Rosa, Nicole TI Age differences in self-referencing: Evidence for common and distinct encoding strategies SO BRAIN RESEARCH LA English DT Review DE self; fMRI; aging; memory ID MEDIAL PREFRONTAL CORTEX; EVENT-RELATED FMRI; EMOTIONAL MEMORY; OLDER-ADULTS; NEURAL BASIS; METAANALYSIS; INFORMATION; RELEVANCE; VALENCE; AROUSAL AB Although engagement of medial prefrontal cortex (MPFC) underlies self-referencing of information for younger and older adults, the region has not consistently been implicated across age groups for the encoding of self-referenced information. We sought to determine whether making judgments about others as well as the self influenced findings in the previous study. During an fMRI session, younger and older adults encoded adjectives using only a self-reference task. For items later remembered compared to those later forgotten, both age groups robustly recruited medial prefrontal cortex, indicating common neural regions support encoding across younger and older adults when participants make only self-reference judgments. Focal age differences emerged in regions related to emotional processing and cognitive control, though these differences are more limited than in tasks in which judgments also are made about others. We conclude that making judgments about another person differently affects the ways that younger and older adults make judgments about the self, with results of a follow-up behavioral study supporting this interpretation. This article is part of a Special Issue entitled Memory and Aging. (C) 2014 Elsevier B.V. All rights reserved. C1 [Gutchess, Angela H.; Sokal, Rebecca; Coleman, Jennifer A.; Gotthilf, Gina; Grewal, Lauren; Rosa, Nicole] Brandeis Univ, Waltham, MA 02454 USA. [Gutchess, Angela H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Sokal, Rebecca] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Coleman, Jennifer A.] Virginia Commonwealth Univ, Richmond, VA USA. [Grewal, Lauren] Univ Pittsburgh, Pittsburgh, PA USA. [Rosa, Nicole] Harvard Univ, Cambridge, MA 02138 USA. RP Gutchess, AH (reprint author), Brandeis Univ, Dept Psychol, 415 South St,MS 062, Waltham, MA 02454 USA. EM gutchess@brandeis.edu OI Coleman, Jennifer/0000-0002-0158-2589 FU National Institute on Aging [R21AG032382]; National Center for Research Resources [P41 RR14075]; MIND Institute FX We gratefully acknowledge experimental assistance from Allie Indeck, Maya Siegel, Christine Hosey, Deborah Chamama, and Brian Dahlben. This research was funded by National Institute on Aging (Grant R21AG032382), and portions of the research were conducted while A.H.G. was a fellow of the American Federation for Aging Research. The Athinoula A. Martinos Center for Biomedical Imaging is supported by the National Center for Research Resources (Grant P41 RR14075) and by the MIND Institute. NR 37 TC 1 Z9 1 U1 1 U2 7 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 JUL 1 PY 2015 VL 1612 BP 118 EP 127 DI 10.1016/j.brainres.2014.08.033 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CK9HR UT WOS:000356551700010 PM 25223905 ER PT J AU Viswanathan, AN Moughan, J Miller, BE Xiao, Y Jhingran, A Portelance, L Bosch, WR Matulonis, UA Horowitz, NS Mannel, RS Souhami, L Erickson, BA Winter, KA Small, W Gaffney, DK AF Viswanathan, Akila N. Moughan, Jennifer Miller, Brigitte E. Xiao, Ying Jhingran, Anuja Portelance, Lorraine Bosch, Walter R. Matulonis, Ursula A. Horowitz, Neil S. Mannel, Robert S. Souhami, Luis Erickson, Beth A. Winter, Kathryn A. Small, William, Jr. Gaffney, David K. TI NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer SO CANCER LA English DT Article DE endometrial cancer; radiation; bevacizumab; chemotherapy; intensity-modulated radiotherapy (IMRT) ID PELVIC RADIATION-THERAPY; III TRIAL; CISPLATIN/PACLITAXEL CHEMOTHERAPY; GASTROINTESTINAL TOXICITY; ADJUVANT CHEMOTHERAPY; CERVICAL-CANCER; RISK; CARCINOMA; IRRADIATION; SURGERY AB BACKGROUNDThe current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. METHODSPatients underwent a hysterectomy and lymph node removal, and had 1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade 3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). RESULTSA total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade 3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade 3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. CONCLUSIONSPostoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma. Cancer 2015;121:2156-2163. (c) 2015 American Cancer Society. C1 [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Moughan, Jennifer; Winter, Kathryn A.] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Miller, Brigitte E.] Carolinas Healthcare Syst NorthEast, Levine Canc Inst, Concord, NC USA. [Xiao, Ying] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Jhingran, Anuja] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Portelance, Lorraine] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Bosch, Walter R.] Washington Univ, St Louis, MO USA. [Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Mannel, Robert S.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Souhami, Luis] McGill Univ, Montreal, PQ, Canada. [Erickson, Beth A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Small, William, Jr.] Loyola Univ, Chicago, IL 60611 USA. [Gaffney, David K.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU National Cancer Institute [U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA81647, U24CA180803]; NIH [R21 167800] FX Supported by National Cancer Institute grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA81647, and U24CA180803. Dr. Viswanathan receives support through NIH R21 167800. Dr. Bosch has received a grant and other research support from Augmenix for work performed outside of the current study. Ms. Winter has acted as a paid statistical member of the Data Monitoring Committee for an ovarian trial performed for Roche outside of the current study. NR 19 TC 4 Z9 4 U1 1 U2 6 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 JUL 1 PY 2015 VL 121 IS 13 BP 2156 EP 2163 DI 10.1002/cncr.29337 PG 8 WC Oncology SC Oncology GA CK7SU UT WOS:000356433600012 PM 25847373 ER PT J AU Castillo, JJ Olszewski, AJ Hunter, ZR Kanan, S Meid, K Treon, SP AF Castillo, Jorge J. Olszewski, Adam J. Hunter, Zachary R. Kanan, Sandra Meid, Kirsten Treon, Steven P. TI Incidence of secondary malignancies among patients with Waldenstrom macroglobulinemia: An analysis of the SEER database SO CANCER LA English DT Article DE epidemiology; incidence; lymphoplasmacytic lymphoma; secondary malignancies; Waldenstrom macroglobulinemia ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOPLASMACYTIC LYMPHOMA; CANCER; POPULATION; RISK; CHLORAMBUCIL; FLUDARABINE; NEOPLASMS; ANTIBODY; THERAPY AB BACKGROUNDWaldenstrom macroglobulinemia (WM) is an indolent malignancy that predominantly affects older individuals who are at risk for secondary malignancies (SMs). The objective of this study was to characterize the incidence of SMs after a diagnosis of WM with the Surveillance, Epidemiology, and End Results (SEER) database. METHODSWith SEER-13 data (1992-2011), standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for the rates of solid and hematologic SMs in WM patients versus the general population. The analysis was stratified by age, sex, race, year of diagnosis, and latency from the WM diagnosis. RESULTSAmong 4676 patients with WM, 681 SMs were recorded. The overall SIR was 1.49 (95% CI, 1.38-1.61), and the median time to an SM was 3.7 years. The cumulative incidence of SMs was 10% at 5 years and 16% at 10 years. The risk was significantly increased for cancers of the lungs, urinary tract, and thyroid; melanoma; aggressive lymphoma; and acute leukemia. The SIR for SMs in patients with WM was increased, regardless of age, sex, race, or year of diagnosis. CONCLUSIONSPatients with WM had a 49% higher risk of SMs than the general population. The selectively increased risk for hematologic SMs and certain solid SMs may be associated with transformation, therapy, and immune dysregulation. Cancer 2015;121:2230-2236. (c) 2015 American Cancer Society. C1 [Castillo, Jorge J.; Hunter, Zachary R.; Kanan, Sandra; Meid, Kirsten; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02215 USA. [Castillo, Jorge J.; Treon, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. [Olszewski, Adam J.] Brown Univ, Mem Hosp Rhode Isl, Warren Alpert Med Sch, Div Hematol & Oncol, Pawtucket, RI 02860 USA. RP Castillo, JJ (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Olszewski, Adam/0000-0002-6472-6658; Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 NR 30 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2015 VL 121 IS 13 BP 2230 EP 2236 DI 10.1002/cncr.29334 PG 7 WC Oncology SC Oncology GA CK7SU UT WOS:000356433600021 PM 25757851 ER PT J AU Hanna, NH Dahlberg, SE Kolesar, JM Aggarwal, C Hirsch, FR Ramalingam, SS Schiller, JH AF Hanna, Nasser H. Dahlberg, Suzanne E. Kolesar, Jill M. Aggarwal, Charu Hirsch, Fred R. Ramalingam, Suresh S. Schiller, Joan H. TI Three-arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508) SO CANCER LA English DT Article DE carboplatin; cetuximab; cixutumumab; non-small cell lung cancer; paclitaxel ID GROWTH-FACTOR-I; RECEPTOR MONOCLONAL-ANTIBODY; GENE COPY NUMBER; III TRIAL; BINDING PROTEIN-3; EGFR MUTATIONS; OPEN-LABEL; CHEMOTHERAPY; ADENOCARCINOMA; SENSITIVITY AB BACKGROUNDPreclinical evidence supports the clinical investigation of inhibitors to the insulin-like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) either alone or in combination as treatment for patients with non-small cell lung cancer (NSCLC). METHODSPatients with chemotherapy-naive, advanced NSCLC who had an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomized to receive carboplatin intravenously at an area under the plasma drug concentration-time curve of 6.0 plus paclitaxel 200 mg/m(2) intravenously on day 1 every 3 weeks combined with either intravenous cetuximab weekly (arm A), intravenous cixutumumab every 2 weeks (arm B), or both (arm C). Patients who had nonprogessing disease after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until they developed progressive disease. The primary endpoint was progression-free survival (PFS). The study design required 180 eligible patients and had 88% power to detect a 60% increase in median PFS for either comparison (arm A vs arm C or arm B vs arm C) using the log-rank test. RESULTSFrom September 2009 to December 2010, 140 patients were accrued. The study was closed to accrual early because of an excessive number of grade 5 events reported on arms A and C. Thirteen patients died during treatment (6 patients on arm A, 2 patients on arm B, and 5 patients on arm C), including 9 within approximately 1 month of starting therapy. The estimated median PFS for arms A, B, and C were similar at 3.4 months, 4.2 months, and 4 months, respectively. CONCLUSIONSOn the basis of the apparent lack of efficacy and excessive premature deaths, the current results do not support the continued investigation of carboplatin, paclitaxel, and cixutumumab either alone or in combination with cetuximab for patients with advanced NSCLC. Cancer 2015;121:2253-2261. (c) 2015 American Cancer Society. C1 [Hanna, Nasser H.] Indiana Univ, Hlth Simon Canc Ctr, Indianapolis, IN 46202 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kolesar, Jill M.] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Aggarwal, Charu] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Hirsch, Fred R.] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, Dallas, TX 75390 USA. RP Hanna, NH (reprint author), Indiana Univ, Indiana Univ Sch Med, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. EM nhanna@iupui.edu FU Public Health Service Grants [CA180820, CA180794, CA180795, CA180799, CA180864, CA180834, CA180870]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA180795, CA180799, CA180864, CA180834, CA180870, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. NR 28 TC 8 Z9 8 U1 0 U2 8 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 JUL 1 PY 2015 VL 121 IS 13 BP 2253 EP 2261 DI 10.1002/cncr.29308 PG 9 WC Oncology SC Oncology GA CK7SU UT WOS:000356433600024 PM 25740387 ER PT J AU Cohen, JM Granter, SR Werchniak, AE AF Cohen, J. M. Granter, S. R. Werchniak, A. E. TI Risk stratification in extramammary Paget disease SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Review ID LYMPH-NODE BIOPSY; PROGNOSTIC-FACTORS; MANAGEMENT; EXPRESSION AB Extramammary Paget disease (EMPD) is an uncommon intraepithelial adenocarcinoma that involves body sites with apocrine glands such as the genital, perineal and perianal regions. Risk stratification and treatment planning for EMPD can be challenging. This review presents important prognostic information in EMPD to assist physicians with risk stratification of patients with EMPD. The best-understood prognostic factors are depth of invasion and involvement of extracutaneous sites. Tumours that invade into the reticular dermis or have a depth of >1mm are associated with poorer prognosis. Additionally, tumours spreading outside the skin into lymph nodes or other tissues are higher risk. There is an emerging understanding of the importance of tumour genetics in risk stratification, and we review the data on Ki-67, cyclin D1, Mucin 5AC and E-cadherin. There is less evidence supporting the importance of lesion site and patient age in risk stratification. This succinct review will be helpful in clinical practice and in EMPD research. C1 [Cohen, J. M.; Granter, S. R.; Werchniak, A. E.] Harvard Univ, Sch Med, Boston, MA USA. [Granter, S. R.] Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. [Werchniak, A. E.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Werchniak, A. E.] Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. RP Werchniak, AE (reprint author), Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM awerchniak@partners.org NR 16 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0307-6938 EI 1365-2230 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD JUL PY 2015 VL 40 IS 5 BP 473 EP 478 DI 10.1111/ced.12690 PG 6 WC Dermatology SC Dermatology GA CL0JL UT WOS:000356628600001 PM 26011765 ER PT J AU Toosi, KK Hogaboom, NS Oyster, ML Boninger, ML AF Toosi, Kevin K. Hogaboom, Nathan S. Oyster, Michelle L. Boninger, Michael L. TI Computer keyboarding biomechanics and acute changes in median nerve indicative of carpal tunnel syndrome SO CLINICAL BIOMECHANICS LA English DT Article DE Carpal tunnel syndrome; Computer keyboarding biomechanics; Ultrasound; Ergonomics ID FOREARM POSTURES; CANAL PRESSURES; WRIST; DIAGNOSIS; SONOGRAPHY; ULTRASOUND; MOVEMENT; WORKERS; USERS AB Background: Carpal tunnel syndrome is a common and costly peripheral neuropathy. Occupations requiring repetitive, forceful motions of the hand and wrist may play a role in the development of carpal tunnel syndrome. Computer keyboarding is one such task, and has been associated with upper-extremity musculoskeletal disorder development. The purpose of this study was to determine whether continuous keyboarding can cause acute changes in the median nerve and whether these changes correlate with wrist biomechanics during keyboarding. Methods: A convenience sample of 37 healthy individuals performed a 60-minute typing task. Ultrasound images were collected at baseline, after 30 and 60 min of typing, then after 30 min of rest. Kinematic data were collected during the typing task. Variables of interest were median nerve cross-sectional area, flattening ratio, and swelling ratio at the pisiform; subject characteristics (age, gender, BMI, wrist circumference, typing speed) and wrist joint angles. Findings: Cross-sectional area and swelling ratio increased after 30 and 60 min of typing, and then decreased to baseline after 30 min of rest. Peak ulnar deviation contributed to changes in cross-sectional area after 30 min of typing. Interpretation: Results from this study confirmed a typing task causes changes in the median nerve, and changes are influenced by level of ulnar deviation. Furthermore, changes in the median nerve are present until cessation of the activity. While it is unclear if these changes lead to long-term symptoms or nerve injury, their existence adds to the evidence of a possible link between carpal tunnel syndrome and keyboarding. Published by Elsevier Ltd. C1 [Toosi, Kevin K.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Toosi, Kevin K.; Hogaboom, Nathan S.; Oyster, Michelle L.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Hogaboom, Nathan S.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Oyster, Michelle L.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Hogaboom, Nathan/0000-0002-0601-5751; Boninger, Michael/0000-0001-6966-919X FU U.S. Department of Veterans Affairs [B3142C]; National Institutes of Health [T32HD049307] FX This material is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. This study was supported by the U.S. Department of Veterans Affairs (B3142C) and the National Institutes of Health (T32HD049307). NR 30 TC 0 Z9 0 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD JUL PY 2015 VL 30 IS 6 BP 546 EP 550 DI 10.1016/j.clinbiomech.2015.04.008 PG 5 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA CK9FI UT WOS:000356545600004 PM 25933812 ER PT J AU Oliveira, SEH Esteves, FG Pereira, EG Carvalho, M Boyd, JE AF Oliveira, Sandra E. H. Esteves, Francisco G. Pereira, Edgar G. Carvalho, Marina Boyd, Jennifer E. TI The Internalized Stigma of Mental Illness: Cross-Cultural Adaptation and Psychometric Properties of the Portuguese Version of the ISMI Scale SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE ISMI; Self-stigma; Portuguese; Mental disorders; Diagnosis ID SCHIZOPHRENIA SPECTRUM DISORDERS; SELF-STIGMA; PERCEIVED DISCRIMINATION; EUROPEAN COUNTRIES; GAMIAN-EUROPE; PEOPLE; CONSEQUENCES; EMPOWERMENT; EXPERIENCES; OUTPATIENTS AB This study examined the psychometric properties of the Portuguese version of the ISMI scale in a sample of 253 adult psychiatric outpatients. The exploratory factor analysis replicated the five factor structure of the scale. The results revealed good internal consistency. Criterion-related validity supported the variability in response to stigma across clinical diagnoses. Thus, the Portuguese version of the ISMI scale can be considered appropriate to measure and differentiate between stigmatization experiences. Also, in order to design more focused approaches aimed to reduce the negative effects of internalized stigma, its use in institutional and in community-based mental health services is recommended. C1 [Oliveira, Sandra E. H.; Esteves, Francisco G.] Inst Univ Lisboa ISCTE IUL, CIS IUL, P-1649026 Lisbon, Portugal. [Pereira, Edgar G.; Carvalho, Marina] Univ Lusofona Humanidades & Tecnol, Fac Psicol, Lisbon, Portugal. [Carvalho, Marina] CHBA, Serv Psiquiatria, Algarve, Portugal. [Boyd, Jennifer E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Boyd, Jennifer E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Oliveira, SEH (reprint author), Inst Univ Lisboa ISCTE IUL, CIS IUL, Av Forcas Armadas, P-1649026 Lisbon, Portugal. EM seholiveira@gmail.com NR 44 TC 4 Z9 4 U1 2 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 EI 1573-2789 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD JUL PY 2015 VL 51 IS 5 BP 606 EP 612 DI 10.1007/s10597-015-9828-x PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA CK9DX UT WOS:000356541900013 PM 25612794 ER PT J AU Pierrotti, LC Kotton, CN AF Pierrotti, Ligia C. Kotton, Camille N. TI Transplantation in the Tropics: Lessons on Prevention and Management of Tropical Infectious Diseases SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Transplant; Solid organ transplantation; Hematopoietic stem cell transplantation; Tropical infectious diseases; Tuberculosis; Chagas disease; Leishmaniasis ID SOLID-ORGAN TRANSPLANTATION; LATENT TUBERCULOSIS INFECTION; STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; OF-THE-LITERATURE; REAL-TIME PCR; ALLOGENEIC HEMATOPOIETIC SCT; RENAL-ALLOGRAFT RECIPIENTS; LIPOSOMAL AMPHOTERICIN-B; DONOR-DERIVED INFECTIONS AB Tropical infectious diseases (IDs) remain a rare complication in transplant recipients even in tropical settings, but this topic has become increasingly important during the last decade due to multiple factors. Interestingly, non-tropical countries report most of the experiences with tropical diseases. The reported experience from non-endemic regions, however, does not always reflect the experience of endemic areas. Most of the guidelines and recommendations in the literature may not be applicable in tropical settings due to logistical difficulties, cost, and lack of proven benefit. In addition, certain post-transplant prevention measures, as prophylaxis and reducing exposure risk, are not feasible. Nonetheless, risk assessment and post-transplant management of tropical IDs in tropical areas should not be neglected, and clinicians need to have a higher clinical awareness for tropical ID occurring in this population. Herein, we review the more significant tropical ID in transplant patients, focusing on relevant experience reported by tropical settings. C1 [Pierrotti, Ligia C.] Univ Sao Paulo, Fac Med, Div Infect Dis, Hosp Clin, BR-05403900 Sao Paulo, SP, Brazil. [Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Pierrotti, LC (reprint author), Univ Sao Paulo, Fac Med, Div Infect Dis, Hosp Clin, Av Dr Eneas de Carvalho Aguiar 255,4 Andar, BR-05403900 Sao Paulo, SP, Brazil. EM pierrot@usp.br NR 179 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD JUL PY 2015 VL 17 IS 7 AR 34 DI 10.1007/s11908-015-0492-7 PG 20 WC Infectious Diseases SC Infectious Diseases GA CK9DF UT WOS:000356540100004 ER PT J AU Deutsch, V Havens, A Snow, K AF Deutsch, Varda Havens, Andrew Snow, Karen TI International Society for Cell Therapy Facility Sanitization Survey Laboratory Practices Committee Report SO CYTOTHERAPY LA English DT Article DE classification; processing facilities; regulation; sanitization AB Background aims. Quality cell manufacturing processes require a clean laboratory environment. Methods. This report was aimed at describing current cleaning and sanitization practices reported by facilities that manufacture many types of cellular therapy products for clinical use. It is our hope that this report may provide the groundwork for guidance recommendations directed at developing consensus standards for cleaning and sanitization practices across the globe. Facility sanitization is a central issue to regulatory and accreditation bodies. Facilities are required to develop plans to assess sanitization practices and test cleaning effectiveness. Results. This document provides information on how this is performed in different facilities and may allow newer, smaller or less developed facilities to build, enhance or revise their current quality program by using experience and expertise in facility sanitization reported herein. Conclusions. This report summarizes the results of the latest survey and compares results with those previously reported. New and relevant trends in the field provide important information and will provide important information for establishing guidelines. C1 [Deutsch, Varda] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Hematol & Bone Marrow Transplant Lab, IL-69978 Tel Aviv, Israel. [Havens, Andrew] Univ Texas Houston, Evelyn H Griffin cGMP Facil, Program Regenerat Med, Houston, TX USA. [Havens, Andrew] Univ Texas Houston, Judith R Hoffberger cGMP Facil, Program Regenerat Med, Houston, TX USA. [Snow, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Snow, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ksnow1@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD JUL PY 2015 VL 17 IS 7 BP 850 EP 859 DI 10.1016/j.jcyt.2015.03.688 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA CL0KS UT WOS:000356632200003 PM 25958337 ER PT J AU Edelman, EJ Tate, JP Fiellin, DA Brown, ST Bryant, K Gandhi, N Gibert, CL Goetz, MB Gordon, KS Rodriguez-Barradas, MC Braithwaite, RS Rimland, D Justice, AC AF Edelman, E. J. Tate, J. P. Fiellin, D. A. Brown, S. T. Bryant, K. Gandhi, N. Gibert, C. L. Goetz, M. B. Gordon, K. S. Rodriguez-Barradas, M. C. Braithwaite, R. S. Rimland, D. Justice, A. C. TI Impact of defined clinical population and missing data on temporal trends in HIV viral load estimation within a health care system SO HIV MEDICINE LA English DT Article DE community viral load; epidemiological methods; HIV; population surveillance; quality of health care ID OF-VETERANS-AFFAIRS; MEDICAL-CARE; COHORT; INFORMATION; ENGAGEMENT; MORTALITY; INDEX AB ObjectivesCommunity viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. MethodsWe included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n=37318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. ResultsThe clinical population size varied by definition, increasing from 16000-19000 patients in 2000 to 23000-26000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. ConclusionsThe CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data. C1 [Edelman, E. J.; Tate, J. P.; Fiellin, D. A.; Justice, A. C.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Edelman, E. J.; Fiellin, D. A.; Justice, A. C.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Tate, J. P.; Gordon, K. S.; Justice, A. C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Brown, S. T.] James J Peters VA Med Ctr, Bronx, NY USA. [Brown, S. T.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Bryant, K.] NIAAA, Bethesda, MD USA. [Gandhi, N.] Emory Rollins Sch Publ Hlth, Atlanta, GA USA. [Gandhi, N.; Rimland, D.] Emory Univ, Sch Med, Atlanta, GA USA. [Gibert, C. L.] Washington DC VA Med Ctr, Washington, DC USA. [Gibert, C. L.] George Washington Univ, Sch Med, Washington, DC USA. [Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rodriguez-Barradas, M. C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Houston, TX 77030 USA. [Braithwaite, R. S.] NYU, Sch Med, New York, NY USA. [Rimland, D.] Atlanta Vet Affairs Med Ctr, Decatur, GA USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, Gen Internal Med, POB 208025, New Haven, CT 06520 USA. EM ejennifer.edelman@yale.edu OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU NIAAA NIH HHS [U01-AA020790, U10 AA013566, U10-AA13566, U01 AA020790, U24 AA020794, U24-AA020794]; NIAID NIH HHS [K24 AI114444, P30AI050409]; NIDA NIH HHS [K12 DA033312, K12DA033312-01A1]; PHS HHS [K24114444-01] NR 38 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD JUL PY 2015 VL 16 IS 6 BP 346 EP 354 DI 10.1111/hiv.12219 PG 9 WC Infectious Diseases SC Infectious Diseases GA CK9XL UT WOS:000356592700003 PM 25688937 ER PT J AU Wu, WE Babb, JS Tal, A Kirov, II George, AE Ratai, EM Gonzalez, RG Gonen, O AF Wu, W. E. Babb, J. S. Tal, A. Kirov, I. I. George, A. E. Ratai, E-M Gonzalez, R. G. Gonen, O. TI Early glial activation precedes neurodegeneration in the cerebral cortex after SIV infection: A 3D, multivoxel proton magnetic resonance spectroscopy study SO HIV MEDICINE LA English DT Article DE cerebral cortex; magnetic resonance imaging; magnetic resonance spectroscopy; neuroglia; simian immunodeficiency virus ID WHITE-MATTER; IMMUNODEFICIENCY-VIRUS; MR SPECTROSCOPY; GRAY; SEGMENTATION; HIV/AIDS; BRAIN AB ObjectivesAs approximate to 40% of HIV-infected individuals experience neurocognitive decline, we investigated whether proton magnetic resonance spectroscopic imaging (H-1-MRSI) detects early metabolic abnormalities in the cerebral cortex of a simian immunodeficiency virus (SIV)-infected rhesus monkey model of neuroAIDS. MethodsThe brains of five rhesus monkeys before and 4 or 6 weeks after SIV infection (with CD8(+) T-cell depletion) were assessed with T-2-weighted quantitative magnetic resonance imaging (MRI) and 16x16x4 multivoxel H-1-MRSI (echo time/repetition time=33/1440ms). Grey matter and white matter masks were segmented from the animal MRIs and used to produce cortical masks co-registered to H-1-MRSI data to yield cortical metabolite concentrations of the glial markers myo-inositol (mI), creatine (Cr) and choline (Cho), and of the neuronal marker N-acetylaspartate (NAA). The cortex volume within the large, 28cm(3) (approximate to 35% of total monkey brain) volume of interest was also calculated for each animal pre- and post-infection. Mean metabolite concentrations and cortex volumes were compared pre- and post-infection using paired sample t-tests. ResultsThe mean (standard deviation) pre-infection concentrations of the glial markers mI, Cr and Cho were 5.8 +/- 0.9, 7.2 +/- 0.4 and 0.9 +/- 0.1mM, respectively; these concentrations increased 28% (p approximate to 0.06), 15% and 10% (both p<0.05), respectively, post-infection. The mean concentration of neuronal marker NAA remained unchanged (7.0 +/- 0.6mM pre-infection vs. 7.3 +/- 0.8mM post-infection; p approximate to 0.37). The mean cortex volume was also unchanged (8.1 +/- 1.1 cm(3) pre-infection vs. 8.3 +/- 0.5 cm(3) post-infection; p approximate to 0.76). ConclusionsThese results support the hypothesis that early cortical glial activation occurs after SIV infection prior to the onset of neurodegeneration. This suggests HIV therapeutic interventions should potentially target early glial activation in the cerebral cortex. C1 [Wu, W. E.; Babb, J. S.; Kirov, I. I.; George, A. E.; Gonen, O.] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Tal, A.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel. [Ratai, E-M; Gonzalez, R. G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ratai, E-M; Gonzalez, R. G.] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA. RP Wu, WE (reprint author), NYU, Sch Med, Dept Radiol, 660 First Ave 2nd Floor, New York, NY 10016 USA. EM wew226@nyu.edu OI Wu, William/0000-0003-0990-4164; george, ajax/0000-0001-6355-2951; Kirov, Ivan/0000-0001-5641-8578; Gonen, Oded/0000-0002-3148-2028 FU NCRR NIH HHS [S10RR019933, S10RR022976]; NIBIB NIH HHS [EB01015]; NINDS NIH HHS [NS040237, NS050041, NS050520, NS059331] NR 23 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD JUL PY 2015 VL 16 IS 6 BP 381 EP 387 DI 10.1111/hiv.12222 PG 7 WC Infectious Diseases SC Infectious Diseases GA CK9XL UT WOS:000356592700008 PM 25689120 ER PT J AU Barron, DS Eickhoff, SB Clos, M Fox, PT AF Barron, Daniel S. Eickhoff, Simon B. Clos, Mareike Fox, Peter T. TI Human pulvinar functional organization and connectivity SO HUMAN BRAIN MAPPING LA English DT Article DE pulvinar; functional anatomy; fMRI; cognitive neuroscience; attention ID ACTIVATION-BASED PARCELLATION; HUMAN BRAIN; INFERIOR PULVINAR; ATTENTION SYSTEM; MEDIAL PULVINAR; CEREBRAL-CORTEX; HUMAN AMYGDALA; HUMAN THALAMUS; METAANALYSIS; NETWORKS AB The human pulvinar is the largest thalamic area in terms of size and cortical connectivity. Although much is known about regional pulvinar structural anatomy, relatively little is known about pulvinar functional anatomy in humans. Cooccurrence of experimentally induced brain activity is a traditional metric used to establish interregional brain connectivity and forms the foundation of functional neuroimaging connectivity analyses. Because functional neuroimaging studies report task-related coactivations within a standardized space, meta-analysis of many whole-brain studies can define the brain's interregional coactivation across many tasks. Such an analysis can also detect and define variations in functional coactivations within a particular region. Here we use coactivation profiles reported in approximate to 7,700 functional neuroimaging studies to parcellate and define the pulvinar's functional anatomy. Parcellation of the pulvinar's coactivation profile identified five clusters per pulvinar of distinct functional coactivation. These clusters showed a high degree of symmetry across hemispheres and correspondence with the human pulvinar's cytoarchitecture. We investigated the functional coactivation profiles of each resultant pulvinar cluster with meta-analytic methods. By referencing existent neuroimaging and lesion-deficit literature, these profiles make a case for regional pulvinar specialization within the larger human attention-controlling network. Reference to this literature also informs specific hypotheses that can be tested in subsequent studies in healthy and clinical populations. Hum Brain Mapp 36:2417-2431, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Barron, Daniel S.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Barron, Daniel S.] Yale Univ, Sch Med, New Haven, CT USA. [Eickhoff, Simon B.] Res Ctr Julich, INM 1, Julich, Germany. [Clos, Mareike] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Simon B.; Clos, Mareike] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany. [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, Res Serv, San Antonio, TX USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Fox, Peter T.] Shenzhen Univ, Neuroimaging Lab, Sch Med, Shenzhen, Peoples R China. RP Fox, PT (reprint author), 8407 Floyd Curl Dr, San Antonio, TX 78229 USA. EM fox@uthscsa.edu RI Eickhoff, Simon/K-2061-2013 OI Eickhoff, Simon/0000-0001-6363-2759 FU National Institute of Neurological Disorder Stroke [1-F31-NS083160-01]; National Institute of Mental Health [RO1-MH074457]; Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model); DFG [IRTG 1328] FX Contract grant sponsor: National Institute of Neurological Disorder & Stroke; Contract grant number: 1-F31-NS083160-01(D.S.B.); Contract grant sponsor: National Institute of Mental Health; Contract grant sponsor: RO1-MH074457 (P.T.F.), Contract grant sponsor: Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model) (S.B.E. and M.C.); Contract grant sponsor: DFG; Contract grant number: IRTG 1328 (S.B.E.) NR 62 TC 4 Z9 4 U1 0 U2 9 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 JUL PY 2015 VL 36 IS 7 BP 2417 EP 2431 DI 10.1002/hbm.22781 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CL1QP UT WOS:000356719200001 PM 25821061 ER PT J AU Carmona, S Hoekzema, E Castellanos, FX Garcia-Garcia, D Lage-Castellanos, A Van Dijk, KRA Navas-Sanchez, FJ Martinez, K Desco, M Sepulcre, J AF Carmona, Susana Hoekzema, Elseline Castellanos, Francisco X. Garcia-Garcia, David Lage-Castellanos, Agustin Van Dijk, Koene R. A. Navas-Sanchez, Francisco J. Martinez, Kenia Desco, Manuel Sepulcre, Jorge TI Sensation-to-cognition cortical streams in attention-deficit/hyperactivity disorder SO HUMAN BRAIN MAPPING LA English DT Article DE attention-deficit; hyperactivity disorder; resting-state functional magnetic resonance imaging; ventral attention network; default mode network; sensorimotor network ID DEFICIT HYPERACTIVITY DISORDER; INTRINSIC FUNCTIONAL CONNECTIVITY; BRAIN-DYSFUNCTION; NAIVE BOYS; ADHD; NETWORK; CORTEX; CHILDREN; FMRI; SYSTEMS AB We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortexvisual, auditory, and somatosensorywe used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naive children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. Hum Brain Mapp 36:2544-2557, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Carmona, Susana; Van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Carmona, Susana; Garcia-Garcia, David; Martinez, Kenia; Desco, Manuel] Inst Invest Sanitaria Gregorio Maranon, Unidad Med & Cirugia Expt, Madrid, Spain. [Carmona, Susana; Garcia-Garcia, David; Navas-Sanchez, Francisco J.; Desco, Manuel] Univ Carlos III Madrid, Dept Bioingn & Ingn Aeroespacial, Madrid, Spain. [Hoekzema, Elseline] Netherlands Inst Neurosci, Neuroendocrinol Bakker Grp, Amsterdam, Netherlands. [Castellanos, Francisco X.] NYU, Langone Med Ctr, Ctr Child Study, Ctr Neurodev Disorders, New York, NY USA. [Castellanos, Francisco X.] Nathan S Kline Inst Psychiat Res, Div Child & Adolescent Psychiat Res, Orangeburg, NY 10962 USA. [Lage-Castellanos, Agustin] Cuba Neurosci Ctr, Dept Neurostat, Havana, Cuba. [Van Dijk, Koene R. A.; Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Van Dijk, Koene R. A.; Sepulcre, Jorge] Harvard Univ, Sch Med, Charlestown, MA USA. [Navas-Sanchez, Francisco J.; Desco, Manuel] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. [Sepulcre, Jorge] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA USA. RP Carmona, S (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, Northwest Lab Bldg 290,52 Oxford St, Cambridge, MA 02138 USA. EM susannacarmona@gmail.com RI Garcia-Garcia, David/I-2105-2015; Desco, Manuel/D-2822-2009; Van Dijk, Koene/G-3317-2012; OI Garcia-Garcia, David/0000-0001-5224-3280; Desco, Manuel/0000-0003-0989-3231; Van Dijk, Koene/0000-0001-6137-4282; Castellanos, Francisco/0000-0001-9192-9437 FU Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid; European Union [291820]; NIH-NIBIB [1K23EB019023-01RM] FX Contract grant sponsors: The Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid, and the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013); Contract grant number: REA grant agreement no 291820 (SC).; Contract grant sponsors: NIH-NIBIB 1K23EB019023-01RM grant (JS) NR 60 TC 4 Z9 4 U1 0 U2 20 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 JUL PY 2015 VL 36 IS 7 BP 2544 EP 2557 DI 10.1002/hbm.22790 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CL1QP UT WOS:000356719200010 PM 25821110 ER PT J AU Xu, M Wang, TF Chen, SP Fox, PT Tan, LH AF Xu, Min Wang, Tianfu Chen, Siping Fox, Peter T. Tan, Li Hai TI Effective connectivity of brain regions related to visual word recognition: An fMRI study of Chinese reading SO HUMAN BRAIN MAPPING LA English DT Article DE connectivity; functional magnetic resonance imaging; reading; Chinese reading; dynamic causal modeling; ventral pathway; dorsal pathway; writing systems ID VENTRAL OCCIPITOTEMPORAL CORTEX; INFERIOR PREFRONTAL CORTEX; DEVELOPMENTAL DYSLEXIA; FUNCTIONAL SPECIALIZATION; ALPHABETIC WORDS; NEURAL SYSTEMS; WRITTEN WORDS; CHARACTERS; LANGUAGE; METAANALYSIS AB Past neuroimaging studies have focused on identifying specialized functional brain systems for processing different components of reading, such as orthography, phonology, and semantics. More recently, a few experiments have been performed to look into the integration and interaction of distributed neural systems for visual word recognition, suggesting that lexical processing in alphabetic languages involves both ventral and dorsal neural pathways originating from the visual cortex. In the present functional magnetic resonance imaging study, we tested the multiple pathways model with Chinese character stimuli and examined how the neural systems interacted in reading Chinese. Using dynamic causal modeling, we demonstrated that visual word recognition in Chinese engages the ventral pathway from the visual cortex to the left ventral occipitotemporal cortex, but not the dorsal pathway from the visual cortex to the left parietal region. The ventral pathway, however, is linked to the superior parietal lobule and the left middle frontal gyrus (MFG) so that a dynamic neural network is formed, with information flowing from the visual cortex to the left ventral occipitotemporal cortex to the parietal lobule and then to the left MFG. The findings suggest that cortical dynamics is constrained by the differences in how visual orthographic symbols in writing systems are linked to spoken language. Hum Brain Mapp 36:2580-2591, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Xu, Min; Wang, Tianfu; Chen, Siping; Fox, Peter T.; Tan, Li Hai] Shenzhen Univ, Sch Med, Dept Biomed Engn, Shenzhen 518060, Peoples R China. [Xu, Min; Wang, Tianfu; Chen, Siping; Tan, Li Hai] Guangdong Key Lab Biomed Informat Detect & Ultras, Shenzhen, Peoples R China. [Xu, Min] Univ Hong Kong, Sch Humanities, Hong Kong, Hong Kong, Peoples R China. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Tan, LH (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Shenzhen 518060, Peoples R China. EM fox@uthscsa.edu; tanlh@szu.edu.cn FU National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China [2012CB720701]; National Natural Science Foundation of China [61372006] FX Contract grant sponsor: National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China; Contract grant number: 2012CB720701; Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 61372006. NR 74 TC 3 Z9 3 U1 15 U2 53 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 JUL PY 2015 VL 36 IS 7 BP 2580 EP 2591 DI 10.1002/hbm.22792 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CL1QP UT WOS:000356719200012 PM 25788100 ER PT J AU Petersen, N Touroutoglou, A Andreano, JM Cahill, L AF Petersen, Nicole Touroutoglou, Alexandra Andreano, Joseph M. Cahill, Larry TI Oral contraceptive pill use is associated with localized decreases in cortical thickness SO HUMAN BRAIN MAPPING LA English DT Article DE cortical thickness; hormonal contraception; morphometric analysis; neuroendocrinology ID MENSTRUAL-CYCLE PHASE; HUMAN CEREBRAL-CORTEX; PREMENSTRUAL DYSPHORIC DISORDER; DIFFERENT ENDOCRINE STATES; ESTROGEN-RECEPTOR-ALPHA; BRAINS DEFAULT NETWORK; CENTRAL-NERVOUS-SYSTEM; HUMAN FEMALE BRAIN; CINGULATE CORTEX; NEGATIVE EMOTION AB Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology. Hum Brain Mapp 36:2644-2654, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Petersen, Nicole] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst, Los Angeles, CA 90024 USA. [Petersen, Nicole; Cahill, Larry] Univ Calif Irvine, Dept Neurobiol & Behav, Bonney Res Lab, Irvine, CA USA. [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Touroutoglou, Alexandra; Andreano, Joseph M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Touroutoglou, Alexandra; Andreano, Joseph M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Touroutoglou, Alexandra; Andreano, Joseph M.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, Boston, MA 02114 USA. RP Petersen, N (reprint author), Westwood Plaza C8-539, Los Angeles, CA 90095 USA. EM npetersen@ucla.edu FU NIH [R01MH57508] FX Contract grant sponsor: NIH; Contract grant number: R01MH57508 (to L.C.) NR 64 TC 3 Z9 3 U1 9 U2 13 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 JUL PY 2015 VL 36 IS 7 BP 2644 EP 2654 DI 10.1002/hbm.22797 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CL1QP UT WOS:000356719200017 PM 25832993 ER PT J AU Wang, ZM Rajaraman, P Melin, BS Chung, CC Zhang, WJ McKean-Cowdin, R Michaud, D Yeager, M Ahlbom, A Albanes, D Andersson, U Freeman, LEB Buring, JE Butler, MA Carreon, T Feychting, M Gapstur, SM Gaziano, JM Giles, GG Hallmans, G Henriksson, R Hoffman-Bolton, J Inskip, PD Kitahara, CM Marchand, LL Linet, MS Li, SC Peters, U Purdue, MP Rothman, N Ruder, AM Sesso, HD Severi, G Stampfer, M Stevens, VL Visvanathan, K Wang, SS White, E Zeleniuch-Jacquotte, A Hoover, R Fraumeni, JF Chatterjee, N Hartge, P Chanock, SJ AF Wang, Zhaoming Rajaraman, Preetha Melin, Beatrice S. Chung, Charles C. Zhang, Weijia McKean-Cowdin, Roberta Michaud, Dominique Yeager, Meredith Ahlbom, Anders Albanes, Demetrius Andersson, Ulrika Freeman, Laura E. Beane Buring, Julie E. Butler, Mary Ann Carreon, Tania Feychting, Maria Gapstur, Susan M. Gaziano, J. Michael Giles, Graham G. Hallmans, Goran Henriksson, Roger Hoffman-Bolton, Judith Inskip, Peter D. Kitahara, Cari M. Marchand, Loic Le Linet, Martha S. Li, Shengchao Peters, Ulrike Purdue, Mark P. Rothman, Nathaniel Ruder, Avima M. Sesso, Howard D. Severi, Gianluca Stampfer, Meir Stevens, Victoria L. Visvanathan, Kala Wang, Sophia S. White, Emily Zeleniuch-Jacquotte, Anne Hoover, Robert Fraumeni, Joseph F. Chatterjee, Nilanjan Hartge, Patricia Chanock, Stephen J. TI Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data SO HUMAN MUTATION LA English DT Article DE glioma; TP53; rare SNP; TCGA ID GENOME-WIDE ASSOCIATION; SQUAMOUS-CELL CARCINOMA; NERVOUS-SYSTEM TUMORS; POLYADENYLATION SIGNAL; CANCER SUSCEPTIBILITY; SNPS; RARE AB We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 x 10(-11)), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with approximate to 3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. (C) 2015 Wiley Periodicals, Inc. C1 [Wang, Zhaoming; Rajaraman, Preetha; Chung, Charles C.; Yeager, Meredith; Albanes, Demetrius; Freeman, Laura E. Beane; Inskip, Peter D.; Kitahara, Cari M.; Linet, Martha S.; Li, Shengchao; Purdue, Mark P.; Rothman, Nathaniel; Hoover, Robert; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Hartge, Patricia; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Wang, Zhaoming; Chung, Charles C.; Yeager, Meredith; Li, Shengchao] Leidos Biomed Res Inc, Canc Genom Res Lab, Gaithersburg, MD USA. [Melin, Beatrice S.; Andersson, Ulrika; Henriksson, Roger] Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden. [Zhang, Weijia] Icahn Sch Med Mt Sinai, Dept Med Bioinformat Core, New York, NY 10029 USA. [McKean-Cowdin, Roberta] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Michaud, Dominique] Brown Univ, Dept Epidemiol, Div Biol & Med, Providence, RI 02912 USA. [Michaud, Dominique] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Ahlbom, Anders; Feychting, Maria] Karolinska Inst, Inst Environm Med, Div Epidemiol, S-10401 Stockholm, Sweden. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA. [Butler, Mary Ann; Carreon, Tania; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden. [Hoffman-Bolton, Judith; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Marchand, Loic Le] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Stampfer, Meir] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Zeleniuch-Jacquotte, Anne] NYU Sch Med, Dept Environm Med, Div Epidemiol, New York, NY USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr Rm 7E412,MSC 9776, Bethesda, MD 20892 USA. EM wangzha@mail.nih.gov; chanocks@mail.nih.gov RI Purdue, Mark/C-9228-2016; Kitahara, Cari/R-8267-2016; OI Purdue, Mark/0000-0003-1177-3108; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI; NIH [N01-CO-12400]; Department of Health and Human Services FX Contract grant sponsors: NCI; NIH; Department of Health and Human Services; NCI; NIH (N01-CO-12400). NR 18 TC 3 Z9 3 U1 1 U2 5 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 JUL PY 2015 VL 36 IS 7 BP 684 EP 688 DI 10.1002/humu.22799 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CK8NT UT WOS:000356495700005 PM 25907361 ER PT J AU Sharma, PK Wong, EB Napier, RJ Bishai, WR Ndung'u, T Kasprowicz, VO Lewinsohn, DA Lewinsohn, DM Gold, MC AF Sharma, Prabhat K. Wong, Emily B. Napier, Ruth J. Bishai, William R. Ndung'u, Thumbi Kasprowicz, Victoria O. Lewinsohn, Deborah A. Lewinsohn, David M. Gold, Marielle C. TI High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells SO IMMUNOLOGY LA English DT Article DE bacteria; cell surface molecules; human; MHC; MR1 and MAIT cells; T cells ID INVARIANT T-CELLS; ACTIVATION ANTIGEN; ALPHA-CHAIN; COMPLEX; MR1; LYMPHOCYTES; PATHWAY; DEFINES AB Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim). Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis. C1 [Sharma, Prabhat K.; Napier, Ruth J.; Lewinsohn, David M.; Gold, Marielle C.] Oregon Hlth & Sci Univ, Pulm & Crit Care Med, Portland, OR 97239 USA. [Wong, Emily B.; Ndung'u, Thumbi; Kasprowicz, Victoria O.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Wong, Emily B.; Bishai, William R.; Ndung'u, Thumbi] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bishai, William R.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Kasprowicz, Victoria O.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Kasprowicz, Victoria O.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Durban, South Africa. [Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Pediat, Portland, OR 97239 USA. [Lewinsohn, Deborah A.; Lewinsohn, David M.; Gold, Marielle C.] Oregon Hlth & Sci Univ, Mol Microbiol & Immunol, Portland, OR 97239 USA. [Lewinsohn, David M.; Gold, Marielle C.] Portland VA Med Ctr, Portland, OR USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Pulm & Crit Care Med, 3181 SW Sam Jackson Pk Rd,Mail Code VA R&D 11, Portland, OR 97239 USA. EM lewinsod@ohsu.edu; goldm@ohsu.edu RI Lewinsohn, David/I-4936-2013; OI Ndung'u, Thumbi/0000-0003-2962-3992; Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291 FU National Institutes of Health (NIH) under the NIAID funded MIST Consortium [AI095776]; National Institutes of Health (NIH) [T32AI007387]; Burroughs Wellcome Fund/ASTMH Postdoctoral Fellowship in Tropical Infectious Diseases and Merit Review from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development [I01 BX001231, I01 BX000533] FX Funding was provided by National Institutes of Health (NIH) grant AI095776, under the NIAID funded MIST Consortium (mucosal.org) and T32AI007387, and in part by the Burroughs Wellcome Fund/ASTMH Postdoctoral Fellowship in Tropical Infectious Diseases and Merit Review Awards # I01 BX001231 and I01 BX000533 from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development and resources and the use of facilities at the VA Portland Health Care System. The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 34 TC 14 Z9 14 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD JUL PY 2015 VL 145 IS 3 BP 443 EP 453 DI 10.1111/imm.12461 PG 11 WC Immunology SC Immunology GA CL1JR UT WOS:000356699200012 PM 25752900 ER PT J AU Cluzet, VC Gerber, JS Nachamkin, I Metlay, JP Zaoutis, TE Davis, MF Julian, KG Linkin, DR Coffin, SE Margolis, DJ Hollander, JE Bilker, WB Han, XY Mistry, RD Gavin, LJ Tolomeo, P Wise, JA Wheeler, MK Hu, BF Fishman, NO Royer, D Lautenbach, E AF Cluzet, Valerie C. Gerber, Jeffrey S. Nachamkin, Irving Metlay, Joshua P. Zaoutis, Theoklis E. Davis, Meghan F. Julian, Kathleen G. Linkin, Darren R. Coffin, Susan E. Margolis, David J. Hollander, Judd E. Bilker, Warren B. Han, Xiaoyan Mistry, Rakesh D. Gavin, Laurence J. Tolomeo, Pam Wise, Jacqueleen A. Wheeler, Mary K. Hu, Baofeng Fishman, Neil O. Royer, David Lautenbach, Ebbing CA Ctr Dis Control Prevention CDC TI Risk Factors for Recurrent Colonization With Methicillin-Resistant Staphylococcus aureus in Community-Dwelling Adults and Children SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HOUSEHOLD CONTACTS; SKIN INFECTIONS; EMERGENCY-DEPARTMENT; HIGH PREVALENCE; SWAB SPECIMENS; CARRIAGE; MRSA; TRANSMISSION; ERADICATION; SURVEILLANCE AB OBJECTIVE. To identify risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization. DESIGN. Prospective cohort study conducted from January 1, 2010, through December 31, 2012. SETTING. Five adult and pediatric academic medical centers. PARTICIPANTS. Subjects (ie, index cases) who presented with acute community-onset MRSA skin and soft-tissue infection. METHODS. Index cases and all household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as 2 consecutive sampling periods with negative surveillance cultures. Recurrent colonization was defined as any positive MRSA surveillance culture after clearance. Index cases with recurrent MRSA colonization were compared with those without recurrence on the basis of antibiotic exposure, household demographic characteristics, and presence of MRSA colonization in household members. RESULTS. The study cohort comprised 195 index cases; recurrent MRSA colonization occurred in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36-84 days). Treatment with clindamycin was associated with lower risk of recurrence (odds ratio, 0.52; 95% CI, 0.29-0.93). Higher percentage of household members younger than 18 was associated with increased risk of recurrence (odds ratio, 1.01; 95% CI, 1.00-1.02). The association between MRSA colonization in household members and recurrent colonization in index cases did not reach statistical significance in primary analyses. CONCLUSION. A large proportion of patients initially presenting with MRSA skin and soft-tissue infection will have recurrent colonization after clearance. The reduced rate of recurrent colonization associated with clindamycin may indicate a unique role for this antibiotic in the treatment of such infection. C1 [Cluzet, Valerie C.; Linkin, Darren R.; Fishman, Neil O.; Lautenbach, Ebbing] Univ Penn, Dept Med, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Gerber, Jeffrey S.; Zaoutis, Theoklis E.; Linkin, Darren R.; Coffin, Susan E.; Margolis, David J.; Bilker, Warren B.; Han, Xiaoyan; Tolomeo, Pam; Wise, Jacqueleen A.; Wheeler, Mary K.; Lautenbach, Ebbing] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gerber, Jeffrey S.; Zaoutis, Theoklis E.; Coffin, Susan E.; Margolis, David J.; Bilker, Warren B.; Han, Xiaoyan; Lautenbach, Ebbing] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gerber, Jeffrey S.; Zaoutis, Theoklis E.; Coffin, Susan E.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Infect Dis,Perelman Sch Med, Philadelphia, PA 19104 USA. [Nachamkin, Irving; Hu, Baofeng] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Metlay, Joshua P.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Davis, Meghan F.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Julian, Kathleen G.] Penn State Hershey Med Ctr, Div Infect Dis, Hershey, PA USA. [Linkin, Darren R.] Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA. [Margolis, David J.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hollander, Judd E.] Thomas Jefferson Univ Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. [Mistry, Rakesh D.] Childrens Hosp Colorado, Sect Emergency Med, Aurora, CO USA. [Gavin, Laurence J.] Penn Presbyterian Med Ctr, Dept Emergency Med, Philadelphia, PA USA. [Royer, David] Lincoln Univ, Dept Biol, Lincoln Univ, PA USA. RP Cluzet, VC (reprint author), Hosp Univ Penn, Dept Med, Div Infect Dis, 3400 Spruce St,3rd Fl,Silverstein Bldg,Ste E, Philadelphia, PA 19104 USA. EM valeriec@mail.med.upenn.edu OI Davis, Meghan/0000-0002-3475-4578 FU Pennsylvania State Department of Health (Commonwealth Universal Research Enhancement Program); National Institutes of Health [K24-AI080942]; Centers for Disease Control and Prevention Epicenters Program [U54-CK000163] FX Pennsylvania State Department of Health (Commonwealth Universal Research Enhancement Program grant to E.L.); the National Institutes of Health (grant K24-AI080942 to E.L.); and the Centers for Disease Control and Prevention Epicenters Program (grant U54-CK000163 to E.L.). The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 40 TC 4 Z9 4 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2015 VL 36 IS 7 BP 786 EP 793 DI 10.1017/ice.2015.76 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CK8UE UT WOS:000356513400005 PM 25869756 ER PT J AU Sillesen, NH Greene, ME Nebergall, AK Nielsen, PT Laursen, MB Troelsen, A Malchau, H AF Sillesen, Nanna H. Greene, Meridith E. Nebergall, Audrey K. Nielsen, Poul T. Laursen, Mogens B. Troelsen, Anders Malchau, Henrik TI Three Year RSA Evaluation of Vitamin E Diffused Highly Cross-linked Polyethylene Liners and Cup Stability SO JOURNAL OF ARTHROPLASTY LA English DT Article DE hip arthroplasty; RSA; liner; vitamin E; polyethylene ID TOTAL HIP-ARTHROPLASTY; RADIOSTEREOMETRIC ANALYSIS; STEPWISE INTRODUCTION; WEAR AB Vitamin E diffusion into highly cross-linked polyethylene (E-XLPE) is a method for enhancing oxidative stability of acetabular liners. The purpose of this study was to evaluate in vivo penetration of E-XLPE using radiostereometric analysis (RSA). Eighty-four hips were recruited into a prospective 10-year RSA. This is the first evaluation of the multicenter cohort after 3-years. All patients received E-XLPE liners (E1, Biomet) and porous-titanium coated cups (Regenerex, Biomet). There was no difference (P = 0.450) in median femoral head penetration into the E-XLPE liners at 3-years comparing cobalt-chrome heads (-0.028 mm; inter-quartile range (IQR) -0.065 to 0.047) with ceramic heads (-0.043 mm, IQR -0.143 to 0.042). The 3-year follow-up indicates minimal E-XLPE liner penetration regardless of head material and minimal early cup movement. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sillesen, Nanna H.; Greene, Meridith E.; Nebergall, Audrey K.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Nielsen, Poul T.; Laursen, Mogens B.] Aalborg Univ Hosp, Dept Orthopaed, Aalborg, Denmark. [Sillesen, Nanna H.; Troelsen, Anders] Copenhagen Univ Hosp, Dept Orthoped, Clin Orthoped Res Hvidovre, DK-2650 Hvidovre, Denmark. RP Sillesen, NH (reprint author), Copenhagen Univ Hosp, Dept Orthoped, Clin Orthoped Res Hvidovre, Kettegaards 30,Afd 333, DK-2650 Hvidovre, Denmark. OI Laursen, Mogens/0000-0002-2791-3921 NR 17 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUL PY 2015 VL 30 IS 7 BP 1260 EP 1264 DI 10.1016/j.arth.2015.02.018 PG 5 WC Orthopedics SC Orthopedics GA CK4HG UT WOS:000356184300035 PM 25754257 ER PT J AU Warfield, ME Crossman, MK Delahaye, J Weerd, ED Kuhlthau, KA AF Warfield, Marji Erickson Crossman, Morgan K. Delahaye, Jennifer Weerd, Emma Der Kuhlthau, Karen A. TI Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Adults with autism spectrum disorders; Health care; Physician perspectives; Physician training ID HEALTH-CARE; YOUNG-ADULTS; DISABILITIES; TRANSITION; PEOPLE; NEEDS; CHILDREN; STUDENTS; PERFORMANCE; ATTITUDES AB We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this care. Qualitative data were gathered by phone using a structured interview guide and analyzed using the framework approach. Challenges to providing care were identified at the systems, practice and provider, and education and training levels. Solutions and interventions targeting needed changes at each level were also proposed. The findings have implications for health care reform, medical school and residency training programs, and the development of best practices. C1 [Warfield, Marji Erickson; Crossman, Morgan K.] Brandeis Univ, Starr Ctr Intellectual & Dev Disabil, Heller Sch Social Policy & Management, Waltham, MA 02453 USA. [Delahaye, Jennifer; Weerd, Emma Der; Kuhlthau, Karen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. RP Warfield, ME (reprint author), Brandeis Univ, Starr Ctr Intellectual & Dev Disabil, Heller Sch Social Policy & Management, MS035,415 South St, Waltham, MA 02453 USA. EM mew@brandeis.edu FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC 19925] FX This project was supported with funding from a Grant, R40 MC 19925 through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. We thank the providers who participated in the study. NR 46 TC 3 Z9 3 U1 2 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUL PY 2015 VL 45 IS 7 BP 2209 EP 2217 DI 10.1007/s10803-015-2386-9 PG 9 WC Psychology, Developmental SC Psychology GA CK6QD UT WOS:000356351800025 PM 25724445 ER PT J AU Bernard, KRL Rivera, M AF Bernard, Kenneth R. L. Rivera, Morris TI REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE headache; thunderclap; subarachnoid hemorrhage; reversible cerebrovasconstriction syndrome ID CRANIAL COMPUTED-TOMOGRAPHY; SUBARACHNOID HEMORRHAGE; THUNDERCLAP HEADACHE; DIAGNOSIS AB Background: Reversible cerebral vasoconstriction syndrome (RCVS) is an underappreciated and poorly understood cause of thunderclap headache (TCH). Although self-limited in the majority of patients, incidence is increasing, with presentations overlapping considerably with life-threatening conditions, such as aneurysmal subarachnoid hemorrhage and stroke. In addition, radiographic findings seen in RCVS are also present in primary angiitis of the central nervous system (PACNS). Misdiagnosis of RCVS might subject patients to unnecessary invasive testing and immunosuppressive therapy. Furthermore, the recommended treatment of glucocorticoids used in PACNS can be harmful in RCVS. RCVS is not a benign condition, as patients can have ischemic or hemorrhagic complications leading to persistent neurologic deficits and even death. Current treatments, guided only by expert consensus, have no proven effect on these complications, which argues the need for accurate identification of patients with RCVS and prospective studies to validate treatment and inform prognoses. Case Report: We describe a previously healthy male who presented to the emergency department after 2 episodes of TCH and angiography consistent with RCVS. Why Should An Emergency Physician Be Aware of This?: RCVS is a common but underappreciated cause of TCH. The likelihood of misdiagnosing RCVS following the accepted diagnostic algorithm of acute headache in the emergency department is high due to a lack of clinical awareness and common features shared with other headache syndromes. Emergency department physicians must broaden the differential in patients presenting to the emergency department with TCH to include RCVS and be familiar with the accepted treatments and appropriate follow-up. (C) 2015 Elsevier Inc. C1 [Bernard, Kenneth R. L.] Brigham & Womens Massachusetts Gen Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Progam, Boston, MA 02115 USA. [Rivera, Morris] Marthas Vineyard Hosp, Partners Healthcare, Oak Bluffs, MA USA. RP Bernard, KRL (reprint author), Brigham & Womens Massachusetts Gen Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Progam, 75 Francis St,Neville House, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2015 VL 49 IS 1 BP 26 EP 31 DI 10.1016/j.jemermed.2015.01.012 PG 6 WC Emergency Medicine SC Emergency Medicine GA CK7YA UT WOS:000356451600018 PM 25858343 ER PT J AU Lam, SHF Bailitz, J Blehar, D Becker, BA Hoffmann, B Liteplo, AS Rajan, KB Lambert, M AF Lam, Samuel H. F. Bailitz, John Blehar, David Becker, Brent A. Hoffmann, Beatrice Liteplo, Andrew S. Rajan, Kumar B. Lambert, Michael TI MULTI-INSTITUTION VALIDATION OF AN EMERGENCY ULTRASOUND IMAGE RATING SCALE-A PILOT STUDY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE ultrasound education; competency; image rating scale; bedside ultrasound ID LEARNING-CURVE; ULTRASONOGRAPHY; MEDICINE; SONOGRAPHY; PHYSICIANS; PERFORMANCE; QUALITY; TRAUMA; MODEL AB Background: As bedside ultrasound (BUS) is being increasingly taught and incorporated into emergency medicine practice, measurement of BUS competency is becoming more important. The commonly adopted experiential approach to BUS competency has never been validated on a large scale, and has some limitations by design. Objective: Our aim was to introduce and report preliminary testing of a novel emergency BUS image rating scale (URS). Methods: Gallbladder BUS was selected as the test case. Twenty anonymous BUS image sets (still images and clips) were forwarded electronically to 16 reviewers (13 attendings, 3 fellows) at six training sites across the United States. Each reviewer rated the BUS sets using the pilot URS that consisted of three components, with numerical values assigned to each of the following aspects: Landmarks, Image Quality, and Annotations. Reviewers also decided whether or not each BUS set would be "Clinically Useful." Kendall tau s were calculated as a measure of concordance among the reviewers. Results: Among the 13 attendings, image review experience ranged from 2-15 years, 5-300 scans per week, and averaged 7.8 years and 60 images. Kendall tau s for each aspect of the URS were: Landmarks: 0.55; Image Quality: 0.57; Annotation: 0.26; Total Score: 0.63, and Clinical Usefulness: 0.45. All URS elements correlated significantly with clinical usefulness (p < 0.001). The correlation coefficient between each attending reviewer and the entire group ranged from 0.48-0.69, and was independent of image review experience beyond fellowship training. Conclusion: Our novel URS had moderate-to-good inter-rater agreement in this pilot study. Based on these results, the URS will be modified for use in future investigations. (C) 2015 Elsevier Inc. C1 [Lam, Samuel H. F.; Lambert, Michael] Advocate Christ Med Ctr, Dept Emergency Med, Oak Lawn, IL 60453 USA. [Lam, Samuel H. F.] Univ Illinois, Dept Emergency Med, Chicago, IL USA. [Bailitz, John] Cook Cty Stroger Hosp, Dept Emergency Med, Chicago, IL USA. [Blehar, David] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Becker, Brent A.] York Hosp Wellspan Health, Dept Emergency Med, York, PA USA. [Hoffmann, Beatrice] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Liteplo, Andrew S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rajan, Kumar B.] Rush Univ, Rush Inst Hlth Aging, Dept Internal Med, Chicago, IL 60612 USA. RP Lam, SHF (reprint author), Advocate Christ Med Ctr, Dept Emergency Med, 4440 W 95th St, Oak Lawn, IL 60453 USA. OI Rajan, Kumar/0000-0003-1268-4617 FU Advocate Christ Medical Center Med Fund FX Grant support was provided to Dr. Lam by the Advocate Christ Medical Center Med Fund. We thank Mark Mycyk, MD, Rebecca R. Roberts, MD, P. John Konicki, DO, and Martha Villalba, MD, for reviewing the manuscript and providing insightful comments for revision. We also thank Ibrar Ahmed, BS for his statistical support. NR 26 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2015 VL 49 IS 1 BP 32 EP 39 DI 10.1016/j.jemermed.2015.01.010 PG 8 WC Emergency Medicine SC Emergency Medicine GA CK7YA UT WOS:000356451600019 PM 25907634 ER PT J AU Kline, JA Kabrhel, C AF Kline, Jeffrey A. Kabrhel, Christopher TI EMERGENCY EVALUATION FOR PULMONARY EMBOLISM, PART 2: DIAGNOSTIC APPROACH SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE pulmonary embolism; medicolegal; defensive medicine; decision making; venous thromboembolism; pregnancy; diagnosis; pregnancy ID DEEP-VEIN THROMBOSIS; RULE-OUT CRITERIA; CONTRAST-INDUCED NEPHROPATHY; ACUTE VENOUS THROMBOEMBOLISM; REVISED GENEVA SCORE; LOW-RISK PATIENTS; D-DIMER CUTOFF; COMPUTED-TOMOGRAPHY; DEPARTMENT PATIENTS; PRETEST PROBABILITY AB Background: In part 1 of this two-part review, we discussed which risk factors, historical features, and physical findings increase risk for pulmonary embolism (PE) in symptomatic emergency department (ED) patients. Objectives: Use published evidence to describe criteria that a reasonable and prudent clinician can use to initiate and guide the process of excluding and diagnosing PE. Discussion: The careful and diligent emergency physician can use clinical criteria to safely obviate a formal evaluation of PE, including the use of gestalt reasoning and the pulmonary embolism rule-out criteria (PERC rule, Table 2, part 1). We present published clinical and radiographic features of patients with PE who eluded diagnosis in the ED. D-dimer can be used to exclude PE in many patients, and employing age-based adjustments to the threshold to define an abnormal value can further reduce patient exposure to pulmonary vascular imaging. Moreover, we discuss benefits, limitations, and potential harms of computed tomographic pulmonary vascular imaging relevant to patients and the practice of emergency care. We present algorithms to guide exclusion and diagnosis of PE in patients with suspected PE, including those who are pregnant. Conclusions: Reasonable and prudent emergency clinicians can exclude PE in symptomatic ED patients on clinical grounds alone in many patients, and many more can have PE ruled out by use of the D-dimer. (C) 2015 Elsevier Inc. C1 [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Kabrhel, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Vasc Emergencies,Dept Emergency Med, Boston, MA USA. [Kabrhel, Christopher] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. RP Kline, JA (reprint author), Indiana Univ Sch Med, Dept Emergency Med, 720 Eskanazi Ave, Indianapolis, IN 46202 USA. OI Kabrhel, Christopher/0000-0002-8699-7176 NR 117 TC 3 Z9 3 U1 4 U2 13 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 JUL PY 2015 VL 49 IS 1 BP 104 EP 117 DI 10.1016/j.jemermed.2014.12.041 PG 14 WC Emergency Medicine SC Emergency Medicine GA CK7YA UT WOS:000356451600034 PM 25800524 ER PT J AU Fisichella, PM DeMeester, SR Hungness, E Perretta, S Soper, NJ Rosemurgy, A Torquati, A Sachdeva, AK Patti, MG AF Fisichella, P. Marco DeMeester, Steven R. Hungness, Eric Perretta, Silvana Soper, Nathaniel J. Rosemurgy, Alexander Torquati, Alfonso Sachdeva, Ajit K. Patti, Marco G. TI Emerging Techniques in Minimally Invasive Surgery. Pros and Cons SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Review DE Esophageal achalasia; Pneumatic dilatation; Laparoscopic Heller myotomy; Dor fundoplication; Per oral endoscopic myotomy; POEM; Transvaginal access; Transgastric access; Single-site surgery; Laparoscopy ID PERORAL ENDOSCOPIC MYOTOMY; LAPAROSCOPIC HELLER MYOTOMY; RANDOMIZED CONTROLLED-TRIAL; SITE LESS CHOLECYSTECTOMY; LEARNING-CURVE; ESOPHAGEAL ACHALASIA; SINGLE-INCISION; CONSENSUS STATEMENT; FUNDOPLICATION; MULTICENTER AB New trends have emerged regarding the best minimally invasive access approaches to perform gastrointestinal surgery. However, these newer approaches are seen critically by those who demand a more strict assessment of outcomes and safety. An international panel of expert gathered at the 2014 American College of Surgeons Meeting with the goal of providing an evidence-based understanding of the real value of these approaches in gastrointestinal surgery. The panel has compared the efficacy and safety of most established approaches to gastrointestinal diseases to those of new treatment modalities: peroral esophageal myotomy vs. laparoscopic myotomy for achalasia, transgastric vs. transvaginal approach, and single-incision vs. multi-port access minimally invasive surgery. The panel found that (1) the outcome of these new approaches was not superior to that of established surgical procedures; (2) the new approaches are generally performed in few highly specialized centers; and (3) transgastric and transvaginal approaches might be safe and feasible in very experienced hands, but cost, training, operative time, and tools seem to limit their application for the treatment of common procedures such as cholecystectomy and appendectomy. Because the expected advantages of new approaches have yet to be proven in controlled trials, new approaches should be considered for adoption into practice only after thorough analyses of their efficacy and effectiveness and appropriate training. C1 [Fisichella, P. Marco] Brigham & Womens Hosp, Dept Surg, Boston, MA 02132 USA. [Fisichella, P. Marco] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Boston, MA 02132 USA. [DeMeester, Steven R.] Univ So Calif, Dept Surg, Los Angeles, CA USA. [Hungness, Eric; Soper, Nathaniel J.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Perretta, Silvana] Univ Strasbourg, Dept Digest & Endocrine Surg, IRCAD, Strasbourg, France. [Rosemurgy, Alexander] Florida Hosp, Dept Surg, Tampa, FL USA. [Torquati, Alfonso] Duke Univ, Dept Surg, Durham, NC USA. [Sachdeva, Ajit K.] Amer Coll Surg, Div Educ, Chicago, IL USA. [Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Ctr Esophageal Dis, Chicago, IL 60637 USA. RP Fisichella, PM (reprint author), Brigham & Womens Hosp, Dept Surg, 1400 VFW Pkwy, Boston, MA 02132 USA. EM marco6370@yahoo.com FU Division of Education, Committee on Emergent Surgical Technologies (CESTE), American College of Surgeons FX This paper is sponsored by the Division of Education, Committee on Emergent Surgical Technologies (CESTE), American College of Surgeons. NR 61 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2015 VL 19 IS 7 BP 1355 EP 1362 DI 10.1007/s11605-015-2766-7 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CK8AH UT WOS:000356458900019 PM 25678255 ER PT J AU Kaiser, AM Hogen, R Bordeianou, L Alavi, K Wise, PE Sudan, R AF Kaiser, Andreas M. Hogen, Rachel Bordeianou, Liliana Alavi, Karim Wise, Paul E. Sudan, Ranjan CA SSAT TI Clostridium Difficile Infection from a Surgical Perspective SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Clostridium difficile; Antibiotic-associated colitis; Antibiotic-associated diarrhea; Pseudo-membranous colitis; Toxic colitis; Total colectomy; Fecal microbiota transfer ID INFLAMMATORY-BOWEL-DISEASE; INTENSIVE-CARE-UNIT; RISK-FACTORS; MICROBIOTA TRANSPLANTATION; HOSPITALIZED-PATIENTS; DIAGNOSTIC YIELD; RANDOMIZED-TRIAL; FOLLOW-UP; COLITIS; DIARRHEA AB The incidence and the severity of Clostridium difficile infection (CDI) have increased significantly over the last decade, especially in high-risk populations such as patients with inflammatory bowel disease (IBD). Surgeons must be able to both identify and minimize the risk of CDI in their own surgical patients and determine which CDI patients will benefit from surgery. We sought to define the risk factors, compare the treatment options, define the surgical indications, and identify factors that affect surgical outcomes for CDI based on the currently available literature. Antibiotic use, exposure to the C. difficile bacteria, IBD, and higher levels of co-morbidity are all risk factors for CDI. The majority of CDI can be treated with antibiotics. Severe or fulminant colitis, however, has a high potential for poor outcome, but experience and some data suggest a lower mortality rate with colectomy rather than with continued medical treatment. Open total abdominal colectomy with end ileostomy is typically the preferred surgical strategy. It is often difficult to determine which patients will fail medical management as some may not manifest clinical signs of severe infection. Surrogate parameters of failure of medical therapy include respiratory and/or renal insufficiency, age greater than 60 years, peripheral vascular disease, congestive heart failure, and coagulopathy, all of which have been associated with worse surgical outcomes. Evidence suggests that in appropriately selected patients, colectomy performed before the development of shock requiring vasopressors, respiratory failure, renal failure, multi-organ dysfunction, and mental status changes may reduce mortality of the most severe forms of colitis. For less severe or recurrent presentations, creation of a loop ileostomy with intra-operative colonic lavage, fecal microbiota transfer, and C. difficile vaccinations are being discussed but have only been studied in small case-controlled series. Prevention, containment, and non-surgical treatment are the cornerstone of management for CDI. However, the most severe forms with toxic colitis benefit from involvement of a surgical team. Swift open total abdominal colectomy with end ileostomy in patients with severe or fulminant C. difficile colitis has the best chance to reduce mortality if it is not delayed until shock, end organ damage, vasopressor requirement, mental status changes develop. Less aggressive approaches may be appropriate for milder and refractory forms but require further study before their applicability can be determined. C1 [Kaiser, Andreas M.; Hogen, Rachel] Univ So Calif, Keck Sch Med, Div Colorectal Surg, Dept Surg, Los Angeles, CA 90033 USA. [Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Colorectal Surg Program, Boston, MA 02114 USA. [Alavi, Karim] UMass Mem Med Ctr, Dept Surg, Worcester, MA USA. [Wise, Paul E.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Sudan, Ranjan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Kaiser, AM (reprint author), Univ So Calif, Keck Sch Med, Div Colorectal Surg, Dept Surg, 1441 Eastlake Ave,Suite 7418, Los Angeles, CA 90033 USA. EM akaiser@usc.edu OI Wise, Paul/0000-0003-3798-7913 FU GI Health Foundation FX Disclosure Information: Authors: Karim Alavi, M.D., MPH has nothing to disclose; Sook Yee Chan, M.D. has nothing to disclose. Paul Wise, M.D. has nothing to disclose. Andreas M. Kaiser, M.D. receives speaker fees from GI Health Foundation, and royalties from Uptodate and McGraw Hill Publisher. Ranjan Sudan, M.D. has nothing to disclose. Liliana Bordeianou, M.D. has nothing to disclose. Editors-in-Chief: Jeffrey B. Matthews, M.D., has nothing to disclose; Charles Yeo, M.D., has nothing to disclose. CME Overseers: Arbiter: Jeffrey B. Matthews, M.D., has nothing to disclose; Vice-Arbiter: Guilherme M. Campos, M.D., Ph.D., has nothing to disclose; Question Reviewers: Deepa Taggarshe, M.D. has nothing to disclose; I. Michael Leitman, M.D., has nothing to disclose. NR 117 TC 4 Z9 4 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2015 VL 19 IS 7 BP 1363 EP 1377 DI 10.1007/s11605-015-2785-4 PG 15 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CK8AH UT WOS:000356458900020 PM 25917533 ER PT J AU Kaminetzky, CP Nelson, KM AF Kaminetzky, Catherine P. Nelson, Karin M. TI In the Office and In-Between: The Role of Panel Management in Primary Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID HEALTH; OUTCOMES C1 [Kaminetzky, Catherine P.] VA Puget Sound Hlth Care Syst, Ctr Educ & Dev, Seattle, WA 98108 USA. [Kaminetzky, Catherine P.; Nelson, Karin M.] Univ Washington, Sch Med, Div Gen Internal Med, Seattle, WA USA. [Nelson, Karin M.] VA Puget Sound Hlth Care Syst, VA Hlth Serv Res & Dev, Seattle, WA 98108 USA. RP Kaminetzky, CP (reprint author), VA Puget Sound Hlth Care Syst, Ctr Educ & Dev, 1660 South Columbian Way, Seattle, WA 98108 USA. EM catherine.kaminetzky@va.gov NR 12 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2015 VL 30 IS 7 BP 876 EP 877 DI 10.1007/s11606-015-3310-x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CK8AL UT WOS:000356459400005 PM 25851305 ER PT J AU Berkowitz, SA Percac-Lima, S Ashburner, JM Chang, YC Zai, AH He, W Grant, RW Atlas, SJ AF Berkowitz, Seth A. Percac-Lima, Sanja Ashburner, Jeffrey M. Chang, Yuchiao Zai, Adrian H. He, Wei Grant, Richard W. Atlas, Steven J. TI Building Equity Improvement into Quality Improvement: Reducing Socioeconomic Disparities in Colorectal Cancer Screening as Part of Population Health Management SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; cancer screening; health status disparities; socioeconomic factors; quality improvement ID RANDOMIZED-CONTROLLED-TRIAL; INTERRUPTED TIME-SERIES; UNITED-STATES; PATIENT NAVIGATION; PRIMARY-CARE; COLONOSCOPY; INTERVENTIONS; IMPACT; ORGANIZATIONS AB Improving colorectal cancer (CRC) screening rates for patients from socioeconomically disadvantaged backgrounds is a recognized public health priority. Our aim was to determine if implementation of a system-wide screening intervention could reduce disparities in the setting of improved overall screening rates. This was an interrupted time series (ITS) analysis before and after a population management intervention. Patients eligible for CRC screening (age 52-75 years without prior total colectomy) in an 18-practice research network from 15 June 2009 to 15 June 2012 participated in the study. The Technology for Optimizing Population Care (TopCare) intervention electronically identified patients overdue for screening and facilitated contact by letter or telephone scheduler, with or without physician involvement. Patients identified by algorithm as high risk for non-completion entered into intensive patient navigation. Patients were dichotomized as a parts per thousand currency signaEuro parts per thousand high school diploma (a parts per thousand currency sign HS), an indicator of socioeconomic disadvantage, vs. > HS diploma (> HS). The monthly disparity between a parts per thousand currency signaEuro parts per thousand HS and > HS with regard to CRC screening completion was examined. At baseline, 72 % of 47,447 eligible patients had completed screening, compared with 75 % of 51,442 eligible patients at the end of follow-up (p < 0.001). CRC screening completion was lower in a parts per thousand currency signaEuro parts per thousand HS vs. > HS patients in June 2009 (65.7 % vs. 74.5 %, p < 0.001) and remained lower in June 2012 (69.4 % vs. 76.7 %, p < 0.001). In the ITS analysis, which accounts for secular trends, TopCare was associated with a significant decrease in the CRC screening disparity (0.7 %, p < 0.001). The effect of TopCare represents approximately 99 additional a parts per thousand currency signaEuro parts per thousand HS patients screened above prevailing trends, or 26 life-years gained had these patients remained unscreened. A multifaceted population management intervention sensitive to the needs of vulnerable patients modestly narrowed disparities in CRC screening, while also increasing overall screening rates. Embedding interventions for vulnerable patients within larger population management systems represents an effective approach to increasing overall quality of care while also decreasing disparities. C1 [Berkowitz, Seth A.; Percac-Lima, Sanja; Ashburner, Jeffrey M.; Chang, Yuchiao; He, Wei; Atlas, Steven J.] Massachusetts Gen Hosp, Med Serv, Div Gen Internal Med, Boston, MA USA. [Berkowitz, Seth A.; Percac-Lima, Sanja; Chang, Yuchiao; Zai, Adrian H.; Atlas, Steven J.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Zai, Adrian H.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Berkowitz, SA (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM SABerkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU Agency for Healthcare Research and Quality [AHRQ R18-HS018161]; Controlled Risk Insurance Company/Risk Management Foundation; Massachusetts General Hospital Primary Care Operations Improvement Program; Massachusetts General Physicians Organization; Institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; Division of General Internal Medicine at Massachusetts General Hospital FX This study was supported by grants from the Agency for Healthcare Research and Quality (AHRQ R18-HS018161), the Controlled Risk Insurance Company/Risk Management Foundation, and institutional funding through the Massachusetts General Hospital Primary Care Operations Improvement Program and the Massachusetts General Physicians Organization. Seth A. Berkowitz was supported by an Institutional National Research Service Award #T32HP10251, the Ryoichi Sasakawa Fellowship Fund, and by the Division of General Internal Medicine at Massachusetts General Hospital. NR 39 TC 8 Z9 8 U1 4 U2 11 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 JUL PY 2015 VL 30 IS 7 BP 942 EP 949 DI 10.1007/s11606-015-3227-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CK8AL UT WOS:000356459400017 PM 25678378 ER PT J AU Soley-Bori, M Soria-Saucedo, R Ryan, CM Schneider, JC Haynes, AB Gerrard, P Cabral, HJ Lillemoe, KD Kazis, LE AF Soley-Bori, Marina Soria-Saucedo, Rene Ryan, Colleen M. Schneider, Jeffrey C. Haynes, Alex B. Gerrard, Paul Cabral, Howard J. Lillemoe, Keith D. Kazis, Lewis E. TI Functional Status and Hospital Readmissions Using the Medical Expenditure Panel Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE functional status; physical status; medical expenditure panel survey; hospital admission; readmission ID QUALITY-OF-LIFE; HEART-FAILURE PATIENTS; RISK-FACTORS; ACUTE-CARE; DISCHARGE; OLDER; REHOSPITALIZATION; REHABILITATION; PREDICTORS; PROGRAM AB Hospital readmissions are expensive and they may signal poor quality of care. Whether functional status is related to hospital readmissions using a representative U.S sample remains unexplored . We aimed to assess the relationship between functional status and all-cause 30-day hospital readmissions using a representative sample of the US population. This was a retrospective observational study (2003-2011). The study included 3,772 patients who completed the SF-12 before being hospitalized. Three hundred and eighteen (8.4 %) were readmitted within 30 days after being discharged. The Medical Expenditure Panel Survey (MEPS) was employed. Functional status was measured with the Short-Form 12-Item Health Survey Version 2A (R) (SF-12). The probability of being readmitted was estimated using a logistic model controlling for demographic characteristics, comorbid conditions, insurance coverage, physical (PCS) and mental (MCS) summaries of the SF-12, reason for hospitalization, length of hospital stay, region, and residential area. A one-unit difference in PCS reduced the odds of readmission by 2 % (odds ratio 0.98 [95 % CI, 0.97 to 0.99]; p < 0.001), which implies an 18 % reduction in the odds of readmissions for a ten-unit difference (one standard deviation) in PCS. The c-statistic of the model was 0.72. Baseline physical function is associated with hospital readmissions. The SF-12 improves the ability to identify patients at high risk of hospital readmission. C1 [Soley-Bori, Marina; Soria-Saucedo, Rene; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, CAPP, Boston, MA 02138 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Ryan, Colleen M.; Haynes, Alex B.; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Charlestown, MA USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. [Haynes, Alex B.] Harvard Univ, Sch Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. [Haynes, Alex B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gerrard, Paul] New England Rehabil Hosp Portland, Portland, ME USA. RP Kazis, LE (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, CAPP, Boston, MA 02138 USA. EM lek@bu.edu NR 45 TC 5 Z9 5 U1 3 U2 10 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 JUL PY 2015 VL 30 IS 7 BP 965 EP 972 DI 10.1007/s11606-014-3170-9 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CK8AL UT WOS:000356459400020 PM 25691236 ER PT J AU Liu, QL Rehman, H Krishnasamy, Y Schnellmann, RG Lemasters, JJ Zhong, Z AF Liu, Qinlong Rehman, Hasibur Krishnasamy, Yasodha Schnellmann, Rick G. Lemasters, John J. Zhong, Zhi TI Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice SO JOURNAL OF HEPATOLOGY LA English DT Article DE c-Jun N-terminal kinase; Inducible nitric oxide synthase; Liver transplantation; Mitochondrial permeability transition; Non-heart-beating donors; Primary non-function; Sab ID MITOCHONDRIAL PERMEABILITY TRANSITION; NITRIC-OXIDE SYNTHASE; HEART-BEATING DONORS; N-TERMINAL KINASE; HEPATIC ISCHEMIA-REPERFUSION; GRAFT INJURY; ISCHEMIA/REPERFUSION INJURY; SIGNALING PATHWAYS; OXIDATIVE STRESS; INHIBITION AB Background & Aims: Inclusion of liver grafts from cardiac death donors (CDD) would increase the availability of donor livers but is hampered by a higher risk of primary non-function. Here, we seek to determine mechanisms that contribute to primary non-function of liver grafts from CDD with the goal to develop strategies for improved function and outcome, focusing on c-Jun-N-terminal kinase (JNK) activation and mitochondrial depolarization, two known mediators of graft failure. Methods: Livers explanted from wild-type, inducible nitric oxide synthase knockout (iNOS(-/-)), JNK1(-/-) or JNK2(-/-) mice after 45-min aorta clamping were implanted into wild-type recipients. Mitochondrial depolarization was detected by intravital confocal microscopy in living recipients. Results: After transplantation of wild-type CDD livers, graft iNOS expression and 3-nitrotyrosine adducts increased, but hepatic endothelial NOS expression was unchanged. Graft injury and dysfunction were substantially higher in CDD grafts than in non-CDD grafts. iNOS deficiency and inhibition attenuated injury and improved function and survival of CDD grafts. JNK1/2 and apoptosis signal-regulating kinase-1 activation increased markedly in wild-type CDD grafts, which was blunted by iNOS deficiency. JNK inhibition and JNK2 deficiency, but not JNK1 deficiency, decreased injury and improved function and survival of CDD grafts. Mitochondrial depolarization and binding of phospho-JNK2 to Sab, a mitochondrial protein linked to the mitochondrial permeability transition, were higher in CDD than in non-CDD grafts. iNOS deficiency, JNK inhibition and JNK2 deficiency all decreased mitochondrial depolarization and blunted ATP depletion in CDD grafts. JNK inhibition and deficiency did not decrease 3-nitrotyrosine adducts in CDD grafts. Conclusion: The iNOS-JNK2-Sab pathway promotes CDD graft failure via increased mitochondrial depolarization, and is an attractive target to improve liver function and survival in CDD liver transplantation recipients. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi] Med Univ S Carolina, Dept Drug Discovery & Biol Sci, Charleston, SC 29425 USA. [Liu, Qinlong] Dalian Med Univ, Affiliated Hosp 2, Dalian, Liaoning, Peoples R China. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Zhong, Z (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biol Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM zhong@musc.edu FU National Institute of Health [DK70844, DK037034]; Chinese National Natural Foundation [81470878] FX This study was supported, in part, by Grant DK70844 and DK037034 from the National Institute of Health and Grant #81470878 from Chinese National Natural Foundation. NR 49 TC 1 Z9 1 U1 0 U2 6 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 JUL PY 2015 VL 63 IS 1 BP 68 EP 74 DI 10.1016/j.jhep.2015.02.017 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CK6CC UT WOS:000356314400011 PM 25703084 ER PT J AU Simon, TG King, LY Chung, RT AF Simon, Tracey G. King, Lindsay Y. Chung, Raymond T. TI Reply to: "Coagulation and fibrosis: A potential non-negligible target of statins in chronic hepatitis'' SO JOURNAL OF HEPATOLOGY LA English DT Letter C1 [Simon, Tracey G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Simon, Tracey G.; King, Lindsay Y.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM rtchung@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2015 VL 63 IS 1 BP 279 EP 279 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CK6CC UT WOS:000356314400031 PM 25728638 ER PT J AU Peterson, DS Fling, BW Mancini, M Cohen, RG Nutt, JG Horak, FB AF Peterson, Daniel S. Fling, Brett W. Mancini, Martina Cohen, Rajal G. Nutt, John G. Horak, Fay B. TI Dual-task interference and brain structural connectivity in people with Parkinson's disease who freeze SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; PEDUNCULOPONTINE NUCLEUS; BASAL GANGLIA; GAIT; NETWORK; MOTOR AB Background Freezing of gait in people with Parkinson's disease (PD) is likely related to attentional control (ie, ability to divide and switch attention). However, the neural pathophysiology of altered attentional control in individuals with PD who freeze is unknown. Structural connectivity of the pedunculopontine nucleus has been related to freezing and may play a role in altered attentional control; however, this relationship has not been investigated. We measured whether dual-task interference, defined as the reduction in gait performance during dual-task walking, is more pronounced in individuals with PD who freeze, and whether dual-task interference is associated with structural connectivity and/or executive function in this population. Methods We measured stride length in 13 people with PD with and 12 without freezing of gait during normal and dual-task walking. We also assessed asymmetry of pedunculopontine nucleus structural connectivity via diffusion tensor imaging and performance on cognitive tests assessing inhibition and set-shifting, cognitive domains related to freezing. Results Although stride length was not different across groups, change in stride length between normal and dual-task gait (ie, dual-task interference) was more pronounced in people with PD who freeze compared to non-freezers. Further, in people with PD who freeze, dual-task interference was correlated with asymmetry of pedunculopontine nucleus structural connectivity, Go-NoGo target accuracy (ability to release a response) and simple reaction time. Conclusions These results support the hypothesis that freezing is related to altered attentional control during gait, and suggest that differences in pedunculopontine nucleus connectivity contribute to poorer attentional control in people with PD who freeze. C1 [Peterson, Daniel S.; Fling, Brett W.; Mancini, Martina; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97239 USA. [Peterson, Daniel S.; Fling, Brett W.; Horak, Fay B.] Portland VA Med Ctr, Portland, OR USA. [Cohen, Rajal G.] Univ Idaho, Dept Psychol & Commun Studies, Moscow, ID 83843 USA. RP Peterson, DS (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM petedani@ohsu.edu OI Peterson, Daniel/0000-0002-4639-6544 FU National Institutes of Health via the Morris K. Udall Center for Excellence in Parkinson's Disease Research at the University of Washington; Portland Veterans Affairs Medical Center (VA Merit Award) [E1075-R]; NIH [AG006457]; Medical Research Foundation of Oregon FX This work was supported by grants from National Institutes of Health via the Morris K. Udall Center for Excellence in Parkinson's Disease Research at the University of Washington, Portland Veterans Affairs Medical Center (VA Merit Award: E1075-R), NIH (AG006457) and the Medical Research Foundation of Oregon. NR 39 TC 13 Z9 13 U1 7 U2 23 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2015 VL 86 IS 7 BP 786 EP 792 DI 10.1136/jnnp-2014-308840 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CK4FU UT WOS:000356179000016 PM 25224677 ER PT J AU Tsoukas, MA Ko, BJ Witte, TR Dincer, F Hardman, WE Mantzoros, CS AF Tsoukas, Michael A. Ko, Byung-Joon Witte, Theodore R. Dincer, Fadime Hardman, W. Elaine Mantzoros, Christos S. TI Dietary walnut suppression of colorectal cancer in mice: Mediation by miRNA patterns and fatty acid incorporation SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Walnut; Colon cancer; miRNA; Fatty acids; Anti-inflammation; Apoptosis; Angiogenesis ID ALPHA-LINOLENIC ACID; MAMMARY-GLAND TUMORIGENESIS; COLON-CANCER; ELLAGIC ACID; EXPRESSION PROFILES; MICRORNA EXPRESSION; BETA-SITOSTEROL; DOWN-REGULATION; RISK-FACTORS; RAT COLON AB Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer; however, the underlying mechanisms are not fully understood. An emerging concept suggests that microribonucleic acids (miRNAs) may help explain the relationship between walnut consumption and decreased colorectal neoplasia risk. Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25 days of diet treatment. Thirty samples of tumor and of omental adipose were analyzed to determine changes in lipid composition in each dietary group. In the tumors of the walnut-containing diet, we found significant increases in alpha-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage of total omega-3 fatty acid composition (r=-0.641, P=.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNAs 1903, 467c and 3068 (P<.05) and increased expression of miRNA 297a* (P=.0059) in the walnut-treated group as compared to control diet. Our results indicate that changes in the miRNA expression profiles likely affect target gene transcripts involved in pathways of anti-inflammation, antivascularization, antiproliferation and apoptosis. We also demonstrate the incorporation of protective fatty acids into colonic epithelium of walnut-fed mice, which may independently alter miRNA expression profiles itself. Future studies of the mechanism of widespread miRNA regulation by walnut consumption are needed to offer potential prognostic and therapeutic targets. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tsoukas, Michael A.; Ko, Byung-Joon; Dincer, Fadime; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Tsoukas, Michael A.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Witte, Theodore R.; Hardman, W. Elaine] Marshall Univ, Sch Med, Dept Biochem & Microbiol, Huntington, WV USA. RP Tsoukas, MA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. EM mtsouka1@bidmc.harvard.edu FU American Institute for Cancer Research [276688]; California Walnut Commission FX This study was supported from a grant by the American Institute for Cancer Research (276688) and the California Walnut Commission. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Institute for Cancer Research and the California Walnut Commission; sponsors had no input on interpretation or reporting of findings. NR 70 TC 6 Z9 7 U1 4 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUL PY 2015 VL 26 IS 7 BP 776 EP 783 DI 10.1016/j.jnutbio.2015.02.009 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA CK9LM UT WOS:000356561600012 PM 25882694 ER PT J AU Friedlander, AH Chang, TI Hazboun, RC Aghazadehsanai, N AF Friedlander, Arthur H. Chang, Tina I. Hazboun, Renna C. Aghazadehsanai, Nona TI Critique of American Dental Association Council on Scientific Affairs Clinical Practice Guideline: Use of Prophylactic Antibiotics Before Dental Procedures in Patients With Prosthetic Joints SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID INFECTIONS C1 [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA. [Friedlander, Arthur H.; Chang, Tina I.] Univ Calif Los Angeles, Sch Dent, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA. [Chang, Tina I.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Fellowship & Inpatient Oral & Maxillofacial S, Los Angeles, CA 90073 USA. [Hazboun, Renna C.; Aghazadehsanai, Nona] Vet Affairs Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Dent Serv, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 5 TC 1 Z9 1 U1 1 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2015 VL 73 IS 7 BP 1242 EP 1243 DI 10.1016/j.joms.2015.03.052 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CK5ZI UT WOS:000356306900007 PM 25896570 ER PT J AU Busch, RA Curtis, CS Leverson, GE Kudsk, KA AF Busch, Rebecca A. Curtis, Caitlin S. Leverson, Glen E. Kudsk, Kenneth A. TI Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE parenteral nutrition; nutrition; parenteral formulas; compounding; outcomes research; quality; nutrition support practice; reimbursement ID BLOOD-STREAM INFECTIONS; OUTBREAK AB Background: Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN and to quantify any effect on difference in the cost of therapy. Methods: We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were potassium chloride, 10 and 20 mEq; magnesium sulfate, 2 g and 4 g; potassium phosphate, 7.5 and 15 mmol; and sodium phosphate, 7.5 and 15 mmol IVPB. Results: There was no statistical difference in the number of PN formulations administered per day during each period (14.7 +/- 3.9 vs 14.0 +/- 2.6, individualized vs premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 +/- 3.8 vs 13.8 +/- 6.8; P < .0001). The additional IVPB electrolyte supplementation required in patients receiving premixed PN was associated with an additional $11,855.74 cost per 30 days of therapy compared with those who received individualized PN. Conclusion: Inpatient use of premixed PN results in a significant increase in IVPB electrolyte supplementation and cost compared with individualized PN use. C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Busch, Rebecca A.; Leverson, Glen E.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Curtis, Caitlin S.] Univ Wisconsin Hosp & Clin, Dept Pharm, Madison, WI 53792 USA. RP Kudsk, KA (reprint author), Univ Wisconsin, G5-341 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU Surgical Oncology Research Training Program [T32CA090217-13] FX The project described was supported by the Surgical Oncology Research Training Program (grant number T32CA090217-13). NR 17 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JUL PY 2015 VL 39 IS 5 BP 586 EP 590 DI 10.1177/0148607113518583 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CK8SE UT WOS:000356507600010 PM 24390715 ER PT J AU Horan, WP Reise, SP Kern, RS Lee, J Penn, DL Green, MF AF Horan, William P. Reise, Steven P. Kern, Robert S. Lee, Junghee Penn, David L. Green, Michael F. TI Structure and correlates of self-reported empathy in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Empathy; Social functioning; Social cognition; QCAE ID SOCIAL NEUROSCIENCE MEASURES; EMOTION REGULATION; COGNITIVE EMPATHY; CLINICAL-TRIALS; ACCURACY; PERSPECTIVE; SUPPRESSION; COMPETENCE; PSYCHOSIS; DEFICITS AB Research on empathy in schizophrenia has relied on dated self-report scales that do not conform to contemporary social neuroscience models of empathy. The current study evaluated the structure and correlates of the recently-developed Questionnaire of Cognitive and Affective Empathy (QCAE) in schizophrenia. This measure, whose structure and validity was established in healthy individuals, includes separate scales to assess the two main components of empathy: Cognitive Empathy (assessed by two subscales) and Affective Empathy (assessed by three subscales). Stable outpatients with schizophrenia (n = 145) and healthy individuals (n = 45) completed the QCAE, alternative measures of empathy, and assessments of clinical symptoms, neurocognition, and functional outcome. Exploratory and confirmatory factor analyses provided consistent support for a two-factor solution in the schizophrenia group, justifying the use of separate cognitive and affective empathy scales in this population. However, one of the three Affective Empathy subscales was not psychometrically sound and was excluded from further analyses. Patients reported significantly lower Cognitive Empathy but higher Affective Empathy than controls. Among patients, the QCAE scales showed significant correlations with an alternative self-report empathy scale, but not with performance on an empathic accuracy task. The QCAE Cognitive Empathy subscales also showed significant, though modest, correlations with negative symptoms and functional outcome. These findings indicate that structure of self-reported empathy is similar in people with schizophrenia and healthy subjects, and can be meaningfully compared between groups. They also contribute to emerging evidence that some aspects of empathy may be intact or hyper-responsive in schizophrenia. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Horan, William P.; Kern, Robert S.; Lee, Junghee; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Horan, William P.; Kern, Robert S.; Lee, Junghee; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Reise, Steven P.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Penn, David L.] Univ N Carolina, Chapel Hill, NC USA. [Penn, David L.] Australian Catholic Univ, Melbourne, Vic, Australia. RP Horan, WP (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC 210A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health [MH087618, MH043292, MH065707] FX National Institute of Mental Health (MH087618, MH043292, and MH065707 to M.F.G.) NR 51 TC 6 Z9 6 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUL-AUG PY 2015 VL 66-67 BP 60 EP 66 DI 10.1016/j.jpsychires.2015.04.016 PG 7 WC Psychiatry SC Psychiatry GA CL2AT UT WOS:000356746700008 PM 25985922 ER PT J AU Tsai, J Armour, C Southwick, SM Pietrzak, RH AF Tsai, Jack Armour, Cherie Southwick, Steven M. Pietrzak, Robert H. TI Dissociative subtype of DSM-5 posttraumatic stress disorder in US veterans SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Posttraumatic stress disorder; Dissociation; Veterans; Substance abuse ID QUALITY-OF-LIFE; AFGHANISTAN VETERANS; NATIONAL-HEALTH; LATENT PROFILE; PTSD TREATMENT; IRAQ; RESILIENCE; DEPRESSION; VALIDATION; HOSTILITY AB The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) formally introduced a dissociative subtype of posttraumatic stress disorder (PTSD). This study examined the proportion of U.S. veterans with DSM-5 PTSD that report dissociative symptoms; and compared veterans with PTSD with and without the dissociative subtype and trauma-exposed controls on sociodemographics, clinical characteristics, and quality of life. Multivariable analyses were conducted on a nationally representative sample of 1484 veterans from the National Health and Resilience in Veterans Study (second baseline survey conducted September October, 2013). Of the 12.0% and 5.2% of veterans who screened positive for lifetime and past-month DSM-5 PTSD, 19.2% and 16.1% screened positive for the dissociative subtype, respectively. Among veterans with PTSD, those with the dissociative subtype reported more severe PTSD symptoms, comorbid depressive and anxiety symptoms, alcohol use problems, and hostility than those without the dissociative subtype. Adjusting for PTSD symptom severity, those with the dissociative subtype continued to report more depression and alcohol use problems. These results underscore the importance of assessing, monitoring, and treating the considerable proportion of veterans with PTSD and dissociative symptoms. Published by Elsevier Ltd. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Armour, Cherie] Univ Ulster, Psychol Res Inst, Coleraine BT52 1SA, Londonderry, North Ireland. [Southwick, Steven M.; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM jack.Tsai@yale.edu OI Tsai, Jack/0000-0002-0329-648X; Armour, Cherie/0000-0001-7649-3874 FU U.S. Department of Veterans Affairs, National Center for Posttraumatic Stress Disorder; U.S. Department of Veterans Affairs, Health Services Research and Development FX This work received no specific grant from any funding agency, commercial or not-for-profit sectors. This work was supported by the U.S. Department of Veterans Affairs, National Center for Posttraumatic Stress Disorder and the U.S. Department of Veterans Affairs, Health Services Research and Development. The views presented here are those of the authors alone and do not represent the position of the United States Government. NR 52 TC 5 Z9 5 U1 7 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUL-AUG PY 2015 VL 66-67 BP 67 EP 74 DI 10.1016/j.jpsychires.2015.04.017 PG 8 WC Psychiatry SC Psychiatry GA CL2AT UT WOS:000356746700009 PM 25969340 ER PT J AU Andersson, MI Rajbhandari, R Kew, MC Vento, S Preiser, W Hoepelman, AIM Theron, G Cotton, M Cohn, J Glebe, D Lesi, O Thursz, M Peters, M Chung, R Wiysonge, C AF Andersson, Monique I. Rajbhandari, Ruma Kew, Michael C. Vento, Sandro Preiser, Wolfgang Hoepelman, Andy I. M. Theron, Gerhard Cotton, Mark Cohn, Jennifer Glebe, Dieter Lesi, Olufunmilayo Thursz, Mark Peters, Marion Chung, Raymond Wiysonge, Charles TI Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: time to act SO LANCET GLOBAL HEALTH LA English DT Editorial Material ID PREVENT PERINATAL TRANSMISSION; TENOFOVIR DISOPROXIL FUMARATE; PREGNANT-WOMEN; INFECTION; IMMUNIZATION; INFANTS; HIV; EFFICACY; VACCINE; SAFETY C1 [Andersson, Monique I.] Univ Stellenbosch, Div Med Virol, ZA-7505 Cape Town, South Africa. [Rajbhandari, Ruma; Chung, Raymond] Massachusetts Gen Hosp, Dept Hepatol, Boston, MA 02114 USA. [Rajbhandari, Ruma; Chung, Raymond] Harvard Univ, Boston, MA 02115 USA. [Kew, Michael C.] Univ Cape Town, Dept Med, ZA-7700 Rondebosch, South Africa. [Vento, Sandro] Univ Botswana, Gaborone, Botswana. [Preiser, Wolfgang] Univ Stellenbosch, Div Med Virol, ZA-7600 Stellenbosch, South Africa. [Theron, Gerhard] Univ Stellenbosch, Dept Obstet & Gynaecol, ZA-7600 Stellenbosch, South Africa. [Cotton, Mark] Univ Stellenbosch, Dept Child Hlth, ZA-7600 Stellenbosch, South Africa. [Wiysonge, Charles] Univ Stellenbosch, Dept Evidence Based Med, ZA-7600 Stellenbosch, South Africa. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Hoepelman, Andy I. M.] Univ Utrecht, Dept Med, Utrecht, Netherlands. [Glebe, Dieter] Univ Giessen, Inst Med Virol, D-35390 Giessen, Germany. [Lesi, Olufunmilayo] Univ Lagos, Dept Hepatol, Lagos, Nigeria. [Thursz, Mark] Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London, England. [Peters, Marion] Univ Calif San Francisco, Dept Hepatol, San Francisco, CA 94143 USA. RP Andersson, MI (reprint author), Univ Stellenbosch, Div Med Virol, Francie van Zijl Ave, ZA-7505 Cape Town, South Africa. EM andersson_m@sun.ac.za RI Preiser, Wolfgang/J-4875-2016 OI Preiser, Wolfgang/0000-0002-0254-7910 FU Poliomyelitis Research Foundation; National Health Laboratory Service Research Trust FX We declare no competing interests. We acknowledge funding from the Poliomyelitis Research Foundation and National Health Laboratory Service Research Trust. NR 15 TC 5 Z9 6 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD JUL PY 2015 VL 3 IS 7 BP E358 EP E359 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK6CH UT WOS:000356314900010 PM 26087980 ER PT J AU Lee, MS Liu, CY Su, L Christiani, DC AF Lee, Mi-Sun Liu, Chen-yu Su, Li Christiani, David C. TI Polymorphisms in ERCC1 and ERCC2/XPD genes and carcinogen DNA adducts in human lung SO LUNG CANCER LA English DT Article DE ERCC1; ERCC2/XPD; DNA repair; DNA adduct; Non-small cell lung cancer ID NUCLEOTIDE EXCISION-REPAIR; CANCER SUSCEPTIBILITY; CHINESE POPULATION; RISK; XPD; SMOKING; DAMAGE; GENOTYPES; METAANALYSIS; CAPACITY AB Objectives: In this exploratory study, we aimed to investigate whether polymorphisms in excision repair cross-complementing group 1 (ERCC1) and excision repair cross-complementing group 2/xeroderma pigmentosum group D (ERCC2/XPD) in the nucleotide excision repair (NER) pathways associated with DNA adducts in human lung tissue. We also analyzed the association stratified by the major histologic subtypes of non-small cell lung cancer (NSCLC): adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). Methods: The study population consisted of 107 early stage NSCLC patients from the Massachusetts General Hospital (MGH) in Boston who underwent curative surgical resection. Genotyping was completed for SNPs in ERCC1 [C8092A (rs3212986) and C11 8T (rs11615)] and ERCC2/XPD [Asp312Asn (rs1799793) and Lys751Gln (rs1052559)] using a PCR-RFLP method and the PCR with fluorescent allele-specific oligonucleotide probes (Taqman). DNA adduct levels were measured as relative adduct levels per 10(10) nucleotides by P-32-postlabeling in non-tumor lung tissue. Results: After adjusting for potential confounders, lung DNA adduct levels increased by 103.2% [95% confidence interval (CI), -11.5 to 366.6] for ERCC2/XPD rs1799793AA genotype compared with their corresponding wild type homozygous genotypes in overall NSCLC, but the difference did not reach statistical significance. When we stratified by the subtypes of NSCLC, we found that DNA adducts levels in lung increased by 204.9% (95% CI, 0.8 to 822.2, P=0.059) for ERCC2/XPD rs1799793AA genotype in subjects with SQCC and the trend was statistically significant (P for trend = 0.0489). Conclusions: Polymorphisms in ERCC2/XPD Asp312Asn may be associated with increased DNA adduct levels in the lung, especially among subjects with SQCC. Further large scale studies are needed to confirm our findings. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Lee, Mi-Sun; Su, Li; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Liu, Chen-yu] Natl Taiwan Univ, Coll Publ Hlth, Inst Environm Hlth, Taipei 10764, Taiwan. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1 Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu OI LIU, CHEN-YU/0000-0002-4693-5667 FU National Institutes of Health [CA074386, CA092824, CA090578] FX The authors gratefully acknowledge the patients and physicians from the Massachusetts General Hospital in Boston, Drs. John Wain and Eugene Mark, and Dr. John Wiencke. This study was supported by grants from National Institutes of Health (CA074386, CA092824, CA090578). NR 32 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2015 VL 89 IS 1 BP 8 EP 12 DI 10.1016/j.lungcan.2015.05.001 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CK9FP UT WOS:000356546300003 PM 26001533 ER PT J AU Owonikoko, TK Dahlberg, SE Khan, SA Gerber, DE Dowell, J Moss, RA Belani, CP Hann, CL Aggarwal, C Ramalingam, SS AF Owonikoko, Taofeek K. Dahlberg, Suzanne E. Khan, Saad A. Gerber, David E. Dowell, Jonathan Moss, Rebecca A. Belani, Chandra P. Hann, Christine L. Aggarwal, Charu Ramalingam, Suresh S. TI A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511) SO LUNG CANCER LA English DT Article DE Small cell; Veliparib; PARP; Phase I ID REFRACTORY SOLID TUMORS; I COMBINATION; III TRIAL; CHEMOTHERAPY; ADULTS; IRINOTECAN/CISPLATIN; ETOPOSIDE/CISPLATIN; INHIBITOR; LYMPHOMAS; ABT-888 AB Objectives: Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to establish the safety of the combination in human subjects. Materials and methods: The study employed the 3 +3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100 mg/m(2) on days 1-3) in a 21-day cycle. The starting dose of V was 60 mg (bid days 1-7) with plan to escalate to 100 mg (days 1-7) or de-escalate to 40 mg (days 1-7) depending on the dose limiting toxicity (DLT) experience during cycle 1. Patients with treatment-naive, extensive stage SCLC were included. Results: The study enrolled 9 patients: M/F (4/5); median age (60); White/African American (8/1). V was tolerated at the 60 mg (DLT in 0 of 3 patients) and 100 mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100 mg in combination with standard doses of C and E was established as the RP2D. Grades 3-5 adverse events irrespective of attribution during cycle 1 included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1), heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8), respiratory failure (1), and thrombocytopenia (2). Investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial response in 4/7 (57.1%), and complete response in 1/7 (14.3%) patients. Conclusions: This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Owonikoko, Taofeek K.; Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khan, Saad A.; Gerber, David E.; Dowell, Jonathan] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Moss, Rebecca A.] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Moss, Rebecca A.] Rutgers State Univ, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Hann, Christine L.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Aggarwal, Charu] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Owonikoko, TK (reprint author), Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Room C380,3rd Floor,1365C Clifton Rd NE, Atlanta, GA 30322 USA. EM towonik@emory.edu OI Moss, Rebecca/0000-0002-0139-5396 FU Public Health Service Grants [CA180820, CA180794, CA180864, CA180870, CA180802]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services; NIH/NCI grant [5K23CA164015] FX This study was conducted by the ECOG ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA180864, CA180870, CA180802, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. T.K. Owonikoko was supported by NIH/NCI grant 5K23CA164015. NR 21 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2015 VL 89 IS 1 BP 66 EP 70 DI 10.1016/j.lungcan.2015.04.015 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CK9FP UT WOS:000356546300013 PM 25985977 ER PT J AU Chatnuntawech, I Gagoski, B Bilgic, B Cauley, SF Setsompop, K Adalsteinsson, E AF Chatnuntawech, Itthi Gagoski, Borjan Bilgic, Berkin Cauley, Stephen F. Setsompop, Kawin Adalsteinsson, Elfar TI Accelerated H-1 MRSI using randomly undersampled spiral-based k-space trajectories SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance spectroscopic imaging (MRSI); random undersampling; spiral trajectory; compressed sensing; parallel imaging ID SPECTROSCOPIC IMAGING PEPSI; OUTER-VOLUME SUPPRESSION; N-ACETYL ASPARTATE; HUMAN-BRAIN; MAGNETIC-RESONANCE; CHEMICAL-SHIFT; MULTIPLE-SCLEROSIS; MRI RECONSTRUCTION; ARRAY COIL; SENSE AB PurposeTo develop and evaluate the performance of an acquisition and reconstruction method for accelerated MR spectroscopic imaging (MRSI) through undersampling of spiral trajectories. Theory and MethodsA randomly undersampled spiral acquisition and sensitivity encoding (SENSE) with total variation (TV) regularization, random SENSE+TV, is developed and evaluated on single-slice numerical phantom, in vivo single-slice MRSI, and in vivo three-dimensional (3D)-MRSI at 3 Tesla. Random SENSE+TV was compared with five alternative methods for accelerated MRSI. ResultsFor the in vivo single-slice MRSI, random SENSE+TV yields up to 2.7 and 2 times reduction in root-mean-square error (RMSE) of reconstructed N-acetyl aspartate (NAA), creatine, and choline maps, compared with the denoised fully sampled and uniformly undersampled SENSE+TV methods with the same acquisition time, respectively. For the in vivo 3D-MRSI, random SENSE+TV yields up to 1.6 times reduction in RMSE, compared with uniform SENSE+TV. Furthermore, by using random SENSE+TV, we have demonstrated on the in vivo single-slice and 3D-MRSI that acceleration factors of 4.5 and 4 are achievable with the same quality as the fully sampled data, as measured by RMSE of reconstructed NAA map, respectively. ConclusionWith the same scan time, random SENSE+TV yields lower RMSEs of metabolite maps than other methods evaluated. Random SENSE+TV achieves up to 4.5-fold acceleration with comparable data quality as the fully sampled acquisition. Magn Reson Med 74:13-24, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Chatnuntawech, Itthi; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Gagoski, Borjan] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Bilgic, Berkin; Cauley, Stephen F.; Setsompop, Kawin] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Setsompop, Kawin] Harvard Univ, Sch Med, Boston, MA USA. [Adalsteinsson, Elfar] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Chatnuntawech, I (reprint author), MIT, Room 36-776A,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ichatnun@mit.edu FU NIH [R01 EB017337] FX Grant sponsor: NIH; Grant number: R01 EB017337. NR 53 TC 4 Z9 4 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2015 VL 74 IS 1 BP 13 EP 24 DI 10.1002/mrm.25394 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK7XZ UT WOS:000356451500003 ER PT J AU Miloslavsky, EM McSparron, JI Richards, JB Puig, A Sullivan, AM AF Miloslavsky, Eli M. McSparron, Jakob I. Richards, Jeremy B. Puig, Alberto Sullivan, Amy M. TI Teaching during consultation: factors affecting the resident-fellow teaching interaction SO MEDICAL EDUCATION LA English DT Article ID EMERGENCY-DEPARTMENT; QUALITATIVE DATA; COMMUNICATION; FRAMEWORK AB ObjectivesThe subspecialty consultation represents a potentially powerful opportunity for resident learning, but barriers may limit the educational exchanges between fellows (subspecialty registrars) and residents (house officers). We conducted a focus group study of internal medicine (IM) residents and subspecialty fellows to determine barriers against and factors facilitating resident-fellow teaching interactions on the wards, and to identify opportunities for maximising teaching and learning. MethodsWe conducted four focus groups of IM residents (n=18) and IM subspecialty fellows (n=16) at two academic medical centres in the USA during February and March 2013. Participants represented trainees in all 3years of residency training and seven IM subspecialties. Four investigators analysed the transcripts using a structured qualitative framework approach, which was informed by literature on consultation and the theoretical framework of activity theory. ResultsWe identified two domains of barriers and facilitating factors: personal and systems-based. Sub-themes in the personal domain included fellows' perceived resistance to consultations, residents' willingness to engage in teaching interactions, and perceptions and expectations. Sub-themes in the systems-based domain included the process of requesting the consult, the quality of the consult request, primary team structure, familiarity between residents and fellows, workload, work experience, culture of subspecialty divisions, and fellows' teaching skills. These barriers differentially affected the two stages of the consult identified in the focus groups (initial interaction and follow-up interaction). ConclusionsResidents and fellows want to engage in positive teaching interactions in the context of the clinical consult; however, multiple barriers influence both parties in the hospital environment. Many of these barriers are amenable to change. Interventions aimed at reducing barriers to teaching in the setting of consultation hold promise for improving teaching and learning on the wards. Discuss ideas arising from the article at discuss. C1 [Miloslavsky, Eli M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol,Dept Med, Boston, MA USA. [McSparron, Jakob I.; Richards, Jeremy B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Dept Med,Med Sch, Boston, MA 02215 USA. [Puig, Alberto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clinician Educ Serv,Dept Med, Boston, MA USA. [Sullivan, Amy M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Shapiro Inst Educ & Res, Sch Med, Boston, MA 02215 USA. RP Miloslavsky, EM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol, 55 Fruit St,Suite 2C, Boston, MA 02114 USA. EM emiloslavsky@mgh.harvard.edu FU Partners Center of Expertise in Medical Education Research Grant FX This research was supported by a Partners Center of Expertise in Medical Education Research Grant (2012). NR 30 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0308-0110 EI 1365-2923 J9 MED EDUC JI Med. Educ. PD JUL PY 2015 VL 49 IS 7 BP 717 EP 730 DI 10.1111/medu.12760 PG 14 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CK7CM UT WOS:000356388100011 PM 26077219 ER PT J AU Boehm, JS Golub, TR AF Boehm, Jesse S. Golub, Todd R. TI An ecosystem of cancer cell line factories to support a cancer dependency map SO NATURE REVIEWS GENETICS LA English DT Editorial Material ID DRUG-SENSITIVITY C1 [Boehm, Jesse S.; Golub, Todd R.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Boehm, JS (reprint author), Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA. EM boehm@broadinstitute.org OI Boehm, Jesse/0000-0002-6795-6336 FU Howard Hughes Medical Institute NR 5 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD JUL PY 2015 VL 16 IS 7 BP 373 EP 374 DI 10.1038/nrg3967 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA CK7WV UT WOS:000356447500001 PM 26077369 ER PT J AU Barrett, LF Simmons, WK AF Barrett, Lisa Feldman Simmons, W. Kyle TI Interoceptive predictions in the brain SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID MEDIAL PREFRONTAL CORTEX; ANTERIOR INSULAR CORTEX; OLD-WORLD MONKEY; INTRINSIC FUNCTIONAL CONNECTIVITY; LARGE-SCALE BRAIN; CORTICAL STRUCTURE; RESTING-STATE; MOTOR CORTEX; CINGULATE CORTEX; MACAQUE MONKEYS AB Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Barrett, Lisa Feldman] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Simmons, W. Kyle] Laureate Inst Brain Res, Tulsa, OK 74133 USA. [Simmons, W. Kyle] Univ Tulsa, Fac Community Med, Tulsa, OK 74104 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM l.barrett@neu.edu; wksimmons@laureateinstitute.org RI Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU US National Institute on Aging [R01AG030311]; US National Science Foundation grant [BCS-1052790]; US Army Research Institute for the Behavioural and Social Sciences [W5J9CQ-12-C-0049, W5J9CQ-11-C-0046]; US National Institute of Mental Health grant [K01MH096175-01]; US National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award; Oklahoma Tobacco Research Center FX The authors thank M.A. Garcia-Cabezas for helpful discussions and advice in preparing figure 1. They also thank K. Friston, H. Barbas, B. Finlay, H. Mayberg, J. Feinstein, S. Khalsa, J. Avery, M. Paulus, A. Satpute, L. Chanes, A. Touroutoglou and I. Kleckner for helpful discussions about the EPIC model and comments offered on the manuscript. In addition, they thank L. Chanes, A. Touroutoglou and J. Zhang for their assistance in summarizing the interoceptive system from the macaque tract-tracing literature. This work was supported by a US National Institute on Aging grant (R01AG030311), a US National Science Foundation grant (BCS-1052790) and contracts from the US Army Research Institute for the Behavioural and Social Sciences (contracts W5J9CQ-12-C-0049 and W5J9CQ-11-C-0046) to L.F.B., as well as a US National Institute of Mental Health grant (K01MH096175-01), a US National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award, and funding from the Oklahoma Tobacco Research Center to W.K.S. The views, opinions and findings contained in this article are those of the authors and should not be construed as an official position, policy or decision of the US National Institutes of Health or Department of the Army unless so designated by other documents. NR 149 TC 67 Z9 67 U1 10 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUL PY 2015 VL 16 IS 7 BP 419 EP 429 DI 10.1038/nrn3950 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CK9UV UT WOS:000356585900009 PM 26016744 ER PT J AU Janes, AC Pedrelli, P Whitton, AE Pechtel, P Douglas, S Martinson, MA Huz, I Fava, M Pizzagalli, DA Evins, AE AF Janes, Amy C. Pedrelli, Paola Whitton, Alexis E. Pechtel, Pia Douglas, Samuel Martinson, Max A. Huz, Ilana Fava, Maurizio Pizzagalli, Diego A. Evins, A. Eden TI Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID GENDER-DIFFERENCES; DOPAMINE NEURONS; HEDONIC CAPACITY; SEX-DIFFERENCES; NICOTINE; CESSATION; BUPROPION; ANHEDONIA; MODEL; MOOD AB Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that similar to 50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N = 198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD. C1 [Janes, Amy C.; Pizzagalli, Diego A.] Harvard Univ, McLean Hosp, Sch Med, McLean Imaging Ctr, Belmont, MA USA. [Janes, Amy C.; Pedrelli, Paola; Whitton, Alexis E.; Pechtel, Pia; Fava, Maurizio; Pizzagalli, Diego A.; Evins, A. Eden] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pedrelli, Paola; Martinson, Max A.; Huz, Ilana; Fava, Maurizio; Pizzagalli, Diego A.] Massachusetts Gen Hosp, Depress Clin Res Program, Boston, MA 02114 USA. [Whitton, Alexis E.; Pechtel, Pia; Douglas, Samuel; Pizzagalli, Diego A.] Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Belmont, MA USA. [Evins, A. Eden] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. RP Janes, AC (reprint author), McLean Hosp, Brain Imaging Ctr, Mail Stop 310,115 Mill St, Belmont, MA 02478 USA. EM ajanes@mclean.harvard.edu RI Janes, Amy/A-5322-2013; Whitton, Alexis/H-4098-2016 OI Janes, Amy/0000-0002-3749-5006; Whitton, Alexis/0000-0002-7944-2172 FU National Institute of Health [U01DA019378, K01DA029645, K24DA030443, R10MH68376, R21MH078979, K23AA020064, R01MH068376]; GlaxoSmithKline; Pfizer; Forum Pharmaceuticals; Otsuka America Pharmaceutical; Servier; Abbot Laboratories; Alkermes, Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen RD, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante; Methylation Sciences Inc; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem, Inc.; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates., Inc.; Pharmavite LLC; PharmoRx Therapeutics; Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Stanley Medical Research Institute (SMRI); Synthelabo; Wyeth-Ayerst Laboratories FX This work was supported by National Institute of Health Grants U01DA019378 (MF), K01DA029645 (AJ), K24DA030443 (AEE) R10MH68376 (DP), R21MH078979 (DP), K23AA020064 (PP), and R01MH068376. Dr Evins has received research support in the form of funding and/or study supplies from GlaxoSmithKline, Pfizer, and Forum Pharmaceuticals. Over the past 2 years, Dr Pizzagalli has received honoraria/consulting fees from Otsuka America Pharmaceutical, Pfizer, and Servier for activities unrelated to this project. Maurizio Fava, M.D., Research Support: Abbot Laboratories; Alkermes, Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara, LLC; Covance; Covidien; Eli Lilly and Company;EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante; Methylation Sciences Inc; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem, Inc.; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates., Inc.; Pharmavite LLC;PharmoRx Therapeutics; Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Stanley Medical Research Institute (SMRI); Synthelabo; Wyeth-Ayerst LaboratoriesAdvisory/Consulting: Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Cerecor; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuralstem, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite (R) LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; Psycho-Genics; Psylin Neurosciences, Inc.; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; ; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc. Speaking/Publishing: Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource, Corp.; Wyeth-Ayerst Laboratories. Equity Holdings: Compellis; PsyBrain, Inc. Royalty/patent, other income: Patent for Sequential Parallel Comparison Design (SPCD), which are licensed by MGH to Pharmaceutical Product Development, LLC (PPD); and patent application for a combination of Ketamine plus Scopolamine in Major Depressive Disorder (MDD). Copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolters Kluwer; World Scientific Publishing Co. Pte. Ltd. The remaining authors declare no conflict of interest. NR 49 TC 4 Z9 4 U1 3 U2 5 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 JUL PY 2015 VL 40 IS 8 BP 1940 EP 1946 DI 10.1038/npp.2015.43 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CK4IE UT WOS:000356186700014 PM 25662839 ER PT J AU Yu, DK Zheng, J Zhu, RL Wu, N Guan, A Cho, KS Chen, DF Luo, G AF Yu, Dekuang Zheng, Jin Zhu, Ruilin Wu, Nan Guan, Alex Cho, Kin-Sang Chen, Dong Feng Luo, Gang TI Computer-aided analyses of mouse retinal OCT images - an actual application report SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS LA English DT Article DE image segmentation; mouse study; optical coherence tomography; photoreceptor degeneration ID OPTICAL COHERENCE TOMOGRAPHY; SEGMENTATION; LAYERS AB PurposeThere is a need for automated retinal optical coherence tomography (OCT) image analysis tools for quantitative measurements in small animals. Some image processing techniques for retinal layer analysis have been developed, but reports about how useful those techniques are in actual animal studies are rare. This paper presents the use of a retinal layer detection method we developed in an actual mouse study that involves wild type and mutated mice carrying photoreceptor degeneration. MethodsSpectral domain OCT scanning was performed by four experimenters over 12months on 45 mouse eyes that were wild-type, deficient for ephrin-A2 and ephrin-A3, deficient for rhodopsin, or deficient for rhodopsin, ephrin-A2 and ephrin-A3. The thickness of photoreceptor complex between the outer plexiform layer and retinal pigment epithelium was measured on two sides of the optic disc as the biomarker of retinal degeneration. All the layer detection results were visually confirmed. ResultsOverall, 96% (8519 out of 9000) of the half-side images were successfully processed using our technique in a semi-automatic manner. There was no significant difference in success rate between mouse lines (p=0.91). Based on a human observer's rating of image quality for images successfully and unsuccessfully processed, the odds ratios for easily visible' images and not clear' images to be successfully processed is 62 and 4, respectively, against indistinguishable' images. Thickness of photoreceptor complex was significantly different across the quadrants compared (p<0.001). It was also found that the average thickness based on 4-point sparse sampling was not significantly different from the full analysis, while the range of differences between the two methods could be up to about 6m or 16% for individual eyes. Differences between mouse lines and progressive thickness reduction were revealed by both sampling measures. ConclusionsAlthough the thickness of the photoreceptor complex layer is not even, manual sparse sampling may be as sufficiently accurate as full analysis in some studies such as ours, where the error of sparse sampling was much smaller than the effect size of rhodopsin deficiency. It is also suggested that the image processing method can be useful in actual animal studies. Even for images poorly visible to human eyes the image processing method still has a good chance to extract the complex layer. C1 [Yu, Dekuang] Southern Med Univ, Guangzhou, Guangdong, Peoples R China. [Zheng, Jin; Zhu, Ruilin; Wu, Nan; Guan, Alex; Cho, Kin-Sang; Chen, Dong Feng; Luo, Gang] Harvard Univ, Schepens Eye Res Inst, Sch Med, Massachusetts Eye & Ear, Boston, MA 02163 USA. [Zheng, Jin] Beihang Univ, Beijing Key Lab Digital Media, Sch Comp Sci & Engn, Beijing 100191, Peoples R China. [Zhu, Ruilin] Peking Univ, Dept Ophthalmol, Hosp 1, Beijing 100871, Peoples R China. [Zhu, Ruilin] Minist Educ, Key Lab Vis Loss & Restorat, Beijing, Peoples R China. [Wu, Nan] Third Mil Med Univ, Southwest Eye Hosp, Dept Ophthalmol, Chongqing, Peoples R China. [Chen, Dong Feng] VA Boston Healthcare Syst, Boston, MA USA. RP Luo, G (reprint author), Harvard Univ, Schepens Eye Res Inst, Sch Med, Massachusetts Eye & Ear, Boston, MA 02163 USA. EM Gang_Luo@meei.harvard.edu FU NIH [R01 EY017641]; Department of Veterans Affairs [VA241-P-2285]; National Youth Natural Science Foundation of China [30901645]; National Science Foundation of China [61370124]; National Scholarship Foundation of China [201303070205] FX This work is supported in part by NIH grant R01 EY017641 to DFC, the Department of Veterans Affairs grant VA241-P-2285 to DFC, National Youth Natural Science Foundation of China (#30901645), National Science Foundation of China (#61370124), and National Scholarship Foundation of China (#201303070205). NR 14 TC 0 Z9 0 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0275-5408 EI 1475-1313 J9 OPHTHAL PHYSL OPT JI Ophthalmic Physiol. Opt. PD JUL PY 2015 VL 35 IS 4 BP 442 EP 449 DI 10.1111/opo.12213 PG 8 WC Ophthalmology SC Ophthalmology GA CL0JA UT WOS:000356627100010 PM 25959043 ER PT J AU Nair, A Gan, J Bush-Joseph, C Verma, N Tetreault, MW Saha, K Margulis, A Fogg, L Scanzello, CR AF Nair, A. Gan, J. Bush-Joseph, C. Verma, N. Tetreault, M. W. Saha, K. Margulis, A. Fogg, L. Scanzello, C. R. TI Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Osteoarthritis; Synovitis; Relative expression; Knee disability; KOOS ID GENE-EXPRESSION; CARTILAGE LOSS; OSTEOARTHRITIS; PAIN; INFLAMMATION; PROGRESSION; BIOMARKERS; FEATURES; SURGERY; INJURY AB Objective: In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA. Design: Synovial fluid (SF) and biopsies were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors. Results: 90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living (ADL) scores (95% CI [-8.071, -0.331], P = 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors. Conclusion: In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with ADL, independent of other factors including presence of radiographic knee OA. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Nair, A.; Gan, J.; Saha, K.] Rush Univ, Med Ctr, Div Rheumatol, Chicago, IL 60612 USA. [Bush-Joseph, C.; Verma, N.; Tetreault, M. W.] Rush Univ, Med Ctr, Dept Orthoped, Chicago, IL 60612 USA. [Margulis, A.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Fogg, L.] Rush Univ, Med Ctr, Dept Community Syst & Mental Hlth Nursing, Chicago, IL 60612 USA. [Scanzello, C. R.] Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Scanzello, C. R.] Univ Penn, Perelman Sch Med, Dept Orthoped, Philadelphia, PA 19104 USA. [Scanzello, C. R.] Philadelphia Vet Affairs Med Ctr, Dept Med, Rheumatol Sect, Philadelphia, PA USA. RP Scanzello, CR (reprint author), Univ Penn, Perelman Sch Med, Div Rheumatol, 3400 Spruce St,8th Floor Penn Tower, Philadelphia, PA 19104 USA. EM cscanz@upenn.edu OI Tetreault, Matthew/0000-0003-3584-9285 FU NIAMS NIH HHS [K08 AR057859, K08AR057859] NR 32 TC 3 Z9 3 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JUL PY 2015 VL 23 IS 7 BP 1158 EP 1164 DI 10.1016/j.joca.2015.02.016 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CK7WM UT WOS:000356446300017 PM 25724256 ER PT J AU Kobayashi, T Papaioannou, G Mirzamohammadi, F Kozhemyakina, E Zhang, M Blelloch, R Chong, MW AF Kobayashi, T. Papaioannou, G. Mirzamohammadi, F. Kozhemyakina, E. Zhang, M. Blelloch, R. Chong, M. W. TI Early postnatal ablation of the microRNA-processing enzyme, Drosha, causes chondrocyte death and impairs the structural integrity of the articular cartilage SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE microRNA; Drosha; Prg4; Chondrocyte; Osteoarthritis; Articular cartilage ID TRANSGENIC MICE; OSTEOARTHRITIS; EXPRESSION; MOUSE; DIFFERENTIATION; PATHWAYS; CELLS AB Objective: In growth plate chondrocytes, loss of Dicer, a microRNA (miRNA)-processing enzyme, causes defects in proliferation and differentiation, leading to a lethal skeletal dysplasia. However roles of miRNAs in articular chondrocytes have not been defined in vivo. To investigate the role of miRNAs in articular chondrocytes and to explore the possibility of generating a novel mouse osteoarthritis (OA) model caused by intrinsic cellular dysfunction, we ablated Drosha, another essential enzyme for miRNA biogenesis, exclusively in articular chondrocytes of postnatal mice. Design: First, to confirm that the essential role of miRNAs in skeletal development, we ablated the miRNA biogenesis pathway by deleting Drosha or DGCR8 in growth plate chondrocytes. Next, to investigate the role of miRNAs in articular cartilage, we deleted Drosha using Prg4-CreERT transgenic mice expressing a tamoxifen-activated Cre recombinase (CreERT) exclusively in articular chondrocytes. Tamoxifen was injected at postnatal days, 7, 14, 21, and 28 to ablate Drosha. Results: Deletion of Drosha or DGCR8 in growth plate chondrocytes caused a lethal skeletal defect similar to that of Dicer deletion, confirming the essential role of miRNAs in normal skeletogenesis. Early postnatal Drosha deletion in articular chondrocytes significantly increased cell death and decreased SafraninO staining. Mild OA-like changes, including surface erosion and cleft formation, were found in male mice at 6 months of age; however such changes in females were not observed even at 9 months of age. Conclusions: Early postnatal Drosha deficiency induces articular chondrocyte death and can cause a mild OA-like pathology. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Kobayashi, T.; Papaioannou, G.; Mirzamohammadi, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Kozhemyakina, E.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, M.] Boston Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Zhang, M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Blelloch, R.] Univ Calif San Francisco, Ctr Reprod Sci, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Chong, M. W.] St Vincents Inst Med Res, Genom & Immunol Lab, Fitzroy, Vic 3065, Australia. [Chong, M. W.] Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. RP Kobayashi, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM tkobayashi1@mgh.harvard.edu; GPAPAIOANNOU@mgh.harvard.edu; FMIRZAMOHAMMADI@mgh.harvard.edu; eKozhemyakina@dresourcesgroup.com; Minjie.Zhang@childrens.harvard.edu; blellochr@stemcell.ucsf.edu; mchong@svi.edu.au RI Chong, Mark/H-6684-2016; OI Kobayashi, Tatsuya/0000-0003-4264-5117; Chong, Mark/0000-0002-3701-7397 FU NIAMS NIH HHS [R01 AR056645, P30 AR066261, AR056645] NR 30 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JUL PY 2015 VL 23 IS 7 BP 1214 EP 1220 DI 10.1016/j.joca.2015.02.015 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CK7WM UT WOS:000356446300023 PM 25707934 ER PT J AU Jermoumi, M Korideck, H Bhagwat, M Zygmanski, P Makrigiogos, GM Berbeco, RI Cormack, RC Ngwa, W AF Jermoumi, M. Korideck, H. Bhagwat, M. Zygmanski, P. Makrigiogos, G. M. Berbeco, R. I. Cormack, R. C. Ngwa, W. TI Comprehensive quality assurance phantom for the small animal radiation research platform (SARRP) SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE SARRP; QA phantom; Micro-irradiator ID RADIOTHERAPY; CT; SYSTEM; CALIBRATION; VALIDATION; DOSIMETRY AB Purpose: To develop and test the suitability and performance of a comprehensive quality assurance (QA) phantom for the Small Animal Radiation Research Platform (SARRP). Methods and materials: A QA phantom was developed for carrying out daily, monthly and annual QA tasks including: imaging, dosimetry and treatment planning system (TPS) performance evaluation of the SARRP. The QA phantom consists of 15 (60 x 60 x 5 mm(3)) kV-energy tissue equivalent solid water slabs. The phantom can incorporate optically stimulated luminescence dosimeters (OSLD), Mosfet or film. One slab, with inserts and another slab with hole patterns are particularly designed for image QA. Results: Output constancy measurement results showed daily variations within 3%. Using the Mosfet in phantom as target, results showed that the difference between TPS calculations and measurements was within 5%. Annual QA results for the Percentage depth dose (PDD) curves, lateral beam profiles, beam flatness and beam profile symmetry were found consistent with results obtained at commissioning. PDD curves obtained using film and OSLDs showed good agreement. Image QA was performed monthly, with image-quality parameters assessed in terms of CBCT image geometric accuracy, CT number accuracy, image spatial resolution, noise and image uniformity. Conclusions: The results show that the developed QA phantom can be employed as a tool for comprehensive performance evaluation of the SARRP. The study provides a useful reference for development of a comprehensive quality assurance program for the SARRP and other similar small animal irradiators, with proposed tolerances and frequency of required tests. (C) 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Jermoumi, M.; Ngwa, W.] Univ Massachusetts, Dept Appl Phys, Med Phys Program, Lowell, MA USA. [Jermoumi, M.; Korideck, H.; Bhagwat, M.; Zygmanski, P.; Makrigiogos, G. M.; Berbeco, R. I.; Cormack, R. C.; Ngwa, W.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jermoumi, M.; Korideck, H.; Bhagwat, M.; Zygmanski, P.; Makrigiogos, G. M.; Berbeco, R. I.; Cormack, R. C.; Ngwa, W.] Harvard Univ, Sch Med, Boston, MA USA. RP Jermoumi, M (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM mohammed_jermoumi@dfci.harvard.edu FU NCI NIH HHS [K01 CA172478] NR 25 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD JUL PY 2015 VL 31 IS 5 BP 529 EP 535 DI 10.1016/j.ejmp.2015.04.010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK4WD UT WOS:000356223100014 PM 25964129 ER PT J AU Nisavic, M Shuster, JL Gitlin, D Worley, L Stern, TA AF Nisavic, Mladen Shuster, John L. Gitlin, David Worley, Linda Stern, Theodore A. TI Readings on Psychosomatic Medicine: Survey of Resources for Trainees SO PSYCHOSOMATICS LA English DT Review ID CONSULTATION-LIAISON PSYCHIATRY; INTENSIVE-CARE-UNIT; INTRAVENOUS HALOPERIDOL; MEDICALLY ILL; TASK-FORCE; DELIRIUM; DEPRESSION; GUIDELINES; MANAGEMENT; DIAGNOSIS AB Background: As systems care become more complex and comorbid medical and psychiatric illness becomes more evident, it is essential to prepare psychiatric trainees for practice in more integrated models of care. Objective: We sought to identify readings available for residency training in consultation-liaison C-L) psychiatry/psychosomatic medicine with the intent to help educators and trainees identify appropriate and essential learning resources within the field. Methods: We reviewed readings available to the residents (including commonly used textbooks in C-L psychiatry and C-L training programs' required reading lists') and identified areas of consensus regarding the topics germane to the care of patients with comorbid medical and psychiatric illness (namely depression, dementia, and delirium) and the education of trainees. Results: There was considerable variation in the references cited by well-regarded textbooks and by reading lists created for trainees in C-L psychiatry. In the 4 textbooks reviewed, there were 83 shared citations on delirium (including 10 citations that were common to all 4 textbooks and 17 citations shared by 3 textbooks.). Markedly less overlap was noted in the chapters on depression (only 2 references cited in all of the textbooks with relevant content) and dementia (only 7 shared references). Conclusion: Given the paucity of overlap of citations in commonly used textbooks., we recommend that practical topical reviews or textbook chapters be used as core (required) or recommended readings for residents on C-L psychiatry rotations, supplemented by a small number of studies or case series that illustrate key tea lung points on each essential topic. C1 [Nisavic, Mladen; Stern, Theodore A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Shuster, John L.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37235 USA. [Gitlin, David] Brigham & Womens Hosp, Psychiat, Boston, MA 02115 USA. [Worley, Linda] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Worley, Linda] Vanderbilt Univ, Sch Med, Dept Obstet & Gynecol, Nashville, TN 37212 USA. RP Nisavic, M (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM mnisavic@partners.org NR 56 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2015 VL 56 IS 4 BP 319 EP 328 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CL0IR UT WOS:000356626100001 PM 26002223 ER PT J AU Janssen, SJ ter Meulen, DP Nota, SPFT Hageman, MGJS Ring, D AF Janssen, Stein J. ter Meulen, Dirk P. Nota, Sjoerd P. F. T. Hageman, Michiel G. J. S. Ring, David TI Does Verbal and Nonverbal Communication of Pain Correlate With Disability? SO PSYCHOSOMATICS LA English DT Article ID QUALITY-OF-LIFE; LOW-BACK-PAIN; COPING STRATEGIES; HEALTH-STATUS; ITEM BANK; OUTCOMES; PROMIS; DEPRESSION; BEHAVIOR; PREDICTORS AB Background: Illness (symptoms and disability) consistently correlates more with coping strategies and symptoms of depression than with pathophysiology or impairment. Objective: This study tested the primary null hypothesis that there is no correlation between verbal and nonverbal communication of pain (pain behavior) and upper extremity specific disability in patients with hand and upper extremity illness. Methods: A total of 139 new and followed up adult patients completed the QuickDASH, an ordinal rating of pain, and 4 Patient-Reported Outcomes Measurement Information System (PROMIS) Computer Adaptive Testing instruments: (PROMIS pain behavior, (2) PROMIS pain interference (measuring the degree to which pain interferes with achieving ones physical goals), (3) PROIVIIS physical function., and (4) PROMIS depression. Results: Factors associated with a higher QuickDASH score in bivariate analysis included a higher PROMIS pain behavior score, not working, being separated/divorced or widowed, having sought treatment before, having other pain conditions, a higher PROMIS pain interference score, a higher PROMIS depression score, and lower education level. The final multivariable model of factors' associated with QuickDASH included PROMIS pain interference, having other pain conditions, and being separated/divorced or widowed, and it explained 64% of the variability. Conclusion: PROMIS pain behavior (verbal and nonverbal communication of pain) correlates with upper extremity disability, but PROMIS pain interference (the degree to which pain interferes with activity) is a more important,factor. Level of Evidence: Level IV cross-sectional study. C1 [Janssen, Stein J.; ter Meulen, Dirk P.; Nota, Sjoerd P. F. T.; Hageman, Michiel G. J. S.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu NR 27 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2015 VL 56 IS 4 BP 338 EP 344 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CL0IR UT WOS:000356626100003 PM 25627313 ER PT J AU Maher, TM Piper, A Song, YL Restrepo, MI Eves, ND AF Maher, Toby M. Piper, Amanda Song, Yuanlin Restrepo, Marcos I. Eves, Neil D. TI Year in review 2014: Interstitial lung disease, physiology, sleep and ventilation, acute respiratory distress syndrome, cystic fibrosis, bronchiectasis and rare lung disease SO RESPIROLOGY LA English DT Review DE acute respiratory distress syndrome; bronchiectasis; interstitial lung disease; lung function; obstructive sleep apnoea ID IDIOPATHIC PULMONARY-FIBROSIS; POSITIVE AIRWAY PRESSURE; THORACIC GAS-COMPRESSION; OBESITY HYPOVENTILATION SYNDROME; MESENTERIC FAT THICKNESS; NON-CF BRONCHIECTASIS; SERUM CYSTATIN-C; HEART-FAILURE; TRANSBRONCHIAL CRYOBIOPSY; NONINVASIVE VENTILATION C1 [Maher, Toby M.] Royal Brompton Hosp, Natl Inst Hlth Res, Resp Biomed Res Unit, London SW3 6LY, England. [Maher, Toby M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart Lung Inst, Ctr Leukocyte Biol, Fibrosis Res Grp, London SW7 2AZ, England. [Piper, Amanda] Royal Prince Alfred Hosp, Dept Resp & Sleep Med, Sydney, NSW, Australia. [Piper, Amanda] Univ Sydney, Woolcock Inst Med Res, Circadian Grp, Sydney, NSW 2006, Australia. [Song, Yuanlin] Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai 200433, Peoples R China. [Song, Yuanlin] Fudan Univ, Qingpu Branch, Shanghai 200433, Peoples R China. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Eves, Neil D.] Univ British Columbia, Sch Hlth & Exercise Sci, Fac Hlth & Social Dev, Ctr Heart Lung & Vasc Hlth, Kelowna, BC, Canada. RP Maher, TM (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart Lung Inst, Ctr Leukocyte Biol, Fibrosis Res Grp, Sir Alexander Fleming Bldg, London SW7 2AZ, England. EM t.maher@imperial.ac.uk FU National Heart, Lung, and Blood Institute [K23HL096054] FX M.I.R.'s time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health, nor the Department of Veteran Affairs. NR 117 TC 1 Z9 1 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD JUL PY 2015 VL 20 IS 5 BP 834 EP 845 DI 10.1111/resp.12532 PG 12 WC Respiratory System SC Respiratory System GA CK6XH UT WOS:000356371600023 PM 25824415 ER PT J AU Wilkinson, H AF Wilkinson, Harold TI ELECTRICAL MEDICINE SO SCIENTIFIC AMERICAN LA English DT Letter C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Wilkinson, H (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD JUL PY 2015 VL 313 IS 1 BP 6 EP 6 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL0KY UT WOS:000356632800006 ER PT J AU Pusztaszeri, MP Faquin, WC AF Pusztaszeri, Marc P. Faquin, William C. TI Update in salivary gland cytopathology: Recent molecular advances and diagnostic applications SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE Salivary gland; Fine-needle aspiration; PLAG1; MYB; CRTC1; ETV6 ID ADENOID CYSTIC CARCINOMA; FINE-NEEDLE-ASPIRATION; ANALOG SECRETORY CARCINOMA; CLEAR-CELL-CARCINOMA; IN-SITU HYBRIDIZATION; ETV6-NTRK3 GENE FUSION; MUCOEPIDERMOID CARCINOMA; PLEOMORPHIC ADENOMA; CRIBRIFORM ADENOCARCINOMA; WARTHINS TUMOR AB Salivary gland tumors (SGT) are notorious for their extraordinary diversity and for the morphological overlap that exists between many of these entities. Fine-needle aspiration biopsy (FNAB) has a well-established role in the evaluation of patients with a salivary gland lesion, helping to guide clinical management. However, salivary gland FNAB has several limitations and does not allow for a specific diagnosis in some cases. For these reasons, salivary gland FNAB is considered one of the most challenging areas in cytopathology. Over the last decade, new salivary gland entities have been recognized, enlarging SGT diversity and complexity even more. In addition, a subset of SGT, including common entities such as pleomorphic adenoma and uncommon new entities such as mammary analog secretory carcinoma, have been characterized cytogenetically by the presence of specific translocations. The molecular consequences of these translocations and their potential prognostic and therapeutic values are not yet well characterized. However, these translocations and their resulting fusion oncogenes and oncoproteins can be used as diagnostic clues in salivary gland FNAB material in order to overcome the limitations of cytomorphological evaluation alone. In this review, we focus on SGTs currently known to harbor translocations and fusion genes, including uncommon and recently recognized entities, and discuss their potential application to salivary gland FNAB. (C) 2015 Elsevier Inc. All rights reserved. C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, CH-1211 Geneva 14, Switzerland. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Pusztaszeri, MP (reprint author), Univ Hosp Geneva, Dept Pathol, 1 Rue Michel Servet, CH-1211 Geneva 14, Switzerland. EM Marc.Pusztaszeri@hcuge.ch NR 91 TC 5 Z9 5 U1 1 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 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD JUL PY 2015 VL 32 IS 4 BP 264 EP 274 DI 10.1053/j.semdp.2014.12.008 PG 11 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA CL0MB UT WOS:000356635700004 PM 25613003 ER PT J AU Mitchell, C Fredricks, D Agnew, K Hitti, J AF Mitchell, Caroline Fredricks, David Agnew, Kathy Hitti, Jane TI Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1 beta, Independent of Bacterial Vaginosis SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRETERM DELIVERY; GENITAL-TRACT; IN-VITRO; BIRTH; INFLAMMATION; INFECTION; WOMEN; COLONIZATION; FLUID AB Background The presence of hydrogen peroxide (H2O2)-producing lactobacilli in the vagina is associated with decreased rates of preterm birth and HIV acquisition. We hypothesize that this is due to immunomodulatory effects of these species. Methods Concentrations of interleukin (IL)-1 beta, IL-6, IL-8, secretory leukocyte protease inhibitor, and human beta-defensin 2 were quantified from vaginal swabs from 4 groups of women: women with and without bacterial vaginosis (BV) by Nugent score, further stratified by detection of H2O2-producing lactobacilli by semiquantitative culture. Ten quantitative polymerase chain reaction assays characterized the presence and quantity of select Lactobacillus and BV-associated species in each group. Levels of immune markers and bacteria were compared between the 4 groups using analysis of variance, Kruskal-Wallis, Mann-Whitney U, or chi(2) tests. Results Swabs from 110 women from 4 groups were included: 26 had a normal Nugent score (BV-), and no H2O2-producing lactobacilli detected (H2O2-); 47 were BV-, H2O2+; 27 BV+, H2O2-; and 10 BV+, H2O2+. The groups were similar in age, marital status, and reproductive history, but not ethnicity: the BV-, H2O2- group had more white participants (P = 0.02). In women with and without BV, IL-1 beta was lower in the H2O2+ groups. Human beta-defensin 2 was lowest in BV+ H2O2- women and highest in BV-, H2O2-. Secretory leukocyte protease inhibitor was lower in women with BV and did not differ by the presence of H2O2-producing lactobacilli. In regression analysis, higher quantities of Lactobacillus crispatus were associated with lower quantities of IL-1 beta. Detection and quantity of BV-associated species by quantitative polymerase chain reaction was significantly different between women with and without BV, but not between women with and without H2O2-producing lactobacilli within those groups. Conclusions The presence of H2O2-producing lactobacilli is associated with lower levels of some vaginal proinflammatory cytokines, even in women with BV. C1 [Mitchell, Caroline] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Fredricks, David] Univ Washington, Dept Obstet & Gynecol, Boston, MA USA. [Agnew, Kathy; Hitti, Jane] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Mitchell, C (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, 55 Fruit St, Boston, MA 02114 USA. EM caroline.mitchell@mgh.harvard.edu FU National Institutes of Health [HD-41682]; K08 from the National Institute of Allergy and Infectious Diseases [1K08AI087969]; Clinical Scientist Development Award from the Doris Duke Foundation FX The data in this study were derived from a study supported by National Institutes of Health Grant HD-41682 (J.H.). Dr Mitchell is supported by a K08 from the National Institute of Allergy and Infectious Diseases (1K08AI087969) and a Clinical Scientist Development Award from the Doris Duke Foundation. NR 38 TC 3 Z9 3 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL PY 2015 VL 42 IS 7 BP 358 EP 363 DI 10.1097/OLQ.0000000000000298 PG 6 WC Infectious Diseases SC Infectious Diseases GA CK8MH UT WOS:000356491700002 PM 26222747 ER PT J AU Zhong, WY Driscoll, SJ Tsai, TY Wang, SB Mao, HQ Cha, TD Wood, KB Li, GA AF Zhong, Weiye Driscoll, Sean J. Tsai, Tsung-Yuan Wang, Shaobai Mao, Haiqing Cha, Thomas D. Wood, Kirkham B. Li, Guoan TI In vivo dynamic changes of dimensions in the lumbar intervertebral foramen SO SPINE JOURNAL LA English DT Article DE Lumbar intervertebral foramen; Foramen area; Lumbar stenosis; Lumbar kinematics; Weight-lifting activity; In-vivo; Dual-fluoroscopy ID CONFIGURATION MR SYSTEM; IMAGE MATCHING METHOD; FORAMINAL STENOSIS; FLEXION-EXTENSION; KINEMATICS; SPINE; KNEE; COMPRESSION; VALIDATION; PATHOLOGY AB BACKGROUND CONTEXT: Previous studies have reported position-dependent changes of the lumbar intervertebral foramen (LIVF) dimensions at different static flexion-extension postures. However, the changes of the LIVF dimensions during dynamic body motion have not been reported. PURPOSE: The objective of this study was to investigate the in vivo dimensions of the LIVF during a dynamic weight-lifting activity. STUDY DESIGN/SETTING: This was a retrospective study. METHODS: Ten asymptomatic subjects were recruited for this study. Three-dimensional (3D) vertebral models of the lumbar segments from L2 to S1 were constructed for each subject using magnetic resonance images. The lumbar spine was then imaged using a dual fluoroscopic imaging system as the subject performed a dynamic weight-lifting activity from an upper body position of 45 degrees to a maximal extension position. The in vivo positions of the vertebrae along the motion path were reproduced using the 3D vertebral models and the fluoroscopic images. The minimal area, height, and width of each LIVF during the dynamic body motion were analyzed. RESULTS: The LIVF area and width monotonically decreased with lumbar extension at all levels except L5-S1 (p<05). On average, the LIVF area decreased by 7.4 +/- 6.7%, 10.8 +/- 7.7%, and 10.068.0% at the L2-L3, L3-L4, and L4-L5 levels, respectively, from the flexion to the upright standing position, and by 6.4 +/- 5.0%, 7.7 +/- 7.4%, and 5.1 +/- 5.1%, respectively, from the upright standing to the extension position. The LIVF height remained relatively constant at all segments during the dynamic activity. The foramen area, height, and width of the L5-S1 remained relatively constant throughout the activity. CONCLUSIONS: Human lumbar foramen dimensions show segment-dependent characteristics during the dynamic weight-lifting activity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhong, Weiye; Driscoll, Sean J.; Tsai, Tsung-Yuan; Wang, Shaobai; Mao, Haiqing; Cha, Thomas D.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Zhong, Weiye] Cent S Univ, Changsha 410011, Hunan, Peoples R China. [Zhong, Weiye] Xiangya Hosp 2, Dept Spinal Surg, Changsha 410011, Hunan, Peoples R China. [Mao, Haiqing] Soochow Univ, Affiliated Hosp 1, Dept Orthoped Surg, Suzhou 215006, Jiangsu, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org OI Tsai, Tsung-Yuan/0000-0003-1522-2987 FU National Institutes of Health [R21AR057989]; Synthes, Inc.; China Scholarship Council [201306370122] FX The authors would like to gratefully acknowledge the financial support from the National Institutes of Health (R21AR057989), Synthes, Inc., and China Scholarship Council (201306370122). NR 30 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD JUL 1 PY 2015 VL 15 IS 7 BP 1653 EP 1659 DI 10.1016/j.spinee.2015.03.015 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CK6BY UT WOS:000356314000021 PM 25797808 ER PT J AU Meara, JG Leather, AJM Hagander, L Alkire, BC Alonso, N Ameh, EA Bickler, SW Conteh, L Dare, AJ Davies, J Merisier, ED El-Halabi, S Farmer, PE Gawande, A Gullies, R Greenberg, SLM Grimes, CE Gruen, RL Ismail, EA Kamara, TB Lavy, C Ganbold, L Mkandawire, NC Raykar, NP Riesel, JN Rodas, E Rose, J Roy, N Shrime, MG Sullivan, R Verguet, S Watters, D Weiser, TG Wilson, IH Yamey, G Yip, W AF Meara, John G. Leather, Andrew J. M. Hagander, Lars Alkire, Blake C. Alonso, Nivaldo Ameh, Emmanuel A. Bickler, Stephen W. Conteh, Lesong Dare, Anna J. Davies, Justine Merisier, Eunice Derivois El-Halabi, Shenaaz Farmer, Paul E. Gawande, Atul Gullies, Rowan Greenberg, Sarah L. M. Grimes, Canis E. Gruen, Russell L. Ismail, Edna Adan Kamara, Thaim Buya Lavy, Chris Ganbold, Lundeg Mkandawire, Nyengo C. Raykar, Nakul P. Riesel, Johanna N. Rodas, Edgar Rose, John Roy, Nobhojit Shrime, Mark G. Sullivan, Richard Verguet, Stephane Watters, David Weiser, Thomas G. Wilson, Iain H. Yamey, Gavin Yip, Winnie TI Global Surgery 2030: Evidence and solutions for achieving health, welfare, and economic development SO SURGERY LA English DT Article C1 [Meara, John G.; Greenberg, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Meara, John G.; Hagander, Lars; Raykar, Nakul P.; Riesel, Johanna N.] Boston Childrens Hosp, Boston, MA USA. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Canis E.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Canis E.] Kings Coll London, London, England. [Hagander, Lars] Lund Univ, Clin Sci Lund, Dept Pediat, Pediat Surg & Global Pediat, Lund, Sweden. [Alkire, Blake C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Alonso, Nivaldo] Univ Sao Paulo, Dept Plast Surg, Sao Paulo, Brazil. [Ameh, Emmanuel A.] Natl Hosp, Dept Surg, Div Peadiat Surg, Abuja, Nigeria. [Bickler, Stephen W.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Rose, John] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Conteh, Lesong] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Davies, Justine] Lancet, London, England. [Merisier, Eunice Derivois] Dept Minist Hlth, Grassier, Ouest, Haiti. [El-Halabi, Shenaaz] Minist Hlth, Gaborone, Botswana. [Farmer, Paul E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Div Global Hlth Equ, Boston, MA 02115 USA. [Farmer, Paul E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Farmer, Paul E.] Partners Hlth, Boston, MA USA. [Gawande, Atul; Rose, John] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gawande, Atul] Ariadne Labs, Boston, MA USA. [Gullies, Rowan] Royal N Shore Hosp, St Leonards, NSW 2065, Australia. [Greenberg, Sarah L. M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gruen, Russell L.] Alfred Hosp, Melbourne, Vic, Australia. [Gruen, Russell L.] Monash Univ, Melbourne, Vic 3004, Australia. Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Ismail, Edna Adan] Edna Adan Univ Hosp, Hargeisa, Somalia. [Kamara, Thaim Buya] Connaught Hosp, Freetown, Sierra Leone. [Kamara, Thaim Buya] Univ Sierra Leone, Dept Surg, Freetown, Sierra Leone. [Lavy, Chris] Univ Oxford, Nuffield Dept Orthopaed, Rheumatol & Musculoskeletal Sci, Oxford, England. [Ganbold, Lundeg] Mongolian Natl Univ Med Sci, Ulaanbaatar, Mongol Peo Rep. [Mkandawire, Nyengo C.] Univ Malawi, Coll Med, Dept Surg, Blantyre, Malawi. [Mkandawire, Nyengo C.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia. [Raykar, Nakul P.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rodas, Edgar] Univ Cuenca, Cinterandes Fdn, Cuenca, Ecuador. [Rodas, Edgar] Univ Azuay, Cuenca, Ecuador. [Rodas, Edgar] Univ Azuay, Cuenca, Ecuador. [Roy, Nobhojit] BARC Hosp, Mumbai, Maharashtra, India. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Sullivan, Richard] Kings Coll London, Kings Ctr Global Hlth, Li Kings Hlth Partners Integrated Canc Ctr, Inst Canc Policy, London, England. [Verguet, Stephane] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Watters, David] Royal Australasian Coll Surg, East Melbourne, Vic, Australia. [Watters, David] Deakin Univ, Melbourne, Vic, Australia. [Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA USA. [Wilson, Iain H.] Royal Devon & Exeter NHS Fdn Trust, Dept Anaesthesia, Exeter, Devon, England. [Yamey, Gavin] Univ Calif San Francisco, Global Hlth Grp, Evidence Policy Initiat, San Francisco, CA USA. [Yip, Winnie] Univ Oxford, Blavatnik Sch Govt, Oxford, England. RP Meara, JG (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu OI Sullivan, Richard/0000-0002-6435-1825 NR 1 TC 19 Z9 19 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2015 VL 158 IS 1 BP 3 EP 6 DI 10.1016/j.surg.2015.04.011 PG 4 WC Surgery SC Surgery GA CK6ED UT WOS:000356320400002 PM 25987187 ER PT J AU Shrime, MG Daniels, KM Meara, JG AF Shrime, Mark G. Daniels, Kimberly M. Meara, John G. TI Half a billion surgical cases: Aligning surgical delivery with best-performing health systems SO SURGERY LA English DT Article ID CLEFT-LIP; SURGERY; BURDEN; PALATE; CARE AB Background. Surgical delivery varies 200-fold across countries. No direct correlation exists, however, between surgical delivery and health outcomes, making it difficult to pinpoint a goal for surgical scale-up. This report determines the amount of surgery that would be delivered worldwide if the world aligned itself with countries providing the best health outcomes. Methods. Annual rates of surgical delivery have been published previously for 129 countries. Five health outcomes were plotted against reported surgical delivery. Univariate and multivariate polynomial regression curves were fit, and the optimal point on each regression curve was determined by solving for first-order conditions. The country closest to the optimum for each health outcome was taken as representative of the best-performing health system. Monetary inputs to and surgical procedures provided by these systems were scaled to the global population. Results. For 3 of the 5 health outcomes, optima could be found. Globally, 315 million procedures currently are provided annually. If global delivery mirrored the 3 best-performing countries, between 360 million and 460 million cases would be provided annually. With population growth, this will increase to approximately half a billion cases by 2030. Health systems delivering these outcomes spend approximately 10% of their GDP on health. Conclusion. This is the first study to provide empirical evidence for the surgical output that an ideal health system would provide. Our results project ideal delivery worldwide of approximately 550 million annual surgical cases by 2030. C1 [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.; Meara, John G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA USA. [Daniels, Kimberly M.; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. RP Shrime, MG (reprint author), Harvard Interfac Initiat Hlth Policy, 14 Story St,4th Floor, Cambridge, MA 02138 USA. EM shrime@mail.harvard.edu FU National Institutes of Health/National Cancer Institute [R25CA92203] FX M.G.S. received partial funding from National Institutes of Health/National Cancer Institute R25CA92203. NR 20 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2015 VL 158 IS 1 BP 27 EP 32 DI 10.1016/j.surg.2015.03.025 PG 6 WC Surgery SC Surgery GA CK6ED UT WOS:000356320400005 PM 25934078 ER PT J AU Lainas, P Camerlo, A Conrad, C Shivathirthan, N Fuks, D Gayet, B AF Lainas, Panagiotis Camerlo, Antoine Conrad, Claudius Shivathirthan, Nayruthia Fuks, David Gayet, Brice TI Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: Is it feasible and reasonable? SO SURGERY LA English DT Article ID LONG-TERM OUTCOMES; HEPATOCELLULAR-CARCINOMA; HEPATIC RESECTION; MATCHED ANALYSIS; METAANALYSIS; INVASION; INVOLVEMENT; APPRAISAL; BENEFITS AB Background. The impact of diaphragmatic invasion in patients with colorectal liver metastases (CRLMs) remains poorly evaluated. We aimed to evaluate feasibility and safety of laparoscopic right hepatectomy (LRH) with or without diaphragmatic resection for CRLM. Methods. From 2002 to 2012, 52 patients underwent LRH for CRLM. Of them, 7 patients had combined laparoscopic partial diaphragmatic resection ("diaphragm" group). Data were retrospectively collected and short and long-term outcomes analyzed. Results. Operative time was lower in the control group (272 vs 345 min, P = .06). Six patients required conversion to open surgery. Blood loss and transfusion rate were similar. Portal triad clamping was used more frequently in the "diaphragm" group (42.8% vs 6.6%, P = .02). Maximum tumor size was greater in the "diaphragm" group (74.5 vs 37.1 mm, P = .002). Resection margin was negative in all cases. Mortality was nil and general morbidity similar in the 2 groups. Specific liver-related complications occurred in 2 patients in the "diaphragm" group and 17 in the control group (P = .69). Mean hospital stay was similar (P = 56). Twenty-two (42.3%) patients experienced recurrence. One-, 3-, and 5-year overall survival after surgery in "diaphragm" and control groups were 69%, 34%, 34%, and 97%, 83%, 59%, respectively (P = .103). One- and 3-year disease-free survival after surgery in "diaphragm" and control groups were 57%, 47% and 75%, 54%, respectively (P = .310). Conclusion. LRH with en-bloc diaphragmatic resection could be reasonably performed for selected patients in expert centers. Technical difficulties related to diaphragmatic invasion must be circumvented. Further experience must be gained to confirm our results. C1 [Lainas, Panagiotis; Camerlo, Antoine; Conrad, Claudius; Shivathirthan, Nayruthia; Fuks, David; Gayet, Brice] Univ Paris 05, Inst Mutualiste Montsouris, Dept Digest Pathol, F-75014 Paris, France. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gayet, B (reprint author), Univ Paris 05, Inst Mutualiste Montsouris, Dept Digest Dis, 42 Blvd Jourdan, F-75014 Paris, France. EM brice.gayet@imm.fr NR 32 TC 5 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2015 VL 158 IS 1 BP 128 EP 134 DI 10.1016/j.surg.2015.02.003 PG 7 WC Surgery SC Surgery GA CK6ED UT WOS:000356320400018 PM 25799466 ER PT J AU Dzik, W Kyeyune, D Otekat, G Natukunda, B Hume, H Kasirye, PG Ddungu, H Kajja, I Dhabangi, A Mugyenyi, GR Seguin, C Barnes, L Delaney, M AF Dzik, Walter Sunny Kyeyune, Dorothy Otekat, Grace Natukunda, Bernard Hume, Heather Kasirye, Phillip G. Ddungu, Henry Kajja, Isaac Dhabangi, Aggrey Mugyenyi, Godfrey R. Seguin, Claire Barnes, Linda Delaney, Meghan TI Transfusion Medicine in Sub-Saharan Africa: Conference Summary SO TRANSFUSION MEDICINE REVIEWS LA English DT Review DE Transfusion medicine; Sub-Saharan Africa; Conference proceedings ID SICKLE-CELL-DISEASE; PLATELET-TRANSFUSION; DEVELOPING-COUNTRIES; BLOOD-TRANSFUSION; CLINICAL-TRIAL; EXPERT PANEL; HEMORRHAGE; UGANDA; MULTICENTER; PREVENTION AB In November 2014, a 3-day conference devoted to transfusion medicine in sub-Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in Uganda provided a broad overview of issues pertinent to transfusion medicine in Africa. The conference consisted of lectures, demonstrations, and discussions followed by 5 small group workshops held at the Uganda Blood Transfusion Service Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral Hospital. Highlighted topics included the challenges posed by increasing clinical demands for blood, the need for better patient identification at the time of transfusion, inadequate application of the antiglobulin reagent during pretransfusion testing, concern regarding proper recognition and evaluation of transfusion reactions, the expanded role for nurse leadership as a means to improve patient outcomes, and the need for an epidemiologic map of blood usage in Africa. Specialty areas of focus included the potential for broader application of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African-specific guidelines for transfusion support of cancer patients, the challenges of transfusion support in trauma, and the importance of African-centered clinical research in pediatric and obstetric transfusion medicine. The course concluded by summarizing the benefits derived from an organized quality program that extended from the donor to the recipient As an educational tool, the slide-audio presentation of the lectures will be made freely available at the International Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dzik, Walter Sunny; Seguin, Claire] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kyeyune, Dorothy; Otekat, Grace] Uganda Blood Transfus Serv, Kampala, Uganda. [Hume, Heather; Kasirye, Phillip G.; Ddungu, Henry; Kajja, Isaac; Dhabangi, Aggrey] Makerere Univ, Coll Hlth Sci, Kampala, Uganda. [Natukunda, Bernard; Mugyenyi, Godfrey R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Barnes, Linda; Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA. RP Dzik, W (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Kasirye, Phillip/0000-0001-6620-483X FU International Society of Blood Transfusion; American Association of Blood Banks; Puget Sound Blood Center; Fred Hutchinson Cancer Institute; Massachusetts General Hospital; NHLBI grant [1R21HL10918-01A1] FX The authors gratefully acknowledge Mr Jason Barrett of the Fred Hutchinson-Uganda Cancer Institute Alliance for his outstanding contribution as project manager of the conference. Financial support was provided by grants from the International Society of Blood Transfusion, the American Association of Blood Banks, the Puget Sound Blood Center, the Fred Hutchinson Cancer Institute, and the Massachusetts General Hospital. Additional support was provided in part by NHLBI grant 1R21HL10918-01A1. NR 37 TC 2 Z9 2 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 0887-7963 EI 1532-9496 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2015 VL 29 IS 3 BP 195 EP 204 DI 10.1016/j.tmrv.2015.02.003 PG 10 WC Hematology SC Hematology GA CK6EU UT WOS:000356322100005 PM 25752939 ER PT J AU Dilwali, S Kao, SY Fujita, T Landegger, LD Stankovic, KM AF Dilwali, Sonam Kao, Shyan-Yuan Fujita, Takeshi Landegger, Lukas D. Stankovic, Konstantina M. TI Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas SO TRANSLATIONAL RESEARCH LA English DT Article ID KAPPA-B ACTIVATION; SODIUM-SALICYLATE; ASPIRIN; APOPTOSIS; GROWTH; CANCER; CELLS; INHIBITION; MECHANISMS; MESALAZINE AB Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle. Significant clinical need exists for pharmacotherapies against VSs. Motivated by previous findings that immunohistochemical expression of cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was found to be aberrantly expressed in human VS and primary human VS cells in comparison with control human nerve specimens and primary Schwann cells (SCs), respectively. Furthermore, levels of prostaglandin E2, the downstream enzymatic product of COX-2, were correlated with primary VS culture proliferation rate. Because COX-2 inhibiting salicylates such as aspirin are well tolerated and frequently clinically used, we assessed their repurposing for VS. Changes in proliferation, cell death, and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate, or 5-aminosalicylic acid. These drugs neither increased VS cell death nor affected healthy SCs. The cytostatic effect of aspirin in vitro was in concurrence with our previous clinical finding that patients with VS taking aspirin demonstrate reduced tumor growth. Overall, this work suggests that COX-2 is a key modulator in VS cell proliferation and survival and highlights salicylates as promising pharmacotherapies against VS. C1 [Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA. Harvard MIT Program Speech & Hearing Biosci & Tec, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu OI Landegger, Lukas D./0000-0002-9660-2625 FU National Institute on Deafness and Other Communication Disorders [T32 DC00038, K08DC010419]; Bertarelli Foundation; Department of Defense Grant [W81XWH-14-1-0091] FX This study was supported by the National Institute on Deafness and Other Communication Disorders Grants T32 DC00038 (S.D., K.M.S.), K08DC010419 (K.M.S.), the Bertarelli Foundation (K.M.S.) and the Department of Defense Grant W81XWH-14-1-0091 (K.M.S.). NR 38 TC 3 Z9 3 U1 0 U2 4 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 JUL PY 2015 VL 166 IS 1 BP 1 EP 11 DI 10.1016/j.trsl.2014.12.007 PG 11 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA CK6DC UT WOS:000356317700001 PM 25616959 ER PT J AU Beckers, CML Knezevic, N Valent, ET Tauseef, M Krishnan, R Rajendran, K Hardin, CC Aman, J van Bezu, J Sweetnam, P van Hinsbergh, VWM Mehta, D Amerongen, GPV AF Beckers, Cora M. L. Knezevic, Nebojsa Valent, Erik T. Tauseef, Mohammad Krishnan, Ramaswamy Rajendran, Kavitha Hardin, C. Corey Aman, Jurjan van Bezu, Jan Sweetnam, Paul van Hinsbergh, Victor W. M. Mehta, Dolly Amerongen, Geerten P. van Nieuw TI ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension SO VASCULAR PHARMACOLOGY LA English DT Article DE Contraction; HUVEC; Endothelial; Permeability; Rho kinase ID CELL-CELL CONTACTS; VE-CADHERIN; RHO-KINASE; ACTOMYOSIN CONTRACTILITY; BARRIER FUNCTION; PERMEABILITY; ACTIVATION; INHIBITION; THROMBIN; GTPASES AB Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROM is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response. (C) 2015 Elsevier Inc. All rights reserved. C1 [Beckers, Cora M. L.; Valent, Erik T.; Aman, Jurjan; van Bezu, Jan; van Hinsbergh, Victor W. M.; Amerongen, Geerten P. van Nieuw] Vrije Univ Amsterdam, Med Ctr, Inst Cardiovasc Res, Dept Physiol, NL-1081 BT Amsterdam, Netherlands. [Knezevic, Nebojsa; Tauseef, Mohammad; Mehta, Dolly; Amerongen, Geerten P. van Nieuw] Univ Illinois, Dept Pharmacol, Coll Med, Ctr Lung & Vasc Biol, Chicago, IL 60612 USA. [Krishnan, Ramaswamy; Rajendran, Kavitha] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Hardin, C. Corey] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Sweetnam, Paul] Surface Logix, Cambridge, MA 02138 USA. RP Amerongen, GPV (reprint author), Vrije Univ Amsterdam, Med Ctr, Inst Cardiovasc Res, Dept Physiol, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM nieuwamerongen@vumc.nl FU Netherlands Heart Foundation (NHF) (The Hague) [2003T032, 2011T072]; Parker B. Francis Foundation; National Institute of Health [HL71784]; National Institutes of Health (NIH) [1K25HL111212] FX GPvNA was supported by the Netherlands Heart Foundation (NHF) (The Hague, grants 2003T032 and 2011T072), RK in part by the Parker B. Francis Foundation, DM by National Institute of Health (HL71784) and CCH in part by the National Institutes of Health (NIH, 1K25HL111212). NR 53 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1537-1891 EI 1879-3649 J9 VASC PHARMACOL JI Vasc. Pharmacol. PD JUL PY 2015 VL 70 BP 45 EP 54 DI 10.1016/j.vph.2015.03.017 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CK9ND UT WOS:000356565900006 PM 25869521 ER PT J AU Stein, TD Montenigro, PH Alvarez, VE Xia, WM Crary, JF Tripodis, Y Daneshvar, DH Mez, J Solomon, T Meng, GY Kubilus, CA Cormier, KA Meng, S Babcock, K Kiernan, P Murphy, L Nowinski, CJ Martin, B Dixon, D Stern, RA Cantu, RC Kowall, NW McKee, AC AF Stein, Thor D. Montenigro, Philip H. Alvarez, Victor E. Xia, Weiming Crary, John F. Tripodis, Yorghos Daneshvar, Daniel H. Mez, Jesse Solomon, Todd Meng, Gaoyuan Kubilus, Caroline A. Cormier, Kerry A. Meng, Steven Babcock, Katharine Kiernan, Patrick Murphy, Lauren Nowinski, Christopher J. Martin, Brett Dixon, Diane Stern, Robert A. Cantu, Robert C. Kowall, Neil W. McKee, Ann C. TI Beta-amyloid deposition in chronic traumatic encephalopathy SO ACTA NEUROPATHOLOGICA LA English DT Article DE Chronic traumatic encephalopathy; Alzheimer's disease; Beta-amyloid; Neurodegenerative disorders; Dementia; Tau ID SEVERE BRAIN-INJURY; ALZHEIMERS-DISEASE; HEAD-INJURY; PROTEIN DEPOSITION; DIFFUSE PLAQUES; PATHOLOGY; APOE; RISK; TAU; AGE AB Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (A beta) levels, the extent of A beta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that A beta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that A beta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, A beta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with A beta plaques and those without. A beta deposition was significantly associated with the presence of the APOE epsilon 4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both A beta plaques and total levels of A beta 1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that A beta deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that A beta is associated with both pathological and clinical progression of CTE independent of age. C1 [Stein, Thor D.; Meng, Gaoyuan; Kowall, Neil W.; McKee, Ann C.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Stein, Thor D.; Xia, Weiming; McKee, Ann C.] Dept Vet Affairs Med Ctr, Bedford, MA 01730 USA. [Stein, Thor D.; Montenigro, Philip H.; Alvarez, Victor E.; Daneshvar, Daniel H.; Mez, Jesse; Solomon, Todd; Kubilus, Caroline A.; Cormier, Kerry A.; Meng, Steven; Babcock, Katharine; Kiernan, Patrick; Murphy, Lauren; Nowinski, Christopher J.; Martin, Brett; Dixon, Diane; Stern, Robert A.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Stein, Thor D.; McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Montenigro, Philip H.; Stern, Robert A.; Cantu, Robert C.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Alvarez, Victor E.; Daneshvar, Daniel H.; Mez, Jesse; Solomon, Todd; Kubilus, Caroline A.; Cormier, Kerry A.; Kiernan, Patrick; Murphy, Lauren; Stern, Robert A.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Crary, John F.] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA. [Crary, John F.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Crary, John F.] Icahn Sch Med Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA. [Tripodis, Yorghos] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Tripodis, Yorghos; Martin, Brett; Dixon, Diane] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Nowinski, Christopher J.; Cantu, Robert C.] Sports Legacy Inst, Waltham, MA 02451 USA. [Stern, Robert A.; Cantu, Robert C.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA 01742 USA. RP Stein, TD (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM tdstein@bu.edu RI Kowall, Neil/G-6364-2012; xia, weiming/E-5465-2016; OI Kowall, Neil/0000-0002-6624-0213; xia, weiming/0000-0002-7463-3295; Stein, Thor/0000-0001-6954-4477; Daneshvar, Daniel/0000-0003-3691-9513; Stern, Robert/0000-0002-5008-077X; Tripodis, Yorghos/0000-0003-2190-7608; Montenigro, Philip/0000-0003-4442-9207 FU Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award; Alzheimer's Association [NIRG-305779]; Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering [U01NS086659-01]; National Institute of Aging Boston University AD Center [P30AG13846, 0572063345-5]; Department of Defense Peer Reviewed Alzheimer's Research Program (DoD-PRARP) [13267017]; Sports Legacy Institute FX We gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA) as well as all the individuals whose participation and contributions made this work possible. This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award; Alzheimer's Association (NIRG-305779); Veterans Affairs Biorepository (CSP 501); Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C); National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering (U01NS086659-01); National Institute of Aging Boston University AD Center (P30AG13846; supplement 0572063345-5); Department of Defense Peer Reviewed Alzheimer's Research Program (DoD-PRARP #13267017); Sports Legacy Institute. This work was also supported by unrestricted gifts from the Andlinger Foundation and WWE. NR 51 TC 32 Z9 32 U1 5 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUL PY 2015 VL 130 IS 1 BP 21 EP 34 DI 10.1007/s00401-015-1435-y PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CK5EQ UT WOS:000356245500002 PM 25943889 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, A. N. TI Editorial: diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases - author's reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2015 VL 42 IS 1 BP 120 EP 120 DI 10.1111/apt.13241 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA CK1EV UT WOS:000355950300014 PM 26040521 ER PT J AU Almli, LM Stevens, JS Smith, AK Kilaru, V Meng, Q Flory, J Abu-Amara, D Hammamieh, R Yang, RT Mercer, KB Binder, EB Bradley, B Hamilton, S Jett, M Yehuda, R Marmar, CR Ressler, KJ AF Almli, Lynn M. Stevens, Jennifer S. Smith, Alicia K. Kilaru, Varun Meng, Qian Flory, Janine Abu-Amara, Duna Hammamieh, Rasha Yang, Ruoting Mercer, Kristina B. Binder, Elizabeth B. Bradley, Bekh Hamilton, Steven Jett, Marti Yehuda, Rachel Marmar, Charles R. Ressler, Kerry J. TI A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE GWAS; PTSD; fMRI; meQTL; epigenetic ID POSTTRAUMATIC-STRESS-DISORDER; DNA METHYLATION; ASSOCIATION; SYMPTOMS; AMYGDALA; POLYMORPHISM; POPULATION; EXPRESSION; INVENTORY; RECEPTOR AB Genetic factors appear to be highly relevant to predicting differential risk for the development of post-traumatic stress disorder (PTSD). In a discovery sample, we conducted a genome-wide association study (GWAS) for PTSD using a small military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N=147) that was designed as a case-controlled sample of highly exposed, recently returning veterans with and without combat-related PTSD. A genome-wide significant single nucleotide polymorphism (SNP), rs717947, at chromosome 4p15 (N=147, =31.34, P=1.28x10(-8)) was found to associate with the gold-standard diagnostic measure for PTSD (the Clinician Administered PTSD Scale). We conducted replication and follow-up studies in an external sample, a larger urban community cohort (Grady Trauma Project, GTP, N=2006), to determine the robustness and putative functionality of this risk variant. In the GTP replication sample, SNP rs717947 associated with PTSD diagnosis in females (N=2006, P=0.005), but not males. SNP rs717947 was also found to be a methylation quantitative trait locus (meQTL) in the GTP replication sample (N=157, P=0.002). Further, the risk allele of rs717947 was associated with decreased medial and dorsolateral cortical activation to fearful faces (N=53, P<0.05) in the GTP replication sample. These data identify a genome-wide significant polymorphism conferring risk for PTSD, which was associated with differential epigenetic regulation and with differential cortical responses to fear in a replication sample. These results may provide new insight into understanding genetic and epigenetic regulation of PTSD and intermediate phenotypes that contribute to this disorder. (c) 2015 Wiley Periodicals, Inc. C1 [Almli, Lynn M.; Stevens, Jennifer S.; Smith, Alicia K.; Kilaru, Varun; Mercer, Kristina B.; Binder, Elizabeth B.; Bradley, Bekh; Ressler, Kerry J.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Meng, Qian] Univ Med Ctr, Dept Psychiat, New York, NY USA. [Flory, Janine; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY USA. [Flory, Janine; Yehuda, Rachel] Traumat Stress Studies Div, New York, NY USA. [Abu-Amara, Duna; Marmar, Charles R.] NYU, Dept Psychiat, Steven & Alexandra Cohen Vet Ctr Posttraumat Stre, New York, NY 10016 USA. [Hammamieh, Rasha; Jett, Marti] US Army Ctr Environm Hlth Res, Integrat Syst Biol, Ft Detrick, MD USA. [Yang, Ruoting] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA. [Binder, Elizabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany. [Bradley, Bekh] Dept Vet Affairs Med Ctr, Mental Hlth Serv Line, Atlanta, GA USA. [Hamilton, Steven] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Ressler, Kerry J.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Ressler, KJ (reprint author), Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. EM kressle@emory.edu FU National Institutes of Mental Health [MH071537, MH096764]; Department of Defense [W81XWH-09-2-0044, W911NF-09-1-0298]; Emory and Grady Memorial Hospital General Clinical Research Center; NIH National Centers for Research Resources [M01RR00039]; Howard Hughes Medical Institute; Steven and Alexandra Cohen Foundation; National Center for Advancing Translational Sciences [UL1TR000067] FX Grant sponsor: National Institutes of Mental Health; Grant numbers: MH071537, MH096764; Grant sponsor: Department of Defense; Grant numbers: W81XWH-09-2-0044, W911NF-09-1-0298; Grant sponsor: Emory and Grady Memorial Hospital General Clinical Research Center; Grant sponsor: NIH National Centers for Research Resources; Grant number: M01RR00039; Grant sponsor: Howard Hughes Medical Institute; Grant sponsor: Steven and Alexandra Cohen Foundation; Grant sponsor: National Center for Advancing Translational Sciences; Grant number: #UL1TR000067. NR 43 TC 12 Z9 12 U1 3 U2 13 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 JUL PY 2015 VL 168 IS 5 BP 327 EP 336 DI 10.1002/ajmg.b.32315 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA CK2XW UT WOS:000356079700002 PM 25988933 ER PT J AU Admon, R Holsen, LM Aizley, H Remington, A Whitfield-Gabrieli, S Goldstein, JM Pizzagalli, DA AF Admon, Roee Holsen, Laura M. Aizley, Harlyn Remington, Anne Whitfield-Gabrieli, Susan Goldstein, Jill M. Pizzagalli, Diego A. TI Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Caudate; Depression; fMRI; Psychophysiologic Interaction (PPI); Reward; Stress ID INDUCED DOPAMINE RELEASE; POSITRON-EMISSION-TOMOGRAPHY; REWARD SYSTEM ACTIVITY; CHRONIC MILD STRESS; MAJOR DEPRESSION; PSYCHOSOCIAL STRESS; NUCLEUS-ACCUMBENS; HPA-AXIS; PSYCHOPHYSIOLOGICAL INTERACTIONS; ANTIDEPRESSANT TREATMENT AB BACKGROUND: Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of major depressive disorder (MDD) that may persist after remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression. METHODS: A validated mild psychological stress task involving viewing of negative stimuli during functional magnetic resonance imaging was conducted in 33 remitted individuals with a history of recurrent major depressive disorder (rMDD) and 35 matched healthy control subjects. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens, and putamen. Psychophysiologic interaction analyses probed connectivity of regions with central structures of the neural stress circuitry, such as the amygdala and hippocampus. RESULTS: The task increased cortisol and anxiety levels, although to a greater extent in rMDD individuals than healthy control subjects. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, nucleus accumbens, and putamen activations and increased caudate-amygdala and caudate-hippocampus connectivity. CONCLUSIONS: The findings highlight striatal hypersensitivity in response to a mild psychological stress in rMDD, as manifested by hyperactivation and hyperconnectivity with the amygdala and hippocampus. Striatal hypersensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD. C1 [Admon, Roee; Pizzagalli, Diego A.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02478 USA. [Pizzagalli, Diego A.] McLean Hosp, McLean Imaging Ctr, Belmont, MA 02478 USA. [Admon, Roee; Holsen, Laura M.; Goldstein, Jill M.; Pizzagalli, Diego A.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Holsen, Laura M.; Aizley, Harlyn; Remington, Anne; Goldstein, Jill M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Holsen, Laura M.; Aizley, Harlyn; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Whitfield-Gabrieli, Susan; Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. MIT, Charlestown, MA USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Pizzagalli, DA (reprint author), McLean Hosp, Ctr Depress Anxiety & Stress Res, Room 233C,115 Mill St, Belmont, MA 02478 USA. EM dap@mclean.harvard.edu FU National Institutes of Health Office for Research on Women's Health and Mental Health [P50 MH082679]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center [UL1 RR025758]; National Institute of Mental Health [K01 MH091222, R01 MH068376, R01 MH095809]; Adam Corneel Young Investigator Award; Brain & Behavior Research Foundation Young Investigator Award; Advanced Neuro Technology North America; AstraZeneca; Pfizer FX This work was supported by the National Institutes of Health Office for Research on Women's Health and Mental Health Grant No. P50 MH082679 (JMG); Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center Grant No. UL1 RR025758; National Institute of Mental Health Grant No. K01 MH091222 (LMH); National Institute of Mental Health Grant Nos. R01 MH068376 and R01 MH095809 (DAP); and The Adam Corneel Young Investigator Award (McLean Hospital) and a Brain & Behavior Research Foundation Young Investigator Award (RA).; Over the past 3 years, DAP has received honoraria or consulting fees from Advanced Neuro Technology North America, AstraZeneca, Pfizer, and Servier for activities unrelated to this project. All other authors report no biomedical financial interests or potential conflicts of interest. NR 88 TC 12 Z9 12 U1 5 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2015 VL 78 IS 1 BP 67 EP 76 DI 10.1016/j.biopsych.2014.09.019 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CK0WA UT WOS:000355924800012 PM 25483401 ER PT J AU Rose, BS Jiang, W Punglia, RS AF Rose, Brent S. Jiang, Wei Punglia, Rinaa S. TI Effect of lymph node metastasis size on breast cancer-specific and overall survival in women with node-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Lymph node metastasis size; Breast cancer; Breast cancer-specific survival; SEER ID EXTRACAPSULAR EXTENSION; AXILLARY NODES; RECURRENCE; MACROMETASTASES; RADIOTHERAPY; INVOLVEMENT; MASTECTOMY; RISK AB We investigated whether increasing size of lymph nodes (LN) metastases is associated with lower breast cancer-specific survival (BCSS) and overall survival (OS) independent of the number of positive LNs. Using Surveillance, Epidemiology, and End Results registry data, we identified 8791 women diagnosed between 1990 and 2003 with node-positive, non-metastatic invasive breast cancer treated with surgery and axillary LN dissection. Size of the largest involved LN metastasis was categorized as a parts per thousand currency sign2 mm, > 2 mm to < 2 cm, and a parts per thousand yen2 cm. BCSS and OS were estimated using the Kaplan-Meier method and compared using log-rank statistics. Adjusted hazard ratios (HR) were calculated using Cox proportional hazards models. Median follow-up was 109 months. Largest LN size was a parts per thousand currency sign2 mm, > 2 mm to < 2 cm, and a parts per thousand yen2 cm in 2219 (25.2 %), 5047 (57.4 %), and 1525 (17.3 %) women, respectively. The 10-year BCSS for women with LNs a parts per thousand currency sign2 mm, > 2 mm to < 2 cm, and a parts per thousand yen2 cm was 82.9, 75.5, 64.8 %, respectively (p < 0.001). On multivariable analysis, large (a parts per thousand yen2 cm) LN size was significantly associated with worsened BCSS (HR: 1.169; p = 0.026) and OS (HR: 1.169; p = 0.006) in addition to age, race, grade, PR status, adjuvant radiation, T-stage, and number of positive LNs. Large (a parts per thousand yen2 cm) LNs metastases were associated with lower BCSS and OS after controlling for other known prognostic factors including number of positive LNs. LN size could be useful to risk-stratify patients for adjuvant therapy if these results are validated in future prospective studies. C1 [Rose, Brent S.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Jiang, Wei] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Punglia, Rinaa S.] Brigham & Womens Hospital, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Punglia, Rinaa S.] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02115 USA. RP Punglia, RS (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, 450 Brookline Ave, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu NR 23 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2015 VL 152 IS 1 BP 209 EP 216 DI 10.1007/s10549-015-3451-y PG 8 WC Oncology SC Oncology GA CK5FT UT WOS:000356248900022 PM 26041688 ER PT J AU Ogino, S Campbell, PT Nishihara, R Phipps, AI Beck, AH Sherman, ME Chan, AT Troester, MA Bass, AJ Fitzgerald, KC Irizarry, RA Kelsey, KT Nan, H Peters, U Poole, EM Qian, ZR Tamimi, RM Tchetgen, EJT Tworoger, SS Zhang, XH Giovannucci, EL van den Brandt, PA Rosner, BA Wang, ML Chatterjee, N Begg, CB AF Ogino, Shuji Campbell, Peter T. Nishihara, Reiko Phipps, Amanda I. Beck, Andrew H. Sherman, Mark E. Chan, Andrew T. Troester, Melissa A. Bass, Adam J. Fitzgerald, Kathryn C. Irizarry, Rafael A. Kelsey, Karl T. Nan, Hongmei Peters, Ulrike Poole, Elizabeth M. Qian, Zhi Rong Tamimi, Rulla M. Tchetgen, Eric J. Tchetgen Tworoger, Shelley S. Zhang, Xuehong Giovannucci, Edward L. van den Brandt, Piet A. Rosner, Bernard A. Wang, Molin Chatterjee, Nilanjan Begg, Colin B. TI Proceedings of the second international molecular pathological epidemiology (MPE) meeting SO CANCER CAUSES & CONTROL LA English DT Review DE Epidemiologic method; Molecular pathologic epidemiology; Personalized medicine; Systems biology; Translational epidemiology; Unique disease principle ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; LIFE-STYLE FACTORS; MICROSATELLITE INSTABILITY STATUS; DISEASE CLASSIFICATION DATA; EPITHELIAL OVARIAN-CANCER; UNIQUE TUMOR PRINCIPLE; BODY-MASS INDEX; BREAST-CANCER; FAMILY-HISTORY AB Disease classification system increasingly incorporates information on pathogenic mechanisms to predict clinical outcomes and response to therapy and intervention. Technological advancements to interrogate omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, interactomics, etc.) provide widely open opportunities in population-based research. Molecular pathological epidemiology (MPE) represents integrative science of molecular pathology and epidemiology. This unified paradigm requires multidisciplinary collaboration between pathology, epidemiology, biostatistics, bioinformatics, and computational biology. Integration of these fields enables better understanding of etiologic heterogeneity, disease continuum, causal inference, and the impact of environment, diet, lifestyle, host factors (including genetics and immunity), and their interactions on disease evolution. Hence, the Second International MPE Meeting was held in Boston in December 2014, with aims to: (1) develop conceptual and practical frameworks; (2) cultivate and expand opportunities; (3) address challenges; and (4) initiate the effort of specifying guidelines for MPE. The meeting mainly consisted of presentations of method developments and recent data in various malignant neoplasms and tumors (breast, prostate, ovarian and colorectal cancers, renal cell carcinoma, lymphoma, and leukemia), followed by open discussion sessions on challenges and future plans. In particular, we recognized need for efforts to further develop statistical methodologies. This meeting provided an unprecedented opportunity for interdisciplinary collaboration, consistent with the purposes of the Big Data to Knowledge, Genetic Associations and Mechanisms in Oncology, and Precision Medicine Initiative of the US National Institute of Health. The MPE meeting series can help advance transdisciplinary population science and optimize training and education systems for twenty-first century medicine and public health. C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Ogino, Shuji; Nishihara, Reiko; Bass, Adam J.; Qian, Zhi Rong] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. [Ogino, Shuji; Nishihara, Reiko; Fitzgerald, Kathryn C.; Tamimi, Rulla M.; Tchetgen, Eric J. Tchetgen; Tworoger, Shelley S.; Giovannucci, Edward L.; Wang, Molin] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Nishihara, Reiko; Irizarry, Rafael A.; Tchetgen, Eric J. Tchetgen; Rosner, Bernard A.; Wang, Molin] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Nishihara, Reiko; Fitzgerald, Kathryn C.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Phipps, Amanda I.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Phipps, Amanda I.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Beck, Andrew H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Beck, Andrew H.; Bass, Adam J.] Broad Inst, Cambridge, MA USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Sherman, Mark E.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Poole, Elizabeth M.; Tamimi, Rulla M.; Tworoger, Shelley S.; Zhang, Xuehong; Giovannucci, Edward L.; Rosner, Bernard A.; Wang, Molin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02215 USA. [Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Irizarry, Rafael A.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kelsey, Karl T.] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Nan, Hongmei] Indiana Univ, Dept Epidemiol, Richard M Fairbanks Sch Publ Hlth, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands. [Begg, Colin B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institute of Health (NIH) [R01 CA151993, K07 CA190673, R01 CA137178, K24 DK098311, K07 CA172298]; Dana-Farber Cancer Institute FX We thank all of the members of the program committee, the speakers, the discussants, and the other participants of the Second International MPE Meeting on December 4-5, 2014 in Boston, MA, USA. We thank the Dana-Farber Cancer Institute (Edward J. Benz, Jr., President and CEO) for providing the meeting venue and the Department of Pathology, the Brigham and Women's Hospital (Jeffrey A. Golden, Chairperson), and Enzymatics, Inc., for providing meals and refreshments, respectively. We also thank the Department of Pathology, the Brigham and Women's Hospital (Jeffrey A. Golden, Chairperson); the Department of Epidemiology, the Harvard T.H. Chan School of Public Health (Michelle A. Williams, Chairperson); the Dana-Farber Harvard Cancer Center (Giovanni Parmigiani, Meir J. Stampfer, Lorelei A. Mucci, Deborah Schrag, and Charles S. Fuchs; Program Leaders); and the Channing Division of Network Medicine, the Department of Medicine, the Brigham and Women's Hospital (Edwin K. Silverman, Division Chief) for providing morale supports and helping in announcements. This work was supported in part by grants from the US National Institute of Health (NIH) [R01 CA151993 (to SO), K07 CA190673 (to RN), R01 CA137178 (to ATC), K24 DK098311 (to ATC), and K07 CA172298 (to AIP)], and the friends of the Dana-Farber Cancer Institute (to SO). ATC is Damon Runyon Clinical Investigator. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders (including Enzymatics, Inc.) did not have any role in planning the meeting, the decision to submit the manuscript for publication, or the writing of the manuscript. Use of Human Genome Organisation (HUGO) Gene Nomenclature Committee (HGNC)-approved symbols for genes and gene products: We use symbols approved by HGNC and described at www.genenames.org; those include BRAF, CD274, ERBB2, ESR1, FASN, KRAS, MLH1, PDCD1LG2, PGR, PIK3CA, and VHL. Gene names are italicized, while names of gene products are non-italicized. Non-official names are described in parenthesis where helpful. NR 148 TC 18 Z9 18 U1 9 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 2015 VL 26 IS 7 BP 959 EP 972 DI 10.1007/s10552-015-0596-2 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CK2DN UT WOS:000356020900001 PM 25956270 ER PT J AU Dey, N Bera, A Das, F Ghosh-Choudhury, N Kasinath, BS Choudhury, GG AF Dey, Nirmalya Bera, Amit Das, Falguni Ghosh-Choudhury, Nandini Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI High glucose enhances microRNA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression SO CELLULAR SIGNALLING LA English DT Article DE MicroRNA; Diabetic nephropathy; mTOR; Mesangial cell pathology ID INDUCED COLLAGEN EXPRESSION; MESSENGER-RNA TRANSLATION; TUBULAR EPITHELIAL-CELLS; NF-KAPPA-B; DIABETIC-NEPHROPATHY; PTEN EXPRESSION; TENSIN HOMOLOG; AKT KINASE; TARGETING PHOSPHATASE; DOWN-REGULATION AB High glucose milieu inhibits PTEN expression to activate Akt kinase and induces glomerular mesangial cell hypertrophy and matrix protein expression in diabetic nephropathy. Specific mechanism by which high glucose inhibits PTEN expression is not clear. We found that high glucose increased the expression of the microRNA-26a (miR-26a) in mesangial cells. Using a sensor plasmid with 3'UTR-driven luciferase, we showed PTEN as a target of miR-26a in response to high glucose. Overexpression of miR-26a reduced the PTEN protein levels resulting in increased Akt kinase activity similar to high glucose treatment. In contrast, anti-miR-26a reversed high glucose-induced suppression of PTEN with concomitant inhibition of Akt kinase activity. Akt-mediated phosphorylation of tuberin and PRAS40 regulates mTORC1, which is necessary for mesangial cell hypertrophy and matrix protein expression. Inhibition of high glucose-induced miR-26a blocked phosphorylation of tuberin and PRAS40, which lead to suppression of phosphorylation of S6 kinase and 4EBP-1, two substrates of mTORC1. Furthermore, we show that expression of miR-26a induced mesangial cell hypertrophy and increased fibronectin and collagen I (alpha 2) expression similar to that observed with the cells incubated with high glucose. Anti-miR-26a inhibited these phenomena in response to high glucose. Together our results provide the first evidence for the involvement of miR-26a in high glucose-induced mesangial cell hypertrophy and matrix protein expression. These data indicate the potential therapeutic utility of anti-miR-26a for the complications of diabetic kidney disease. Published by Elsevier Inc. C1 [Dey, Nirmalya; Bera, Amit; Das, Falguni; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIH [RO1 DK50190]; VA Research Service Merit Review [5I01BX000926]; VA Senior Research Career Scientist Award; VA Merit Review grants [5I01BX000150, 5I01BX001340] FX This work was supported by the NIH RO1 DK50190 and VA Research Service Merit Review 5I01BX000926 grants to GGC. GGC is a recipient of VA Senior Research Career Scientist Award. NGC AND BSK are supported by VA Merit Review grants 5I01BX000150 and 5I01BX001340, respectively. NR 55 TC 10 Z9 11 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD JUL PY 2015 VL 27 IS 7 BP 1276 EP 1285 DI 10.1016/j.cellsig.2015.03.007 PG 10 WC Cell Biology SC Cell Biology GA CK0HY UT WOS:000355887500002 PM 25797045 ER PT J AU Bedair, H Goyal, N Dietz, MJ Urish, K Hansen, V Manrique, J Hamilton, W Deirmengian, G AF Bedair, Hany Goyal, Nitin Dietz, Mathew J. Urish, Kenneth Hansen, Viktor Manrique, Jorge Hamilton, William Deirmengian, Greg TI A History of Treated Periprosthetic Joint Infection Increases the Risk of Subsequent Different Site Infection SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; MORTALITY AB After the successful treatment of periprosthetic joint infection (PJI), patients may present with degenerative joint disease in another joint with symptoms severe enough to warrant arthroplasty. However, it is not known whether patients with a history of treated PJI at one site will have an increased risk of PJI in the second arthroplasty site. The primary objective of this study is to determine if there is a difference in the risk of developing a PJI after a second total hip arthroplasty (THA) or total knee arthroplasty (TKA) in patients who have had a previous PJI at another anatomic site compared with patients who have had no history of PJI. The secondary objective is to determine other potential risk factors that may predict PJI at the site of the second arthroplasty. A retrospective matched cohort study was performed to identify all patients at four academic institutions successfully treated for PJI who subsequently underwent a second primary THA or TKA (n = 90), constituting our study group. Patients were matched (one-to-one) to control subjects who had no history of PJI after their first arthroplasty (n = 90); they were matched based on age, sex, diabetic status, BMI, American Society of Anesthesiologists, institution, joint of interest, and year of surgery (+/- A 2 years). We compared the case and control groups to determine whether a prior infection increased the relative risk of a subsequent PJI at another anatomic site. To identify other potential risk factors for subsequent PJI, a subgroup univariate analysis of our study group (n = 90) was performed. To identify other potential risk factors for subsequent PJI, a subgroup univariate analysis of our study group (n = 90) was performed. Patients with a history of PJI had a greater risk of developing PJI in a subsequent THA or TKA (10 of 90 versus zero of 90 in the control group; relative risk, 21.00; 95% confidence interval [CI], 1.25-353.08; p = 0.035). Excluding PJI, we identified no other factors associated with a second joint infection. In patients with a history of PJI, a second PJI occurred more frequently in female patients (female: nine of 10 [90%] versus female: 40 of 80 [50%]; odds ratio [OR], 8.83; 95% CI, 1.13-403.33; p = 0.02) and in those whose initial infection was a staphylococcal species (subsequent PJI seven of 10 [70%] versus no subsequent PJI 28 of 80 [35%]; OR, 4.26; 95% CI, 0.89-27.50; p = 0.04). A history of PJI predisposes patients to subsequent PJI in primary THA or THA. Patients and surgeons must be aware of the higher risk of this devastating complication before proceeding with a second arthroplasty. Level III, prognostic study. C1 [Bedair, Hany; Hansen, Viktor] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Goyal, Nitin; Hamilton, William] Anderson Orthopaed Clin, Alexandria, VA USA. [Dietz, Mathew J.] W Virginia Univ, Dept Orthopaed, Morgantown, WV 26506 USA. [Urish, Kenneth] Univ Pittsburgh, Dept Orthopaed, Pittsburgh, PA USA. [Manrique, Jorge; Deirmengian, Greg] Thomas Jefferson Univ, Dept Orthopaed, Philadelphia, PA 19107 USA. [Manrique, Jorge] Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. RP Manrique, J (reprint author), Thomas Jefferson Univ, Rothman Inst, 125 S 9th St,Suite 1000, Philadelphia, PA 19107 USA. EM jorgemanriquemd@gmail.com NR 12 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 2015 VL 473 IS 7 BP 2300 EP 2304 DI 10.1007/s11999-015-4174-4 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CJ8LM UT WOS:000355752200025 PM 25670654 ER PT J AU Janssen, SJ Braun, Y Ready, JE Raskin, KA Ferrone, ML Hornicek, FJ Schwab, JH AF Janssen, Stein J. Braun, Yvonne Ready, John E. Raskin, Kevin A. Ferrone, Marco L. Hornicek, Francis J. Schwab, Joseph H. TI Are Allogeneic Blood Transfusions Associated With Decreased Survival After Surgery for Long-bone Metastatic Fractures? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CHARLSON COMORBIDITY INDEX; CANCER RECURRENCE; SURGICAL-TREATMENT; COLORECTAL-CANCER; DISEASE; RISK; MORBIDITY AB Previous studies have shown that perioperative blood transfusion increases cancer recurrence and decreases patient survival after resection of primary malignancies. The question arises whether this association also exists in patients with already disseminated disease undergoing surgery for metastatic long-bone fractures. We sought to determine whether perioperative allogeneic blood transfusion is associated with decreased survival after operative treatment of long-bone metastatic fractures after accounting for clinical, laboratory, and treatment factors. Secondarily, we aimed to identify potential factors that are associated with decreased survival. We included 789 patients in our retrospective study who underwent surgery at two institutions for a pathologic or impending metastatic long-bone fracture. We used multivariable Cox proportional hazards regression model analysis to assess the relationship of perioperative allogeneic blood transfusion with survival, and accounted for patient age, sex, comorbidities, BMI, tumor type, fracture type and location, presence of other bone and visceral metastases, previous radiotherapy and systemic therapy, preoperative embolization, preoperative hemoglobin level, treatment type, anesthesia time, blood loss, duration of hospital admission, year of surgery, and hospital. Considering transfusion as an "exposure," and comparing patients who received transfusions with those who did not, we found that blood transfusion was not associated with decreased survival after accounting for all explanatory variables (hazard ratio [HR] 1.06; 95% CI, 0.87-1.30; p = 0.57). Evaluating transfusion in terms of dose-response, we found that patients who received more transfusions had lower survival compared with those who had fewer transfusions after accounting for all explanatory variables (HR per unit of blood transfused, 1.07; 95% CI, 1.02-1.12; p = 0.005). We found that age (HR, 1.02; 95% CI, 1.01-1.02; p < 0.001), comorbidity status (HR, 1.06; 95% CI, 1.01-1.10; p = 0.014), duration of hospital stay (HR, 1.02; 95% CI 1.00-1.03; p = 0.021), tumor type (HR, 1.71; 95% CI, 1.44-2.03; p < 0.001), and visceral metastases (HR, 1.59; 95% CI, 1.34-1.88; p < 0.001) were independently associated with survival. We found that exposure to perioperative allogeneic blood transfusion does not decrease survival, with the numbers available. However, our sample size might have been insufficient to reveal a small but potentially relevant effect. Our results do suggest a dose-response relationship; patients who received more transfusions had lower survival compared with those with fewer transfusions. Risk of death increased by 7% per unit of blood transfused. Level III, prognostic study. C1 [Janssen, Stein J.; Braun, Yvonne; Raskin, Kevin A.; Hornicek, Francis J.; Schwab, Joseph H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA 02114 USA. [Ready, John E.; Ferrone, Marco L.] Brigham & Womens Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Janssen, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Serv, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM steinjanssen@gmail.com FU Anna Foundation (Oegstgeest, The Netherlands); Michael van Vloten Foundation (Rotterdam, The Netherlands); Stryker (Kalamazoo, MI, USA); Biom'up (Saint-Priest, Lyon, France) FX One of the authors (SJ) received funding, an amount less than USD 10,000, from the Anna Foundation (Oegstgeest, The Netherlands) and an amount less than USD10,000, from the Michael van Vloten Foundation (Rotterdam, The Netherlands). One author (JS) certifies that he or a member of his family has or may receive payments or benefits, an amount less than USD 10,000, from Stryker (Kalamazoo, MI, USA), and an amount less than USD 10,000, from Biom'up (Saint-Priest, Lyon, France). NR 26 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 2015 VL 473 IS 7 BP 2343 EP 2351 DI 10.1007/s11999-015-4167-3 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CJ8LM UT WOS:000355752200031 PM 25637400 ER PT J AU Teunis, T Thornton, ER Jayakumar, P Ring, D AF Teunis, Teun Thornton, Emily R. Jayakumar, Prakash Ring, David TI Time Seeing a Hand Surgeon Is Not Associated With Patient Satisfaction SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PRIMARY-CARE; ITEM BANK; OUTCOMES; DEPRESSION; HEALTH; PHYSICIAN; EXTREMITY AB Previous studies, predominantly in the primary care setting, identified time spent with the physician as an important predictor of satisfaction. It is unknown if the same holds true in hand surgery. Is patient satisfaction measured immediately after an office visit associated with the duration of time spent with the hand surgeon? What other factors are associated with satisfaction directly after the visits and 2 weeks after the appointment? We prospectively enrolled 81 patients visiting our hand and upper extremity surgery outpatient clinic. We recorded their demographics and measured physical function, pain behavior, symptoms of depression, time spent in the waiting room, time spent with the physician, and patient satisfaction. Office times were measured using our patient ambulatory tracking system and by a research assistant outside the clinic room. To assess satisfaction we used items from the Consumer Assessment of Healthcare Providers and Systems survey (a federally developed standardized survey instrument) relevant to our study. Two weeks later, 51 (64%) patients were available for telephone followup and the same measures were completed. Mean time spent with the hand surgeon was 8 +/- A 5 minutes and mean in-office wait time to see the hand surgeon was 32 +/- A 18 minutes. A priori power analyses indicated that 77 patients would provide 80% power to detect an effect size f(2) = 0.18 for a regression with five predictors. This means that we would detect time spent with the physician as a significant factor if it accounted for 7% or more of the variability in satisfaction. Time spent with the hand surgeon was not associated with patient satisfaction measured directly after the visit (r = -0.023; p = 0.84). Longer time waiting to see the physician correlated with decreased patient satisfaction (r = -0.30; p = 0.0057). The final multivariable model for increased satisfaction directly after the office visit included shorter waiting time (regression coefficient [beta] -0.0014; partial R-2 0.094; 95% confidence interval [CI], -0.0024 to -0.00042; p = 0.006) and being married/living with a partner (beta 0.057; partial R-2 0.11; 95% CI, 0.021-0.093; p = 0.002 [adjusted R-2 0.18; p < 0.001]). Similarly, multivariable analysis found higher patient satisfaction 2 weeks after the visit to be independently associated with shorter waiting time (beta -0.0037; partial R-2 0.10; 95% CI, -0.0070 to -0.00054; p = 0.023) and being married/living with a partner (beta 0.15; partial R-2 0.12; 95% CI, 0.033-0.26; p = 0.012 [adjusted R-2 0.16; p = 0.0052]). Patient satisfaction among patients undergoing hand surgery may relate more to shorter time in the waiting room and to the quality more than the quantity of time spent with the patient. Level II, prognostic study. C1 [Teunis, Teun; Thornton, Emily R.; Jayakumar, Prakash; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu FU Wright Medical (Memphis, TN, USA); Skeletal Dynamics (Miami, FL, USA); Biomet (Warsaw, IN, USA); AO North America (Paoli, PA, USA); AO International (Dubendorf, Switzerland) FX One of the authors (DR) certifies that he, or a member of his immediate family, has or may receive payments or benefits, during the study period, from Wright Medical (Memphis, TN, USA) of less than USD 10,000; Skeletal Dynamics (Miami, FL, USA) of less than USD 10,000; Biomet (Warsaw, IN, USA) of less than USD 10,000; AO North America (Paoli, PA, USA) of less than USD 10,000; and AO International (Dubendorf, Switzerland) of less than USD 10,000. NR 30 TC 5 Z9 5 U1 0 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 JUL PY 2015 VL 473 IS 7 BP 2362 EP 2368 DI 10.1007/s11999-014-4090-z PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CJ8LM UT WOS:000355752200034 PM 25475717 ER PT J AU Menendez, ME Ring, D Bateman, BT AF Menendez, Mariano E. Ring, David Bateman, Brian T. TI Preoperative Opioid Misuse is Associated With Increased Morbidity and Mortality After Elective Orthopaedic Surgery SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID NATIONWIDE INPATIENT SAMPLE; QUALITY IMPROVEMENT PROGRAM; ADVERSE DRUG EVENTS; CHRONIC BACK-PAIN; UNITED-STATES; RISK-FACTORS; PRESCRIBED OPIOIDS; IDENTIFY PATIENTS; NARCOTIC USE; ABUSE AB Many patients having discretionary orthopaedic surgery take opioids daily, either with a prescription or illicitly, however little is known regarding the prevalence and effect of high-risk opioid use (eg, abuse, dependence) in the perioperative orthopaedic setting. We sought (1) to determine the prevalence of opioid abuse and dependence in patients undergoing major elective orthopaedic surgery; (2) to characterize the relationship of opioid abuse and dependence with in-hospital postoperative mortality and adverse events, failure to rescue, prolonged length of stay, and nonroutine disposition; and (3) to identify factors associated with high-risk opioid use. We used coding data collected in discharge records from the Nationwide Inpatient Sample (2002-2011). We analyzed changes with time in the prevalence of opioid abuse and dependence on admission. Finally, we used multivariate regression modeling to measure the association of opioid abuse and dependence with in-hospital postoperative mortality, morbidity, and resource utilization, and to identify factors associated with high-risk opioid use. The prevalence of opioid abuse and dependence increased from 0.095% in 2002 to 0.24% in 2011, an increase of 152% (p < 0.001). Opioid abuse and dependence were associated with increased inpatient mortality (odds ratio [OR], 3.7; 95% CI, 2.7-5.1) and aggregate morbidity (OR, 2.3 l; 95% CI, 2.2-2.4), including induced mental disorder (OR, 5.9; 95% CI, 5.4-6.3), respiratory failure (OR, 3.1; 95% CI, 2.7-3.6), surgical site infection (OR, 2.5; 95% CI, 2.0-3.0), mechanical ventilation (OR, 2.3; 95% CI, 2.0-2.5), pneumonia (OR, 2.1; 95% CI, 1.8-2.3), myocardial infarction (OR, 1.9; 95% CI, 1.3-2.6), and postoperative ileus or other gastrointestinal events (OR, 1.4; 95% CI, 1.3-1.6) (p < 0.001 for all listed entities). Abuse and dependence also were associated with increased risk for prolonged hospital length of stay (OR, 2.5; 95% CI, 2.4-2.5), nonroutine discharge (OR, 2.2; 95% CI, 2.2-2.3), and failure to rescue (OR, 2.0; 95% CI, 1.4-2.8). High-risk opioid users were more likely to be younger, male, nonwhite, Medicaid-insured patients with mental health and substance use disorders, and to be undergoing spine surgery. Hospital-related characteristics included urban setting, geographic location in the Northeast or West, and serving as a teaching facility. Opioid abuse and dependence are increasing rapidly among orthopaedic surgical inpatients and are associated with considerable postoperative morbidity and mortality and resource utilization. We recommend that orthopaedic surgeons screen patients carefully for opioid misuse preoperatively, help patients who are using opioids inappropriately to discontinue them before scheduling elective surgery, decline to perform elective surgery in patients who misuse opioids, and closely monitor patients who are habituated to opioids at the time they undergo surgery. Level III, prognostic study. C1 [Menendez, Mariano E.; Ring, David] Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. RP Menendez, ME (reprint author), Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100, Boston, MA 02114 USA. EM marianofurrer@gmail.com NR 57 TC 18 Z9 18 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 JUL PY 2015 VL 473 IS 7 BP 2402 EP 2412 DI 10.1007/s11999-015-4173-5 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CJ8LM UT WOS:000355752200039 PM 25694266 ER PT J AU Cahana-Amitay, D Albert, ML AF Cahana-Amitay, Dalia Albert, Martin L. TI Neuroscience of Aphasia Recovery: the Concept of Neural Multifunctionality SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Recovery from aphasia; Neural multifunctionality; Linguistic; Nonlinguistic; Cognition; Aphasia treatment ID SHORT-TERM-MEMORY; POSITRON-EMISSION-TOMOGRAPHY; INFERIOR FRONTAL-CORTEX; COGNITIVE REHABILITATION; POSTSTROKE APHASIA; EXECUTIVE FUNCTION; PREFRONTAL CORTEX; LANGUAGE THERAPY; SEMANTIC CONTROL; INDUCED NEUROPLASTICITY AB Aphasia therapy, while demonstrably successful, has been limited by its primary focus on language, with relatively less attention paid to nonlinguistic factors (cognitive, affective, praxic) that play a major role in recovery from aphasia. Neuroscientific studies of the past 15-20 years have opened a breach in the wall of traditional clinico-anatomical teachings on aphasia. It is not an exaggeration to talk of a paradigm shift. The term "neural multifunctionality" denotes a complex web of neural networks supporting both linguistic and nonlinguistic functions in constant and dynamic interaction, creating language as we know it and contributing to recovery from aphasia following brain damage. This paper reviews scientific underpinnings of neural multifunctionality and suggests ways in which this new approach to understanding the neural basis of language can lead to meaningful, practical steps for improvements in aphasia therapy. C1 [Cahana-Amitay, Dalia; Albert, Martin L.] VA Boston Healthcare Syst, Boston, MA 02114 USA. [Cahana-Amitay, Dalia; Albert, Martin L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Cahana-Amitay, Dalia; Albert, Martin L.] VA Boston Healthcare Syst, Harold Goodglass Aphasia Res Ctr, Boston, MA 02130 USA. [Cahana-Amitay, Dalia; Albert, Martin L.] VA Boston Healthcare Syst, Language Aging Brain Lab, Boston, MA 02130 USA. RP Cahana-Amitay, D (reprint author), VA Boston Healthcare Syst, Boston, MA 02114 USA. EM dcamitay@bu.edu FU National Institutes of Health NIA [R01AG14345]; Boston University, Department of Neurology, Language in the Aging Brain FX We would like to thank Abigail Oveis and Adonai Sebastian for compiling literature and formatting this paper. Support for this research was provided by the National Institutes of Health NIA grant R01AG14345, Boston University, Department of Neurology, Language in the Aging Brain (PIs: Albert and Obler). NR 98 TC 2 Z9 2 U1 6 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JUL PY 2015 VL 15 IS 7 AR 41 DI 10.1007/s11910-015-0568-7 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CK5HC UT WOS:000356253200010 PM 26008816 ER PT J AU Ozieh, MN Dismuke, CE Lynch, CP Egede, LE AF Ozieh, Mukoso N. Dismuke, Clara E. Lynch, Cheryl P. Egede, Leonard E. TI Medical care expenditures associated with chronic kidney disease in adults with diabetes: United States 2011 SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Chronic kidney disease; Cost; MEPS ID COMPLICATIONS; MORTALITY; MELLITUS; BURDEN; COSTS AB Objective: Approximately 1 in 3 adults with diabetes have CKD. However, there are no recent national estimates of the association of CKD with medical care expenditures in individuals with diabetes. Our aim is to assess the association of CKD with total medical expenditures in US adults with diabetes using a national sample and novel cost estimation methodology. Research design and methods: Data on 2,053 adults with diabetes in the 2011 Medical Expenditure Panel Survey (MEPS) was analyzed. Individuals with CKD were identified based on self-report. Adjusted mean health services expenditures per person in 2011 were estimated using a two-part model after adjusting for demographic and clinical covariates. Results: Of the 2,053 individuals with diabetes, approximately 9.7% had self-reported CKD. Unadjusted mean expenditures for individuals with CKD were $ 20,726 relative to $ 9,689.49 for no CKD. Adjusted mean expenditures from the 2-part model for individuals with CKD were $ 8473 higher relative to individuals without CKD. Additional significant covariates were Hispanic/other race, uninsured, urban dwellers, CVD, stroke, high cholesterol, arthritis, and asthma. The estimated unadjusted total expenditures for individuals with CKD were estimated to be in excess of $ 43 billion in 2011. Conclusions: We showed that CKD is a significant contributor to the financial burden among individuals with diabetes, and that minorities and the uninsured with CKD may experience barriers in access to care. Our study also provides a baseline national estimate of CKD cost in Diabetes by which future studies can be used for comparison. Published by Elsevier Ireland Ltd. C1 [Ozieh, Mukoso N.] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Ozieh, Mukoso N.; Dismuke, Clara E.; Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med, Charleston, SC 29425 USA. [Dismuke, Clara E.; Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699] FX This study was supported by Grant K24DK093699 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 17 TC 11 Z9 11 U1 3 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JUL PY 2015 VL 109 IS 1 BP 185 EP 190 DI 10.1016/j.diabres.2015.04.011 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK4YA UT WOS:000356228100026 PM 25935258 ER PT J AU Wilson, RG Stevens, BW Guo, AY Russell, CN Thornton, A Cohen, MA Sturgeon, HC Giallourakis, C Khalili, H Nguyen, DD Yajnik, V Sauk, J Ananthakrishnan, AN AF Wilson, Robin G. Stevens, Betsy W. Guo, Abra Y. Russell, Caitlin N. Thornton, Anna Cohen, Melissa A. Sturgeon, Holly C. Giallourakis, Cosmas Khalili, Hamed Nguyen, Deanna D. Yajnik, Vijay Sauk, Jenny Ananthakrishnan, Ashwin N. TI High C-Reactive Protein Is Associated with Poor Sleep Quality Independent of Nocturnal Symptoms in Patients with Inflammatory Bowel Disease SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Sleep; Inflammatory bowel disease; C-reactive protein; Inflammation ID CROHNS-DISEASE; ULCERATIVE-COLITIS; OF-LIFE; DURATION; DISTURBANCES; DEPRIVATION; DISORDERS; RISK; INTERLEUKIN-6; METAANALYSIS AB Sleep disruption is common in inflammatory bowel diseases (IBD). However, studies demonstrating a similar prevalence in irritable bowel syndrome suggest that nighttime disruption due to diarrhea and abdominal pain may be key drivers of poor sleep quality. Whether inflammation is associated with poor sleep independently has not been examined previously. This single-center study included subjects with IBD recruited to an ongoing prospective registry who completed a questionnaire assessing sleep quality and mood. Inflammatory marker levels [C-reactive protein (CRP), erythrocyte sedimentation rate] and clinical disease activity including nighttime disruption on the day of enrollment were obtained from the medical record. Logistic regression models were used to identify predictors of sleep quality. The study included 131 subjects (72 women) with a median age of IBD diagnosis of 25 years. Twenty-three subjects (19 %) had a high C-reactive protein level (a parts per thousand yen8 mg/dL). Poor sleep was more common in those with high CRP levels than with normal values (70 vs. 39 %, p = 0.009). This association remained significant on multivariate analysis [Odds ratio (OR) 4.12, 95 % confidence interval (CI) 1.38-12.29]. Adjusting for the presence of nighttime disruption did not significant alter this association (OR 3.16, 95 % CI 1.01-9.90). High CRP correlated with poor sleep even in patients not experiencing nocturnal symptoms (n = 101, OR 4.89, 95 % CI 1.24-19.36). High CRP is associated with poor sleep quality in IBD independent of the presence of nighttime disruptions, suggesting that a relationship exists between circulating inflammatory markers and sleep. C1 [Wilson, Robin G.; Stevens, Betsy W.; Guo, Abra Y.; Russell, Caitlin N.; Thornton, Anna; Cohen, Melissa A.; Sturgeon, Holly C.; Giallourakis, Cosmas; Khalili, Hamed; Nguyen, Deanna D.; Yajnik, Vijay; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Giallourakis, Cosmas; Khalili, Hamed; Nguyen, Deanna D.; Yajnik, Vijay; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health (NIH) [P30 DK043351]; National Institutes of Health [K23 DK097142] FX We acknowledge the valuable contributions of the participants and the research staff of our registry. This work was presented as a poster at the American College of Gastroenterology Annual Meeting 2014, Philadelphia, PA. This work is supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). NR 47 TC 3 Z9 4 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2015 VL 60 IS 7 BP 2136 EP 2143 DI 10.1007/s10620-015-3580-5 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CK2DT UT WOS:000356021500035 PM 25701321 ER PT J AU Sharaiha, RZ Sethi, A Weaver, KR Gonda, TA Shah, RJ Fukami, N Kedia, P Kumta, NA Clavo, CMR Saunders, MD Cerecedo-Rodriguez, J Barojas, PF Widmer, JL Gaidhane, M Brugge, WR Kahaleh, M AF Sharaiha, Reem Z. Sethi, Amrita Weaver, Kristen R. Gonda, Tamas A. Shah, Raj J. Fukami, Norio Kedia, Prashant Kumta, Nikhil A. Clavo, Carlos M. Rondon Saunders, Michael D. Cerecedo-Rodriguez, Jorge Barojas, Paola Figueroa Widmer, Jessica L. Gaidhane, Monica Brugge, William R. Kahaleh, Michel TI Impact of Radiofrequency Ablation on Malignant Biliary Strictures: Results of a Collaborative Registry SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Radiofrequency ablation; Biliary obstruction; Stent patency; Survival; Cholangiocarcinoma; Pancreatic cancer ID BILE-DUCT CARCINOMA; RANDOMIZED-TRIAL; METAL STENTS; INTRALUMINAL BRACHYTHERAPY; PHOTODYNAMIC THERAPY; HILAR CHOLANGIOCARCINOMA; ENDOSCOPIC PALLIATION; OBSTRUCTIVE-JAUNDICE; PLASTIC STENTS; EXTERNAL-BEAM AB Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. A total of 69 patients (22 male, aged 66.1 +/- A 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (n = 45), pancreatic cancer (n = 19), gallbladder cancer (n = 2), gastric cancer (n = 1), and liver metastasis from colon cancer (n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation (p < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03-5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2-25 months). Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival. C1 [Sharaiha, Reem Z.; Weaver, Kristen R.; Kedia, Prashant; Kumta, Nikhil A.; Clavo, Carlos M. Rondon; Cerecedo-Rodriguez, Jorge; Barojas, Paola Figueroa; Widmer, Jessica L.; Gaidhane, Monica; Kahaleh, Michel] Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY 10021 USA. [Sethi, Amrita; Gonda, Tamas A.] Columbia Univ, Med Ctr, Gastroenterol, New York, NY USA. [Shah, Raj J.; Fukami, Norio] Univ Colorado, Gastroenterol, Denver, CO 80202 USA. [Saunders, Michael D.] Univ Washington, Gastroenterol, Seattle, WA 98195 USA. [Brugge, William R.] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. RP Kahaleh, M (reprint author), Weill Cornell Med Coll, Div Gastroenterol & Hepatol, 1305 York Ave,4th Floor, New York, NY 10021 USA. EM mkahaleh@gmail.com RI Gaidhane, Monica/B-9414-2009 OI Gaidhane, Monica/0000-0001-6773-7080 FU Boston Scientific; Fujinon; EMcison; Xlumena Inc.; W.L. Gore; MaunaKea; Apollo Endosurgery; Cook Endoscopy; ASPIRE Bariatrics; GI Dynamics; MI Tech FX Michel Kahaleh MD has received grant support from Boston Scientific, Fujinon, EMcison, Xlumena Inc., W.L. Gore, MaunaKea, Apollo Endosurgery, Cook Endoscopy, ASPIRE Bariatrics, GI Dynamics, and MI Tech. He is a consultant for Boston Scientific and Xlumena Inc.; Amrita Sethi MD is a consultant for Boston Scientific. All other authors have no conflicts of interest to report. NR 45 TC 7 Z9 8 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2015 VL 60 IS 7 BP 2164 EP 2169 DI 10.1007/s10620-015-3558-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CK2DT UT WOS:000356021500039 PM 25701319 ER PT J AU Johnson, KB Mueller, JL Simon, TG Zheng, H King, LY Makar, RS Gervais, DA Chung, RT AF Johnson, Kara B. Mueller, Jessica L. Simon, Tracey G. Zheng, Hui King, Lindsay Y. Makar, Robert S. Gervais, Debra A. Chung, Raymond T. TI Reduced Albumin Dosing During Large-Volume Paracentesis Is Not Associated with Adverse Clinical Outcomes SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Paracentesis; Albumin; Cirrhosis; Renal disease ID INDUCED CIRCULATORY DYSFUNCTION; CIRRHOSIS; PREVENTION; ASCITES; MIDODRINE AB LVP is used to manage diuretic-resistant ascites in cirrhotic patients. Albumin administration prevents complications including acute kidney injury and paracentesis-induced circulatory dysfunction, but the optimal dose is unclear. We sought to assess adherence to guidelines enacted in July 2011 at our center for reducing the albumin dose administered at large-volume paracentesis (LVP) and evaluate the cost and rate of complications of LVPs before and after guideline enactment. All LVPs performed on cirrhotic patients in our center's Department of Radiology between July 2009 and January 2014 were studied. Outcomes included adherence to guidelines, LVP complications, and administered albumin cost. Groups were compared using Student's t tests for continuous data and Chi-square or Fisher's exact tests for categorical data. A repeated measurements model accounted for patients with multiple LVPs. Of the 935 LVPs, 288 occurred before guideline implementation (group 1) and 647 occurred after (group 2). The mean dose of albumin administered was 13.7 g/L of ascites removed in group 1 versus 10.3 g/L in group 2 (p < 0.0001). Of the group 2 LVPs, 235 (36.3 %) adhered to guidelines. There were no significant differences in LVP complications. Guidelines were followed in one-third of LVPs. Despite this limited adherence, a reduction in albumin administration and associated cost savings was still observed. There was no increase in LVP-related complications after guideline implementation or in the adherent group, suggesting that albumin dose can be safely reduced. Future efforts should be directed at enhancing guideline adherence and potentially further reducing albumin dosing. C1 [Johnson, Kara B.; Mueller, Jessica L.; King, Lindsay Y.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Johnson, Kara B.; Mueller, Jessica L.; King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Simon, Tracey G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. [Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM KARA.B.JOHNSON@GMAIL.COM; JMUELLER2@PARTNERS.ORG; TGSIMON@PARTNERS.ORG; HZHENG1@PARTNERS.ORG; LYKING@PARTNERS.ORG; RMAKAR@PARTNERS.ORG; DGERVAIS@PARTNERS.ORG; RTCHUNG@PARTNERS.ORG FU NIH [K24 DK078772, T32 DK007191] FX All of the authors had access to the study data and reviewed and approved the manuscript. The authors would like to gratefully acknowledge the assistance of Kent Eliason. The following authors would like to acknowledge NIH grants; these grants were not connected specifically to this project but contributed to the work. Raymond T. Chung MD: NIH K24 DK078772, Kara B. Johnson MD: NIH T32 DK007191, Jessica L. Mueller BA: NIH T32 DK007191, Lindsay Y. King MD, MPH: NIH T32 DK007191. NR 10 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2015 VL 60 IS 7 BP 2190 EP 2195 DI 10.1007/s10620-015-3578-z PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CK2DT UT WOS:000356021500043 PM 25724164 ER PT J AU Iezzoni, LI Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffrey L. TI "How did that happen?" Public responses to women with mobility disability during pregnancy SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Disability; Pregnancy; Public; Societal attitudes; Qualitative research ID CHRONIC PHYSICAL-DISABILITIES; US WOMEN; BREAST-CANCER; HEALTH-CARE; EXPERIENCES; PREVALENCE; DIAGNOSIS; BARRIERS AB Background: Little is known about current societal attitudes toward women with significant mobility disability who are visibly pregnant. Objective: To use qualitative descriptive analysis methods to examine perceptions of women with significant mobility disability about how strangers reacted to their visible pregnancies. Methods: In late 2013, we conducted 2-h telephone interviews with 22 women with significant mobility difficulties who had delivered babies within the prior 10 years. The semi-structured, open-ended interview protocol addressed wide-ranging pregnancy-related topics, including statements from strangers. Most participants were recruited through social networks, coming from 17 states nationwide. We used NVivo to sort the texts for content analysis. Results: The women's mean (standard deviation) age was 34.8 (5.3) years; most were white, well-educated, and higher income, although half had Medicaid during their pregnancies; and 18 used wheeled mobility aids. Eighteen women described memorable interactions with strangers relating to their pregnancies or newborn babies. Strangers' statements fell into six categories: (1) curious; (2) intrusively and persistently curious; (3) hostile, including concerns that taxpayers would end up supporting the mother and child; (4) questioning woman's competence as a potential parent; (5) oblivious, not recognizing visible pregnancy or motherhood; and (6) positive. Many women reported strangers asking how their pregnancy had happened. The women doubted that visibly pregnant women without disabilities evoke the same reactions from strangers. Conclusions: Women with mobility disability who are visibly pregnant may perceive reactions from strangers that appear intrusive. Planning ahead for handling such encounters could reduce the stresses of these interactions. (C) 2015 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. [Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [1R21HD068756-02] FX The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded this study (Grant No. 1R21HD068756-02). NR 26 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 EI 1876-7583 J9 DISABIL HEALTH J JI Disabil. Health J. PD JUL PY 2015 VL 8 IS 3 BP 380 EP 387 DI 10.1016/j.dhjo.2015.02.002 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA CJ8QM UT WOS:000355768600011 PM 25944504 ER PT J AU Puzanov, I Amaravadi, RK McArthur, GA Flaherty, KT Chapman, PB Sosman, JA Ribas, A Shackleton, M Hwu, P Chmielowski, B Nolop, KB Lin, PS Kim, KB AF Puzanov, Igor Amaravadi, Ravi K. McArthur, Grant A. Flaherty, Keith T. Chapman, Paul B. Sosman, Jeffrey A. Ribas, Antoni Shackleton, Mark Hwu, Patrick Chmielowski, Bartosz Nolop, Keith B. Lin, Paul S. Kim, Kevin B. TI Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Vemurafenib; BRAF inhibitor; Metastatic melanoma ID METASTATIC MELANOMA; B-RAF; ACQUIRED-RESISTANCE; RESPONSE CRITERIA; BRAF INHIBITION; MEK INHIBITION; PLX4032; MUTATIONS; SURVIVAL; KINASE AB Introduction: Vemurafenib induces tumour regression in most patients with BRAF(V600E) - mutant melanoma; eventually, most experience progressive disease (PD). Long-term follow-up of patients with BRAF(V600E) melanoma treated in the phase 1 vemurafenib trial is reported. Methods: Patients received vemurafenib 240-1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. Results: Forty-eight patients (escalation cohort, n = 16; extension cohort, n = 32) received therapeutic doses of vemurafenib (>= 240 mg twice daily). Forty-four patients had PD by the time of this analysis and four remained progression free (follow-up time, 1.2-56.1 months). Median OS was 14 months (range, 1.2-56.1); 3- and 4-year melanoma-specific survival rate in the extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range, 7.7-56.1) among 20 patients who continued vemurafenib after local therapy. Median treatment duration beyond initial PD was 3.8 months (range, 1.1-26.6). In the extension cohort, six and five patients were alive after 3 and 4 years, respectively, on vemurafenib monotherapy. Conclusions: Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Amaravadi, Ravi K.] Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Amaravadi, Ravi K.] Univ Penn, Philadelphia, PA 19104 USA. [McArthur, Grant A.; Shackleton, Mark] Peter MacCallum Canc Ctr, East Melbourne, Vic 3002, Australia. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Ribas, Antoni; Chmielowski, Bartosz] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Hwu, Patrick; Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nolop, Keith B.; Lin, Paul S.] Plexxikon Inc, Berkeley, CA 94710 USA. RP Kim, KB (reprint author), Calif Pacific Med Ctr, Melanoma Clin Res Program, 2333 Buchanan St, San Francisco, CA 94115 USA. EM igor.puzanov@vanderbilt.edu; Ravi.Amaravadi@uphs.upenn.edu; grant.mcarthur@petermac.org; kflaherty@partners.org; chapmanp@mskcc.org; jeff.sosman@vanderbilt.edu; aribas@mednet.ucla.edu; Mark.Shackleton@petermac.org; phwu@mdanderson.org; BChmielowski@mednet.ucla.edu; easybreathe@msn.com; plin@plexxikon.com; KimKB@sutterhealth.org OI Chmielowski, Bartosz/0000-0002-2374-3320 FU F. Hoffmann-La Roche Ltd. FX This study was funded by F. Hoffmann-La Roche Ltd. NR 29 TC 17 Z9 19 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2015 VL 51 IS 11 BP 1435 EP 1443 DI 10.1016/j.ejca.2015.04.010 PG 9 WC Oncology SC Oncology GA CJ8HR UT WOS:000355741300010 PM 25980594 ER PT J AU Treister, R O'Neil, K Downs, HM Oaklander, AL AF Treister, R. O'Neil, K. Downs, H. M. Oaklander, A. L. TI Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE autonomic function testing; autonomic nervous system; dysautonomia; neurodiagnostic skin biopsies; pain ID PRACTICE PARAMETER; SKIN BIOPSY; RECOMMENDATIONS AB Background and purposeThe recently developed composite autonomic symptom score 31 (COMPASS-31) is a questionnaire that assess symptoms of dysautonomia. It was distilled from the well-established Autonomic Symptom Profile questionnaire. COMPASS-31 has not yet been externally validated. To do so, its psychometric properties and convergent validity in patients with and without objective diagnosis of small fiber polyneuropathy (SFPN) were assessed. MethodsInternal validity and reliability of COMPASS-31 were assessed in participants with or without SFPN spanning the full range of severity of autonomic symptoms. Convergent validity was assessed by comparing results of the COMPASS-31 with the gold standard autonomic function testing that measures cardiovagal, adrenergic and sudomotor functions. Additionally, relationships between COMPASS-31 and the Short Form McGill Pain Questionnaire, Short Form Health Survey and 0-10 numeric pain scale were measured. COMPASS-31 and all other questionnaire results were compared between patients with or without evidence of SFPN, objectively confirmed by distal-leg PGP9.5-immunolabeled skin biopsy. ResultsAmongst 66 participants (28 SFPN+, 38 SFPN-), COMPASS-31 total scores had excellent internal validity (Cronbach's =0.919), test-retest reliability (r(s)=0.886; P<0.001) and good convergent validity (r(s)=0.474; P<0.001). COMPASS-31 scores differed between subjects with or without SFPN (Z=-3.296, P<0.001) and demonstrated fair diagnostic accuracy. Area under the Receiver Operating Characteristic curve was 0.749 (P=0.01, 95% confidence interval 0.627-0.871). ConclusionsCOMPASS-31 has good psychometric properties in the population of patients being evaluated for SFPN and thus it might be useful as an initial screening tool for the more expensive SFPN objective tests. C1 [Treister, R.; O'Neil, K.; Downs, H. M.; Oaklander, A. L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Treister, R.; O'Neil, K.; Downs, H. M.; Oaklander, A. L.] Harvard Univ, Sch Med, Boston, MA USA. [Oaklander, A. L.] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Treister, R (reprint author), Massachusetts Gen Hosp, 275 Charles St Warren Bldg 310, Boston, MA 02114 USA. EM treister.roi@gmail.com FU US Department of Defense [GW093049]; Public Health Service [NINDS K24NS59892] FX Financial support was received from the US Department of Defense (GW093049) and the Public Health Service (NINDS K24NS59892). NR 16 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2015 VL 22 IS 7 BP 1124 EP 1130 DI 10.1111/ene.12717 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CK3BP UT WOS:000356090800015 PM 25907824 ER PT J AU Goldman, SM Umbach, DM Kamel, F Tanner, CM AF Goldman, S. M. Umbach, D. M. Kamel, F. Tanner, C. M. TI Head injury, alpha-synuclein Rep1 and Parkinson's disease: a meta-analytic view of gene-environment interaction SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Letter DE alpha-synuclein; epidemiology; gene-environment interaction; genetic association study; Parkinson's disease; traumatic brain injury C1 [Goldman, S. M.; Tanner, C. M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Goldman, S. M.; Tanner, C. M.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Umbach, D. M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Kamel, F.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Goldman, SM (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 127-P, San Francisco, CA 94121 USA. EM samuel.goldman@ucsf.edu OI Kamel, Freya/0000-0001-5052-6615 NR 3 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2015 VL 22 IS 7 BP E75 EP E75 DI 10.1111/ene.12694 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CK3BP UT WOS:000356090800002 PM 26060929 ER PT J AU Sammon, JD Abdollah, F Reznor, G Pucheril, D Choueiri, TK Hu, JC Kim, SP Schmid, M Sood, A Sun, M Kibel, AS Nguyen, PL Menon, M Trinh, QD AF Sammon, Jesse D. Abdollah, Firas Reznor, Gally Pucheril, Daniel Choueiri, Toni K. Hu, Jim C. Kim, Simon P. Schmid, Marianne Sood, Akshay Sun, Maxine Kibel, Adam S. Nguyen, Paul L. Menon, Mani Quoc-Dien Trinh TI Patterns of Declining Use and the Adverse Effect of Primary Androgen Deprivation on All-cause Mortality in Elderly Men with Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Medicare; Androgen deprivation; SEER ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; HORMONE-THERAPY; RADIOTHERAPY; DISEASE; LIFE; SUPPRESSION; IMMEDIATE; CARCINOMA; SURVIVAL AB Background: Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. Objective: To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. Design, setting, and participants: Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. Outcome measurements and statistical analysis: Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. Results and limitations: The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. Conclusions: The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. Patient summary: In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Sammon, Jesse D.; Abdollah, Firas; Pucheril, Daniel; Sood, Akshay; Menon, Mani] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Reznor, Gally; Schmid, Marianne; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Urol Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Reznor, Gally; Schmid, Marianne; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT USA. [Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Ctr Surg & Publ Hlth, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM qtrinh@partners.org FU Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital FX Quoc-Dien Trinh is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital. NR 29 TC 9 Z9 9 U1 0 U2 2 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 JUL PY 2015 VL 68 IS 1 BP 32 EP 39 DI 10.1016/j.eururo.2014.10.018 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CK0YO UT WOS:000355932000014 PM 25457017 ER PT J AU Fizazi, K Massard, C Smith, M Rader, M Brown, J Milecki, P Shore, N Oudard, S Karsh, L Carducci, M Damiao, R Wang, H Ying, W Goessl, C AF Fizazi, Karim Massard, Christophe Smith, Matthew Rader, Michael Brown, Janet Milecki, Piotr Shore, Neal Oudard, Stephane Karsh, Lawrence Carducci, Michael Damiao, Ronaldo Wang, Huei Ying, Wendy Goessl, Carsten TI Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE Castration-resistant prostate cancer; Bone metastases; Survival; Prognostic factors; Nomogram ID CHEMOTHERAPY; MARKERS; MODEL AB Background: Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase <= 143 U/l (p < 0.0001); bone-specific alkaline phosphatase (BSAP) < 146 U/l (p < 0.0001); corrected urinary N-telopeptide (uNTx) <= 50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory-Short Form [BPI-SF] score <= 4) (p < 0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p < 0.0001); and longer time from first bone metastasis to randomization (p < 0.0001). Other significant predictors of improved survival included prostate-specific antigen (PSA) level < 10 ng/ml (p < 0.0001), hemoglobin >128 g/l (p < 0.0001), absence of visceral metastases (p < 0.0001), Eastern Co-operative Oncology Group (ECOG) score <= 1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validated models (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Fizazi, Karim; Massard, Christophe] Univ Paris 11, Inst Gustave Roussy, F-94800 Villejuif, France. [Smith, Matthew] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rader, Michael] Nyack Hosp, Nyack, NY USA. [Brown, Janet] Canc Res UK Expt Canc Med Ctr, Leeds, W Yorkshire, England. [Brown, Janet] Canc Res UK Expt Canc Med Ctr, Sheffield, S Yorkshire, England. [Milecki, Piotr] Med Univ, Dept Radiotherapy, Greater Poland Canc Ctr, Poznan, Poland. [Milecki, Piotr] Med Univ, Dept Electroradiol, Poznan, Poland. [Shore, Neal] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Oudard, Stephane] Hop Europeen Georges Pompidou, Paris, France. [Karsh, Lawrence] Urol Ctr Colorado, Denver, CO USA. [Carducci, Michael] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Damiao, Ronaldo] Univ Pedro Ernesto, Rio De Janeiro, Brazil. [Wang, Huei; Ying, Wendy; Goessl, Carsten] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Fizazi, K (reprint author), Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, 39 Rue Camille Desmoulins, F-94800 Villejuif, France. EM karim.fizazi@igr.fr FU Amgen Inc. (Thousand Oaks, CA, USA) FX Amgen Inc. (Thousand Oaks, CA, USA) sponsored this study/analysis and was involved in the design and conduct of the study; management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. NR 27 TC 19 Z9 19 U1 2 U2 6 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 JUL PY 2015 VL 68 IS 1 BP 42 EP 50 DI 10.1016/j.eururo.2014.10.001 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CK0YO UT WOS:000355932000016 PM 25449207 ER PT J AU Volpe, A Blute, ML Ficarra, V Gill, IS Kutikov, A Porpiglia, F Rogers, C Touijer, KA Van Poppel, H Thompson, RH AF Volpe, Alessandro Blute, Michael L. Ficarra, Vincenzo Gill, Inderbir S. Kutikov, Alexander Porpiglia, Francesco Rogers, Craig Touijer, Karim A. Van Poppel, Hendrik Thompson, R. Houston TI Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature SO EUROPEAN UROLOGY LA English DT Review DE Ischemia; Nephron-sparing surgery; Partial nephrectomy; Renal cell carcinoma; Renal function ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; NEPHRON-SPARING SURGERY; ROBOTIC PARTIAL NEPHRECTOMY; PARENCHYMAL VOLUME PRESERVATION; ASSISTED PARTIAL NEPHRECTOMY; GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; WARM ISCHEMIA; LONG-TERM; SERUM CREATININE AB Context: Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. Objective: To review the current evidence on the relationship of intraoperative ischemia and RF after PN. Evidence acquisition: A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Evidence synthesis: The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT <25 min, although the level of evidence to support this threshold is limited. Cold ischemia safely facilitates longer durations of ischemia. Surgical techniques that minimize or avoid global ischemia may be associated with improved RF outcomes. Conclusions: Although RF recovery after PN is strongly associated with quality and quantity of preserved kidney, efforts should be made to limit prolonged WIT. Cold ischemia should be preferred when longer ischemia is expected, especially in presence of imperative indications for PN. Additional research with higher levels of evidence is needed to clarify the optimal use of renal ischemia during PN. Patient summary: In this review of the literature, we looked at predictors of renal function after surgical resection of renal tumors. There is a strong association between the quality and quantity of renal tissue that is preserved after surgery and long-term renal function. The time of interruption of renal blood flow during surgery is an important, modifiable predictor of postoperative renal function. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Volpe, Alessandro] Univ Piemonte Orientale, Div Urol, Maggiore Carita Hosp, Dept Translat Med, I-28100 Novara, Italy. [Blute, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Ficarra, Vincenzo] Univ Udine, Div Urol, Dept Expt & Clin Med Sci, I-33100 Udine, Italy. [Gill, Inderbir S.] Univ So Calif, Keck Sch Med, Catherine & Joseph Aresty Dept Urol, USC Inst Urol, Los Angeles, CA 90033 USA. [Kutikov, Alexander] Fox Chase Canc Ctr, Dept Surg Oncol, Div Urol Oncol, Philadelphia, PA 19111 USA. [Porpiglia, Francesco] Univ Turin, Dept Oncol, Div Urol, San Luigi Hosp, Turin, Italy. [Rogers, Craig] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Touijer, Karim A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Van Poppel, Hendrik] Univ Ziekenhuis Gasthuisberg, Leuven Canc Inst, Dept Urol, Leuven, Belgium. [Thompson, R. Houston] Mayo Clin, Dept Urol, Rochester, MN USA. RP Volpe, A (reprint author), Univ Piemonte Orientale, Div Urol, Maggiore Carita Hosp, Corso Mazzini 18, I-28100 Novara, Italy. EM alessandro.volpe@med.unipmn.it OI PORPIGLIA, Francesco/0000-0002-0752-4857 NR 94 TC 40 Z9 41 U1 2 U2 13 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 JUL PY 2015 VL 68 IS 1 BP 61 EP 74 DI 10.1016/j.eururo.2015.01.025 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA CK0YO UT WOS:000355932000020 PM 25703575 ER PT J AU Mashmoushi, AK Oates, JC AF Mashmoushi, Ahmad K. Oates, Jim C. TI Lipopolysaccharide induces inducible nitric oxide synthase-dependent podocyte dysfunction via a hypoxia-inducible factor 1 alpha and cell division control protein 42 and Ras-related C3 botulinum toxin substrate 1 pathway SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Podocyte; Toll-like receptor 4; Nitric oxide; Superoxide; Lipopolysaccharide; Hypoxia-inducible factor 1 alpha; Cell division control protein 42; Ras-related C3 botulinum toxin substrate 1; Inducible nitric oxide synthase; Lupus nephritis; Peroxynitrite Free radicals ID TOLL-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IN-VIVO; AUTOIMMUNE-DISEASE; NEPHROTIC SYNDROME; MRL/LPR MICE; EXPRESSION; KIDNEY; NEPHRITIS; INJURY AB Urine protein loss in immune complex-mediated diseases such as lupus nephritis is associated with podocyte foot process effacement (podocytopathy) but is not always dependent on glomerular immune complex deposition. Several murine and human studies have associated lupus nephritis with inducible nitric oxide synthase (iNOS) expression in what appear to be podocytes. This study was conducted to determine mechanisms of immune-complex-independent and iNOS-dependent podocyte dysfunction. Conditionally immortalized podocytes were Cultured with lipopolysaccharide (LPS) and nitric oxide (NO), superoxide (SO), or peroxynitrite donors in the presence or absence of inhibitors of iNOS, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or monocyte chemotactic protein 1 (MCP-1), or with sepiapterin to increase coupling of iNOS homodimers. Podocyte NO, SO, and MCP-1 production and nitrotyrosine modifications were determined. The podocytopathy phenotype was determined by measuring cell Motility and membrane permeability to albumin. This study determined that NO produced by iNOS is sufficient and necessary to induce podocytopathy. NO probably induces this phenotype via hypoxia-inducible factor, its and cell division control protein 42 and Ras-related C3 botulinum toxin substrate 1 pathways. With LPS stimulation, neither SO nor peroxynitrite produced by uncoupled iNOS or NADPH oxidase nor MCP-1 was sufficient to induce the full phenotype. This study supports the notion that iNOS may induce autocrine podocyte dysfunction. Thus, targeting iNOS or the pathways of its induction may have therapeutic benefit. Published by Elsevier Inc. C1 [Mashmoushi, Ahmad K.; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Rheumatol Sect, Med Serv, Charleston, SC 29401 USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU Veterans Affairs Administration [5I01CX000218]; National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01 AR045476] FX We give special thanks to Dr. Jeffery Kopp at the National Institute of Diabetes, Digestive, and Kidney Diseases in Bethesda, Maryland, for generously providing the conditionally immortalized podocytes. Thanks go to Dr. Julie Chao for technical assistance with the lucigenin assay protocol and Ms. May Amria for assistance with the transepithelial resistance assay. This work was funded by grants from the Veterans Affairs Administration (VA Merit Project 5I01CX000218) and the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR045476). None of these funding agencies played a role in the design, conduct, or reporting of this study. NR 57 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL PY 2015 VL 84 BP 185 EP 195 DI 10.1016/j.freeradbiomed.2015.02.031 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CK0LK UT WOS:000355896500017 PM 25765888 ER PT J AU Hung, J Capoulade, R AF Hung, Judy Capoulade, Romain TI Therapy for secondary mitral regurgitation: time to 'cut the chord'? SO HEART LA English DT Editorial Material C1 [Hung, Judy; Capoulade, Romain] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM JHUNG@mgh.harvard.edu FU NHLBI NIH HHS [5 U01 HL088942, R01 HL092101] NR 9 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD JUL 1 PY 2015 VL 101 IS 13 BP 996 EP 997 DI 10.1136/heartjnl-2015-307473 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK4FM UT WOS:000356177600002 PM 25810156 ER PT J AU Harinstein, ME Butler, J Greene, SJ Fonarow, GC Stockbridge, NL O'Connor, CM Pfeffer, MA Mehra, MR Solomon, SD Yancy, CW Fiuzat, M Mentz, RJ Collins, SP McMurray, JJV Vaduganathan, M Dunnmon, PM Rosano, GMC Dinh, W Misselwitz, F Bonow, RO Gheorghiade, M AF Harinstein, Matthew E. Butler, Javed Greene, Stephen J. Fonarow, Gregg C. Stockbridge, Norman L. O'Connor, Christopher M. Pfeffer, Marc A. Mehra, Mandeep R. Solomon, Scott D. Yancy, Clyde W. Fiuzat, Mona Mentz, Robert J. Collins, Sean P. McMurray, John J. V. Vaduganathan, Muthiah Dunnmon, Preston M. Rosano, Giuseppe M. C. Dinh, Wilfried Misselwitz, Frank Bonow, Robert O. Gheorghiade, Mihai TI Site selection for heart failure clinical trials in the USA SO HEART FAILURE REVIEWS LA English DT Article DE Clinical trials; Site selection; Heart failure; United States; Outcomes ID PRESERVED EJECTION FRACTION; VASOPRESSIN ANTAGONISM; MYOCARDIAL-INFARCTION; THROMBUS ASPIRATION; EVEREST EFFICACY; UNITED-STATES; OUTCOMES; TOLVAPTAN; REGISTRY; PROGRAM AB There are more than 1 million primary hospitalizations for heart failure (HF) annually in the USA alone, and post-discharge outcomes remain persistently poor despite available therapies and quality improvement initiatives. Recent international randomized clinical trials in hospitalized HF have repeatedly failed to improve this post-discharge event rate. A potential reason for this persistent lack of clinical trial success that has not previously received significant attention relates to site selection and the generally low level of patient enrollment from the USA. Only similar to 5 % of US hospitals participate in clinical trials, and in four recent randomized trials of hospitalized HF, only one-third of patients were enrolled in North America. This poor participation among US centers has necessitated disproportionate enrollment from non-US sites. Regional variations in HF patient characteristics and clinical outcomes are well documented, and a lack of US patient representation in clinical trials limits the generalizability of results and presents obstacles for US regulatory agency approval. There are multiple impediments to successful US enrollment including a lack of incentive for investigators and institutions, the relative value unit-based compensation system, poor institutional framework for identification of appropriate patients, and increasing liability to conduct trials. In this manuscript, we specifically identify barriers to successful hospitalized HF clinical trial participation in the USA and suggest possible solutions. C1 [Harinstein, Matthew E.] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Butler, Javed] SUNY Stony Brook, Sch Med, Div Cardiol, Stony Brook, NY 11794 USA. [Greene, Stephen J.; Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Stockbridge, Norman L.] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [O'Connor, Christopher M.; Fiuzat, Mona; Mentz, Robert J.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pfeffer, Marc A.; Mehra, Mandeep R.; Solomon, Scott D.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Pfeffer, Marc A.; Mehra, Mandeep R.; Solomon, Scott D.] Harvard Univ, Sch Med, Boston, MA USA. [Yancy, Clyde W.] Northwestern Univ, Div Cardiol, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Collins, Sean P.] Vanderbilt Univ, Sch Med, Dept Emergency Med, Nashville, TN 37212 USA. [McMurray, John J. V.] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dunnmon, Preston M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rosano, Giuseppe M. C.] IRCC San Raffaele, Div Cardiol, Rome, Italy. [Dinh, Wilfried; Misselwitz, Frank] Bayer Pharma AG, Global Drug Discovery, Clin Sci, Expt Med, Berlin, Germany. [Dinh, Wilfried] Univ Witten Herdecke, Dept Cardiol, Witten, Germany. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron St,Galter 3-150, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Mehra, Mandeep/0000-0001-8683-7044; mcmurray, john/0000-0002-6317-3975 FU National Institutes of Health; European Union; Health Resource Services Administration; Food and Drug Administration; Amgen; Celladon; Novartis; Sanofi-Aventis; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline; Gilead; Otsuka; ResMed; NIH/NHLBI; Medtronic; Cardiorentis; Abbott Point-of-Care; Medicines Company; Astellas; Bayer Schering Pharma AG; DebioPharm S.A.; Novartis Pharma AG; Otsuka Pharmaceuticals; Sigma Tau; Solvay Pharmaceuticals; Sticares InterACT; Takeda Pharmaceuticals North America, Inc. FX JB.: Research support: National Institutes of Health, European Union, Health Resource Services Administration, Food and Drug Administration, Consultant: Amgen, Bayer, Celladon, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, Trevena, Stock options: Stemedica; G. C. F.: Research AHRQ significant, NHLBI significant, Consultant: Novartis significant, Medtronic modest, Bayer modest, Gambro modest, Janssen modest; C. M. O.: none; M.A.P.: Research Support: Amgen, Celladon, Novartis, Sanofi-Aventis, Consultant: Aastrom, Abbott Vascular, Amgen, Cerenis, Concert, Fibrogen, GlaxoSmithKline, Hamilton Health Sciences, Medtronic, Merck, Roche, Servier, Teva, University of Oxford; M. R. M.: Consultant: Boston Scientific, St. Jude's, Medtronic, Johnson and Johnson, ABIM, NIH/NHLBI, Baxter, Abbott Vascular, Thoratec; R. J. M. receives research support from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Novartis, Otsuka, and ResMed; honoraria from Thoratec; and has served on an advisory board for Luitpold Pharmaceuticals, Inc; S. P. C.: Research support: NIH/NHLBI, Medtronic, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Consultant: Trevena, Novartis, Otsuka, Radiometer, The Medicines Company, Medtronic, BRAHMS, Insys; J. J. V. M.: none; W. D. is a full time employee of Bayer Pharma; F. M. is a full time employee of Bayer Pharma; M. G.: Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG, Cardiorentis Ltd, CorThera, Cytokinetics, CytoPherx, Inc, DebioPharm S. A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, INC, Johnson and Johnson, Medtronic, Merck, Novartis Pharma AG, Ono Parmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT,Takeda Pharmaceuticals North America, Inc and Trevena Therapeutics; and has received significant (>$10,000) support from Bayer Schering Pharma AG, DebioPharm S.A., Medtronic, Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT and Takeda Pharmaceuticals North America, Inc. All others authors report no conflicts of interest. NR 43 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD JUL PY 2015 VL 20 IS 4 BP 375 EP 383 DI 10.1007/s10741-015-9473-z PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK2KK UT WOS:000356039000001 PM 25649127 ER PT J AU Vaduganathan, M Butler, J Roessig, L Fonarow, GC Greene, SJ Metra, M Cotter, G Kupfer, S Zalewski, A Sato, N Filippatos, G Gheorghiade, M AF Vaduganathan, Muthiah Butler, Javed Roessig, Lothar Fonarow, Gregg C. Greene, Stephen J. Metra, Marco Cotter, Gadi Kupfer, Stuart Zalewski, Andrew Sato, Naoki Filippatos, Gerasimos Gheorghiade, Mihai TI Clinical trials in hospitalized heart failure patients: targeting interventions to optimal phenotypic subpopulations SO HEART FAILURE REVIEWS LA English DT Article DE Clinical trials; Heart failure; Outcomes; Patient selection ID RELAX-AHF; EJECTION FRACTION; DRUG DEVELOPMENT; END-POINTS; STRATEGIES; GUIDELINES; REGISTRIES; SERELAXIN; TOLVAPTAN; ADMISSION AB With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?. C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Butler, Javed] Emory Univ Hosp, Div Cardiol, Atlanta, GA 30322 USA. [Roessig, Lothar] Novartis Pharmaceut, E Hanover, NJ USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Metra, Marco] Univ Brescia, Div Cardiol, Brescia, Italy. [Cotter, Gadi] Momentum Res Inc, Durham, NC USA. [Kupfer, Stuart] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Zalewski, Andrew] Bayer Pharma AG, Berlin, Germany. [Sato, Naoki] Musashi Kosugi Hosp, Dept Internal Med & Cardiol, Nippon Med Sch, Kawasaki, Kanagawa, Japan. [Filippatos, Gerasimos] Attikon Univ Hosp, Athens, Greece. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron St,Galter 3-150, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Metra, Marco/0000-0001-6691-8568 FU National Institutes of Health; European Union; Health Resource Services Administration; Food and Drug Administration; Agency for Healthcare Research and Quality FX Javed Butler: Research Support: National Institutes of Health, European Union, Health Resource Services Administration, Food and Drug Administration; Consultant: Amgen, Bayer, Celladon, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, Trevena; Stock Options: Stemedica. Lothar Roessig: Employee of Bayer Pharma AG. Gregg C Fonarow: Research support: Agency for Healthcare Research and Quality (significant), Consultant: Medtronic (modest), Gambro (significant), and Novartis (significant). Marco Metra: Received honoraria from Bayer, Corthera, Novartis, and Servier for speeches or participation in advisory boards/steering committees. Gadi Cotter: Employee of Momentum-Research, Inc. Stuart Kupfer: Employee of Takeda Global Research and Development Center, Inc. Andrew Zalewski: Employee of Novartis Pharmaceutical Corporation. Naoki Sato: Consultant to Chugai Pharmaceutical Company and honoraria from Daiichi-Sankyo, Otsuka, Philips Respironics, Astellas, Ono, Eisai, Chugai, Mitsubishi-Tanabe, Sanofi-Aventis, and Novartis pharmaceuticals. Mihai Gheorghiade: Consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. Muthiah Vaduganathan, Stephen J Greene, and Gerasimos Filippatos have no conflicts of interest or financial ties to disclose. NR 32 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD JUL PY 2015 VL 20 IS 4 BP 393 EP 400 DI 10.1007/s10741-015-9485-8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK2KK UT WOS:000356039000003 PM 25894076 ER PT J AU Yoong, SL Hall, A Williams, CM Skelton, E Oldmeadow, C Wiggers, J Karimkhani, C Boyers, LN Dellavalle, RP Hilton, J Wolfenden, L AF Yoong, Sze Lin Hall, Alix Williams, Christopher M. Skelton, Eliza Oldmeadow, Christopher Wiggers, John Karimkhani, Chante Boyers, Lindsay N. Dellavalle, Robert P. Hilton, John Wolfenden, Luke TI Alignment of systematic reviews published in the Cochrane Database of Systematic Reviews and the Database of Abstracts and Reviews of Effectiveness with global burden-of-disease data: a bibliographic analysis SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Review ID HEALTH-CARE; ASSOCIATION AB Background Systematic reviews of high-quality evidence are used to inform policy and practice. To improve community health, the production of such reviews should align with burden of disease. This study aims to assess if the volume of research output from systematic reviews proportionally aligns with burden of disease assessed using percentages of mortality and disability-adjusted life years (DALYs). Methods A cross-sectional audit of reviews published between January 2012 and August 2013 in the Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of Effects (DARE) was undertaken. Percentages of mortality and DALYs were obtained from the 2010 Global Burden of Disease study. Standardised residual differences (SRD) based on percentages of mortality and DALYs were calculated, where conditions with SRD of more than or less than three were considered overstudied or understudied, respectively. Results 1029 reviews from CDSR and 1928 reviews from DARE were examined. There was a significant correlation between percentage DALYs and systematic reviews published in CDSR and DARE databases (CDSR: r=0.68, p=0.001; DARE: r=0.60, p<0.001). There was no significant correlation between percentage mortality and number of systematic reviews published in either database (CDSR: r=0.34, p=0.14; DARE: r=0.22, p=0.34). Relative to percentage of mortality, mental and behavioural disorders, musculoskeletal conditions and other non-communicable diseases were overstudied. Maternal disorders were overstudied relative to percentages of mortality and DALYs in CDSR. Conclusions The focus of systematic reviews is moderately correlated with DALYs. A number of conditions may be overstudied relative to percentage of mortality particularly in the context of health and medical reviews. C1 [Yoong, Sze Lin; Williams, Christopher M.; Wiggers, John; Wolfenden, Luke] Hunter New England Populat Hlth, Wallsend, NSW 2287, Australia. [Yoong, Sze Lin; Hall, Alix; Williams, Christopher M.; Skelton, Eliza; Oldmeadow, Christopher; Wiggers, John; Wolfenden, Luke] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Yoong, Sze Lin; Hall, Alix; Williams, Christopher M.; Oldmeadow, Christopher; Wiggers, John; Wolfenden, Luke] Hunter Med Res Inst, New Lambton, NSW, Australia. [Oldmeadow, Christopher] George Inst Global Hlth, Sydney, NSW, Australia. [Karimkhani, Chante] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Dellavalle, Robert P.] Dermatol Serv, US Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Denver, CO USA. [Dellavalle, Robert P.] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Hilton, John] Cochrane Collaborat, Cochrane Editorial Unit, London, England. RP Yoong, SL (reprint author), Hunter New England Populat Hlth, Locked Bag 10, Wallsend, NSW 2287, Australia. EM Serene.Yoong@hnehealth.nsw.gov.au OI Hilton, John/0000-0002-1607-3250; Wolfenden, Luke/0000-0002-6178-3868 FU Australian National and Medical Research Council Career Development Fellowship [APP1041867]; US Department of Veterans Affairs; Centers for Disease Control and Prevention [CDC 3U48DP001938-0451]; National Institutes of Health [NCI R21 CA173654] FX This work was supported by the Hunter Medical Research Institute and Hunter New England Population Health through providing infrastructure support. LW is supported by an Australian National and Medical Research Council Career Development Fellowship APP1041867. RPD is supported by a salary from the US Department of Veterans Affairs and grants from the Centers for Disease Control and Prevention (CDC 3U48DP001938-0451 (PI:Crane), and the National Institutes of Health (NCI R21 CA173654 (PI:Walkocz). JH is an employee of The Cochrane Collaboration which produces the Cochrane Database of Systematic Reviews. NR 32 TC 1 Z9 1 U1 2 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JUL PY 2015 VL 69 IS 7 BP 708 EP 714 DI 10.1136/jech-2014-205389 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK4BS UT WOS:000356164200017 PM 25888595 ER PT J AU Paithankar, DY Sakamoto, FH Farinelli, WA Kositratna, G Blomgren, RD Meyer, TJ Faupel, LJ Kauvar, ANB Lloyd, JR Cheung, WL Owczarek, WD Suwalska, AM Kochanska, KB Nawrocka, AK Paluchowska, EB Podolec, KM Pirowska, MM Wojas-Pelc, AB Anderson, RR AF Paithankar, Dilip Y. Sakamoto, Fernanda H. Farinelli, William A. Kositratna, Garuna Blomgren, Richard D. Meyer, Todd J. Faupel, Linda J. Kauvar, Arielle N. B. Lloyd, Jenifer R. Cheung, Wang L. Owczarek, Witold D. Suwalska, Anna M. Kochanska, Katarzyna B. Nawrocka, Agnieszka K. Paluchowska, Elwira B. Podolec, Katarzyna M. Pirowska, Magdalena M. Wojas-Pelc, Anna B. Anderson, R. Rox TI Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID FREE-ELECTRON LASER; 13-CIS-RETINOIC ACID; PHOTODYNAMIC THERAPY; AMINOLEVULINIC ACID; HAIR-FOLLICLES; DRUG-DELIVERY; SKIN; VULGARIS; NANOPARTICLES; MICROSPHERES AB The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 1050 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P = 0.015) and 16 weeks (P = 0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris. C1 [Paithankar, Dilip Y.; Blomgren, Richard D.; Meyer, Todd J.; Faupel, Linda J.] Sebacia, Duluth, GA USA. [Sakamoto, Fernanda H.; Farinelli, William A.; Kositratna, Garuna; Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sakamoto, Fernanda H.; Farinelli, William A.; Kositratna, Garuna; Anderson, R. Rox] Harvard Univ, Sch Med, Boston, MA USA. [Kauvar, Arielle N. B.] New York Laser & Skin Care, New York, NY USA. [Lloyd, Jenifer R.] Lloyd Dermatol & Laser Ctr, Youngstown, OH USA. [Cheung, Wang L.] Univ Arkansas, Dept Pathol, Little Rock, AR 72204 USA. [Owczarek, Witold D.; Suwalska, Anna M.; Kochanska, Katarzyna B.; Nawrocka, Agnieszka K.; Paluchowska, Elwira B.] Mil Inst Med, Dept Dermatol, Warsaw, Poland. [Podolec, Katarzyna M.; Pirowska, Magdalena M.; Wojas-Pelc, Anna B.] Jagiellonian Univ, Dept Dermatol, Krakow, Poland. RP Paithankar, DY (reprint author), Sebacia Inc, 2905 Premiere Pkwy,Suite 150, Duluth, GA 30097 USA. EM dilip@sebacia.com FU Sebacia, Duluth, GA FX This research was sponsored by Sebacia, Duluth, GA. We acknowledge Apostolos G. Doukas, Stephanie Beall, and Anthony Lando for help with various stages of the project. NR 30 TC 9 Z9 10 U1 4 U2 18 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 JUL PY 2015 VL 135 IS 7 BP 1727 EP 1734 DI 10.1038/jid.2015.89 PG 8 WC Dermatology SC Dermatology GA CK4GB UT WOS:000356180100011 PM 25748556 ER PT J AU Lauss, M Haq, R Cirenajwis, H Phung, B Harbst, K Staaf, J Rosengren, F Holm, K Aine, M Jirstrom, K Borg, A Busch, C Geisler, J Lonning, PE Ringner, M Howlin, J Fisher, DE Jonsson, G AF Lauss, Martin Haq, Rizwan Cirenajwis, Helena Phung, Bengt Harbst, Katja Staaf, Johan Rosengren, Frida Holm, Karolina Aine, Mattias Jirstrom, Karin Borg, Ake Busch, Christian Geisler, Jurgen Lonning, Per E. Ringner, Markus Howlin, Jillian Fisher, David E. Jonsson, Goran TI Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; MAPK PATHWAY INHIBITORS; MALIGNANT-MELANOMA; GENE; CANCER; MUTATIONS; PROFILES; SURVIVAL; HYPERMETHYLATION; MELANOCYTES AB The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development and a lineage-specific oncogene in melanoma; a highly lethal cancer known for its unpredictable clinical course. MITF is regulated by multiple intracellular signaling pathways, although the exact mechanisms that determine MITF expression and activity remain incompletely understood. In this study, we obtained genome-wide DNA methylation profiles from 50 stage IV melanomas, normal melanocytes, keratinocytes, and dermal fibroblasts and utilized The Cancer Genome Atlas data for experimental validation. By integrating DNA methylation and gene expression data, we found that hypermethylation of MITF and its co-regulated differentiation pathway genes corresponded to decreased gene expression levels. In cell lines with a hypermethylated MITF-pathway, overexpression of MITF did not alter the expression level or methylation status of the MITF pathway genes. In contrast, however, demethylation treatment of these cell lines induced MITF-pathway activity, confirming that gene regulation was controlled via methylation. The discovery that the activity of the master regulator of pigmentation, MITF, and its downstream targets may be regulated by hypermethylation has significant implications for understanding the development and evolvement of melanoma. C1 [Lauss, Martin; Cirenajwis, Helena; Phung, Bengt; Harbst, Katja; Staaf, Johan; Rosengren, Frida; Holm, Karolina; Aine, Mattias; Jirstrom, Karin; Borg, Ake; Ringner, Markus; Howlin, Jillian; Jonsson, Goran] Lund Univ, Div Oncol & Pathol, Dept Clin Sci, S-22381 Lund, Sweden. [Lauss, Martin; Cirenajwis, Helena; Harbst, Katja; Staaf, Johan; Holm, Karolina; Borg, Ake; Ringner, Markus; Jonsson, Goran] Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden. [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Jirstrom, Karin] Skane Univ Hosp, Dept Clin Pathol, Lund, Sweden. [Busch, Christian; Lonning, Per E.] Univ Bergen, Inst Med, Sect Oncol, Bergen, Norway. [Geisler, Jurgen] Akershus Univ Hosp, Dept Clin Mol Biol & Lab Sci, Lorenskog, Norway. [Geisler, Jurgen] Univ Oslo, Inst Clin Med, Oslo, Norway. RP Jonsson, G (reprint author), Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Scheelevagen 2, S-22381 Lund, Sweden. EM Goran_B.Jonsson@med.lu.se RI Ringner, Markus/G-3641-2011; OI Ringner, Markus/0000-0001-5469-8940; Aine, Mattias/0000-0002-0851-5952 FU Swedish Cancer Society; Swedish Research Council; BioCARE; Berta Kamprad Foundation; Gunnar Nilsson Cancer Foundation; Gustav Vth Jubilee Foundation; Governmental Support for Medical Research FX The work was supported by the Swedish Cancer Society, The Swedish Research Council, BioCARE, Berta Kamprad Foundation, The Gunnar Nilsson Cancer Foundation, The Gustav Vth Jubilee Foundation, and Governmental Support for Medical Research. We thank Lars Ronnstrand for providing us with PLX4032. NR 43 TC 7 Z9 7 U1 0 U2 8 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 JUL PY 2015 VL 135 IS 7 BP 1820 EP 1828 DI 10.1038/jid.2015.61 PG 9 WC Dermatology SC Dermatology GA CK4GB UT WOS:000356180100021 PM 25705847 ER PT J AU Ji, ZY Chen, YE Kumar, R Taylor, M Njauw, CNJ Miao, BC Frederick, DT Wargo, JA Flaherty, KT Jonsson, G Tsao, H AF Ji, Zhenyu Chen, Yiyin Erin Kumar, Raj Taylor, Michael Njauw, Ching-Ni Jenny Miao, Benchun Frederick, Dennie T. Wargo, Jennifer A. Flaherty, Keith T. Jonsson, Goran Tsao, Hensin TI MITF Modulates Therapeutic Resistance through EGFR Signaling SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RAF INHIBITOR RESISTANCE; BRAF(V600E) INHIBITION; MAPK PATHWAY; MELANOMA; REACTIVATION; MEK; VEMURAFENIB; SENSITIVITY; GROWTH; CANCER AB Response to targeted therapies varies significantly despite shared oncogenic mutations. Nowhere is this more apparent than in BRAF (V600E)-mutated melanomas where initial drug response can be striking and yet relapse is commonplace. Resistance to BRAF inhibitors have been attributed to the activation of various receptor tyrosine kinases (RTKs), although the underlying mechanisms have been largely uncharacterized. Here, we found that EGFR-induced vemurafenib resistance is ligand dependent. We employed whole-genome expression analysis and discovered that vemurafenib resistance correlated with the loss of microphthalmia-associated transcription factor (MITF), along with its melanocyte lineage program, and with the activation of EGFR signaling. An inverse relationship between MITF, vemurafenib resistance, and EGFR was then observed in patient samples of recurrent melanoma and was conserved across melanoma cell lines and patients' tumor specimens. Functional studies revealed that MITF depletion activated EGFR signaling and consequently recapitulated the resistance phenotype. In contrast, forced expression of MITF in melanoma and colon cancer cells inhibited EGFR and conferred sensitivity to BRAF/MEK inhibitors. These findings indicate that an "autocrine drug resistance loop" is suppressed by melanocyte lineage signal(s), such as MITF. This resistance loop modulates drug response and could explain the unique sensitivity of melanomas to BRAF inhibition. C1 [Ji, Zhenyu; Chen, Yiyin Erin; Kumar, Raj; Taylor, Michael; Njauw, Ching-Ni Jenny; Miao, Benchun; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Frederick, Dennie T.; Flaherty, Keith T.; Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Surg Oncol & Genom Med, Houston, TX 77030 USA. [Jonsson, Goran] Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, Lund, Sweden. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Edwards 211,55 Fruit St, Boston, MA 02114 USA. EM htsao@mgh.harvard.edu FU National Institutes of Health [K24 CA149202, P01CA163222, 5T32CA071345, 5T32AR007098]; American Skin Association; Swedish Cancer Society; Swedish Research Council; Berta Kamprad Foundation; Gunnar Nilsson Cancer Foundation; Gustav Vth Jubilee Foundation FX This work was supported in part by the National Institutes of Health (K24 CA149202, P01CA163222, 5T32CA071345, and 5T32AR007098), the American Skin Association, and the generous donors to the MGH Millennium Melanoma Fund. The work was further supported by the Swedish Cancer Society, Swedish Research Council, Berta Kamprad Foundation, Gunnar Nilsson Cancer Foundation, and Gustav Vth Jubilee Foundation. NR 24 TC 9 Z9 9 U1 0 U2 6 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 JUL PY 2015 VL 135 IS 7 BP 1863 EP 1872 DI 10.1038/jid.2015.105 PG 10 WC Dermatology SC Dermatology GA CK4GB UT WOS:000356180100025 PM 25789707 ER PT J AU Ratushny, V Smith, GP AF Ratushny, Vladimir Smith, Gideon P. TI Geographical and Temporal Correlations in the Incidence of Lyme Disease, RMSF, Ehrlichiosis, and Coccidioidomycosis with Search Data SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID GOOGLE FLU TRENDS; VECTOR IXODES-SCAPULARIS; CLIMATE-CHANGE; BIG DATA; INFLUENZA C1 [Ratushny, Vladimir; Smith, Gideon P.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Ratushny, V (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM vratushny@partners.org NR 15 TC 0 Z9 0 U1 5 U2 13 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 JUL PY 2015 VL 135 IS 7 BP 1903 EP 1905 DI 10.1038/jid.2015.93 PG 3 WC Dermatology SC Dermatology GA CK4GB UT WOS:000356180100029 PM 25756797 ER PT J AU Wright, N Mazori, D Patel, M Lin, J Merola, J Femia, A Vleugels, R AF Wright, N. Mazori, D. Patel, M. Lin, J. Merola, J. Femia, A. Vleugels, R. TI Epidemiology and treatment of eosinophilic fasciitis: A retrospective analysis from three tertiary care centers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Medical-Dermatology-Society CY MAR 19, 2015 CL San Francisco, CA SP Med Dermatol Soc C1 [Wright, N.; Mazori, D.; Patel, M.; Merola, J.; Vleugels, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Femia, A.] New York Univ Langone Medical Center, New York, NY USA. [Lin, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 2015 VL 135 IS 7 MA 2 BP 1926 EP 1926 PG 1 WC Dermatology SC Dermatology GA CK4GB UT WOS:000356180100039 ER PT J AU Sforza, C Frigerio, A Mapelli, A Tarabbia, F Annoni, I Colombo, V Latiff, M Ferreira, CLP Rabbiosi, D Sidequersky, FV Zago, M Biglioli, F AF Sforza, Chiarella Frigerio, Alice Mapelli, Andrea Tarabbia, Filippo Annoni, Isabella Colombo, Valeria Latiff, Mahfuz Ferreira, Claudia L. Pimenta Rabbiosi, Dimitri Sidequersky, Fernanda V. Zago, Matteo Biglioli, Federico TI Double-powered free gracilis muscle transfer for smile reanimation: A longitudinal optoelectronic study SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Article DE Facial nerve paresis; 3D; Motion analysis; Mimetics; Asymmetry ID CLIMA EVALUATING SYSTEM; MASSETER MOTOR-NERVE; FACIAL REANIMATION; PARALYSIS; QUANTIFICATION; RECONSTRUCTION; INNERVATION; EXCURSION; MIMICRY; QUALITY AB The choice of the motor donor nerve is a crucial point in free flap transfer algorithms. In the case of unilateral facial paralysis, the contralateral healthy facial nerve can provide coordinated smile animation and spontaneous emotional expression, but with unpredictable axonal ingrowth into the recipient muscle. Otherwise, the masseteric nerve ipsilateral to the paralysis can provide a powerful neural input, without a spontaneous trigger of the smile. Harvesting a bulky muscular free flap may enhance the quantity of contraction but esthetic results are unpleasant. Therefore, the logical solution for obtaining high amplitude of smiling combined with spontaneity of movement is to couple the neural input: the contralateral facial nerve plus the ipsilateral masseteric nerve. Thirteen patients with unilateral dense facial paralysis underwent a one-stage facial reanimation with a gracilis flap powered by a double donor neural input, provided by both the ipsilateral masseteric nerve (coaptation by an end-to-end neurorrhaphy with the obturator nerve) and the contralateral facial nerve (coaptation through a cross-face nerve graft: end-to-end neurorrhaphy on the healthy side and end-to-side neurorrhaphy on the obturator nerve, distal to the masseteric/obturator neurorrhaphy). Their facial movements were evaluated with an optoelectronic motion analyzer. Before surgery, on average, the paretic side exhibited a smaller total three-dimensional mobility than the healthy side, with a 52% activation ratio and >30% of asymmetry. After surgery, the differences significantly decreased (analysis of variance (ANOVA), p < 0.05), with an activation ratio between 75% (maximum smile) and 91% (maximum smile with teeth clenching), and <20% of asymmetry. Similar modifications were seen for the performance of spontaneous smiles. The significant presurgical asymmetry of labial movements reduced after surgery. The use of a double donor neural input permitted both movements that were similar in force to that of the healthy side, and spontaneous movements elicited by emotional triggering. (C) 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Sforza, Chiarella; Mapelli, Andrea; Annoni, Isabella; Ferreira, Claudia L. Pimenta; Sidequersky, Fernanda V.; Zago, Matteo] Univ Milan, Fac Med & Chirurg, FARC, Dipartimento Sci Biomed Salute,LAFAL,LAFAS, I-20133 Milan, Italy. [Frigerio, Alice] Univ Milan, Fac Med & Chirurg, Dept Pathophysiol & Transplantat, Human Physiol Sect, I-20133 Milan, Italy. [Frigerio, Alice] Harvard Univ, Sch Med,Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, Boston, MA USA. [Mapelli, Andrea; Ferreira, Claudia L. Pimenta; Sidequersky, Fernanda V.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Sao Paulo, Brazil. [Tarabbia, Filippo; Colombo, Valeria; Latiff, Mahfuz; Rabbiosi, Dimitri; Biglioli, Federico] Univ Milan, San Paolo Hosp, Fac Med & Chirurg, Surg Unit Maxillofacial Surg, Milan, Italy. RP Sforza, C (reprint author), Dipartimento Sci Biomed Salute, Via Mangiagalli 31, I-20133 Milan, Italy. EM chiarella.sforza@unimi.it RI Zago, Matteo/B-1481-2015; Sidequersky, Fernanda/A-6032-2017; OI Zago, Matteo/0000-0002-0649-3665; mapelli, andrea/0000-0003-0476-836X; Sidequersky, Fernanda/0000-0001-9966-2386; Sforza, Chiarella/0000-0001-6532-6464; Rabbiosi, Dimitri/0000-0001-5207-2055; Frigerio, Alice/0000-0001-9202-9553 FU Ministerio da Ciencia e Tecnologia, MCT Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNP; University of Milan; CNPq, Brazil FX A. Mapelli is currently a recipient of a grant (Atracao de Jovens Talentos, Pesquisador Colaborador no Brasil, BJT, Programa Ciencia sem Fronteiras) from the Ministerio da Ciencia e Tecnologia, MCT Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNP; C.L. Pimenta Ferreira is a fellow of Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq (National Council for Scientific and Technological Development e CNPq, Brazil); F. Sidequersky received a scholarship from the University of Milan, and currently she has a scholarship from CNPq, Brazil (Bolsa Jovens Talentos). For the remaining authors, no conflicts of interest were declared. NR 18 TC 4 Z9 4 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 EI 1878-0539 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD JUL PY 2015 VL 68 IS 7 BP 930 EP 939 DI 10.1016/j.bjps.2015.03.029 PG 10 WC Surgery SC Surgery GA CK4ZO UT WOS:000356232100009 PM 26026222 ER PT J AU Bird, ER Gilmore, AK George, WH Lewis, MA AF Bird, E. R. Gilmore, A. K. George, W. H. Lewis, M. A. TI A CYCLE OF RISK? THE ROLE OF SOCIAL DRINKING FACTORS IN THE RELATIONSHIP BETWEEN INCAPACITATED SEXUAL ASSAULT AND DRINKING BEFORE SEX SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Bird, E. R.; George, W. H.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Gilmore, A. K.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98101 USA. [Lewis, M. A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2015 VL 12 SU 4 SI SI MA 038 BP 285 EP 285 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CK2VJ UT WOS:000356071800034 ER PT J AU Ring, D AF Ring, David TI Regarding "Distal peripheral neuropathy after open and arthroscopic shoulder surgery: an under-recognized complication'' SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUL PY 2015 VL 24 IS 7 BP E200 EP E200 DI 10.1016/j.jse.2015.03.020 PG 1 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA CK2OZ UT WOS:000356051700005 PM 25957109 ER PT J AU Strazzula, L Cotliar, J Fox, LP Hughey, L Shinkai, K Gee, SN Kroshinsky, D AF Strazzula, Lauren Cotliar, Jonathan Fox, Lindy P. Hughey, Lauren Shinkai, Kanade Gee, Sarah N. Kroshinsky, Daniela TI Inpatient dermatology consultation aids diagnosis of cellulitis among hospitalized patients: A multi-institutional analysis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antibiotics; cellulitis; contact dermatitis; internal medicine; medical dermatology; skin and soft-tissue infections; stasis dermatitis ID ERYSIPELAS; CARE AB Background: Given its nonspecific physical examination findings, accurately distinguishing cellulitis from a cellulitis mimicker (pseudocellulitis) is challenging. Objective: We sought to investigate the national incidence of cellulitis misdiagnosis among inpatients. Methods: We conducted a retrospective review of inpatient dermatology consultations at Massachusetts General Hospital, University of Alabama at Birmingham Medical Center, University of California Los Angeles Medical Center, and University of California San Francisco Medical Center in 2008. All consults requested for the evaluation of cellulitis were included. The primary outcomes were determining the incidence of cellulitis misdiagnosis, evaluating the prevalence of associated risk factors, and identifying common pseudocellulitides. Results: Of the 1430 inpatient dermatology consultations conducted in 2008, 74 (5.17%) were requested for the evaluation of cellulitis. In all, 55 (74.32%) patients evaluated for cellulitis were given a diagnosis of pseudocellulitis. There was no statistically significant difference in the rate of misdiagnosis across institutions (P = .12). Patient demographics and associated risk factor prevalence did not statistically vary in patients given a diagnosis of cellulitis versus those with pseudocellulitis (P > .05). Limitations: This study was unable to evaluate all patients admitted with cellulitis and was conducted at tertiary care centers, which may affect the generalizability of the results. Conclusions: Cellulitis is commonly misdiagnosed in the inpatient setting. Involving dermatologists may improve diagnostic accuracy and decrease unnecessary antibiotic use. C1 [Strazzula, Lauren; Kroshinsky, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cotliar, Jonathan] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Fox, Lindy P.; Shinkai, Kanade] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Hughey, Lauren] Univ Alabama Birmingham, Birmingham, AL USA. [Gee, Sarah N.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM dkroshinsky@mgh.harvard.edu NR 18 TC 12 Z9 12 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2015 VL 73 IS 1 BP 70 EP 75 DI 10.1016/j.jaad.2014.11.012 PG 6 WC Dermatology SC Dermatology GA CK6BZ UT WOS:000356314100026 PM 26089048 ER PT J AU Linos, E Berger, T Chren, MM AF Linos, Eleni Berger, Timothy Chren, Mary-Margaret TI Point: Care of potential low-risk basal cell carcinomas (BCCs) at the end of life The key role of the dermatologist SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material DE basal cell carcinoma; elders; end of life; skin cancer; squamous cell carcinoma ID SKIN-CANCER C1 [Linos, Eleni; Berger, Timothy; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Berger, Timothy; Chren, Mary-Margaret] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. RP Linos, E (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Room N421,Mail Code Box 0808, San Francisco, CA 94143 USA. EM linose@derm.ucsf.edu OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU NCATS NIH HHS [KL2TR000143]; NIA NIH HHS [P30AG044281]; NIAMS NIH HHS [5K24AR052667-09] NR 9 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2015 VL 73 IS 1 BP 158 EP 161 DI 10.1016/j.jaad.2015.02.005 PG 4 WC Dermatology SC Dermatology GA CK6BZ UT WOS:000356314100038 PM 26089051 ER PT J AU Tsao, CK Gray, KP Nakabayashi, M Evan, C Kantoff, PW Huang, JT Galsky, MD Pomerantz, M Oh, WK AF Tsao, Che-kai Gray, Kathryn P. Nakabayashi, Mari Evan, Carolyn Kantoff, Philip W. Huang, Jiaoti Galsky, Matthew D. Pomerantz, Mark Oh, William K. TI Patients with Biopsy Gleason 9 and 10 Prostate Cancer Have Significantly Worse Outcomes Compared to Patients with Gleason 8 Disease SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; biopsy; neoplasm grading; prognosis; mortality ID RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; RADIATION-THERAPY; PATTERN 5; RADIOTHERAPY; PROGRESSION; CARCINOMA AB Purpose: We examined differences in outcome in patients with biopsy Gleason score 8 vs 9-10 who received definitive local therapy. Materials and Methods: Using an institutional database we identified a cohort of 847 patients with biopsy Gleason 8-10 disease who received definitive local therapy with radiation therapy or radical prostatectomy between January 2001 and December 2011. Multivariable Cox modeling was used to assess the association of Gleason score 8 vs 9-10 with time to biochemical recurrence, metastasis and overall survival, and evaluate treatment by Gleason score interaction. Median followup in the cohort was 5.3 years. Results: Baseline patient characteristics were similar for biopsy Gleason 8 vs 9-10. Gleason 9-10 disease was associated with higher prostate specific antigen at diagnosis. As local treatment such patients were also more likely to have received radiation therapy (58% vs 46%, p = 0.001) and neoadjuvant/adjuvant androgen deprivation therapy (64% vs 49%, p < 0.001). Those with higher grade disease were at increased risk for metastasis (HR 1.41, 95% CI 1.11-1.79). There was a trend toward an increased risk of death in Gleason 9-10 vs 8 cases (HR 1.28, 95% CI 0.98-1.66). The increased risk of death for Gleason 9-10 was mainly observed in patients treated with radical prostatectomy with or without additional radiation therapy (HR 1.74, 95% CI 1.15-2.65). Conclusions: Patients with localized biopsy Gleason 9-10 disease treated with definitive local therapy had worse outcomes than those diagnosed with biopsy Gleason 8 disease. Clinical trials are urgently needed that incorporate newer approaches to Gleason 9-10 cancer. C1 [Tsao, Che-kai; Galsky, Matthew D.; Oh, William K.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Gray, Kathryn P.; Nakabayashi, Mari; Evan, Carolyn; Kantoff, Philip W.; Pomerantz, Mark] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Huang, Jiaoti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. RP Tsao, CK (reprint author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM Che-kai.tsao@mssm.edu NR 15 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JUL PY 2015 VL 194 IS 1 BP 91 EP 97 DI 10.1016/j.juro.2015.01.078 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CK2AQ UT WOS:000356012100024 PM 25623747 ER PT J AU Yu, MK Katon, W Young, BA AF Yu, Margaret K. Katon, Wayne Young, Bessie A. TI Associations between sex and incident chronic kidney disease in a prospective diabetic cohort SO NEPHROLOGY LA English DT Article DE chronic renal insufficiency; diabetes mellitus; health disparity; vulnerable population; women's health ID GLOMERULAR-FILTRATION-RATE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; SELF-CARE; DEPRESSION; CKD; NEPHROPATHY; DISPARITIES; MELLITUS; MDRD AB AimWomen with diabetes have a higher prevalence of chronic kidney disease (CKD) risk factors compared with men, but whether they are at higher risk for incident CKD remains uncertain. MethodsThis was a prospective, observational cohort study of 1464 patients with diabetes and normal renal function, recruited from primary care clinics at a vertically integrated healthcare system in Seattle, WA, USA. The primary predictor was sex. Incident CKD was defined by an estimated glomerular filtration rate (eGFR)<60mL/min per 1.73m(2) by Chronic Kidney Disease-Epidemiology equations or sex-specific microalbuminuria (urine albumin/creatinine ratio 25mg/g for women or 17mg/g for men). ResultsOf the 1464 patients (52.0% women), CKD incidence rates were 154.0 and 144.3 cases per 1000 patient-years for women and men, respectively. In the competing risks regression, women had an increased risk of incident CKD (sub-hazard ratio 1.37, 95% confidence interval (CI) 1.17, 1.60) compared with men after adjustment for demographics, baseline eGFR and duration of diabetes, which persisted after additional adjustment for CKD risk factors, depressive symptoms and diabetes self-care (sub-hazard ratio 1.35, 95% CI 1.15, 1.59). Sex differences in incident CKD were consistent across age groups and appeared to be driven by differences in the development of low eGFR rather than microalbuminuria. ConclusionWomen with diabetes had a higher risk of incident CKD compared with men, which could not be entirely explained by differences in biologic CKD risk factors, depression or diabetes self-care. Additional work is needed determine if these sex differences contribute to worse outcomes in women with diabetes. Summary at a Glance The authors have evaluated associations between sex and chronic kidney disease (CKD) incidence in a primary care population with diabetes using Chronic Kidney Disease-Epidemiology equations for estimating glomerular filtration rate (GFR) and sex-specific definitions of microalbuminuria. They found that women had an increased risk of incident CKD compared with men. They also found that this difference in incident CKD was primarily driven by differences in incident eGFR<60mL/min per 1.73m(2). C1 [Yu, Margaret K.; Young, Bessie A.] VA Puget Sound Hlth Care Syst, Ctr Innovat, VA Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Katon, Wayne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Yu, Margaret K.; Young, Bessie A.] Kidney Res Inst, Seattle, WA USA. RP Yu, MK (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way Suite 1400, Seattle, WA 98101 USA. EM mkyu@uw.edu FU National Institutes of Health National Institute of Diabetes, Digestive, and Kidney Diseases [DK079745]; National Institute of Mental Health [MH41739, MH01643]; American Kidney Fund; VA Advanced Fellowship Program in Health Services Research and Development; American Kidney Fund's Clinical Scientist in Nephrology Program; VA Puget Sound Health Care System FX This work was supported by research grants by the National Institutes of Health National Institute of Diabetes, Digestive, and Kidney Diseases (DK079745) and National Institute of Mental Health (MH41739, MH01643) and the American Kidney Fund. Dr. Yu was supported by the VA Advanced Fellowship Program in Health Services Research and Development and the American Kidney Fund's Clinical Scientist in Nephrology Program. Dr. Young was supported by the VA Puget Sound Health Care System. The study sponsor had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. NR 32 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 EI 1440-1797 J9 NEPHROLOGY JI Nephrology PD JUL PY 2015 VL 20 IS 7 BP 451 EP 458 DI 10.1111/nep.12468 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CK2ZK UT WOS:000356084100003 PM 25807970 ER PT J AU Dumas, O Varraso, R Zock, JP Henneberger, PK Speizer, FE Wiley, AS Le Moual, N Camargo, CA AF Dumas, Orianne Varraso, Raphaelle Zock, Jan Paul Henneberger, Paul K. Speizer, Frank E. Wiley, Aleta S. Le Moual, Nicole Camargo, Carlos A., Jr. TI Asthma history, job type and job changes among US nurses SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID WORK-RELATED ASTHMA; HEALTH-CARE PROFESSIONALS; IN-HOSPITAL WORKERS; ADULT-ONSET ASTHMA; OCCUPATIONAL EXPOSURES; RESPIRATORY SYMPTOMS; CLEANING PRODUCTS; SURVEILLANCE DATA; YOUNG-ADULTS; NEW-JERSEY AB Objectives Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. Methods The Nurses' Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 2444 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. Results The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). Conclusions Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses. C1 [Dumas, Orianne; Speizer, Frank E.; Wiley, Aleta S.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Dumas, Orianne; Speizer, Frank E.; Wiley, Aleta S.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Dumas, Orianne; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Varraso, Raphaelle; Le Moual, Nicole] INSERM, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, U1168, F-94807 Villejuif, France. [Varraso, Raphaelle; Le Moual, Nicole] Univ Versailles St Quentin En Yvelines, UMR S 1168, UVSQ, St Quentin En Yveline, France. [Zock, Jan Paul] Netherlands Inst Hlth Serv Res NIVEL, Utrecht, Netherlands. [Henneberger, Paul K.] NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Dumas, O (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM orianne.dumas@channing.harvard.edu RI Varraso, Raphaelle/R-8740-2016; LeMoual, Nicole/R-8976-2016 OI Varraso, Raphaelle/0000-0002-3338-7825; LeMoual, Nicole/0000-0002-2723-5569 FU Centers for Disease Control and Prevention [R01 OH-10359]; National Institutes of Health [UM1 CA176726]; Fondation pour la Recherche Medicale [SPE20130326585]; Fond de dotation Recherche en Sante Respiratoire FX Centers for Disease Control and Prevention R01 OH-10359; National Institutes of Health UM1 CA176726; Fondation pour la Recherche Medicale SPE20130326585 and Fond de dotation Recherche en Sante Respiratoire 2013. NR 41 TC 5 Z9 5 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUL PY 2015 VL 72 IS 7 BP 482 EP 488 DI 10.1136/oemed-2014-102547 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK5WR UT WOS:000356298200005 PM 25713153 ER PT J AU Fisichella, PM Jalilvand, A Lebenthal, A AF Fisichella, P. Marco Jalilvand, Anahita Lebenthal, Abraham TI Diagnostic Evaluation of Achalasia: From the Whalebone to the Chicago Classification SO WORLD JOURNAL OF SURGERY LA English DT Article ID ESOPHAGEAL PRESSURE TOPOGRAPHY; HIGH-RESOLUTION MANOMETRY; MOTILITY DISORDERS; CRITERIA; MYOTOMY; HELLER AB From the earliest description of dysphagia relieved by dilatation with a whalebone in 1674 we have witnessed the evolution of esophageal function testing from the conventional manometry to the high-resolution manometry (HRM) and esophageal topography pressure plotting that have led to the revised Chicago classification for esophageal motility disorders in 2014. The goals of this paper are, therefore, (1) to highlight the historical milestones that have led to the diagnostic definition of achalasia, as we know it today; (2) to describe the evaluation process of patients with suspected achalasia; (3) to describe the diagnostic value of the HRM and the usefulness of the Chicago classification in predicting treatment outcomes. The value of Chicago classification is linked to the ability of the clinician to perform a thorough clinical evaluation to identify and correlate specific clinical phenotypes to specific manometric subtypes and predict treatment outcomes. Chicago classification, however, cannot predict which treatment, pneumatic dilatation, or Heller myotomy, should be selected for those with a specific subtype of achalasia. C1 [Fisichella, P. Marco; Lebenthal, Abraham] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Fisichella, P. Marco; Lebenthal, Abraham] Boston VA Healthcare Syst, Dept Surg, West Roxbury, MA 02132 USA. [Jalilvand, Anahita] Ohio State Univ, Dept Surg, Cleveland, OH USA. RP Fisichella, PM (reprint author), Boston VA Healthcare Syst, Dept Surg, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM marco6370@yahoo.com NR 18 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2015 VL 39 IS 7 BP 1593 EP 1597 DI 10.1007/s00268-014-2939-7 PG 5 WC Surgery SC Surgery GA CJ7SH UT WOS:000355698900002 PM 25575460 ER PT J AU Fisichella, PM Jalilvand, A Dobrowolsky, A AF Fisichella, P. Marco Jalilvand, Anahita Dobrowolsky, Adrian TI Achalasia and Epiphrenic Diverticulum SO WORLD JOURNAL OF SURGERY LA English DT Article ID ESOPHAGEAL DIVERTICULA; SURGICAL-TREATMENT; HELLER MYOTOMY; FUNDOPLICATION; OUTCOMES; SURGERY AB Epiphrenic diverticula are a rare disease almost always associated with an underlying motility disorder of the esophagus, such as achalasia. Treatment of any underlying motility disorder must be included in the management of epiphrenic diverticula to prevent postoperative complications and recurrences. Therefore, the goal of this paper is to describe the pathophysiology, clinical presentation, and proper methods of diagnosis and treatment of patients with epiphrenic diverticula. In addition, we aim to provide an overview of the surgical management and discuss the indications for surgery and choice of surgical approach. In general, surgical intervention is favored for symptomatic patients and the optimal surgical approach depends on the size and location of the diverticulum. Surgery is not without seemingly high rates of morbidity when a myotomy is not performed together with the diverticulectomy, even in those with normal manometry. The risk of carcinoma is exceedingly rare and it is usually discovered at later stages; therefore, no surveillance programs have been established in asymptomatic patients with unresected diverticula. C1 [Fisichella, P. Marco] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Fisichella, P. Marco] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Boston, MA 02115 USA. [Jalilvand, Anahita] Ohio State Univ, Dept Surg, Cleveland, OH USA. [Dobrowolsky, Adrian] Loyola Univ Chicago, Dept Surg, Maywood, IL USA. RP Fisichella, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. EM piero.fisichella@va.gov NR 24 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2015 VL 39 IS 7 BP 1614 EP 1619 DI 10.1007/s00268-015-2950-7 PG 6 WC Surgery SC Surgery GA CJ7SH UT WOS:000355698900006 PM 25609118 ER PT J AU Young, AMH Karri, SK Helmy, A Budohoski, KP Kirolloski, RW Bulters, DO Kirkpatrick, PJ Ogilvy, CS Trivedi, RA AF Young, Adam M. H. Karri, Surya K. Helmy, Adel Budohoski, Karol P. Kirolloski, Ramez W. Bulters, Diederik O. Kirkpatrick, Peter J. Ogilvy, Christopher S. Trivedi, Rikin A. TI Pharmacologic Management of Subarachnoid Hemorrhage SO WORLD NEUROSURGERY LA English DT Article DE Mortality; Outcome; Subarachnoid hemorrhage; Therapy ID CEREBRAL-BLOOD-FLOW; ENDOTHELIN RECEPTOR ANTAGONIST; HIGH-DOSE METHYLPREDNISOLONE; RANDOMIZED CONTROLLED-TRIAL; VEHICLE-CONTROLLED TRIAL; DOUBLE-BLIND; TIRILAZAD MESYLATE; ANTIFIBRINOLYTIC THERAPY; MAGNESIUM-SULFATE; INTRACRANIAL ANEURYSMS AB Subarachnoid hemorrhage (SAH) remains a condition with suboptimal functional outcomes, especially in the young population. Pharmacotherapy has an accepted role in several aspects of the disease and an emerging role in several others. No preventive pharmacologic interventions for SAH currently exist. Antiplatelet medications as well as anticoagulation have been used to prevent thromboembolic events after endovascular coiling. However, the main focus of pharmacologic treatment of SAH is the prevention of delayed cerebral ischemia (DCI). Currently the only evidence-based medical intervention is nimodipine. Other calcium channel blockers have been evaluated without convincing efficacy. Anti-inflammatory drugs such as statins have demonstrated early potential; however, they failed to provide significant evidence for the use in preventing DCI. Similar findings have been reported for magnesium, which showed potential in experimental studies and a phase 2 trial. Clazosentane, a potent endothelin receptor antagonist, did not translate to improve functional outcomes. Various other neuroprotective agents have been used to prevent DCI; however, the results have been, at best inconclusive. The prevention of DCI and improvement in functional outcome remain the goals of pharmacotherapy after the culprit lesion has been treated in aneurysmal SAH. Therefore, further research to elucidate the exact mechanisms by which DCI is propagated is clearly needed. In this article, we review the current pharmacologic approaches that have been evaluated in SAH and highlight the areas in which further research is needed. C1 [Young, Adam M. H.; Helmy, Adel; Budohoski, Karol P.; Kirolloski, Ramez W.; Bulters, Diederik O.; Kirkpatrick, Peter J.; Trivedi, Rikin A.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Div Neurosurg, Cambridge CB2 2QQ, England. [Young, Adam M. H.; Karri, Surya K.; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Boston, MA USA. RP Young, AMH (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Div Neurosurg, Cambridge CB2 2QQ, England. EM ay276@cam.ac.uk NR 74 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JUL PY 2015 VL 84 IS 1 BP 28 EP 35 DI 10.1016/j.wneu.2015.02.004 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CK5DK UT WOS:000356242200012 PM 25701766 ER PT J AU Sayer, NA Orazem, RJ Noorbaloochi, S Gravely, A Frazier, P Carlson, KF Schnurr, PP Oleson, H AF Sayer, Nina A. Orazem, Robert J. Noorbaloochi, Siamak Gravely, Amy Frazier, Patricia Carlson, Kathleen F. Schnurr, Paula P. Oleson, Heather TI Iraq and Afghanistan War Veterans with Reintegration Problems: Differences by Veterans Affairs Healthcare User Status SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Veterans; Healthcare service needs; Mental health; Posttraumatic stress disorder; Traumatic brain injury; Department of Veterans Affairs Healthcare ID TRAUMATIC BRAIN-INJURY; FREEDOM VETERANS; BINGE DRINKING; MEDICAL-CARE; DEPLOYMENT; MILITARY; SOLDIERS; DIAGNOSES; SERVICES; RISK AB We studied 1,292 Iraq and Afghanistan War veterans who participated in a clinical trial of expressive writing to estimate the prevalence of perceived reintegration difficulty and compare Veterans Affairs (VA) healthcare users to nonusers in terms of demographic and clinical characteristics. About half of participants perceived reintegration difficulty. VA users and nonusers differed in age and military background. Levels of mental and physical problems were higher in VA users. In multivariate analysis, military service variables and probable traumatic brain injury independently predicted VA use. Findings demonstrate the importance of research comparing VA users to nonusers to understand veteran healthcare needs. C1 [Sayer, Nina A.; Orazem, Robert J.; Noorbaloochi, Siamak; Gravely, Amy; Oleson, Heather] Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Sayer, Nina A.; Noorbaloochi, Siamak] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Frazier, Patricia] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Carlson, Kathleen F.] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Sayer, NA (reprint author), Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, One Vet Dr, Minneapolis, MN 55417 USA. EM nina.sayer@va.gov RI Sayer, Nina/E-3249-2016 FU Department of Veterans Affairs (VA); Health Services Research and Development (HSRD) Service [DHI-07-150]; Department of Defense (DoD) [08-2-0045] FX This research was supported by the Department of Veterans Affairs (VA), Health Services Research and Development (HSR&D) Service (Grant No. DHI-07-150) and the Department of Defense (DoD) (Grant No. 08-2-0045). The sponsors were not involved in any aspect of the study's design and conduct; data collection, management, analysis, or interpretation of data; or in the preparation, review or approval of the manuscript. The findings and conclusions presented in this manuscript are those of the authors and do not necessarily represent the views of the VA, HSR&D, or DoD. NR 39 TC 5 Z9 5 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2015 VL 42 IS 4 BP 493 EP 503 DI 10.1007/s10488-014-0564-2 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CJ7EC UT WOS:000355656100012 PM 24913102 ER PT J AU Zorbas, KA Economopoulos, KP Vlahos, NF AF Zorbas, Konstantinos A. Economopoulos, Konstantinos P. Vlahos, Nikos F. TI Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Review DE Endometriosis; Continuous; Cyclic; Oral contraceptives; Pelvic pain; Dysmenorrhea ID LAPAROSCOPIC EXCISION; OVARIAN ENDOMETRIOMAS; CONSERVATIVE SURGERY; TRIAL; WOMEN; PAIN; RECURRENCE; QUALITY; PLACEBO; TISSUE AB Purpose Recurrence of endometriosis after conservative surgery has been observed in 40-50 % of patients within the first 5 years. A variety of regimens such as combined oral contraceptives, GnRH agonists, danazol, and progestins have been used postoperatively to reduce recurrence rates. Oral contraceptives (oCP) have been used either in a cyclic or in a continuous (no pill-free interval) fashion. The purpose of this article was to summarize the existing evidence on the efficacy and patient compliance for the use of oCP in a continuous versus cyclic fashion following conservative surgery for endometriosis. Methods A systematic search of Medline identified four eligible studies. Studies were considered eligible, if they have evaluated oCP therapy, either in a cyclic or continuous regimen, after conservative surgery for endometriosis. Specifically, studies (1) reporting on women with endometriosis who were treated postoperatively with both continuous oCP and cyclic oCP, (2) written in English, (3) with minimum 6 months duration of medical treatment, and (4) with minimum 12 months duration of follow-up were considered eligible for our systematic review. Outcome measures of these eligible studies were tabulated and then analyzed cumulatively. A purely descriptive approach was adopted concerning all variables. Results Postoperative use of continuous oCP was associated with a reduction in the recurrence rate of dysmenorrhea, delay in the presentation of dysmenorrhea, reduction in nonspecific pelvic pain, and reduction in the recurrence rate for endometrioma. Conclusions Use of oCP in a continuous fashion following conservative surgery for endometriosis is more beneficial to cyclic use. C1 [Zorbas, Konstantinos A.] Gen Hosp Veria, Dept Obstet & Gynecol, Veria, Greece. [Zorbas, Konstantinos A.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vlahos, Nikos F.] Univ Athens, Sch Med, Dept Obstet & Gynecol 2, Aretaie Hosp, GR-11527 Athens, Greece. RP Economopoulos, KP (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, 101 Merrimack St, Boston, MA 02114 USA. EM keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 29 TC 17 Z9 17 U1 5 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 EI 1432-0711 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD JUL PY 2015 VL 292 IS 1 BP 37 EP 43 DI 10.1007/s00404-015-3641-1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CJ7ES UT WOS:000355657800006 PM 25644508 ER PT J AU Derringer, J Corley, RP Haberstick, BC Young, SE Demmitt, BA Howrigan, DP Kirkpatrick, RM Iacono, WG McGue, M Keller, MC Brown, S Tapert, S Hopfer, CJ Stallings, MC Crowley, TJ Rhee, SH Krauter, K Hewitt, JK McQueen, MB AF Derringer, Jaime Corley, Robin P. Haberstick, Brett C. Young, Susan E. Demmitt, Brittany A. Howrigan, Daniel P. Kirkpatrick, Robert M. Iacono, William G. McGue, Matt Keller, Matthew C. Brown, Sandra Tapert, Susan Hopfer, Christian J. Stallings, Michael C. Crowley, Thomas J. Rhee, Soo Hyun Krauter, Ken Hewitt, John K. McQueen, Matthew B. TI Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample SO BEHAVIOR GENETICS LA English DT Article DE Behavioral disinhibition; GWAS; Pathway analysis; Heritability ID QUANTITATIVE TRAIT LOCI; ALCOHOL DEPENDENCE; SUBSTANCE DEPENDENCE; NICOTINE DEPENDENCE; GENETIC INFLUENCE; SMOKING-BEHAVIOR; RISK LOCI; METAANALYSIS; VARIANTS; IDENTIFY AB Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p a parts per thousand currency sign 2.0 x 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD. C1 [Derringer, Jaime] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Corley, Robin P.; Haberstick, Brett C.; Young, Susan E.; Demmitt, Brittany A.; Keller, Matthew C.; Stallings, Michael C.; Rhee, Soo Hyun; Krauter, Ken; Hewitt, John K.; McQueen, Matthew B.] Univ Colorado, Boulder, CO 80309 USA. [Howrigan, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kirkpatrick, Robert M.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Iacono, William G.; McGue, Matt] Univ Minnesota, Minneapolis, MN USA. [Brown, Sandra; Tapert, Susan] Univ Calif San Diego, La Jolla, CA 92093 USA. [Hopfer, Christian J.; Crowley, Thomas J.] Univ Colorado, Denver, CO 80202 USA. RP Derringer, J (reprint author), Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. EM jderr@illinois.edu OI Derringer, Jaime/0000-0002-7352-9859 FU National Institute on Drug Abuse [P60 DA011015, R01 DA012845, R01 DA021913, R01 DA021905, DA05147, DA13240, DA024417]; USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism [AA09367, AA11886]; National Institute of Mental Health [MH066140, T32 MH016880]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; NIH [HHSN268200782096C] FX The Center on Antisocial Drug Dependence (CADD) data reported here were funded by grants from the National Institute on Drug Abuse (P60 DA011015, R01 DA012845, R01 DA021913, R01 DA021905). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886), the National Institute on Drug Abuse (DA05147, DA13240, and DA024417), and the National Institute of Mental Health (MH066140). Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease'' (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. Jaime Derringer was supported by the National Institute of Mental Health (T32 MH016880). NR 46 TC 8 Z9 8 U1 6 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 EI 1573-3297 J9 BEHAV GENET JI Behav. Genet. PD JUL PY 2015 VL 45 IS 4 BP 375 EP 381 DI 10.1007/s10519-015-9705-y PG 7 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA CJ8KJ UT WOS:000355748700001 PM 25637581 ER PT J AU Papesh, MA Billings, CJ Baltzell, LS AF Papesh, Melissa A. Billings, Curtis J. Baltzell, Lucas S. TI Background noise can enhance cortical auditory evoked potentials under certain conditions SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Electroencephalography; Event related potential; Hearing; Human; Presentation rate; Speech ID STOCHASTIC RESONANCE; BINAURAL INTERACTION; NEUROMAGNETIC FIELDS; MIDDLE-LATENCY; COCHLEAR-NERVE; HEARING-LOSS; BRAIN-STEM; SPEECH; RESPONSES; STIMULATION AB Objective: To use cortical auditory evoked potentials (CAEPs) to understand neural encoding in background noise and the conditions under which noise enhances CAEP responses. Methods: CAEPs from 16 normal-hearing listeners were recorded using the speech syllable/ba/presented in quiet and speech-shaped noise at signal-to-noise ratios of 10 and 30 dB. The syllable was presented binaurally and monaurally at two presentation rates. Results: The amplitudes of N1 and N2 peaks were often significantly enhanced in the presence of low-level background noise relative to quiet conditions, while P1 and P2 amplitudes were consistently reduced in noise. P1 and P2 amplitudes were significantly larger during binaural compared to monaural presentations, while N1 and N2 peaks were similar between binaural and monaural conditions. Conclusions: Methodological choices impact CAEP peaks in very different ways. Negative peaks can be enhanced by background noise in certain conditions, while positive peaks are generally enhanced by binaural presentations. Significance: Methodological choices significantly impact CAEPs acquired in quiet and in noise. If CAEPs are to be used as a tool to explore signal encoding in noise, scientists must be cognizant of how differences in acquisition and processing protocols selectively shape CAEP responses. Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Papesh, Melissa A.; Billings, Curtis J.; Baltzell, Lucas S.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97207 USA. [Billings, Curtis J.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. RP Papesh, MA (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM Melissa.Papesh@va.gov FU NIH-NIDCD [R03DC010914]; VA-RRD [CoE C4844C] FX This work was supported by NIH-NIDCD (R03DC010914) and VA-RR&D (CoE C4844C). These funding sources had no role in the design, interpretation, or publishing of this work. NR 43 TC 2 Z9 2 U1 3 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2015 VL 126 IS 7 BP 1319 EP 1330 DI 10.1016/j.clinph.2014.10.017 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ9QF UT WOS:000355836600008 PM 25453611 ER PT J AU Mehndiratta, A Rabinov, JD Grasruck, M Liao, EC Crandell, D Gupta, R AF Mehndiratta, Amit Rabinov, James D. Grasruck, Michael Liao, Eric C. Crandell, David Gupta, Rajiv TI High-resolution dynamic angiography using flat-panel volume CT: feasibility demonstration for neuro and lower limb vascular applications SO EUROPEAN RADIOLOGY LA English DT Article DE Dynamic imaging; CT angiography; Intracranial aneurysm; Limb ischaemia; Digital flat panel detectors ID BREAST RECONSTRUCTION; PERFUSION AB This paper evaluates a prototype flat-panel volume CT (fpVCT) for dynamic in vivo imaging in a variety of neurovascular and lower limb applications. Dynamic CTA was performed on 12 patients (neuro = 8, lower limb = 4) using an fpVCT with 120 kVp, 50 mA, rotation time varying from 8 to 19 s, and field of view of 25 x 25 x 18 cm(3). Four-dimensional data sets (i.e. 3D images over time) were reconstructed and reviewed. Dynamic CTA demonstrated sufficient spatio-temporal resolution to elucidate first-pass and recirculation dynamics of contrast bolus through neurovasclaur pathologies and phasic blood flow though lower-limb vasculature and grafts. The high spatial resolution of fpVCT resulted in reduced partial volume and metal beam-hardening artefacts. This facilitated assessment of vascular lumen in the presence of calcified plaque and evaluation of fractures, especially in the presence of fixation hardware. Evaluation of arteriovenous malformation using dynamic fpVCT angiography was of limited utility. Dynamic CTA using fpVCT can visualize time-varying phenomena in neuro and lower limb vascular applications and has suffcient diagnostic imaging quality to evaluate a number of pathologies affecting these regions. aEuro cent CTA using fpVCT has sufficient spatial and temporal resolution to study phasic blood flow. aEuro cent CTA using fpVCT reveals recurrence of aneurysms even after clipping/coiling. aEuro cent fpVCT has reduced partial volume and metal beam-hardening artefacts. aEuro cent fpVCT can show vessel lumen in the presence of calcified plaque. aEuro cent CTA using fpVCT can demonstrate vascular supply to transplanted grafts. C1 [Mehndiratta, Amit; Gupta, Rajiv] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mehndiratta, Amit] Univ Oxford, Inst Biomed Engn, Oxford, England. [Mehndiratta, Amit] Univ Oxford Keble Coll, Oxford OX1 3PG, England. [Mehndiratta, Amit] Indian Inst Technol Delhi, Ctr Biomed Engn, New Delhi, India. [Mehndiratta, Amit] All India Inst Med Sci, New Delhi, India. [Rabinov, James D.] Harvard Univ, Sch Med, Intervent Neuroradiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grasruck, Michael] Siemens Med Solut, Forchheim, Germany. [Liao, Eric C.] Harvard Univ, Sch Med, Dept Plast & Reconstruct Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liao, Eric C.] Harvard Univ, Sch Med, Ctr Regenerat Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crandell, David] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA USA. RP Mehndiratta, A (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,GRB 273A, Boston, MA 02114 USA. EM amit.mehndiratta@keble.oxon.org FU Siemens Healthcare [MGH-2010-CT-35702]; Defense Advanced Research Projects Agency [N66001-11-1-4204]; US Army Medical Research Acquisitions [W81XWH-09-2-0001] FX The scientific guarantor of this publication is Dr. Rajiv Gupta, Radiology, MGH, Boston. R. Gupta's research was partially supported by a research grant from Siemens Healthcare (MGH-2010-CT-35702), Defense Advanced Research Projects Agency (N66001-11-1-4204), and US Army Medical Research Acquisitions (W81XWH-09-2-0001). Michael Grasruck is an employee at Siemens Healthcare, Forchheim, Germany. Amit Mehndiratta, James D. Rabinov, Eric C. Liao, and David Crandell declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, diagnostic or prognostic study, performed at one institution. NR 22 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD JUL PY 2015 VL 25 IS 7 BP 1901 EP 1910 DI 10.1007/s00330-015-3612-8 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ8MJ UT WOS:000355755300008 PM 25716938 ER PT J AU Engel, CC Litz, B Magruder, KM Harper, E Gore, K Stein, N Yeager, D Liu, X Coe, TR AF Engel, Charles C. Litz, Brett Magruder, Kathryn M. Harper, Elizabeth Gore, Kristie Stein, Nathan Yeager, Derik Liu, Xian Coe, T. Ray TI Delivery of self training and education for stressful situations (DESTRESS-PC): a randomized trial of nurse assisted online self-management for PTSD in primary care SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Posttraumatic Stress Disorder; Depression; Military mental health; Primary care; Telehealth ID COMORBIDITY SURVEY REPLICATION; MENTAL-HEALTH PROBLEMS; POSTTRAUMATIC-STRESS; DISORDER; DEPRESSION; PREVALENCE; SEVERITY; INTERNET; IRAQ; AFGHANISTAN AB Objective: This randomized controlled trial examined the effectiveness of a nurse assisted online cognitive-behavioral self-management intervention forwar-related posttraumatic stress disorder (PTSD), compared to optimized usual primary care PTSD Treatment (OUC) to reduce PTSD symptoms. Method: Participants were 80 veterans of recent military conflicts with PTSD as assessed by the PTSD Checklist (PCL) seeking primary care treatment at one of three Veterans Affairs (VA) and four Army clinics. DESTRESS-PC consisted of logins to a secure website three times per week for 6 weeks with monitoring by a study nurse. All participants received nurse care management in the form of phone check-ins every two weeks and feedback to their primary care providers. Blinded raters assessed outcomes 6, 12, and 18 weeks post-randomization. Results: DESTRESS-PC was associated with a significantly greater decrease in PTSD symptoms compared to OUC (F(3, 186)=3.72, p=.012). The effect was largest at the 12-week assessment (Delta PCL=12.6 +/- 16.6 versus 5.7 +/- 12.5, p<0.05) with the treatment effect disappearing by the 18-week follow-up. Notably, there was a dose effect; number of logins correlated significantly with PTSD outcomes, with more logins associated with greater PTSD symptom improvement. None of the secondary outcomes (depression, anxiety, somatic symptoms, and functional status) showed statistically significant improvement; however, the treatment effect on depression approached significance (F(3, 186)=2.17, p=.093). Conclusions: DESTRESS-PC shows promise as a means of delivering effective, early PTSD treatment in primary care. Larger trials are needed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Engel, Charles C.; Liu, Xian] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Litz, Brett; Stein, Nathan] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Jamaica Plain, MA USA. [Litz, Brett; Stein, Nathan] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Magruder, Kathryn M.; Yeager, Derik] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Magruder, Kathryn M.; Yeager, Derik] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Harper, Elizabeth; Gore, Kristie; Liu, Xian] Walter Reed Natl Mil Med Ctr, Deployment Hlth Clin Ctr, Bethesda, MD USA. [Liu, Xian] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Coe, T. Ray] Womack Army Med Ctr, Ft Bragg, NC USA. RP Engel, CC (reprint author), RAND Corp, 1200 South Hayes St, Arlington, VA 22202 USA. EM cengel@rand.org FU NIMH NIH HHS [R34 MH078874] NR 32 TC 3 Z9 3 U1 5 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2015 VL 37 IS 4 BP 323 EP 328 DI 10.1016/j.genhosppsych.2015.04.007 PG 6 WC Psychiatry SC Psychiatry GA CJ5UG UT WOS:000355555800010 PM 25929985 ER PT J AU Baldini, EH Wang, D Haas, RLM Catton, CN Indelicato, DJ Kirsch, DG Roberge, D Salerno, K Deville, C Guadagnolo, BA O'Sullivan, B Petersen, IA Le Pechoux, C Abrams, RA DeLaney, TF AF Baldini, Elizabeth H. Wang, Dian Haas, Rick L. M. Catton, Charles N. Indelicato, Daniel J. Kirsch, David G. Roberge, David Salerno, Kilian Deville, Curtiland Guadagnolo, B. Ashleigh O'Sullivan, Brian Petersen, Ivy A. Le Pechoux, Cecile Abrams, Ross A. DeLaney, Thomas F. TI Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Review ID SOFT-TISSUE SARCOMA; ELECTRON-BEAM RADIOTHERAPY; RESECTION PREDICT PATTERN; PROGNOSTIC-FACTORS; LOCOREGIONAL RECURRENCE; SURGICAL-MANAGEMENT; HISTOLOGIC SUBTYPE; RANDOMIZED-TRIAL; DOSE-ESCALATION; TARGET VOLUME AB Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wang, Dian; Abrams, Ross A.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL USA. [Haas, Rick L. M.] Netherlands Canc Inst, Antoni Van Leeuwenhoek Hosp, Dept Radiotherapy, Amsterdam, Netherlands. [Catton, Charles N.; O'Sullivan, Brian] Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [Indelicato, Daniel J.] Univ Florida, Med Ctr, Dept Radiat Oncol, Jacksonville, FL 32209 USA. [Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Roberge, David] Univ Montreal, Ctr Hosp, Dept Radiat Oncol, Montreal, PQ, Canada. [Salerno, Kilian] Roswell Pk Canc Inst, Dept Radiat Oncol, Buffalo, NY 14263 USA. [Deville, Curtiland] Johns Hopkins Sidney Kimmel Canc Ctr, Dept Radiat Oncol & Mol Radiat Sci, Washington, DC USA. [Guadagnolo, B. Ashleigh] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Petersen, Ivy A.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Le Pechoux, Cecile] Inst Gustave Roussy, Dept Radiotherapy, Villejuif, France. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L2,75 Francis St, Boston, MA 02115 USA. EM ebaldini@partners.org RI Deville, Curtiland/B-2819-2013 OI Deville, Curtiland/0000-0003-4846-6486 FU US National Cancer Institute/National Institutes of Health [U10CA21661, U10CA180868, U10CA180822, U10 CA37422, U24CA180803] FX This project was supported by US National Cancer Institute/National Institutes of Health grants U10CA21661, U10CA180868, U10CA180822, U10 CA37422, and U24CA180803. NR 80 TC 16 Z9 17 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 JUL 1 PY 2015 VL 92 IS 3 BP 602 EP 612 DI 10.1016/j.ijrobp.2015.02.013 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CJ6WV UT WOS:000355636800022 PM 26068493 ER PT J AU Hall, DE Hanusa, BH Fine, MJ Arnold, RM AF Hall, Daniel E. Hanusa, Barbara H. Fine, Michael J. Arnold, Robert M. TI Do surgeons and patients discuss what they document on consent forms? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Informed consent; Shared decision making; Ethics; Cholecystectomy; Herniorrhaphy ID INFORMED DECISION-MAKING; GENERAL-PRACTICE; HAWTHORNE; CONSULTATIONS; QUALITY; DOCTORS; BACK; TIME AB Background: Previous studies of surgeon behavior report that surgeons rarely meet basic standards of informed consent, raising concerns that current practice requires urgent remediation. We wondered if the Veterans Affairs Healthcare System's recent implementation of standardized, procedure-specific consent forms might produce a better practice of informed consent than has been reported previously. Our goal was to determine how the discussions shared between surgeons and patients correspond to the VA's standardized consent forms. Methods: We enrolled a prospective cohort of patients presenting for possible cholecystectomy or inguinal herniorrhaphy and the surgical providers for those patients. Audio recordings captured the clinical encounter(s) culminating in a decision to have surgery. Each patient's informed consent was documented using a standardized, computer-generated form. We abstracted and compared the information documented with the information discussed. Results: Of 75 consecutively enrolled patients, 37 eventually decided to have surgery and signed the standardized consent form. Patients and providers discussed 37% (95% confidence interval, 0.07-0.67) and 33% (95% confidence interval, 0.21-0.43) of the information found on the cholecystectomy and herniorrhaphy consent forms, respectively. However, the patienteprovider discussions frequently included relevant details nowhere documented on the standardized forms, culminating in discussions that included a median 27.5 information items for cholecystectomy and 20 items for herniorrhaphy. Fully, 80% of cholecystectomy discussions and 76% of herniorrhaphy discussions mentioned at least one risk, benefit or alternative, indication for, and description of the procedure. Conclusions: The patients and providers observed here collaborated in a detailed process of informed consent that challenges the initial reports suggesting the need to remediate surgeon's practice of informed consent. However, because the discrepancy between the information documented and discussed exposes legal and ethical liability, there is an opportunity to improve the iMed system so that it better reflects what surgeons discuss and more frequently includes all the information patients need. Published by Elsevier Inc. C1 [Hall, Daniel E.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA 15240 USA. [Arnold, Robert M.] Univ Pittsburgh, UPMC Montefiore Hosp, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM hallde@upmc.edu OI Hall, Daniel/0000-0001-6382-0522 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [CDA 08-281]; VISN4 CPPF [XVA 72-057]; VA Center for Health Equity Research and Promotion [LIP 72-043] FX This research was supported by supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (CDA 08-281). It was also supported by the VISN4 CPPF (XVA 72-057) and the VA Center for Health Equity Research and Promotion (LIP 72-043). NR 26 TC 1 Z9 1 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2015 VL 197 IS 1 BP 67 EP 77 DI 10.1016/j.jss.2015.03.058 PG 11 WC Surgery SC Surgery GA CJ5UA UT WOS:000355554900012 PM 25891679 ER PT J AU Zhu, CL Xiao, F Hong, J Wang, K Liu, X Cai, DC Fusco, DN Zhao, L Jeong, SW Brisac, C Chusri, P Schaefer, EA Zhao, H Peng, LF Lin, W Chung, RT AF Zhu, Chuanlong Xiao, Fei Hong, Jian Wang, Kun Liu, Xiao Cai, Dachuan Fusco, Dahlene N. Zhao, Lei Jeong, Soung Won Brisac, Cynthia Chusri, Pattranuch Schaefer, Esperance A. Zhao, Hong Peng, Lee F. Lin, Wenyu Chung, Raymond T. TI EFTUD2 Is a Novel Innate Immune Regulator Restricting Hepatitis C Virus Infection through the RIG-I/MDA5 Pathway SO JOURNAL OF VIROLOGY LA English DT Article ID INTERFERON-STIMULATED GENES; JAK-STAT PATHWAY; I-LIKE RECEPTORS; RIG-I; RNA VIRUSES; RECOGNITION; EXPRESSION; PROTEIN; ACTIVATION; INDUCTION AB The elongation factor Tu GTP binding domain-containing protein 2 (EFTUD2) was identified as an anti-hepatitis C virus (HCV) host factor in our recent genome-wide small interfering RNA (siRNA) screen. In this study, we sought to further determine EFTUD2's role in HCV infection and investigate the interaction between EFTUD2 and other regulators involved in HCV innate immune (RIG-I, MDA5, TBK1, and IRF3) and JAK-STAT1 pathways. We found that HCV infection decreased the expression of EFTUD2 and the viral RNA sensors RIG-I and MDA5 in HCV-infected Huh7 and Huh7.5.1 cells and in liver tissue from in HCV-infected patients, suggesting that HCV infection downregulated EFTUD2 expression to circumvent the innate immune response. EFTUD2 inhibited HCV infection by inducing expression of the interferon (IFN)-stimulated genes (ISGs) in Huh7 cells. However, its impact on HCV infection was absent in both RIG-I knockdown Huh7 cells and RIG-I-defective Huh7.5.1 cells, indicating that the antiviral effect of EFTUD2 is dependent on RIG-I. Furthermore, EFTUD2 upregulated the expression of the RIG-I-like receptors (RLRs) RIG-I and MDA5 to enhance the innate immune response by gene splicing. Functional experiments revealed that EFTUD2-induced expression of ISGs was mediated through interaction of the EFTUD2 downstream regulators RIG-I, MDA5, TBK1, and IRF3. Interestingly, the EFTUD2-induced antiviral effect was independent of the classical IFN-induced JAK-STAT pathway. Our data demonstrate that EFTUD2 restricts HCV infection mainly through an RIG-I/MDA5-mediated, JAK-STAT-independent pathway, thereby revealing the participation of EFTUD2 as a novel innate immune regulator and suggesting a potentially targetable antiviral pathway. IMPORTANCE Innate immunity is the first line defense against HCV and determines the outcome of HCV infection. Based on a recent highthroughput whole-genome siRNA library screen revealing a network of host factors mediating antiviral effects against HCV, we identified EFTUD2 as a novel innate immune regulator against HCV in the infectious HCV cell culture model and confirmed that its expression in HCV-infected liver tissue is inversely related to HCV infection. Furthermore, we determined that EFTUD2 exerts its antiviral activity mainly through governing its downstream regulators RIG-I and MDA5 by gene splicing to activate IRF3 and induce classical ISG expression independent of the JAT-STAT signaling pathway. This study broadens our understanding of the HCV innate immune response and provides a possible new antiviral strategy targeting this novel regulator of the innate response. C1 [Zhu, Chuanlong; Xiao, Fei; Wang, Kun] Anhui Med Univ, Anhui Prov Hosp, Dept Infect Dis, Hefei, Anhui, Peoples R China. [Zhu, Chuanlong; Hong, Jian; Liu, Xiao; Cai, Dachuan; Fusco, Dahlene N.; Zhao, Lei; Jeong, Soung Won; Brisac, Cynthia; Chusri, Pattranuch; Schaefer, Esperance A.; Zhao, Hong; Peng, Lee F.; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Liver Ctr & Gastrointestinal Div,Dept Med, Boston, MA 02115 USA. [Zhu, Chuanlong] Nanjing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Nanjing, Jiangsu, Peoples R China. [Xiao, Fei] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Infect Dis, Wuhan, Hubei, Peoples R China. [Zhao, Hong] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China. RP Lin, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Liver Ctr & Gastrointestinal Div,Dept Med, Boston, MA 02115 USA. EM wlin1@mgh.harvard.edu; Chung.Raymond@mgh.harvard.edu FU National Natural Science Foundation of China [81271713, 81170386]; NIH-MGH Center for Human Immunology Pilot/Feasibility Study grant; NIH [DA033541, DK098079, AI082630] FX This work was supported by National Natural Science Foundation of China grant 81271713 (C.Z.), National Natural Science Foundation of China grant 81170386 (H.Z.), an NIH-MGH Center for Human Immunology Pilot/Feasibility Study grant (W.L.), and NIH grants DA033541 (R.T.C.), DK098079 (R.T.C.), and AI082630 (R.T.C.). NR 47 TC 6 Z9 6 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUL PY 2015 VL 89 IS 13 BP 6608 EP 6618 DI 10.1128/JVI.00364-15 PG 11 WC Virology SC Virology GA CJ6GW UT WOS:000355593000009 PM 25878102 ER PT J AU Hwang, JH Fernando, ATP Faure, N Andrabi, S Adelmant, G Hahn, WC Marto, JA Schaffhausen, BS Roberts, TM AF Hwang, Justin H. Fernando, Arun T. Pores Faure, Nathalie Andrabi, Shaida Adelmant, Guillaume Hahn, William C. Marto, Jarrod A. Schaffhausen, Brian S. Roberts, Thomas M. TI Polyomavirus Small t Antigen Interacts with Yes-Associated Protein To Regulate Cell Survival and Differentiation (vol 88, pg 12055, 2014) SO JOURNAL OF VIROLOGY LA English DT Correction C1 [Hwang, Justin H.; Faure, Nathalie; Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Hwang, Justin H.; Schaffhausen, Brian S.] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Fernando, Arun T. Pores; Andrabi, Shaida; Adelmant, Guillaume; Marto, Jarrod A.; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fernando, Arun T. Pores; Adelmant, Guillaume; Marto, Jarrod A.; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Andrabi, Shaida] Univ Kashmir, Dept Biochem, Kashmir, India. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Hwang, JH (reprint author), Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUL PY 2015 VL 89 IS 13 BP 6971 EP 6971 DI 10.1128/JVI.00952-15 PG 1 WC Virology SC Virology GA CJ6GW UT WOS:000355593000043 PM 26041839 ER PT J AU Winn, K Ozanne, E Sepucha, K AF Winn, Karen Ozanne, Elissa Sepucha, Karen TI Measuring patient-centered care: An updated systematic review of how studies define and report concordance between patients' preferences and medical treatments SO PATIENT EDUCATION AND COUNSELING LA English DT Review DE Quality; Decisions; Decision making; Measurement; Patient-centered; Value concordance ID RANDOMIZED CONTROLLED-TRIAL; DECISION AID; PROSTATE-CANCER; INFORMED CHOICE; PLANNED BEHAVIOR; BREAST-CANCER; WOMEN; SUPPORT; RISK; COMMUNICATION AB Objective: The purpose was to examine recent advances in measuring value concordance and to highlight best practices. Methods: The paper updates a prior systematic review. A systematic review of the literature from 2008 to 2012 identified articles that reported a relationship between patients' preferences concerning health outcomes and/or medical treatments, and treatment (intended or actual). Relevant articles were independently abstracted by two reviewers. Results: The search identified 3635 unique citations, the full text of 187 articles was examined, and 63 articles covering 61 studies were included, nearly a third more articles than identified in the original review. There were 72 different value concordance calculations, the majority of which were clearly reported with significance. More studies assessed knowledge, reported on the association between value concordance and knowledge, and included a decision aid compared to those in the original review. Conclusion: There is increased reporting of value concordance in the literature. However, large differences exist in the way that the measure is defined and calculated. The variability makes it difficult to draw conclusions about the quality of care across studies. Practice implications: Value concordance is a critical component of patient-centered care, and further attention is needed to establish standards for measurement and reporting. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Winn, Karen] MGH Inst Hlth Profess, Boston, MA 02129 USA. [Ozanne, Elissa] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Sepucha, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Sepucha, Karen] Massachusetts Gen Hosp, Div Gen Internal Med, Hlth Decis Sci Ctr, Boston, MA 02114 USA. RP Winn, K (reprint author), MGH Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM kwinn@mghihp.edu NR 79 TC 8 Z9 8 U1 4 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUL PY 2015 VL 98 IS 7 BP 811 EP 821 DI 10.1016/j.pec.2015.03.012 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA CJ7VP UT WOS:000355708800001 PM 25846191 ER PT J AU August, DA Cote, CJ AF August, David A. Cote, Charles J. TI Response to the letter of Dr. B Haydar SO PEDIATRIC ANESTHESIA LA English DT Letter ID EPINEPHRINE C1 [August, David A.; Cote, Charles J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pediat Anesthesia, Boston, MA 02114 USA. RP August, DA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pediat Anesthesia, Boston, MA 02114 USA. EM daugust@mgh.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JUL PY 2015 VL 25 IS 7 BP 753 EP 754 DI 10.1111/pan.12661 PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA CK0FP UT WOS:000355881200016 PM 26053771 ER PT J AU Dunn, EC Masyn, KE Jones, SM Subramanian, SV Koenen, KC AF Dunn, Erin C. Masyn, Katherine E. Jones, Stephanie M. Subramanian, S. V. Koenen, Karestan C. TI Measuring Psychosocial Environments Using Individual Responses: an Application of Multilevel Factor Analysis to Examining Students in Schools SO PREVENTION SCIENCE LA English DT Article DE Multilevel; Factor analysis; School environment; School climate; Latent variable; Ecological ID CONFIRMATORY FACTOR-ANALYSIS; CLIMATE; MODELS AB Interest in understanding how psychosocial environments shape youth outcomes has grown considerably. School environments are of particular interest to prevention scientists as many prevention interventions are school-based. Therefore, effective conceptualization and operationalization of the school environment is critical. This paper presents an illustration of an emerging analytic method called multilevel factor analysis (MLFA) that provides an alternative strategy to conceptualize, measure, and model environments. MLFA decomposes the total sample variance-covariance matrix for variables measured at the individual level into within-cluster (e.g., student level) and between-cluster (e.g., school level) matrices and simultaneously models potentially distinct latent factor structures at each level. Using data from 79,362 students from 126 schools in the National Longitudinal Study of Adolescent to Adult Health (formerly known as the National Longitudinal Study of Adolescent Health), we use MLFA to show how 20 items capturing student self-reported behaviors and emotions provide information about both students (within level) and their school environment (between level). We identified four latent factors at the within level: (1) school adjustment, (2) externalizing problems, (3) internalizing problems, and (4) self-esteem. Three factors were identified at the between level: (1) collective school adjustment, (2) psychosocial environment, and (3) collective self-esteem. The finding of different and substantively distinct latent factor structures at each level emphasizes the need for prevention theory and practice to separately consider and measure constructs at each level of analysis. The MLFA method can be applied to other nested relationships, such as youth in neighborhoods, and extended to a multilevel structural equation model to better understand associations between environments and individual outcomes and therefore how to best implement preventive interventions. C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Dunn, Erin C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dunn, Erin C.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Masyn, Katherine E.] Georgia State Univ, Div Epidemiol & Biostat, Sch Publ Hlth, Atlanta, GA 30303 USA. [Jones, Stephanie M.] Harvard Univ, Harvard Grad Sch Educ, Cambridge, MA 02138 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. EM edunn2@mgh.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; National Institute of Mental Health [F31 MH088074] FX This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from grant P01-HD31921 for this analysis. Visit Add Health online: https://www.cpc.unc.edu/projects/addhealth. Research reported in this publication was supported by the National Institute of Mental Health under Award Number F31 MH088074 to Erin C. Dunn, ScD, MPH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 35 TC 3 Z9 3 U1 2 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-4986 EI 1573-6695 J9 PREV SCI JI Prev. Sci. PD JUL PY 2015 VL 16 IS 5 BP 718 EP 733 DI 10.1007/s11121-014-0523-x PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CJ6WC UT WOS:000355634900009 PM 25421872 ER PT J AU Ventura, J Ered, A Gretchen-Doorly, D Subotnik, KL Horan, WP Hellemann, GS Nuechterlein, KH AF Ventura, J. Ered, A. Gretchen-Doorly, D. Subotnik, K. L. Horan, W. P. Hellemann, G. S. Nuechterlein, K. H. TI Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Disorganization; early-course schizophrenia; functioning; neurocognition; theory of mind ID SOCIAL COGNITION; 1ST EPISODE; 1ST-EPISODE SCHIZOPHRENIA; INTENTIONAL MOVEMENT; ASPERGER-SYNDROME; ANIMATED SHAPES; MENTAL STATES; RATING-SCALE; METAANALYSIS; ATTRIBUTION AB Background. Numerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning. Method. Recent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants' descriptions of scenes depicting abstract visual stimuli 'interacting' in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed. Results. On the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms. Conclusions. The ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning. C1 [Ventura, J.; Ered, A.; Gretchen-Doorly, D.; Subotnik, K. L.; Horan, W. P.; Hellemann, G. S.; Nuechterlein, K. H.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, W. P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nuechterlein, K. H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Ventura, J (reprint author), Univ Calif Los Angeles, Dept Psychiat, 300 Med Plaza,Room 2243, Los Angeles, CA 90095 USA. EM jventura@ucla.edu FU National Institute of Mental Health [MH37705, P50 MH066286]; Janssen Scientific Affairs, LLC. FX This research was supported in part by National Institute of Mental Health grants MH37705 (principal investigator K.H.N.) and P50 MH066286 (principal investigator K.H.N.), and supplemental support from an investigator-initiated grant from Janssen Scientific Affairs, LLC. The authors would like to thank the following research associates who worked on data collection: Sarah Wilson, Robin Kite, Rachel Wood, Sharon Birman, Jackie Hayata and Lilian Medina. NR 54 TC 8 Z9 8 U1 2 U2 17 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 JUL PY 2015 VL 45 IS 10 BP 2031 EP 2043 DI 10.1017/S0033291714003171 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CJ8MW UT WOS:000355757500003 PM 25647289 ER PT J AU Logue, MW Smith, AK Baldwin, C Wolf, EJ Guffanti, G Ratanatharathorn, A Stone, A Schichman, SA Humphries, D Binder, EB Arloth, J Menke, A Uddin, M Wildman, D Galea, S Aiello, AE Koenen, KC Miller, MW AF Logue, Mark W. Smith, Alicia K. Baldwin, Clinton Wolf, Erika J. Guffanti, Guia Ratanatharathorn, Andrew Stone, Annjanette Schichman, Steven A. Humphries, Donald Binder, Elisabeth B. Arloth, Janine Menke, Andreas Uddin, Monica Wildman, Derek Galea, Sandro Aiello, Allison E. Koenen, Karestan C. Miller, Mark W. TI An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Gene expression; Whole blood; DSCAM; ATP6AP1L; Glucocortitoid responsive ID GENOME-WIDE ASSOCIATION; NEUROTROPHIC FACTOR; PERIPHERAL-BLOOD; CHILDHOOD MALTREATMENT; OXIDATIVE STRESS; IMPRINTED GENES; NERVOUS-SYSTEM; DISORDER; BRAIN; METHYLATION AB We examined the association between posttraumatic stress disorder (PTSD) and gene expression using whole blood samples from a cohort of trauma-exposed white non-Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and gene transcripts were analyzed. We found 41 that were differentially expressed in PTSD cases versus controls (multiple-testing corrected p <0.05). The most significant was DSCAM, a neurological gene expressed widely in the developing brain and in the annygdala and hippocampus of the adult brain. We then examined the 41 differentially expressed genes in a meta-analysis using two replication cohorts and found significant associations with PTSD for 7 of the 41 (p <0.05), one of which (ATP6AP1L) survived multiple-testing correction. There was also broad evidence of overlap across the discovery and replication samples for the entire set of genes implicated in the discovery data based on the direction of effect and an enrichment of p <0.05 significant probes beyond what would be expected under the null. Finally, we found that the set of differentially expressed genes from the discovery sample was enriched for genes responsive to glucocorticoid signaling with most showing reduced expression in PTSD cases compared to controls. Published by Elsevier Ltd. C1 [Logue, Mark W.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Logue, Mark W.; Baldwin, Clinton] Boston Univ, Sch Med, Biomed Genet, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Smith, Alicia K.; Binder, Elisabeth B.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Wolf, Erika J.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wolf, Erika J.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Guffanti, Guia] Columbia Univ NYSPI, Dept Psychiat, Div Child & Adolescent Psychiat, New York, NY USA. [Ratanatharathorn, Andrew; Galea, Sandro; Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Stone, Annjanette; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Pharmacogen Anal Lab, Res Serv, Little Rock, AR USA. [Humphries, Donald] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Binder, Elisabeth B.; Arloth, Janine; Menke, Andreas] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany. [Uddin, Monica; Wildman, Derek] Univ Illinois, Inst Genom Biol, Champaign, IL USA. [Uddin, Monica] Univ Illinois, Dept Psychol, Champaign, IL USA. [Wildman, Derek] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Aiello, Allison E.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP Logue, MW (reprint author), VA Boston Healthcare Syst, Mail Stop 151C,150 South Huntington Ave, Boston, MA 02130 USA. EM mark.logue@va.gov OI Wolf, Erika/0000-0003-2666-2435 FU U.S. Department of Veterans Affairs VA CSRD grant; U.S. Department of Veterans Affairs VA BLRD grant; NIH [R21MH102834]; United States (U.S.) Department of Veterans Affairs, Clinical Sciences Research and Development Program; ERC [GSE46743, GxEmolmech-281338] FX This research was supported by U.S. Department of Veterans Affairs VA CSR&D and BLR&D grants and NIH grant R21MH102834 to MWM. This work was also supported by a Career Development Award to EJW from the United States (U.S.) Department of Veterans Affairs, Clinical Sciences Research and Development Program. Data collection and analysis of GSE46743 was supported within the 7th framework programme by an ERC starting grant to EB, GxEmolmech-281338. NR 54 TC 9 Z9 9 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JUL PY 2015 VL 57 BP 1 EP 13 DI 10.1016/j.psyneuen.2015.03.016 PG 13 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA CJ7UY UT WOS:000355707000001 PM 25867994 ER PT J AU Godoy, MCB Marom, EM Carter, BW Sorensen, J Truong, MT Abbott, GF AF Godoy, Myrna C. B. Marom, Edith M. Carter, Brett W. Sorensen, James Truong, Mylene T. Abbott, Gerald F. TI Computed Tomography Imaging of Lung Infection in the Oncologic Setting: Typical Features and Potential Pitfalls SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID REVERSED HALO SIGN; STEM-CELL TRANSPLANTATION; HIGH-RESOLUTION CT; INVASIVE PULMONARY ASPERGILLOSIS; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; BRONCHIOLITIS OBLITERANS; ORGANIZING PNEUMONIA; COMPLICATIONS; CANCER C1 [Godoy, Myrna C. B.; Marom, Edith M.; Carter, Brett W.; Sorensen, James; Truong, Mylene T.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Godoy, MCB (reprint author), Univ Texas MD Anderson Canc Ctr, DI Dept Diagnost Radiol, 1515 Holcombe Blvd,Unit 371, Houston, TX 77030 USA. EM mgodoy@mdanderson.org NR 19 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 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2015 VL 50 IS 3 BP 192 EP 196 DI 10.1053/j.ro.2015.01.009 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ6BA UT WOS:000355576800006 PM 26002239 ER PT J AU de Groot, PM Carter, BW Abbott, GF Wu, CC AF de Groot, Patricia M. Carter, Brett W. Abbott, Gerald F. Wu, Carol C. TI Pitfalls in Chest Radiographic Interpretation: Blind Spots SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID MISSED LUNG-CANCER; PULMONARY NODULES; NEVER SMOKERS; RADIOLOGY; ERRORS; PERFORMANCE; IMPROVEMENT; RETROSPECT; DIAGNOSIS; ACCURACY C1 [de Groot, Patricia M.; Carter, Brett W.; Wu, Carol C.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. RP de Groot, PM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Sect Thorac Imaging, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. EM pdegroot@mdanderson.org NR 34 TC 0 Z9 0 U1 1 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 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2015 VL 50 IS 3 BP 197 EP 209 DI 10.1053/j.ro.2015.01.008 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ6BA UT WOS:000355576800007 PM 26002240 ER PT J AU Lichtenberger, JP Carter, BW Abbott, GF AF Lichtenberger, John P., III Carter, Brett W. Abbott, Gerald F. TI Pitfalls in Imaging of the Chest Wall SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID RADIOLOGIC FINDINGS; PECTUS EXCAVATUM; PATHOLOGICAL CORRELATION; TUMORS; SPECTRUM C1 [Lichtenberger, John P., III] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. [Carter, Brett W.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lichtenberger, JP (reprint author), Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM John.lichtenberger@usuhs.edu NR 24 TC 1 Z9 1 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 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2015 VL 50 IS 3 BP 251 EP 257 DI 10.1053/j.ro.2015.01.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ6BA UT WOS:000355576800014 PM 26002247 ER PT J AU Kidia, K Machando, D Bere, T Macpherson, K Nyamayaro, P Potter, L Makadzange, T Munjoma, R Marufu, M Araya, R Safren, S O'Cleirigh, C Chibanda, D Abas, M AF Kidia, Khameer Machando, Debra Bere, Tarisai Macpherson, Kirsty Nyamayaro, Primrose Potter, Lucy Makadzange, Tariro Munjoma, Ronald Marufu, Marshall Araya, Ricardo Safren, Steven O'Cleirigh, Conall Chibanda, Dixon Abas, Melanie TI 'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE HIV/AIDS; depression; mental health; adherence; antiretroviral therapy; barriers ID QUALITY-OF-LIFE; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-INCOME COUNTRIES; DEPRESSION CBT-AD; SOCIAL SUPPORT; TREATMENT NONADHERENCE; EXPLANATORY MODELS; HIV/AIDS TREATMENT; INFECTED PERSONS AB OBJECTIVE To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. METHODS In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. RESULTS The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. CONCLUSIONS Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy. C1 [Kidia, Khameer] Icahn Sch Med Mt Sinai, Arnhold Global Hlth Inst, New York, NY 10029 USA. [Kidia, Khameer; Machando, Debra; Bere, Tarisai; Nyamayaro, Primrose; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Chibanda, Dixon; Abas, Melanie] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe. [Machando, Debra] Womens Univ Africa, Harare, Zimbabwe. [Macpherson, Kirsty; Potter, Lucy; Abas, Melanie] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Makadzange, Tariro] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Araya, Ricardo] London Sch Hyg & Trop Med, Dept Populat Hlth, London WC1, England. [Safren, Steven; O'Cleirigh, Conall] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kidia, K (reprint author), Icahn Sch Med Mt Sinai, Arnhold Global Hlth Inst, 1 Gustave Levy Pl, New York, NY 10029 USA. EM kkidia@gmail.com FU NIH - National Institute of Mental Health [1R21MH094156-01] FX This study was supported by NIH Research Grant 1R21MH094156-01 funded by the National Institute of Mental Health. We thank Helen Jack and Julia Weigel for reading and commenting on earlier drafts of this manuscript. We would also like to thank Jessica Magidson, Dr. C. Ndlovhu and the personnel on the TENDAI project who have made this study possible. Finally, we thank the participants and healthcare workers at Parirenyatwa OI Clinic for taking time to be part of this study. NR 71 TC 6 Z9 7 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD JUL PY 2015 VL 20 IS 7 BP 903 EP 913 DI 10.1111/tmi.12502 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CJ7FY UT WOS:000355661200008 PM 25754063 ER PT J AU Christopoulos, G Wyman, RM Alaswad, K Karmpaliotis, D Lombardi, W Grantham, JA Yeh, RW Jaffer, FA Cipher, DJ Rangan, BV Christakopoulos, GE Kypreos, MA Lembo, N Kandzari, D Garcia, S Thompson, CA Banerjee, S Brilakis, ES AF Christopoulos, Georgios Wyman, R. Michael Alaswad, Khaldoon Karmpaliotis, Dimitri Lombardi, William Grantham, J. Aaron Yeh, Robert W. Jaffer, Farouc A. Cipher, Daisha J. Rangan, Bavana V. Christakopoulos, Georgios E. Kypreos, Megan A. Lembo, Nicholas Kandzari, David Garcia, Santiago Thompson, Craig A. Banerjee, Subhash Brilakis, Emmanouil S. TI Clinical Utility of the Japan-Chronic Total Occlusion Score in Coronary Chronic Total Occlusion Interventions Results from a Multicenter Registry SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE chronic total occlusion; complication; J-CTO score; outcome; percutaneous coronary intervention; radiation ID IN-HOSPITAL OUTCOMES; US REGISTRY; PROCEDURAL COMPLICATIONS; ANGIOGRAPHIC SUCCESS; HYBRID APPROACH; INSIGHTS; REVASCULARIZATION; RECANALIZATION; EFFICACY; SUPPORT AB Background-The performance of the Japan-chronic total occlusion (J-CTO) score in predicting success and efficiency of CTO percutaneous coronary intervention has received limited study. Methods and Results-We examined the records of 650 consecutive patients who underwent CTO percutaneous coronary intervention between 2011 and 2014 at 6 experienced centers in the United States. Six hundred and fifty-seven lesions were classified as easy (J-CTO= 0), intermediate (J-CTO= 1), difficult (J-CTO= 2), and very difficult (J-CTO= 3). The impact of the J-CTO score on technical success and procedure time was evaluated with univariable logistic and linear regression, respectively. The performance of the logistic regression model was assessed with the Hosmer-Lemeshow statistic and receiver operator characteristic curves. Antegrade wiring techniques were used more frequently in easy lesions (97%) than very difficult lesions (58%), whereas the retrograde approach became more frequent with increased lesion difficulty (41% for very difficult lesions versus 13% for easy lesions). The logistic regression model for technical success demonstrated satisfactory calibration and discrimination (P for Hosmer-Lemeshow = 0.743 and area under curve = 0.705). The J-CTO score was associated with a 2-fold increase in the odds of technical failure (odds ratio 2.04, 95% confidence interval 1.52-2.80, P< 0.001). Procedure time increased by approximate to 20 minutes for every 1-point increase of the J-CTO score (regression coefficient 22.33, 95% confidence interval 17.45-27.22, P< 0.001). Conclusions-J-CTO score was strongly associated with final success and efficiency in this study, supporting its expanded use in CTO interventions. C1 [Christopoulos, Georgios; Rangan, Bavana V.; Christakopoulos, Georgios E.; Banerjee, Subhash; Brilakis, Emmanouil S.] VA N Texas Hlth Care Syst, Dallas, TX USA. [Christopoulos, Georgios; Rangan, Bavana V.; Christakopoulos, Georgios E.; Banerjee, Subhash; Brilakis, Emmanouil S.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Wyman, R. Michael] Torrance Mem Med Ctr, Torrance, CA USA. [Alaswad, Khaldoon] Henry Ford Hosp, Detroit, MI 48202 USA. [Karmpaliotis, Dimitri] Columbia Univ, New York, NY USA. [Lombardi, William] Univ Washington, Seattle, WA 98195 USA. [Grantham, J. Aaron] Mid Amer Heart Inst, Kansas City, MO USA. [Yeh, Robert W.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cipher, Daisha J.] Univ Texas Arlington, Coll Hlth Innovat, Arlington, TX 76019 USA. [Kypreos, Megan A.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, El Paso, TX USA. [Lembo, Nicholas; Kandzari, David] Piedmont Heart Inst, Atlanta, GA USA. [Garcia, Santiago] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Thompson, Craig A.] Boston Sci, Natick, MA USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@gmail.com FU National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR001105] FX Study data were collected and managed using REDCap electronic data capture tools hosted at University of Texas Southwestern Medical Center.27 REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award Number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. NR 27 TC 22 Z9 22 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUL PY 2015 VL 8 IS 7 AR e002171 DI 10.1161/CIRCINTERVENTIONS.114.002171 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EF5XV UT WOS:000390404100004 PM 26162857 ER PT J AU Tritos, NA Yuen, KCJ Kelly, DF AF Tritos, Nicholas A. Yuen, Kevin C. J. Kelly, Daniel F. CA AACE Neuroendocrine Pituitary Sci TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: A NEUROENDOCRINE APPROACH TO PATIENTS WITH TRAUMATIC BRAIN INJURY SO ENDOCRINE PRACTICE LA English DT Article ID GROWTH-HORMONE REPLACEMENT; ANEURYSMAL SUBARACHNOID HEMORRHAGE; ANTERIOR-PITUITARY DYSFUNCTION; ADULT GH DEFICIENCY; QUALITY-OF-LIFE; DIABETES-INSIPIDUS; UNITED-STATES; HYPOTHALAMOPITUITARY DYSFUNCTION; POSTTRAUMATIC HYPOPITUITARISM; TESTOSTERONE THERAPY AB Objective: Traumatic brain injury (TBI) is now recognized as a major public health concern in the United States and is associated with substantial morbidity and mortality in both children and adults. Several lines of evidence indicate that TBI-induced hypopituitarism is not infrequent in TBI survivors and may contribute to the burden of illness in this population. The goal of this article is to review the published data and propose an approach for the neuroendocrine evaluation and management of these patients. Methods: To identify pertinent articles, electronic literature searches were conducted using the following keywords: "traumatic brain injury," "pituitary," "hypopituitarism," "growth hormone deficiency," "hypogonadism," "hypoadrenalism," and "hypothyroidism." Relevant articles were identified and considered for inclusion in the present article. Results: TBI-induced hypopituitarism appears to be more common in patients with severe TBI. However, patients with mild TBI or those with repeated, sports-, or blast-related TBI are also at risk for hypopituitarism. Deficiencies of growth hormone and gonadotropins appear to be most common and have been associated with increased morbidity in this population. A systematic approach is advised in order to establish the presence of pituitary hormone deficiencies and implement appropriate replacement therapies. Conclusion: The presence of traumatic hypopituitarism should be considered during the acute phase as well as during the rehabilitation phase of patients with TBI. All patients with moderate to severe TBI require evaluation of pituitary function. In addition, symptomatic patients with mild TBI and impaired quality of life are at risk for hypopituitarism and should be offered neuroendocrine testing. C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. [Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA USA. [Yuen, Kevin C. J.] Swedish Neurosci Inst, Swedish Pituitary Ctr, Seattle, WA USA. [Kelly, Daniel F.] St Johns Brain Tumor Ctr, Santa Monica, CA USA. [Kelly, Daniel F.] Pituitary Disorders Program, Santa Monica, CA USA. [Kelly, Daniel F.] John Wayne Canc Inst, Santa Monica, CA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org FU Ipsen; Pfizer; Novo Nordisk FX Dr. Tritos has received research support from Ipsen, Pfizer, and Novo Nordisk. The other authors have no multiplicity of interest to disclose. NR 56 TC 2 Z9 2 U1 3 U2 5 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD JUL PY 2015 VL 21 IS 7 BP 823 EP 831 DI 10.4158/EP14567.DSCR PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7LQ UT WOS:000377964500014 PM 26172127 ER PT J AU Wilkinson, CW AF Wilkinson, Charles W. TI COMMENTARY ON A NEUROENDOCRINE APPROACH TO PATIENTS WITH TRAUMATIC BRAIN INJURY SO ENDOCRINE PRACTICE LA English DT Editorial Material ID PITUITARY DYSFUNCTION C1 [Wilkinson, Charles W.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Wilkinson, Charles W.] Washington Univ, Sch Med, Dept Psychiat & Behav Sci, St Louis, MO 63130 USA. RP Wilkinson, CW (reprint author), VA Puget Sound Hlth Care Syst, S-182 GRECC,1660 South Columbian Way, Seattle, WA 98108 USA. EM wilkinso@uw.edu FU RRD VA [I01 RX000509] NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD JUL PY 2015 VL 21 IS 7 BP 851 EP 853 DI 10.4158/EP15854.CO PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7LQ UT WOS:000377964500018 PM 26172130 ER PT J AU Hodges, C Williams, R Crabtree, GR Kadoch, C AF Hodges, C. Williams, R. Crabtree, G. R. Kadoch, C. TI Subunit switching of the BAF (mSWI/SNF) complex is governed by an ordered, branched assembly pathway SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Meeting Abstract CT 10th European-Biophysical-Societies-Association (EBSA) European Biophysics Congress CY JUL 18-22, 2015 CL Dresden, GERMANY SP European Biophys Soc Assoc C1 [Hodges, C.; Crabtree, G. R.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Williams, R.; Kadoch, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kadoch, C.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Crabtree, G. R.] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 EI 1432-1017 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD JUL PY 2015 VL 44 SU 1 MA P-623 BP S206 EP S206 PG 1 WC Biophysics SC Biophysics GA DR6GW UT WOS:000380001400624 ER PT J AU Brooks, GA Kansagra, AJ Rao, SR Weitzman, JI Linden, EA Jacobson, JO AF Brooks, Gabriel A. Kansagra, Ankit J. Rao, Sowmya R. Weitzman, James I. Linden, Erica A. Jacobson, Joseph O. TI A Clinical Prediction Model to Assess Risk for Chemotherapy-Related Hospitalization in Patients Initiating Palliative Chemotherapy SO JAMA ONCOLOGY LA English DT Article ID OLDER-ADULTS; CANCER; TOXICITY; CARE; COST; CRITERIA AB IMPORTANCE Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit development of targeted strategies to prevent chemotherapy-related hospitalizations. OBJECTIVE To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization. DESIGN, SETTING, AND PARTICIPANTS Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in northeastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization. EXPOSURES Putative risk factors for chemotherapy-related hospitalization-including patient characteristics, treatment characteristics, and pretreatment laboratory values-were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization. MAIN OUTCOMES AND MEASURES Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program. RESULTS A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of chemotherapy-related hospitalization was 6.0% (interquartile range [IQR], 3.6%-11.4%) in control patients and 14.7%(IQR, 6.8%-22.5%) in case patients. The bootstrap-adjusted C statistic was 0.71 (95% CI, 0.66-0.75). At a risk threshold of 15%, the model exhibited a sensitivity of 49% (95% CI, 41%-57%) and a specificity of 85%(95% CI, 81%-89%) for predicting chemotherapy-related hospitalization. CONCLUSIONS AND RELEVANCE In patients initiating palliative chemotherapy for cancer, readily available clinical data were associated with the patient-specific risk of chemotherapy-related hospitalization. External validation and evaluation in the context of a clinical decision support tool are warranted. C1 [Brooks, Gabriel A.; Jacobson, Joseph O.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. [Brooks, Gabriel A.; Linden, Erica A.; Jacobson, Joseph O.] Harvard Med Sch, Boston, MA USA. [Kansagra, Ankit J.] Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Rao, Sowmya R.] Bedford Veteran Affairs Med Ctr, Bedford, MA USA. [Weitzman, James I.; Linden, Erica A.] Mass Gen North Shore Canc Ctr, Danvers, MA USA. RP Brooks, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM gabriel_brooks@dfci.harvard.edu FU Read Family Trust; Conquer Cancer Foundation of the American Society of Clinical Oncology; National Cancer Institute of the National Institutes of Health [R25CA09220] FX This research was supported by a grant from the Read Family Trust. Dr Brooks was supported by a Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology and by program grant R25CA09220 from the National Cancer Institute of the National Institutes of Health. NR 22 TC 1 Z9 3 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUL PY 2015 VL 1 IS 4 BP 441 EP 447 DI 10.1001/jamaoncol.2015.0828 PG 7 WC Oncology SC Oncology GA DW5GS UT WOS:000383672100010 PM 26181251 ER PT J AU Oh, KS Loeffler, JS AF Oh, Kevin S. Loeffler, Jay S. TI The Changing Landscape of Whole-Brain Radiation Therapy SO JAMA ONCOLOGY LA English DT Editorial Material ID CONTROLLED-TRIAL; METASTASES; RADIOTHERAPY; RADIOSURGERY; MELANOMA; LUNG C1 [Oh, Kevin S.; Loeffler, Jay S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jloeffler@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUL PY 2015 VL 1 IS 4 BP 464 EP 465 DI 10.1001/jamaoncol.2015.1144 PG 3 WC Oncology SC Oncology GA DW5GS UT WOS:000383672100013 PM 26181255 ER PT J AU Harshman, LC Wang, XD Nakabayashi, M Xie, WL Valenca, L Werner, L Yu, YJ Kantoff, AM Sweeney, CJ Mucci, LA Pomerantz, M Lee, GSM Kantoff, PW AF Harshman, Lauren C. Wang, Xiaodong Nakabayashi, Mari Xie, Wanling Valenca, Loana Werner, Lillian Yu, Yongjiang Kantoff, Aaron M. Sweeney, Christopher J. Mucci, Lorelei A. Pomerantz, Mark Lee, Gwo-Shu Mary Kantoff, Philip W. TI Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate Cancer SO JAMA ONCOLOGY LA English DT Article ID BIOCHEMICAL RECURRENCE; RADICAL PROSTATECTOMY; RISK; METAANALYSIS; CASTRATION; SLCO2B1; TESTOSTERONE; SLCO1B3; PATHWAY; IMPACT AB IMPORTANCE Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and a substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants of SLCO2B1 correlated with time to progression (TTP) during receipt of androgen deprivation therapy (ADT). Statins also use SLCO2B1 to enter cells, and thus we hypothesized that they may compete with DHEAS uptake by the tumor cells. OBJECTIVE To evaluate whether statin use prolongs TTP during ADT for hormone-sensitive prostate cancer. DESIGN, SETTING, AND PARTICIPANTS In vitro studieswere performed using prostate cancer cell lines at an academic, comprehensive cancer center. Statin use was retrospectively analyzed in 926 patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer between January 1996 and November 2013. MAIN OUTCOMES AND MEASURES To determine whether statins interfere with DHEAS uptake, we performed in vitro studies using prostate cancer cell lines. Next, we queried our institutional clinical database to assess for an association between statin use and TTP during ADT using multivariable Cox regression analysis and adjusted for known prognostic factors. RESULTS In vitro, we demonstrated that statins block DHEAS uptake by competitively binding to SLCO2B1. In our ADT cohort of 926 patients, 283 (31%) were taking a statin at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had experienced disease progression while receiving ADT. Median TTP during ADT was 20.3 months (95% CI, 18-24 months). Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; P < .001). The association remained statistically significant after adjusting for predefined prognostic factors (adjusted hazard ratio, 0.83 [95% CI, 0.69-0.99]; P = .04). The positive statin effect was observed for both patients with and without metastases (adjusted hazard ratio, 0.79 [95% CI, 0.58-1.07] forM0 disease and 0.84 [95% CI, 0.67-1.06] forM1 disease; P for interaction = .72). CONCLUSIONS AND RELEVANCE Statin use at the time of ADT initiation was associated with a significantly longer TTP during ADT even after adjustment for known prognostic factors. Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users. C1 [Harshman, Lauren C.; Nakabayashi, Mari; Valenca, Loana; Sweeney, Christopher J.; Pomerantz, Mark; Kantoff, Philip W.] Harvard Med Sch, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Wang, Xiaodong; Yu, Yongjiang; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Harvard Med Sch, Gelb Ctr Translat Oncol, Dana Farber Canc Inst, Boston, MA USA. [Xie, Wanling; Werner, Lillian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yu, Yongjiang] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Urol, Sch Med, Shanghai, Peoples R China. [Kantoff, Aaron M.] Apple Tree Partners, New York, NY USA. [Mucci, Lorelei A.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Div Solid Tumor Oncol, 450 Brookline Ave,Dana 1230, Boston, MA 02215 USA. EM philip_kantoff@dfci.harvard.edu FU Dana-Farber Prostate Cancer SPORE [P50CA090381]; Department of Defense [W81XWH-14-1-0515] FX The research was funded by the Dana-Farber Prostate Cancer SPORE P50CA090381 and by the Department of Defense (W81XWH-14-1-0515). NR 30 TC 16 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUL PY 2015 VL 1 IS 4 BP 495 EP 504 DI 10.1001/jamaoncol.2015.0829 PG 10 WC Oncology SC Oncology GA DW5GS UT WOS:000383672100018 PM 26181260 ER PT J AU Callahan, AB Skondra, D Krzystolik, M Yonekawa, Y Eliott, D AF Callahan, Alison B. Skondra, Dimitra Krzystolik, Magdalena Yonekawa, Yoshihiro Eliott, Dean TI Wyburn-Mason Syndrome Associated With Cutaneous Reactive Angiomatosis and Central Retinal Vein Occlusion SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID COMPLICATION; MALFORMATION AB Retinal venous occlusive events are a rare complication of arteriovenous malformations of the retina found in Wyburn-Mason syndrome. The authors present a case of a 28-year-old man diagnosed with Wyburn-Mason syndrome and cutaneous reactive angiomatosis, a reactive angioproliferative disorder induced by vascular occlusion. He developed a central retinal vein occlusion complicated by macular edema and received treatment with intravitreal bevacizumab, which led to resolution of the edema. To the best of the authors' knowledge, this is the first report of an antivascular endothelial growth factor agent employed as an effective treatment for macular edema in the setting of Wyburn-Mason syndrome. The association between Wyburn-Mason syndrome and cutaneous reactive angiomatosis is also a novel finding. C1 [Callahan, Alison B.; Skondra, Dimitra; Krzystolik, Magdalena; Yonekawa, Yoshihiro; Eliott, Dean] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02115 USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu FU Heed Ophthalmic Foundation FX Dr. Yonekawa is partially funded by the Heed Ophthalmic Foundation. The foundation had no role in the design or conduct of the study. Dr. Eliott is an ad hoc consultant for Genentech. The remaining authors report no relevant financial disclosures. NR 9 TC 0 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD JUL PY 2015 VL 46 IS 7 BP 760 EP 762 DI 10.3928/23258160-20150730-12 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DP9TW UT WOS:000378841300013 PM 26247458 ER PT J AU Awh, CC Miller, JB Wu, DM Eliott, D AF Awh, Caroline C. Miller, John B. Wu, David M. Eliott, Dean TI Leukostasis Retinopathy: A New Clinical Manifestation of Chronic Myeloid Leukemia With Severe Hyperleukocytosis SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA AB The authors report a new clinical manifestation of chronic myeloid leukemia. A 41-year-old man presented with significant visual loss, leading to a diagnosis of chronic myeloid leukemia. His white blood count exceeded that of any previously reported case of the disease with documented retinal findings (562,000/mm(3)), and clinical evaluation revealed the blockage of temporal retinal vessels by white blood cells. Hematologic findings resolved within 1 month of chemotherapy with dasatinib, and further treatment with intravitreal anti-VEGF agents resulted in the complete resolution of fundus findings. The authors propose that leukostasis retinopathy be recognized as a clinical manifestation of this life-threatening disease. C1 [Awh, Caroline C.; Miller, John B.; Wu, David M.; Eliott, Dean] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02115 USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD JUL PY 2015 VL 46 IS 7 BP 768 EP 770 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DP9TW UT WOS:000378841300015 PM 26247460 ER PT J AU MacNamara, A Rabinak, CA Fitzgerald, DA Zhou, XJ Shankman, SA Milad, MR Phan, KL AF MacNamara, Annmarie Rabinak, Christine A. Fitzgerald, Daniel A. Zhou, Xiaohong Joe Shankman, Stewart A. Milad, Mohammed R. Phan, K. Luan TI Neural correlates of individual differences in fear learning SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Fear conditioning; Amygdala; fMRI; Skin conductance response; SCR; Individual differences ID SKIN-CONDUCTANCE RESPONSES; HUMAN AMYGDALA ACTIVITY; ANXIETY DISORDER; EXTINCTION; MEMORY; BRAIN; EXPRESSION; HUMANS; FMRI; PTSD AB Variability in fear conditionability is common, and clarity regarding the neural regions responsible for individual differences in fear conditionability could uncover brain-based biomarkers of resilience or vulnerability to trauma-based psychopathologies (e.g., post-traumatic stress disorder). In recent years, neuroimaging work has yielded a detailed understanding of the neural mechanisms underlying fear conditioning common across participants, however only a minority of studies have investigated the brain basis of inter-individual variation in fear learning. Moreover, the majority of these studies have employed small sample sizes (mean n=17; range n=5-27) and all have failed to meet the minimum recommended sample size for functional magnetic resonance imaging (fMRI) studies of individual differences. Here, using fMRI, we analyzed blood-oxygenation level dependent (BOLD) response recorded simultaneously with skin conductance response (SCR) and ratings of unconditioned stimulus (US) expectancy in 49 participants undergoing Pavlovian fear conditioning. On average, participants became conditioned to the conditioned stimulus (CS+; higher US expectancy ratings and SCR for the CS+ compared to the unpaired conditioned stimulus, CS-); the CS+ also robustly increased activation in the bilateral insula. Amygdala activation was revealed from a regression analysis that incorporated individual differences in fear conditionability (i.e., a between-subjects regressor of mean CS+ > CS- SCR). By replicating results observed using much smaller sample sizes, the results confirm that variation in amygdala reactivity covaries with individual differences in fear conditionability. The link between behavior (SCR) and brain (amygdala reactivity) may be a putative endophenotype for the acquisition of fear memories. (C) 2015 Elsevier B.V. All rights reserved. C1 [MacNamara, Annmarie; Fitzgerald, Daniel A.; Shankman, Stewart A.; Phan, K. Luan] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA. [Rabinak, Christine A.] Wayne State Univ, Dept Pharm Practice, Detroit, MI 48201 USA. [Rabinak, Christine A.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. [Rabinak, Christine A.] Wayne State Univ, Translat Neurosci Program, Detroit, MI 48201 USA. [Fitzgerald, Daniel A.; Phan, K. Luan] Jesse Brown VA Med Ctr, Mental Hlth Serv Line, Chicago, IL 60612 USA. [Zhou, Xiaohong Joe] Univ Illinois, Dept Radiol, Chicago, IL 60612 USA. [Zhou, Xiaohong Joe] Univ Illinois, Ctr Magnet Resonance Res, Chicago, IL 60612 USA. [Shankman, Stewart A.; Phan, K. Luan] Univ Illinois, Dept Psychol, Chicago, IL 60607 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Phan, K. Luan] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. [Phan, K. Luan] Univ Illinois, Grad Program Neurosci, Chicago, IL 60612 USA. RP MacNamara, A (reprint author), Univ Illinois, Dept Psychiat, 1747 West Roosevelt Rd, Chicago, IL 60608 USA. EM annmarie.macnamara@gmail.com OI MacNamara, Annmarie/0000-0003-0399-973X FU National Institutes of Health (NIH) [R21MH093917]; NIH [T32MH067631-09] FX This material is based upon work supported by a National Institutes of Health (NIH) Grant R21MH093917 (K.L.P.); A.M. is supported by NIH Grant T32MH067631-09. The authors would like to thank Katherine Prater for her assistance in the construction of the behavioral-fMRI task, Donald McNair for his assistance in data collection and Edward F. Pace-Schott for his assistance with data analysis. NR 60 TC 3 Z9 3 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUL 1 PY 2015 VL 287 BP 34 EP 41 DI 10.1016/j.bbr.2015.03.035 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CI8QV UT WOS:000355037700005 PM 25819422 ER PT J AU Cougo-Pinto, PT Chandra, RV Simonsen, CZ Hirsch, JA Leslie-Mazwi, T AF Cougo-Pinto, Pedro Telles Chandra, Ronil V. Simonsen, Claus Z. Hirsch, Joshua A. Leslie-Mazwi, Thabele TI Intra-Arterial Therapy for Acute Ischemic Stroke: a Golden Age SO CURRENT TREATMENT OPTIONS IN NEUROLOGY LA English DT Review DE Acute stroke; Ischemic stroke; Large vessel occlusion; Proximal occlusion; Endovascular therapy; Intra-arterial therapy; Reperfusion; Recanalization; Angiography; Treatment ID BASILAR ARTERY-OCCLUSION; EARLY CT SCORE; ENDOVASCULAR TREATMENT; ANTERIOR CIRCULATION; INTERVENTIONAL MANAGEMENT; MECHANICAL THROMBECTOMY; IMAGING SELECTION; CONSENSUS STATEMENT; CEREBRAL-ISCHEMIA; RANDOMIZED-TRIAL AB With the recent publication of multiple trials demonstrating the superiority of the endovascular treatment of patients presenting with stroke from large vessel occlusion (LVO) over medical management, the emergent care of these patients is entering a new era. This realization justifies an aggressive treatment approach with these stroke patients, given the poor natural history of the disease. In general, treatment should occur as quickly as is reasonably possible. Patients with NIHSS >8 should be considered, and if <6 h from onset imaging selection achieved with CT and CTA. Those with ASPECTS 95, LVO and intermediate or good collaterals should be treated emergently. For patients with clinical deficits presenting in later timeframes MRI should be used to define core infarct size and therefore treatment eligibility. MRI might also be considered for the workup of stroke patients in centers that can offer it rapidly. Recanalization should be attempted with a stentriever or using a direct aspiration technique, with the patient under conscious sedation rather than general anesthesia, if that is a safe option. Angiographically, the goal is reperfusion of mTICI 2b/3. Post-procedure, the patient should be admitted to an intensive care setting and assessed for inpatient rehabilitation placement as soon as stable. Continuous institutional process improvement ensures that optimization of treatment times and logistics is an ongoing endeavor. Finally, patient outcomes should be assessed at three months, most commonly using the modified Rankin score. C1 [Cougo-Pinto, Pedro Telles] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Hirsch, Joshua A.; Leslie-Mazwi, Thabele] Massachusetts Gen Hosp, Neuroendovasc Serv, Boston, MA 02114 USA. [Chandra, Ronil V.] Monash Univ, Monash Hlth, Intervent Neuroradiol, Melbourne, Vic 3004, Australia. [Simonsen, Claus Z.] Aarhus Univ Hosp, Stroke, Dept Neurol, DK-8000 Aarhus, Denmark. [Cougo-Pinto, Pedro Telles] Univ Sao Paulo, Dept Neurosci & Behav Sci, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, SP, Brazil. RP Cougo-Pinto, PT (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. EM TLESLIE-MAZWI@MGH.HARVARD.EDU NR 78 TC 0 Z9 0 U1 2 U2 4 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1092-8480 EI 1534-3138 J9 CURR TREAT OPTION NE JI Curr. Treat. Options Neurol. PD JUL PY 2015 VL 17 IS 7 AR 30 DI 10.1007/s11940-015-0360-7 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA CJ2VS UT WOS:000355343400003 ER PT J AU Bui-Nguyen, B Butrynski, JE Penel, N Blay, JY Isambert, N Milhem, M Kerst, JM Reyners, AKL Litiere, S Marreaud, S Collin, F van der Graaf, WTA AF Bui-Nguyen, B. Butrynski, J. E. Penel, N. Blay, J. Y. Isambert, N. Milhem, M. Kerst, J. M. Reyners, A. K. L. Litiere, S. Marreaud, S. Collin, F. van der Graaf, W. T. A. CA EORTC STBSG SARC TI A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Soft-tissue sarcoma; Metastatic; Clinical trial; Trabectedin; Doxorubicin; First line chemotherapy ID ECTEINASCIDIN-743; CHEMOTHERAPY; LIPOSARCOMA; SAFETY; ET-743 AB Purpose: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion) in terms of safety, convenience and efficacy. Patients and methods: In this randomised multicentre prospective dose-selection phase IIb superiority trial, 133 patients were randomised between doxorubicin (n = 43), trabectedin (3-hour infusion, T3h) (n = 47) and trabectedin (24-hour infusion, T24h) (n = 43). PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours (RECIST 1.1), a global deterioration of the health status requiring discontinuation of the treatment, or death from any cause. Results: The study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm. Median PFS was 2.8 months in the T3h arm, 3.1 months in the T24h arm and 5.5 months in the doxorubicin arm. No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm (T24h versus doxorubicin: hazard ratio (HR) 1.13, 95% confidence interval (CI) 0.67-1.90, P = .675; T3h versus doxorubicin: HR 1.50, 95% CI 0.91-2.48, P = .944). Only one toxic death occurred in the T3h arm, but treatment had to be stopped due to toxicity in 7 (15.2%) (T3h), 8 (19.5%) (T24h) and 1 (2.5%) doxorubicin patients. Conclusion: Doxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma (STS). Trabectedin 1.5 mg/m(2)/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Bui-Nguyen, B.] Inst Bergonie, Ctr Comprehens Canc, Dept Med Oncol, F-33076 Bordeaux, France. [Butrynski, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Penel, N.] Ctr Oscar Lambret, F-59020 Lille, France. [Blay, J. Y.] Univ Lyon 1, F-69365 Lyon, France. [Blay, J. Y.] Ctr Leon Berard, F-69373 Lyon, France. [Isambert, N.; Collin, F.] Ctr GF Leclerc, F-21079 Dijon, France. [Milhem, M.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Kerst, J. M.] Antoni van Leeuwenhoek Ziekenhuis, Netherlands Canc Inst NKI, Amsterdam, Netherlands. [Reyners, A. K. L.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Litiere, S.; Marreaud, S.] EORTC Headquarters, Brussels, Belgium. [van der Graaf, W. T. A.] Radboud Univ Nijmegen, Med Ctr Nijmegen, NL-6525 ED Nijmegen, Netherlands. RP Bui-Nguyen, B (reprint author), Inst Bergonie, 229 Cours Argonne, F-33076 Bordeaux, France. EM b.bui@bordeaux.unicancer.fr RI van der Graaf, Winette/A-5006-2014; Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU Pharmamar FX This study was supported by a donation from La Ligue Nationale Contre le Cancer from France through the EORTC Charitable Trust. We are grateful to Pharmamar for supporting this study through an Educational Grant and for providing trabectedin for this study. NR 17 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2015 VL 51 IS 10 BP 1312 EP 1320 DI 10.1016/j.ejca.2015.03.023 PG 9 WC Oncology SC Oncology GA CJ2RK UT WOS:000355332000012 PM 25912752 ER PT J AU Nishino, M Tirumani, SH Ramaiya, NH Hodi, FS AF Nishino, Mizuki Tirumani, Sree H. Ramaiya, Nikhil H. Hodi, F. Stephen TI Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE Immunotherapy; Cancer; Oncologic imaging; Drug toxicity; Tumor response assessment ID CELL LUNG-CANCER; RESISTANT PROSTATE-CANCER; GUIDELINE VERSION 1.1; METASTATIC MELANOMA; CTLA-4 BLOCKADE; TUMOR RESPONSE; SOLID TUMORS; ADVERSE EVENTS; DOUBLE-BLIND; SINGLE-INSTITUTION AB The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists' awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Nishino, Mizuki; Tirumani, Sree H.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Nishino, Mizuki; Tirumani, Sree H.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med, Boston, MA 02215 USA. [Hodi, F. Stephen] Brigham & Womens Hosp, Boston, MA 02215 USA. RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU NCI [1K23CA157631] FX The investigator, M.N., was supported by 1K23CA157631 (NCI). NR 60 TC 14 Z9 15 U1 2 U2 9 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 JUL PY 2015 VL 84 IS 7 BP 1259 EP 1268 DI 10.1016/j.ejrad.2015.03.017 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ1AA UT WOS:000355212100007 PM 25937524 ER PT J AU Gao, YM Saksena, MA Brachtel, EF Termeulen, DC Rafferty, EA AF Gao, Yiming Saksena, Mansi A. Brachtel, Elena F. terMeulen, Deborah C. Rafferty, Elizabeth A. TI How to approach breast lesions in children and adolescents SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE Pediatric breast lesions; Breast evaluation in children and adolescents; Developing breast; Breast cancer in children; Breast ultrasound ID OF-THE-LITERATURE; FOLLOW-UP; POLAND-SYNDROME; SECRETORY CARCINOMA; IMAGING FEATURES; UNITED-STATES; US FINDINGS; MASSES; CANCER; MAMMOGRAPHY AB Assessment of a pediatric breast lesion always starts with clinical evaluation. When imaging of a pediatric breast is indicated, ultrasound is the mainstay. The vast majority of pediatric breast complaints are of benign etiology, therefore the diagnostic/management approach emphasizes "first do no harm". Correlation with age and clinical history helps to direct diagnosis. It is essential to be familiar with the imaging appearance of the normal developing breast at various Tanner stages, in order to diagnose physiologic breast findings and to minimize unnecessary biopsies in young breasts vulnerable to injury. Normal anatomic structures, developmental conditions, benign neoplastic and non-neoplastic lesions are common causes of breast complaints in children. Uncommon benign masses and rarely, secondary more than primary malignancies may present in a pediatric breast. Chest wall masses such as Ewing's sarcoma or rhabdomyosarcoma occur in children and may involve the breast via contiguous growth or locoregional metastasis. In addition, special attention should be given to any breast lesion in a child with risk factors predisposing to breast cancer, such as known extramammary malignancy, genetic mutations, prior mantle irradiation, or strong family history of breast cancer, which usually requires biopsy to exclude the possibility of malignancy. Conclusion: The developing breast is vulnerable to injury, and because breast malignancy is uncommon in children, diagnostic and management approach emphasizes "first do no harm". Understanding normal breast development and the spectrum of common and uncommon pediatric breast lesions are key to the correct diagnosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Gao, Yiming] NYU, Langone Med Ctr, New York, NY 10016 USA. [Gao, Yiming; Saksena, Mansi A.; Brachtel, Elena F.; terMeulen, Deborah C.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gao, YM (reprint author), 221 Lexington Ave, New York, NY 10016 USA. EM yiminggao@gmail.com NR 57 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD JUL PY 2015 VL 84 IS 7 BP 1350 EP 1364 DI 10.1016/j.ejrad.2015.04.011 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ1AA UT WOS:000355212100019 PM 25958188 ER PT J AU Wanasekara, ND Ghosh, S Chen, M Chalivendra, VB Bhowmick, S AF Wanasekara, Nandula D. Ghosh, Shouryadipta Chen, Ming Chalivendra, Vijaya B. Bhowmick, Sankha TI Effect of stiffness of micron/sub-micron electrospun fibers in cell seeding SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE electrospun scaffolds; cell seeding; energy approach; 3T3 fibroblasts; vacuum seeding ID ATOMIC-FORCE MICROSCOPY; MAGNETITE NANOPARTICLES; MECHANICAL-PROPERTIES; TISSUE; NANOFIBERS; BIOREACTOR; SCAFFOLDS; MODULUS; SYSTEM AB The objective of this study was to develop a predictive model for cell seeding depth in electrospun scaffold as a function of fiber stiffness. Electrospun scaffolds (micron and submicron) and 3T3 fibroblasts are used as scaffold-cell systems under vacuum seeding conditions. Atomic force microscopy is used to determine the Young's modulus (E) as a function of fiber diameter. A higher E value led to a lower depth of cell seeding (closer to the surface) indicating that nanofibrous scaffolds offer higher resistance to cell movement compared to microfibrous scaffold. An energy balance model was developed to predict cell seeding depth as a function of E for various vacuum pressures. Experimental data was used in the model to extract unknown parameters to predict cell seeding depth as a function of vacuum pressure for different stiffness scaffolds. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103: 2289-2299, 2015. C1 [Wanasekara, Nandula D.] Univ Exeter, Dept Phys & Astron, Exeter EX4 4SB, Devon, England. [Ghosh, Shouryadipta] Indian Inst Technol, Sch Mech Sci, Bhubaneswar 751013, Orissa, India. [Chen, Ming] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Chalivendra, Vijaya B.; Bhowmick, Sankha] Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP Chalivendra, VB (reprint author), Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02747 USA. EM vchalivendra@umassd.edu FU National Science Foundation (NSF) [CMS0618119]; National Textile Center [F06-MD04, M08-MD13] FX Contract grant sponsor: National Science Foundation (NSF) Contract grant sponsor: CMS0618119; Contract grant sponsor: National Textile Center; contract grant number: F06-MD04, M08-MD13 NR 30 TC 2 Z9 2 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JUL PY 2015 VL 103 IS 7 BP 2289 EP 2299 DI 10.1002/jbm.a.35362 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CJ1LZ UT WOS:000355246400009 PM 25366921 ER PT J AU Lenz, M Wahl, D Gueorguiev, B Jupiter, JB Perren, SM AF Lenz, Mark Wahl, Dieter Gueorguiev, Boyko Jupiter, Jesse B. Perren, Stephan Marcel TI Concept of variable angle lockingevolution and mechanical evaluation of a recent technology SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE variable angle locking; polyaxial locking; fixed angle locking; locking stability; locking strength ID INTERNAL FIXATOR; FRACTURES; PLATE; STABILITY AB Applications for fracture-adapted screw positioning offered by variable angle locking screws are increasing. The locking strength of the variable angle locking mechanism at different insertion angles was compared to conventional fixed angle locking screws. Stainless steel (S) and titanium (Ti) variable and fixed angle 2.4mm locking screws, inserted at different inclinations (0 degrees-15 degrees), and locked at 0.8Nm were subjected to a load-to-failure test. Ultimate failure moment at the screw-head interface and failure mode of the screws were determined. Significant differences were detected by one-way ANOVA (p<0.05). Stainless steel and titanium variable angle locking screws inserted at 2 degrees-10 degrees inclination exhibited a failure moment comparable to the 0 degrees position (S 1.67 +/- 0.04Nm; Ti 1.67 +/- 0.14Nm) and failed predominantly at the screw neck, with the head remaining fixed to the plate. Inserted at 15 degrees inclination, screws revealed a lower failure moment (S 1.33 +/- 0.06Nm, Ti 1.58 +/- 0.05Nm), and failed predominantly by breakout of the head thread. Fixed angle locking screws inserted at an inclination >2 degrees did not lock properly in the plate hole, providing insufficient locking strength. Variable angle locking screws offer a stable head-locking mechanism at different inclinations, comparable to the locking strength of orthogonal inserted fixed angle locking screws. Marginal inclinations >15 degrees should be used with care. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:988-992, 2015. C1 [Lenz, Mark; Wahl, Dieter; Gueorguiev, Boyko; Perren, Stephan Marcel] AO Res Inst Davos, CH-7270 Davos, Switzerland. [Lenz, Mark] Univ Hosp Jena, Dept Trauma Hand & Reconstruct Surg, Jena, Germany. [Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg Hand, Boston, MA 02114 USA. [Jupiter, Jesse B.] Massachusetts Gen Hosp, Upper Extrem Serv, Boston, MA 02114 USA. [Perren, Stephan Marcel] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. RP Lenz, M (reprint author), AO Res Inst Davos, Clavadelerstr 8, CH-7270 Davos, Switzerland. EM mark.lenz@med.uni-jena.de NR 15 TC 2 Z9 2 U1 2 U2 7 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 JUL PY 2015 VL 33 IS 7 BP 988 EP 992 DI 10.1002/jor.22851 PG 5 WC Orthopedics SC Orthopedics GA CJ2SA UT WOS:000355333600007 PM 25676391 ER PT J AU Davies, MR Ravishankar, B Laron, D Kim, HT Liu, XH Feeley, BT AF Davies, Michael R. Ravishankar, Bharat Laron, Dominique Kim, Hubert T. Liu, Xuhui Feeley, Brian T. TI Rat rotator cuff muscle responds differently from hindlimb muscle to a combined tendon-nerve injury SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE rotator cuff tear; fatty infiltration; sciatic nerve denervation; Akt; mTOR signaling; TGF- signaling ID FIBER-TYPE COMPOSITION; FATTY INFILTRATION; MODEL; TEAR; RECOVERY; ATROPHY; REPAIR; MTOR; SUPRASPINATUS; AUTOPHAGY AB Rotator cuff tears (RCTs) are among the most common musculoskeletal injuries seen by orthopaedic surgeons. Clinically, massive cuff tears lead to unique pathophysiological changes in rotator cuff muscle, including atrophy, and massive fatty infiltration, which are rarely seen in other skeletal muscles. Studies in a rodent model for RCT have demonstrated that these histologic findings are accompanied by activation of the Akt/mammalian target of rapamycin (mTOR) and transforming growth factor- (TGF-) pathways following combined tendon-nerve injury. The purpose of this study was to compare the histologic and molecular features of rotator cuff muscle and gastrocnemius musclea major hindlimb muscle, following combined tendon-nerve injury. Six weeks after injury, the rat gastrocnemius did not exhibit notable fatty infiltration compared to the rotator cuff. Likewise, the adipogenic markers SREBP-1 and PPAR as well as the TGF- canonical pathway were upregulated in the rotator cuff, but not the gastrocnemius. Our study suggests that the rat rotator cuff and hindlimb muscles differ significantly in their response to a combined tendon-nerve injury. Clinically, these findings highlight the unique response of the rotator cuff to injury, and may begin to explain the poor outcomes of massive RCTs compared to other muscle-tendon injuries. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1046-1053, 2015. C1 [Davies, Michael R.; Ravishankar, Bharat; Laron, Dominique; Kim, Hubert T.; Liu, Xuhui; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94158 USA. [Ravishankar, Bharat; Kim, Hubert T.; Liu, Xuhui] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. RP Feeley, BT (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens St, San Francisco, CA 94158 USA. EM feeleyb@orthosurg.ucsf.edu FU NIH [R03-AR060871]; OREF Career Development Award FX Grant sponsor: NIH; Grant number: R03-AR060871; Grant sponsor: OREF Career Development Award. NR 32 TC 4 Z9 4 U1 1 U2 4 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 JUL PY 2015 VL 33 IS 7 BP 1046 EP 1053 DI 10.1002/jor.22864 PG 8 WC Orthopedics SC Orthopedics GA CJ2SA UT WOS:000355333600015 PM 25974842 ER PT J AU Dimitriou, D Tsai, TY Li, JS Nam, KW Park, KK Kwon, YM AF Dimitriou, Dimitris Tsai, Tsung-Yuan Li, Jing-Sheng Nam, Kwang Woo Park, Kwan Kyu Kwon, Young-Min TI In vivo kinematic evaluation of total hip arthroplasty during stair climbing SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE in vivo kinematics; step-up; biomechanics; total hip arthroplasty; component orientation ID ANTERIOR APPROACH; GAIT; MOTION; KNEE; REPLACEMENTS; ORIENTATION; SEPARATION; FORCES; RANGE; HEAD AB Stair climbing is a physically demanding task and a painful limitation for patients suffering from severe hip osteoarthritis. Although total hip arthroplasty (THA) is the definitive treatment for end-stage osteoarthritis, it is not well understood whether THA restores hip kinematics during strenuous activities. The purpose of this study was to compare the 3D kinematics of THA and native hip during physically demanding tasks and correlate potential differences with THA components orientations/positions in patients with unilateral THA. In vivo hip kinematics were determined during step-up and leg stance activities using a validated combination of 3D CT-based computer modeling and dual fluoroscopic imaging system (DFIS). The THA side demonstrated an average 3.4 degrees (+/- 6.5 degrees, range: -5.9 degrees to 15.2 degrees) greater internal rotation than the contralateral native hip, during the step-up activity but not during leg stance. The difference in internal rotation was highly correlated to the difference in femoral anteversion and anterior translation of hip joint center between implanted and native hip (R-2=0.71, p<0.01). The results suggest the importance of accurate THA component placement in restoring normal hip kinematics during functional activities. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1087-1093, 2015. C1 [Dimitriou, Dimitris; Tsai, Tsung-Yuan; Li, Jing-Sheng; Nam, Kwang Woo; Park, Kwan Kyu; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. [Park, Kwan Kyu] Yonsei Univ, Coll Med, Dept Orthoped Surg, Seoul, South Korea. [Nam, Kwang Woo] Jeju Natl Univ, Sch Med, Dept Orthoped Surg, Jeju, South Korea. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. EM YMKWON@mgh.harvard.edu OI Tsai, Tsung-Yuan/0000-0003-1522-2987; Dimitriou, Dimitris/0000-0002-9558-7080 FU Department of Orthopaedic Surgery, MGH/MAKO Surgical Corp. FX Grant sponsor: Department of Orthopaedic Surgery, MGH/MAKO Surgical Corp., 2555 Davie Road, Ft. Lauderdale, FL 33317. NR 27 TC 1 Z9 1 U1 2 U2 6 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 JUL PY 2015 VL 33 IS 7 BP 1087 EP 1093 DI 10.1002/jor.22837 PG 7 WC Orthopedics SC Orthopedics GA CJ2SA UT WOS:000355333600020 PM 25626860 ER PT J AU Huh, JY Mantzoros, CS AF Huh, Joo Young Mantzoros, Christos S. TI Irisin physiology, oxidative stress, and thyroid dysfunction: What next? SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID CIRCULATING IRISIN; ADIPOSE-TISSUE; SELF-DISPROPORTIONATION; CELL-PROLIFERATION; INSULIN-RESISTANCE; FNDC5 GENE; EXERCISE; HUMANS; MUSCLE; SERUM C1 [Huh, Joo Young] Chonnam Natl Univ, Coll Pharm, Gwangju 500757, South Korea. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA. RP Huh, JY (reprint author), Chonnam Natl Univ, Coll Pharm, 77 Yongbong Ro, Gwangju 500757, South Korea. EM jooyhuh@jnu.ac.kr; cmantzor@bidmc.harvard.edu NR 43 TC 8 Z9 9 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2015 VL 64 IS 7 BP 765 EP 767 DI 10.1016/j.metabol.2015.02.009 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ1JL UT WOS:000355239800001 PM 25916681 ER PT J AU Chang, WT Jaaskelainen, IP Belliveau, JW Huang, S Hung, AY Rossi, S Ahveninen, J AF Chang, Wei-Tang Jaaskelainen, Iiro P. Belliveau, John W. Huang, Samantha Hung, An-Yi Rossi, Stephanie Ahveninen, Jyrki TI Combined MEG and EEG show reliable patterns of electromagnetic brain activity during natural viewing SO NEUROIMAGE LA English DT Article ID SURFACE-BASED ANALYSIS; CORTICAL ACTIVITY; FMRI; SYSTEM; RECONSTRUCTION; INDIVIDUALS; ATTENTION; CORTEX; SCENES AB Naturalistic stimuli such as movies are increasingly used to engage cognitive and emotional processes during fMRI of brain hemodynamic activity. However, movies have been little utilized during magnetoencephalography (MEG) and EEG that directly measure population-level neuronal activity at a millisecond resolution. Here, subjects watched a 17-min segment from the movie Crash (Lionsgate Films, 2004) twice during simultaneous MEG/EEG recordings. Physiological noise components, including ocular and cardiac artifacts, were removed using the DRIFTER algorithm. Dynamic estimates of cortical activity were calculated using MRI-informed minimum-norm estimation. To improve the signal-to-noise ratio (SNR), principal component analyses (PCA) were employed to extract the prevailing temporal characteristics within each anatomical parcel of the Freesurfer Desikan-Killiany cortical atlas. A variety of alternative inter-subject correlation (ISC) approaches were then utilized to investigate the reliability of inter-subject synchronization during natural viewing. In the first analysis, the ISCs of the time series of each anatomical region over the full time period across all subject pairs were calculated and averaged. In the second analysis, dynamic ISC (dISC) analysis, the correlation was calculated over a sliding window of 200 ms with 3.3 ms steps. Finally, in a between-run ISC analysis, the between-run correlation was calculated over the dynamic ISCs of the two different runs after the Fisher z-transformation. Overall, the most reliable activations occurred in occipital/inferior temporal visual and superior temporal auditory cortices as well as in the posterior cingulate, precuneus, pre- and post-central gyri, and right inferior and middle frontal gyri. Significant between-run ISCs were observed in superior temporal auditory cortices and inferior temporal visual cortices. Taken together, our results show that movies can be utilized as naturalistic stimuli in MEG/EEG similarly as in fMRI studies. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chang, Wei-Tang; Belliveau, John W.; Huang, Samantha; Hung, An-Yi; Rossi, Stephanie; Ahveninen, Jyrki] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Jaaskelainen, Iiro P.] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Brain & Mind Lab, Espoo, Finland. [Belliveau, John W.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hung, An-Yi] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. RP Chang, WT (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM welton@nmr.mgh.harvard.edu RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 FU National Institutes of Health (NIH) [R01MH083744, R21DC014134, R01HD040712, R01NS037462]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [P41EB015896]; National Center for Research Resources Shared Instrumentation [S10RR014978, S10RR021110, S10RR019307, S10RR014798, S10RR023401]; Academy of Finland [138145] FX We thank Nao Suzuki and Drs. Seppo Ahlfors, Naoaki Tanaka, and Matti Hamalainen for their advice and support. This work was supported by the National Institutes of Health (NIH) grant nos. R01MH083744, R21DC014134, R01HD040712, and R01NS037462. The research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The research environment was additionally supported by the National Center for Research Resources Shared Instrumentation grant nos. S10RR014978, S10RR021110, S10RR019307, S10RR014798, and S10RR023401. Author I.P.J. was supported by the Academy of Finland grant no. 138145. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 33 TC 6 Z9 6 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2015 VL 114 BP 49 EP 56 DI 10.1016/j.neuroimage.2015.03.066 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CI8ES UT WOS:000355002900004 PM 25842290 ER PT J AU Milekovic, T Truccolo, W Grun, S Riehle, A Brochier, T AF Milekovic, Tomislav Truccolo, Wilson Gruen, Sonja Riehle, Alexa Brochier, Thomas TI Local field potentials in primate motor cortex encode grasp kinetic parameters SO NEUROIMAGE LA English DT Article DE Macaque; Motor cortex; Kinetics; Grasping; Local field potentials; Movement planning ID CORTICO-MOTONEURONAL CELLS; DORSAL PREMOTOR CORTEX; SPIKING ACTIVITY; MACAQUE MONKEY; HIGH-FREQUENCY; REACH; SIGNALS; MOVEMENTS; TETRAPLEGIA; FORCE AB Reach and grasp kinematics are known to be encoded in the spiking activity of neuronal ensembles and in local field potentials (LFPs) recorded from primate motor cortex during movement planning and execution. However, little is known, especially in LFPs, about the encoding of kinetic parameters, such as forces exerted on the object during the same actions. We implanted two monkeys with microelectrode arrays in the motor cortical areas MI and PMd to investigate encoding of grasp-related parameters in motor cortical LFPs during planning and execution of reach-and-grasp movements. We identified three components of the LFP that modulated during grasps corresponding to low (0.3-7 Hz), intermediate(similar to 10-similar to 40 Hz) and high (similar to 80-250 Hz) frequency bands. We show that all three components can be used to classify not only grip types but also object loads during planning and execution of a grasping movement. In addition, we demonstrate that all three components recorded during planning or execution can be used to continuously decode finger pressure forces and hand position related to the grasping movement. Low and high frequency components provide similar classification and decoding accuracies, which were substantially higher than those obtained from the intermediate frequency component. Our results demonstrate that intended reach and grasp kinetic parameters are encoded in multiple LFP bands during both movement planning and execution. These findings also suggest that the LFP is a reliable signal for the control of parameters related to object load and applied pressure forces in brain-machine interfaces. (C) 2015 Elsevier Inc. All rights reserved. C1 [Milekovic, Tomislav] Univ Freiburg, Bernstein Ctr Freiburg, D-79106 Freiburg, Germany. [Milekovic, Tomislav] Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London, England. [Milekovic, Tomislav] Univ London Imperial Coll Sci Technol & Med, Dept Elect & Elect Engn, London, England. [Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Truccolo, Wilson] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI 02912 USA. [Gruen, Sonja] Res Ctr Julich, Inst Neurosci & Med INM 6, Julich, Germany. [Gruen, Sonja] Res Ctr Julich, Inst Adv Simulat IAS 6, Julich, Germany. [Gruen, Sonja] Rhein Westfal TH Aachen, Theoret Syst Neurobiol, Aachen, Germany. [Gruen, Sonja; Riehle, Alexa] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Riehle, Alexa; Brochier, Thomas] CNRS AMU, Inst Neurosci la Timone, Marseille, France. RP Milekovic, T (reprint author), Swiss Fed Inst Technol EPFL, EPFL SV UPCOURTINE, Ctr Neuroprosthet, Stn 19, CH-1015 Lausanne, Switzerland. EM tomislav.milekovic@epfl.ch; wilson_truccolo@brown.edu; s.gruen@fz-juelich.de; alexa.riehle@univ-amu.fr; thomas.brochier@univ-amu.fr RI Grun, Sonja/I-6321-2013; OI Grun, Sonja/0000-0003-2829-2220; Milekovic, Tomislav/0000-0001-6769-6506 FU German Federal Ministry of Education and Research (BMBF) [01GQ0830]; Imperial College London; IBRO InEurope Short Stay Grant program; RIKEN-CNRS Collaborative Research Agreement; ANR GRASP (France); BrainScaleS (EU) [269912]; Helmoltz portfolio theme "Supercomputing and modeling for the human brain" (SMHB); U.S. National Institute of Neurological Disorders and Stroke (NINDS) [NS057389]; Brown University FX This work was supported by the German Federal Ministry of Education and Research (BMBF) grant 01GQ0830 to BFNT Freiburg and Tubingen, Imperial College London, IBRO InEurope Short Stay Grant program, RIKEN-CNRS Collaborative Research Agreement, ANR GRASP (France), BrainScaleS (EU Grant 269912), Helmoltz portfolio theme "Supercomputing and modeling for the human brain" (SMHB), U.S. National Institute of Neurological Disorders and Stroke (NINDS) K01 Career Award NS057389, and the Pablo J. Salame '88 Goldman Sachs endowed Professorship in Computational Neuroscience, Brown University. NR 63 TC 4 Z9 4 U1 3 U2 20 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 JUL 1 PY 2015 VL 114 BP 338 EP 355 DI 10.1016/j.neuroimage.2015.04.008 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CI8ES UT WOS:000355002900031 PM 25869861 ER PT J AU Freeman, MA Myaskovsky, L AF Freeman, Michael A. Myaskovsky, Larissa TI An overview of disparities and interventions in pediatric kidney transplantation worldwide SO PEDIATRIC NEPHROLOGY LA English DT Review DE Kidney transplantation; Minority health; Organ allocation; Racial disparities; Socioeconomic status ID STAGE RENAL-DISEASE; RACIAL DISPARITIES; ORGAN-TRANSPLANTATION; SOCIOECONOMIC-STATUS; MEDICATION ADHERENCE; REPLACEMENT THERAPY; ETHNIC DISPARITIES; UNITED-STATES; US CHILDREN; DONATION AB Despite the stated goals of the transplant community and the majority of organ allocation systems, persistent racial disparities in pediatric kidney transplantation exist throughout the world. These disparities are evident in both living and deceased donor kidney transplantation and are independent of any clinical differences between racial groups. The reasons for these persistent disparities are multifactorial, reflecting both patient and provider barriers to care. In this review, we examine the most current findings regarding disparities in pediatric kidney transplantation and consider interventions which may help reduce those disparities. C1 [Freeman, Michael A.] Penn State Hershey Childrens Hosp, Div Pediat Nephrol & Hypertens, Hershey, PA 17033 USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Freeman, MA (reprint author), Penn State Hershey Childrens Hosp, Div Pediat Nephrol & Hypertens, Mail Code H085,500 Univ Dr, Hershey, PA 17033 USA. EM MFreeman3@hmc.psu.edu RI Freeman, Michael/O-1837-2016 OI Freeman, Michael/0000-0001-5022-4377 FU National Institute of Diabetes, Digestive and Kidney Disease [T32DKK091202, R01DK081325]; Veterans Affairs Health Services Research and Development Service [IIR 06-220, CIN 13-405] FX The data reported in the USRDS 2013 report were supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. The data and analyses reported in the 2011 and 2012 Annual Data Report of the U.S. Organ Procurement and Transplantation Network and the SRTR have been supplied by UNOS and the Minneapolis Medical Research Foundation under contract with the U.S. Department of Health and Human Services/Health Resources and Services Administration. The authors alone are responsible for reporting and interpreting these data; the views expressed herein are those of the authors and not necessarily those of the U.S. government. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The work of Dr. Freeman on this paper was supported by Grant #T32DKK091202 from the National Institute of Diabetes, Digestive and Kidney Disease and for Dr. Myaskovsky by Grant #R01DK081325 from the National Institute of Diabetes, Digestive and Kidney Disease, and Grants #IIR 06-220 and #CIN 13-405 from the Veterans Affairs Health Services Research and Development Service. NR 67 TC 5 Z9 5 U1 6 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUL PY 2015 VL 30 IS 7 BP 1077 EP 1086 DI 10.1007/s00467-014-2879-3 PG 10 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA CJ0UD UT WOS:000355193100006 PM 25315177 ER PT J AU Pekarya, AE Sattin, A Lloyd, RL AF Pekarya, A. Eugene Sattin, Albert Lloyd, Robert L. TI Ketamine modulates TRH and TRH-like peptide turnover in brain and peripheral tissues of male rats SO PEPTIDES LA English DT Article DE Depression; Anxiety; Limbic system; Neuroendocrine ID RAPID ANTIDEPRESSANT RESPONSE; RESISTANT MAJOR DEPRESSION; NMDA RECEPTOR BLOCKADE; D-ASPARTATE ANTAGONIST; INTRANASAL INSULIN; SUICIDAL IDEATION; HORMONE TRH; THYROTROPIN; ANXIETY; ANESTHESIA AB Major depression is the largest single healthcare burden with treatments of slow onset and often limited efficacy. Ketamine, a NMDA antagonist used extensively as a pediatric and veterinary anesthetic, has recently been shown to be a rapid acting antidepressant, making it a potential lifesaver for suicidal patients. Side effects and risk of abuse limit the chronic use of ketamine. More complete understanding of the neurobiochemical mechanisms of ketamine should lead to safer alternatives. Some of the physiological and pharmacological actions of ketamine are consistent with increased synthesis and release of TRH (pGlu-His-Pro-NH2), and TRH-like peptides (pGlu-X-Pro-NH2) where "X" can be any amino acid residue. Moreover, TRH-like peptides are themselves potential therapeutic agents for the treatment of major depression, anxiety, bipolar disorder, epilepsy, Alzheimer's and Parkinson's diseases. For these reasons, male Sprague-Dawley rats were anesthetized with 162 mg/kg ip ketamine and then infused intranasally with 20 mu l of sterile saline containing either 0 or 5 mg/ml Glu-TRH. One, 2 or 4 h later, the brain levels of TRH and TRH-like peptides were measured in various brain regions and peripheral tissues. At 1 h in brain following ketamine only, the levels of TRH and TRH-like peptides were significantly increased in 52 instances (due to increased biosynthesis and/or decreased release) or decreased in five instances. These changes, listed by brain region in order of decreasing number of significant increases (up arrow) and/or decreases (down arrow), were: hypothalamus (9 up arrow); piriform cortex (8 up arrow); entorhinal cortex (7 up arrow); nucleus accumbens (7 up arrow); posterior cingulate (5 up arrow); striatum (4 up arrow); frontal cortex (2 up arrow,3 down arrow); amygdala (3 up arrow); medulla oblongata (1 up arrow,2 down arrow); cerebellum (2 up arrow); hippocampus (2 up arrow); anterior cingulate (2 up arrow). The corresponding changes in peripheral tissues were: adrenals (8 up arrow); epididymis (4 up arrow); testis (1 up arrow,3 down arrow); pancreas (1 up arrow); prostate (1 up arrow). We conclude that TRH and TRH-like peptides may be downstream mediators of the rapid antidepressant actions of ketamine. Published by Elsevier Inc. C1 [Pekarya, A. Eugene; Sattin, Albert] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. [Pekarya, A. Eugene] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. [Pekarya, A. Eugene] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. [Lloyd, Robert L.] Univ Minnesota, Dept Psychol, Duluth, MN 55812 USA. RP Pekarya, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Albert.Pekary@va.gov FU Department of Veterans Affairs Medical Research funds; Pekary Trust FX This work was supported by the Department of Veterans Affairs Medical Research funds (AEP and AS) and the Pekary Trust. NR 72 TC 4 Z9 4 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD JUL PY 2015 VL 69 BP 66 EP 76 DI 10.1016/j.peptides.2015.04.003 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA CJ1AR UT WOS:000355214300009 PM 25882008 ER PT J AU Kennelty, KA Chewning, B Wise, M Kind, A Roberts, T Kreling, D AF Kennelty, Korey A. Chewning, Betty Wise, Meg Kind, Amy Roberts, Tonya Kreling, David TI Barriers and facilitators of medication reconciliation processes for recently discharged patients from community pharmacists' perspectives SO RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY LA English DT Article DE Community pharmacy; Medication reconciliation; Transitions of care; Qualitative methods ID SOCIAL DESIRABILITY BIAS; INFORMATION-TRANSFER; TRANSITIONAL CARE; PLANNED BEHAVIOR; REHOSPITALIZATION; QUESTIONNAIRE; INTERVENTION; CONTINUITY; EMERGENCY; OUTCOMES AB Background: Community pharmacists play a vital part in reconciling medications for patients transitioning from hospital to community care, yet their roles have not been fully examined in the extant literature. Objectives: The objectives of this study were to: 1) examine the barriers and facilitators community pharmacists face when reconciling medications for recently discharged patients; and 2) identify pharmacists' preferred content and modes of information transfer regarding updated medication information for recently discharged patients. Methods: Community pharmacists were purposively and conveniently sampled from the Wisconsin (U.S. state) pharmacist-based research network, Pharmacy Practice Enhancement and Action Research Link (PEARL Rx). Community pharmacists were interviewed face-to-face, and transcriptions from audio recordings were analyzed using directed content analysis. The Theory of Planned Behavior (TPB) guided the development of questions for the semi-structured interviews. Results: Interviewed community pharmacists (N = 10) described the medication reconciliation process to be difficult and time-consuming for recently discharged patients. In the context of the TPB, more barriers than facilitators of reconciling medications were revealed. Themes were categorized as organizational and individual-level themes. Major organizational-level factors affecting the medication reconciliation process included: pharmacy resources, discharge communication, and hospital resources. Major individual-level factors affecting the medication reconciliation process included: pharmacists' perceived responsibility, relationships, patient perception of pharmacist, and patient characteristics. Interviewed pharmacists consistently responded that several pieces of information items would be helpful when reconciling medications for recently discharged patients, including the hospital medication discharge list and stop-orders for discontinued medications. Conclusions: The TPB was useful for identifying barriers and facilitators of medication reconciliation for recently discharged patients from community pharmacists' perspectives. The elucidation of these specific facilitators and barriers suggest promising avenues for future research interventions to improve exchange of medication information between the community pharmacy, hospitals, and patients. Published by Elsevier Inc. C1 [Kennelty, Korey A.; Kind, Amy; Roberts, Tonya] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Kennelty, Korey A.; Chewning, Betty; Wise, Meg; Kreling, David] Univ Wisconsin, Sch Pharm, Sonderegger Res Ctr, Madison, WI 53706 USA. [Kind, Amy] Univ Wisconsin, Dept Med, Div Geriatr, Madison, WI USA. [Roberts, Tonya] Univ Wisconsin, Sch Nursing, Madison, WI USA. RP Kennelty, KA (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace,11-G, Madison, WI 53705 USA. EM kennelty@wisc.edu FU Agency for Healthcare Research and Quality (AHRQ) Health Services Research Dissertation Grant of the National Institutes of Health [1R36HS021984-01]; UW-Madison School of Pharmacy Sonderegger Research Center Dissertation Grant; Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; National Institute on Aging Beeson Career Development Award [K23AG034551]; National Institute on Aging; American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; Wisconsin Partnership Program New Investigator Award; Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR)from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources [1UL1RR025011] FX Funding support: Research reported in this manuscript was supported by the Agency for Healthcare Research and Quality (AHRQ) Health Services Research Dissertation Grant of the National Institutes of Health under award number 1R36HS021984-01 [PI: Kennelty]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Research reported was also supported by the UW-Madison School of Pharmacy Sonderegger Research Center Dissertation Grant.; The project described was also supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427.; Dr. Kind is supported by a National Institute on Aging Beeson Career Development Award (K23AG034551 [PI: Kind], National Institute on Aging, The American Federation for Aging Research, The John A. Hartford Foundation, The Atlantic Philanthropies and The Starr Foundation). Additional support was provided by the Wisconsin Partnership Program New Investigator Award (PI: Kind) and Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR), grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. NR 47 TC 6 Z9 6 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7411 EI 1934-8150 J9 RES SOC ADMIN PHARM JI Res. Soc. Adm. Pharm. PD JUL-AUG PY 2015 VL 11 IS 4 BP 517 EP 530 DI 10.1016/j.sapharm.2014.10.008 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA CJ2UD UT WOS:000355339200004 PM 25586885 ER PT J AU Pennarola, BW Rodday, AM Bingen, K Schwartz, LA Patel, SK Syrjala, KL Mayer, DK Ratichek, SJ Guinan, EC Kupst, MJ Hibbard, JH Parsons, SK AF Pennarola, Brian W. Rodday, Angie Mae Bingen, Kristin Schwartz, Lisa A. Patel, Sunita K. Syrjala, Karen L. Mayer, Deborah K. Ratichek, Sara J. Guinan, Eva C. Kupst, Mary Jo Hibbard, Judith H. Parsons, Susan K. TI Changing factors associated with parent activation after pediatric hematopoietic stem cell transplant SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Cancer; HSCT; Children; Patient activation; Parent-Patient Activation Measure ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; SELF-MANAGEMENT; DEPRESSIVE SYMPTOMS; EDUCATIONAL-PROGRAM; SOCIAL SUPPORT; CHRONIC GRAFT; HOST-DISEASE; MEASURE PAM; CHILDREN AB To identify factors associated with parent activation in parents of children undergoing pediatric hematopoietic stem cell transplant (HSCT) in the 6 months following HSCT, and to address if their association with parent activation changes over time. Measures for this analysis, including the Parent-Patient Activation Measure (Parent-PAM), were completed by parents (N = 198) prior to their child's HSCT preparative regimen and again at 6 months post-HSCT. Clinical data were also collected. A repeated measures model was built to estimate the association between clinical and demographic factors and parent well-being on Parent-PAM scores. Interactions with time were considered to test for changing effects over time. Throughout the HSCT course, older parent age was associated with lower Parent-PAM scores (beta = -0.29, p = 0.02) and never being married was associated with higher scores (versus married, beta = 12.27, p = 0.03). While higher parent emotional functioning scores were not associated with activation at baseline, they were important at 6 months (baseline, beta = -0.002, p = 0.96; interaction, beta = 0.14, p = 0.03). At baseline, longer duration of illness was associated with increased activation, but this effect diminished with time (baseline, beta = 3.29, p = 0.0002; interaction, beta = -2.40, p = 0.02). Activation levels dropped for parents of children who went from private to public insurance (baseline, beta = 2.95, p = 0.53; interaction, beta = -13.82, p = 0.004). Clinical events did not affect Parent-PAM scores. Our findings reveal important changes in the factors associated with parent activation in the first 6 months after pediatric HSCT. These findings may reflect the emotional and financial toll of pediatric HSCT on parent activation. C1 [Pennarola, Brian W.; Rodday, Angie Mae; Ratichek, Sara J.; Parsons, Susan K.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Bingen, Kristin; Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Schwartz, Lisa A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Pediat, Duarte, CA 91010 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Support Care Med, Duarte, CA 91010 USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Dept Biobehav Sci, Seattle, WA 98104 USA. [Mayer, Deborah K.] Univ North Carolina Chapel Hill, Sch Nursing, Chapel Hill, NC USA. [Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Guinan, Eva C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Hibbard, Judith H.] Univ Oregon, Dept Planning Publ Policy & Management, Eugene, OR 97403 USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. RP Parsons, SK (reprint author), Tufts Univ, Sch Med, Dept Med, 800 Washington St,345, Boston, MA 02111 USA. EM bwpennarola@gmail.com; arodday@tuftsmedicalcenter.org; kbingen@mcw.edu; schwartzl@email.chop.edu; spatel@coh.org; ksyrjala@fhcrc.org; dkmayer@email.unc.edu; sjratichek@gmail.com; eva_guinan@dfci.harvard.edu; mkupst@mcw.edu; judithhibbard@mac.com; sparsons@tuftsmedicalcenter.org FU National Cancer Institute [R01 CA 119196] FX The authors would like to thank Doris Hernandez for her help with manuscript preparation and submission. The authors gratefully acknowledge funding from the National Cancer Institute for this study (R01 CA 119196, SKP). NR 45 TC 1 Z9 1 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JUL PY 2015 VL 23 IS 7 BP 1997 EP 2006 DI 10.1007/s00520-014-2544-1 PG 10 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CJ1PI UT WOS:000355255600021 PM 25519755 ER PT J AU Zhang, SJ Sodroski, J AF Zhang, Shijian Sodroski, Joseph TI Efficient human immunodeficiency virus (HIV-1) infection of cells lacking PDZD8 SO VIROLOGY LA English DT Article DE Retrovirus; Host factor; Uncoating; Capsid; Stabilization; CRISPR-CAS9; Knockout ID STABLE MICROTUBULE FORMATION; RETROVIRAL INFECTION; TYPE-1; CORE; CAPSIDS AB PDZD8 can bind the capsid proteins of different retroviruses, and transient knockdown of PDZD8 results in a decrease in the efficiency of an early, post-entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to create cell lines in which PDZD8 expression is stably eliminated. The PDZD8-knockout cell lines were infected by human immunodeficiency virus (HIV-1) and murine leukemia virus as efficiently as the parental PDZD8-expressing cells. These results indicate that PDZD8 is not absolutely necessary for HIV-1 infection and diminishes its attractiveness as a potential target for intervention. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhang, Shijian; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02215 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,CLS 1010, Boston, MA 02215 USA. EM joseph_sodroski@dfci.harvard.edu RI Zhang, Shijian/P-9353-2015 OI Zhang, Shijian/0000-0002-2017-6754 FU National Institutes of Health [AI063987]; National Institutes of Health (Center for AIDS Research) [AI06354]; International AIDS Vaccine Initiative FX We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for manuscript preparation. We acknowledge the support of the National Institutes of Health (AI063987 and a Center for AIDS Research Award AI06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. NR 25 TC 4 Z9 4 U1 0 U2 10 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 JUL PY 2015 VL 481 BP 73 EP 78 DI 10.1016/j.virol.2015.01.034 PG 6 WC Virology SC Virology GA CI9CW UT WOS:000355069000008 PM 25771112 ER PT J AU Mefford, ME Kunstman, K Wolinsky, SM Gabuzda, D AF Mefford, Megan E. Kunstman, Kevin Wolinsky, Steven M. Gabuzda, Dana TI Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5 SO VIROLOGY LA English DT Article DE HIV; Envelope; Macrophage; Tropism; CD4; CCR5; Bridging sheet; V1/V2 stem ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; TYPE-1 R5 ENVELOPES; CD4 BINDING LOOP; N-LINKED GLYCAN; NEUTRALIZING ANTIBODIES; ENTRY INHIBITORS; MONOCLONAL-ANTIBODIES; VIRAL INFECTIVITY; LYMPHOID-TISSUES AB Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the beta 3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120-CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mefford, Megan E.; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kunstman, Kevin; Wolinsky, Steven M.] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol Microbiol & Immunobiol, Boston, MA USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM megan_mefford@hms.harvard.edu; kunstman@northwestern.edu; s-wolinsky@northwestern.edu; dana_gabuzda@dfci.harvard.edu OI Wolinsky, Steven/0000-0002-9625-6697 FU NIH [MH83588, MH97659, F31NS060611]; DFCI/Harvard Cancer Center [P30 AI060354, P30 CA06516] FX We thank J. Cunningham, J. Sodroski, and B. Chen for helpful discussions, R. Bosch for helpful discussions regarding statistical analysis of HIV sequences, N. Letvin for TZM-bl cells, B. Lee for Affinofile cells, and Will (Po-Jen) Yen for help with structural modeling. The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID: monoclonal antibody 17b from Dr. James E. Robinson, goat anti-gp120, and TAK-779. This work was supported by NIH Grants MH83588 and MH97659 to D.G. M.E.M. was supported in part by NIH fellowship F31NS060611. Core facilities were supported by Harvard Medical School Center for AIDS Research (CFAR) and DFCI/Harvard Cancer Center Grants P30 AI060354 and P30 CA06516. NR 89 TC 3 Z9 3 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 2015 VL 481 BP 210 EP 222 DI 10.1016/j.virol.2015.01.032 PG 13 WC Virology SC Virology GA CI9CW UT WOS:000355069000022 PM 25797607 ER PT J AU Keuthen, NJ Tung, ES Woods, DW Franklin, ME Altenburger, EM Pauls, DL Flessner, CA AF Keuthen, Nancy J. Tung, Esther S. Woods, Douglas W. Franklin, Martin E. Altenburger, Erin M. Pauls, David L. Flessner, Christopher A. TI Replication Study of the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version in a Clinically Characterized Sample SO BEHAVIOR MODIFICATION LA English DT Article DE trichotillomania; hair pulling; styles of pulling; assessment ID RANDOMIZED CONTROLLED-TRIAL; PSYCHOMETRIC PROPERTIES; FUNCTIONAL IMPACT; BEHAVIOR-THERAPY; HABIT REVERSAL; PHENOMENOLOGY; STYLES; SEVERITY; SCALES AB In the present study, we evaluated the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A) in a replication sample of clinically characterized hair pullers using exploratory factor analysis (EFA; N = 193). EFA eigenvalues and visual inspection of our scree plot revealed a two-factor solution. Factor structure coefficients and internal consistencies suggested a 13-item scale with an 8-item Intention scale and a 5-item Emotion scale. Both scales displayed good construct and discriminant validity. These findings indicate the need for a revised scale that provides a more refined assessment of pulling phenomenology that can facilitate future treatment advances. C1 [Keuthen, Nancy J.] Massachusetts Gen Hosp, Trichotillomania Clin, Boston, MA 02114 USA. [Tung, Esther S.] Massachusetts Gen Hosp, Trichotillomania Clin, OCD & Related Disorders Clin, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Psychiat Genet, Boston, MA 02114 USA. [Woods, Douglas W.] Texas A&M Univ, Dept Psychol, College Stn, TX USA. [Franklin, Martin E.] Univ Penn, Clin Psychol Psychiat, Philadelphia, PA 19104 USA. [Altenburger, Erin M.] Ohio State Univ, Clin Psychol Program, Columbus, OH 43210 USA. [Flessner, Christopher A.] Kent State Univ, Dept Psychol, Wright Patterson AFB, OH USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, OCD & Related Disorders Program, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Flessner, Christopher/K-1483-2015 FU Greater Kansas City Foundation; Trichotillomania Learning Center and its Body-Focused Repetitive Behaviors Precision Medicine Initiative 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 grants from the Greater Kansas City Foundation and the Trichotillomania Learning Center and its Body-Focused Repetitive Behaviors Precision Medicine Initiative. NR 30 TC 1 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2015 VL 39 IS 4 BP 580 EP 599 DI 10.1177/0145445515580533 PG 20 WC Psychology, Clinical SC Psychology GA CI8BQ UT WOS:000354992900006 PM 25868534 ER PT J AU Pfarr, N Kriegsmann, M Sinn, P Klauschen, F Endris, V Herpel, E Muckenhuber, A Jesinghaus, M Klosterhalfen, B Penzel, R Lennerz, JK Weichert, W Stenzinger, A AF Pfarr, Nicole Kriegsmann, Mark Sinn, Peter Klauschen, Frederick Endris, Volker Herpel, Esther Muckenhuber, Alexander Jesinghaus, Moritz Klosterhalfen, Bernd Penzel, Roland Lennerz, Jochen K. Weichert, Wilko Stenzinger, Albrecht TI Distribution of MED12 mutations in fibroadenomas and phyllodes tumors of the breastimplications for tumor biology and pathological diagnosis SO GENES CHROMOSOMES & CANCER LA English DT Article ID SMOOTH-MUSCLE TUMORS; COLORECTAL-CANCER; UTERINE LEIOMYOMA; EXON-2 MUTATIONS; BREAST; MEDIATOR; LEIOMYOSARCOMA; PROGNOSIS; FEATURES; LESIONS AB Somatic mutations in exon 2 of MED12 have been described in benign and malignant smooth muscle cell tumors suggesting a functional role in these neoplasms. Recently fibroadenomas of the breast were also reported to harbor MED12 mutations. Hence, we explored MED12 mutations in fibroepithelial tumors of the breast, histological subtypes of fibroadenomas and phyllodes tumors, to validate and extend previous efforts. Using conventional Sanger sequencing, we profiled 39 cases of fibroepithelial breast tumors comprising classic histological subtypes of fibroadenomas as well as benign and malignant phyllodes tumors for mutations in exon 2 of MED12. MED12 mutations were detected in 60% of all tumor samples with the majority being missense mutations affecting codon 44. Additionally, we report novel in-frame deletions that have not been described previously. Sixty-two percent of the fibroadenomas harbored mutated MED12 with intracanalicular fibroadenomas being the most frequently mutated histological subtype (82%). Of note, 8/11 of benign phyllodes tumors had MED12 mutations while only 1/5 of malignant phyllodes tumors showed mutations in exon 2 of MED12. In conclusion, we confirm the frequent occurrence of MED12 mutations in fibroadenomas, provide evidence that most intracanalicular fibroadenomas closely resembling benign phyllodes as well as benign phyllodes tumors harbor MED12 mutations, and conclude that MED12 mutations in malignant phyllodes tumors appear to be relatively rare. (c) 2015 Wiley Periodicals, Inc. C1 [Pfarr, Nicole; Kriegsmann, Mark; Sinn, Peter; Endris, Volker; Herpel, Esther; Muckenhuber, Alexander; Jesinghaus, Moritz; Penzel, Roland; Weichert, Wilko; Stenzinger, Albrecht] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany. [Klauschen, Frederick] Charite, Inst Pathol, D-10117 Berlin, Germany. [Herpel, Esther] Natl Ctr Tumor Dis NCT, Tissue Bank, Heidelberg, Germany. [Klosterhalfen, Bernd] Dueren Hosp, Inst Pathol, D-52351 Duren, Germany. [Lennerz, Jochen K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,CID, Boston, MA 02114 USA. [Weichert, Wilko] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany. RP Stenzinger, A (reprint author), Univ Heidelberg Hosp, Inst Pathol, Neuenheimer Feld 224, D-69120 Heidelberg, Germany. EM albrecht.stenzinger@med.uni-heidelberg.de FU German Cancer Consortium (DKTK) FX Supported by: The German Cancer Consortium (DKTK; to WW). NR 36 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2015 VL 54 IS 7 BP 444 EP 452 DI 10.1002/gcc.22256 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA CI4SY UT WOS:000354745000005 PM 25931199 ER PT J AU Muller, LPD Sargoy, A Fernandez-Sanchez, L Rodriguez, A Liu, J Cuenca, N Brecha, N AF Mueller, Luis Perez de Sevilla Sargoy, Allison Fernandez-Sanchez, Laura Rodriguez, Allen Liu, Janelle Cuenca, Nicolas Brecha, Nicholas TI Expression and cellular localization of the voltage-gated calcium channel alpha(2)delta(3) in the rodent retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE calcium channel; retina; alpha(2)delta(3) subunit; amacrine cell; ganglion cell; photoreceptor ID PHOTORECEPTOR RIBBON SYNAPSE; ACID TRANSPORTER EXPRESSION; TISSUE-SPECIFIC EXPRESSION; DISPLACED AMACRINE CELLS; DEVELOPING MOUSE RETINA; PIG HORIZONTAL CELLS; RNA-BINDING PROTEIN; MAMMALIAN RETINA; RAT RETINA; BIPOLAR CELLS AB High-voltage-activated calcium channels are hetero-oligomeric protein complexes that mediate multiple cellular processes, including the influx of extracellular Ca2+, neurotransmitter release, gene transcription, and synaptic plasticity. These channels consist of a primary (1) pore-forming subunit, which is associated with an extracellular (2) subunit and an intracellular auxiliary subunit, which alter the gating properties and trafficking of the calcium channel. The cellular localization of the (23) subunit in the mouse and rat retina is unknown. In this study using RT-PCR, a single band at approximate to 305 bp corresponding to the predicted size of the (23) subunit fragment was found in mouse and rat retina and brain homogenates. Western blotting of rodent retina and brain homogenates showed a single 123-kDa band. Immunohistochemistry with an affinity-purified antibody to the (23) subunit revealed immunoreactive cell bodies in the ganglion cell layer and inner nuclear layer and immunoreactive processes in the inner plexiform layer and the outer plexiform layer. (23) immunoreactivity was localized to multiple cell types, including ganglion, amacrine, and bipolar cells and photoreceptors, but not horizontal cells. The expression of the (23) calcium channel subunit to multiple cell types suggests that this subunit participates widely in Ca-channel-mediated signaling in the retina. J. Comp. Neurol. 523:1443-1460, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Mueller, Luis Perez de Sevilla; Sargoy, Allison; Rodriguez, Allen; Liu, Janelle; Brecha, Nicholas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Sargoy, Allison; Brecha, Nicholas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Sargoy, Allison; Brecha, Nicholas] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fernandez-Sanchez, Laura; Cuenca, Nicolas] Univ Alicante, Physiol Genet & Microbiol, Alicante 03690, Spain. [Brecha, Nicholas] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Brecha, Nicholas] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Muller, LPD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM luisperez@mednet.ucla.edu FU U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC) [W81XWH-10-2-0077]; National Institutes of Health [EY04067]; VA Merit Review FX Grant sponsor: U.S. Army Medical Research & Materiel Command (USAMRMC); Grant sponsor: Telemedicine & Advanced Technology Research Center (TATRC); Grant number: W81XWH-10-2-0077; Grant sponsor: National Institutes of Health; Grant number: EY04067; Grant sponsor: VA Merit Review (to N.B.). NR 110 TC 1 Z9 1 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 1 PY 2015 VL 523 IS 10 BP 1443 EP 1460 DI 10.1002/cne.23751 PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA CI4QQ UT WOS:000354737600001 ER PT J AU Gow, DW Olson, BB AF Gow, David W., Jr. Olson, Bruna B. TI Lexical mediation of phonotactic frequency effects on spoken word recognition: A Granger causality analysis of MRI-constrained MEG/EEG data SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE Phonotactic frequency; Effective connectivity; Magnetoencephalography; Granger causation; Speech perception; Lexical effect ID CONTINUOUS SPEECH RECOGNITION; EVENT-RELATED POTENTIALS; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; NEIGHBORHOOD ACTIVATION; TIME-COURSE; COORDINATE SYSTEM; WORKING-MEMORY; PERCEPTION; MODEL AB Phonotactic frequency effects play a crucial role in a number of debates over language processing and representation. It is unclear however, whether these effects reflect prelexical sensitivity to phonotactic frequency, or lexical "gang effects" in speech perception. In this paper, we use Granger causality analysis of MR-constrained MEG/EEG data to understand how phonotactic frequency influences neural processing dynamics during auditory lexical decision. Effective connectivity analysis showed weaker feedforward influence from brain regions involved in acoustic-phonetic processing (superior temporal gyrus) to lexical areas (supramarginal gyrus) for high phonotactic frequency words, but stronger top-down lexical influence for the same items. Low entropy nonwords (nonwords judged to closely resemble real words) showed a similar pattern of interactions between brain regions involved in lexical and acoustic-phonetic processing. These results contradict the predictions of a feedforward model of phonotactic frequency facilitation, but support the predictions of a lexically mediated account. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gow, David W., Jr.; Olson, Bruna B.] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. [Gow, David W., Jr.] Salem State Univ, Dept Psychol, Salem, MA 01970 USA. [Gow, David W., Jr.; Olson, Bruna B.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gow, David W., Jr.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, 175 Cambridge St,CPZ S340, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu; bbolson@partners.org FU National Institute of Deafness and Communicative Disorders [R01 DC003108]; NCRR Regional Resource Grant [41RR14075]; MIND Institute FX We would like to thank Nao Suzuki, and Reid Vancelette for their assistance in running the experiment, Conrad Nied for all aspects of the work including the development of our processing stream, Jennifer Michaud, Mark Vangel and Juliane Venturelli Silva Lima for statistical advice and review, and Michael Vitevitch, James Magnuson, David Caplan, James McQueen, Arthur Samuel and an anonymous reviewer for their thoughtful feedback. This work was supported by the National Institute of Deafness and Communicative Disorders (R01 DC003108) to D.W.G. and benefited from support from the MIND Institute and the NCRR Regional Resource Grant (41RR14075) for the development of technology and analysis tools at the Athinoula A. Martinos Center for Biomedical Imaging. NR 91 TC 3 Z9 3 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X EI 1096-0821 J9 J MEM LANG JI J. Mem. Lang. PD JUL PY 2015 VL 82 BP 41 EP 55 DI 10.1016/j.jml.2015.03.004 PG 15 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA CI8SL UT WOS:000355041900003 PM 25883413 ER PT J AU Marron, JM Mack, JW AF Marron, Jonathan M. Mack, Jennifer W. TI When to say when: How aggressively to care for children with multiply relapsed cancer? SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID PALLIATIVE CARE; PARENTS; CHEMOTHERAPY C1 [Marron, Jonathan M.; Mack, Jennifer W.] Harvard Univ, Sch Med, Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. RP Marron, JM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D-1109, Boston, MA 02215 USA. EM jonathan_marron@dfci.harvard.edu OI Marron, Jonathan/0000-0001-8935-8524 FU NCI NIH HHS [5T32 CA136432, T32 CA136432] NR 10 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2015 VL 62 IS 7 BP 1119 EP 1120 DI 10.1002/pbc.25476 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CI1YQ UT WOS:000354541600002 PM 25755229 ER PT J AU Lim, SY Pannikath, D Nugent, K AF Lim, Sian Yik Pannikath, Deepa Nugent, Kenneth TI A retrospective study of septic arthritis in a tertiary hospital in West Texas with high rates of methicillin-resistant Staphylococcus aureus infection SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE Septic arthritis; Methicillin-resistant Staphylococcus aureus; Outcomes; Epidemiology ID ANTIBIOTIC-TREATMENT; BACTERIAL ARTHRITIS; PATIENT OUTCOMES; RISK-FACTORS; BACTEREMIA; PERIOD; ADULTS; HEALTH; IMPACT AB Septic arthritis is an important concern for rheumatologists in the evaluation of joint disease. Very few studies have addressed the microbiologic epidemiology and outcomes of septic arthritis in the USA since the year 2000. We performed a retrospective study of septic arthritis in a tertiary hospital in West Texas from the year 2000 to 2013. We recorded data on patient demographics, microbiologic etiology, treatment patterns, and outcomes. The most common causative organisms were Staphylococcus aureus and Streptococcus spp. Methicillin-resistant Staphylococcus aureus (MRSA) caused septic arthritis in 22.6 % of the cases. MRSA septic arthritis was associated with low rates of adequate empiric antimicrobial therapy. The mortality due to sepsis in our study was 5.5 %. Patients with septic arthritis had a mean length of stay of 13.5 +/- A 12.1 days and required 2.1 +/- A 1.4 joint operations. Many patients (29.2 %) had readmissions due to complications, and these patients had high rates of home health utilization and transfers to other facilities post hospital discharge. In our logistic regression analysis model, factors associated with poor outcomes in septic arthritis were MRSA, older age, and prosthetic joint infection. Septic arthritis is associated with significant mortality, morbidity, and health care costs, and more studies are needed to improve outcomes, especially considering the increasing rates of MRSA as the pathogen. C1 [Lim, Sian Yik] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pannikath, Deepa; Nugent, Kenneth] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA. RP Lim, SY (reprint author), Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, 55 Fruit St Bulfinch 165, Boston, MA 02114 USA. EM limsianyik@gmail.com NR 24 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 EI 1437-160X J9 RHEUMATOL INT JI Rheumatol. Int. PD JUL PY 2015 VL 35 IS 7 BP 1251 EP 1256 DI 10.1007/s00296-014-3206-9 PG 6 WC Rheumatology SC Rheumatology GA CI4HO UT WOS:000354709500015 PM 25572838 ER PT J AU Surov, A Nagata, S Abd Razek, AA Tirumani, SH Wienke, A Kahn, T AF Surov, Alexey Nagata, Shuji Abd Razek, Ahmed A. Tirumani, Sree Harsha Wienke, Andreas Kahn, Thomas TI Comparison of ADC values in different malignancies of the skeletal musculature: a multicentric analysis SO SKELETAL RADIOLOGY LA English DT Article DE Skeletal muscle tumors; Magnetic resonance imaging; Diffusion-weighted imaging; Apparent diffusion coefficient ID SOFT-TISSUE TUMORS; DIFFUSION-WEIGHTED MRI; COEFFICIENT AB Diffusion-weighted imaging (DWI) provides essential information regarding tumor composition, such as cellularity and/or perfusion. DWI is helpful in distinguishing between malignant and benign lesions. Malignant intramuscular/soft tissue lesions consist of a wide spectrum of tumors that have different cell counts and matrix. It is presumed that these different tumors have different DWI findings and have different apparent diffusion coefficient (ADC) values. The aim of this study was to analyze DWI findings of different intramuscular malignancies in a multicentric study by using a standardized DWI protocol, and to compare the ADC values acquired. The data banks of four radiology departments were screened retrospectively for malignant intramuscular tumors. Only lesions that were investigated by MRI (with a 1.5-T scanner) using DWI (multishot EPI sequence with b values of 0 and 1,000 s/mm(2)) were included in the study. Overall, 51 patients (28 women, 23 men; mean age 58.8 +/- 16.1 years) with 57 different malignant intramuscular lesions were collected. In every case apparent diffusion constant (ADC) maps were calculated. In 14 patients muscle lymphoma, 11 patients intramuscular metastases from different primary tumors, and in 26 cases several muscle sarcomas were identified. The mean ADC value of the estimated lesions was 1.24 +/- 0.53 x 10(-3) mm(2)s(-1), median value, 1.11 x 10(-3) mm(2)s(-1), range, 0.54-2.9 x 10(-3) mm(2)s(-1). The mean ADC value in muscle metastases was 1.28 +/- 0.24 x 10(-3) mm(2)s(-1), in muscle lymphoma 0.76 +/- 0.14 x 10(-3) mm(2)s(-1), and in muscle sarcomas 1.82 +/- 0.63 x 10(-3) mm(2)s(-1). Muscle lymphoma showed statistically significant lower ADC values in comparison to muscle metastases (p = 0.01) and muscle sarcoma (p = 0.001). There was no significant differences between ADC values in muscle metastases and sarcomas (p = 0.48). ADC values in muscle lymphoma were homogeneous with less inter-patient variability and were within a relatively close range. Muscle sarcomas had a broad range of ADC values. Intramuscular malignant lesions had different ADC values on DWI. 22.8 % of the tumors analyzed had low ADC values, 26.3 % moderate, and 50.9 % high ADC values. Muscle lymphoma had statistically significantly lower ADC values in comparison to muscle metastases and sarcomas. Muscle sarcomas presented with a broad range of ADC values. C1 [Surov, Alexey] Univ Halle Wittenberg, Dept Radiol, D-06108 Halle, Germany. [Surov, Alexey; Kahn, Thomas] Univ Leipzig, Dept Diagnost & Intervent Radiol, D-04109 Leipzig, Germany. [Nagata, Shuji] Kurume Univ, Sch Med, Dept Radiol, Kurume, Fukuoka 830, Japan. [Abd Razek, Ahmed A.] Mansoura Fac Med, Dept Diagnost Radiol, Mansoura, Egypt. [Tirumani, Sree Harsha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Imaging,Dana Farber Canc Inst, Boston, MA 02115 USA. [Tirumani, Sree Harsha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wienke, Andreas] Univ Halle Wittenberg, Inst Med Epidemiol Biometry & Stat, D-06108 Halle, Germany. RP Surov, A (reprint author), Univ Halle Wittenberg, Dept Radiol, D-06108 Halle, Germany. EM alex.surow@medizin.uni-halle.de RI Abdel Razek, Ahmed/J-6737-2016; OI Abdel Razek, Ahmed/0000-0002-9613-5932; Surov, Alexey/0000-0002-9273-3943 NR 17 TC 2 Z9 2 U1 1 U2 2 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 JUL PY 2015 VL 44 IS 7 BP 995 EP 1000 DI 10.1007/s00256-015-2141-5 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CI4KZ UT WOS:000354718800008 PM 25916616 ER PT J AU Kacimi, R Yenari, MA AF Kacimi, Rachid Yenari, Midori A. TI Pharmacologic Heat Shock Protein 70 Induction Confers Cytoprotection against Inflammation in Gliovascular Cells SO GLIA LA English DT Article DE cytoprotection; HSP70; HSP90; microglia; endothelial cells ID HEAT-SHOCK-PROTEIN; ISCHEMIA-REPERFUSION INJURY; OXYGEN-GLUCOSE DEPRIVATION; BLOOD-BRAIN-BARRIER; NF-KAPPA-B; MATRIX METALLOPROTEINASES; EXPERIMENTAL STROKE; HSP90 INHIBITORS; CLINICAL DEVELOPMENT; CEREBRAL-ISCHEMIA AB The inhibition of the 90-kDa heat shock protein (HSP90) leads to upregulation of the 70-kDa-inducible HSP70. HSP70 has been previously shown to be neuroprotective and anti-inflammatory. Geldanamycin (GA) and other HSP90 inhibitors have emerged as promising therapeutic agents in cancer, presumably owing to their ability to upregulate HSP70. However, the effects of HSP90 inhibition in brain inflammation are still unclear. We investigate the effect of a panel of HSP90 inhibitors on endotoxin-activated microglia and eventual protection from brain-derived endothelial cells. Prior studies have shown that GA protects brain cells from oxidative stress. We show here that when astrocytes or microglial BV2 cells were pretreated with GA or other HSP90 inhibitors, endotoxin-induced cell death was reduced in cocultures of BV2 microglia and brain-derived endothelial cells (bEND.3). Endotoxin-stimulated BV2 cells led to increased nitric oxide (NO) and inducible nitric oxide synthase which was prevented by treatment with all HSP90 inhibitors. HSP90 inhibitors also prevented lipopolysaccharide (LPS)-induced BV2 cell death. We also found that HSP90 inhibition blocked nuclear translocation of nuclear factor kappa B and attenuated IB degradation, and inhibited LPS-activated JAK-STAT phosphorylation. We show that pharmacologic inhibition of HSP90 with subsequent HSP70 induction protects cells that comprise the cerebral vasculature against cell death owing to proinflammatory stimuli. This approach may have therapeutic potential in neurological conditions with an inflammatory component. C1 [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, Neurol 127 VAMC 4150 Clement St, San Francisco, CA 94143 USA. EM yenari@alum.mit.edu FU National Institutes of Health [NS40516]; Veteran's Merit Award [BX000589]; Department of Defense [DAMD17-03-1-0532]; Northern California Institute for Research and Education, Resources of the Veterans Affairs Medical Center, San Francisco, California FX Grant sponsor: The National Institutes of Health; Grant number: NS40516; Grant sponsor: Veteran's Merit Award; Grant number: BX000589; Grant sponsor: The Department of Defense;; Grant number: DAMD17-03-1-0532; Grant sponsor: The Northern California Institute for Research and Education, Resources of the Veterans Affairs Medical Center, San Francisco, California. NR 42 TC 5 Z9 6 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 EI 1098-1136 J9 GLIA JI Glia PD JUL PY 2015 VL 63 IS 7 BP 1200 EP 1212 DI 10.1002/glia.22811 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CG6IC UT WOS:000353402100007 PM 25802219 ER PT J AU Song, MY Gong, J Giovannucci, EL Berndt, SI Brenner, H Chang-Claude, J Curtis, KR Harrison, TA Hoffmeister, M Hsu, L Jiao, S Le Marchand, L Potter, JD Schoen, RE Seminara, D Slattery, ML White, E Wu, KN Ogino, S Fuchs, CS Hunter, DJ Tworoger, SS Hu, FB Rimm, E Jensen, M Peters, U Chan, AT AF Song, Mingyang Gong, Jian Giovannucci, Edward L. Berndt, Sonja I. Brenner, Hermann Chang-Claude, Jenny Curtis, Keith R. Harrison, Tabitha A. Hoffmeister, Michael Hsu, Li Jiao, Shuo Le Marchand, Loic Potter, John D. Schoen, Robert E. Seminara, Daniela Slattery, Martha L. White, Emily Wu, Kana Ogino, Shuji Fuchs, Charles S. Hunter, David J. Tworoger, Shelley S. Hu, Frank B. Rimm, Eric Jensen, Majken Peters, Ulrike Chan, Andrew T. TI Genetic variants of adiponectin and risk of colorectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE adiponectin; single-nucleotide polymorphism; Mendelian randomization; colorectal cancer; lifestyle factors ID MOLECULAR-WEIGHT ADIPONECTIN; GENOME-WIDE ASSOCIATION; SOLUBLE LEPTIN RECEPTOR; PLASMA ADIPONECTIN; INSULIN-RESISTANCE; MENDELIAN RANDOMIZATION; CIRCULATING ADIPONECTIN; SUSCEPTIBILITY LOCI; METABOLIC SYNDROME; SERUM ADIPONECTIN AB Circulating adiponectin has been associated with lower risk of colorectal cancer (CRC). Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with adiponectin levels. However, it is unclear whether these SNPs are associated with CRC risk. In addition, previous data on SNPs in the adiponectin pathway and their associations with CRC are inconsistent. Therefore, we examined 19 SNPs in genes related to adiponectin or its receptors and their associations with CRC using logistic regression among 7,020 cases and 7,631 controls drawn from ten studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium. Using data from a subset of two large cohort studies, we also assessed the contribution of individual SNPs and an adiponectin genetic score to plasma adiponectin after accounting for lifestyle factors among 2,217 women and 619 men. We did not find any statistically significant association between the 19 adiponectin-associated SNPs and CRC risk (multivariable-adjusted odds ratios ranged from 0.89 to 1.05, all p>0.05). Each SNP explained less than 2.50% of the variance of plasma adiponectin, and the genetic score collectively accounted for 2.95 and 1.42% of the variability of adiponectin in women and men, respectively, after adjustment for age, body mass index, physical activity, smoking, alcohol consumption, regular use of aspirin or nonsteroidal anti-inflammatory drug and postmenopausal hormone use. In conclusion, our findings do not support an association between known adiponectin-related common SNPs and CRC incidence. However, known common SNPs account for only a limited proportion of the interindividual variance in circulating adiponectin. Further work is warranted to investigate the relationship between adiponectin and CRC while accounting for other components in the pathway. What's new? Obesity is a well-established risk factor for colorectal cancer, and mounting evidence suggests that the adipocyte-derived hormone adiponectin is behind that link. In the present investigation, common genetic variants in the adiponectin (ADIPOQ) gene were analyzed for potential relationships with colorectal cancer risk. However, no statistically significant associations were identified. Because common genetic determinants account for only a limited proportion of the variance in circulating adiponectin concentrations, factors that influence adiponectin receptors and other components of the adiponectin pathway should be investigated. C1 [Song, Mingyang; Giovannucci, Edward L.; Wu, Kana; Hunter, David J.; Hu, Frank B.; Rimm, Eric; Jensen, Majken] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji; Hunter, David J.; Tworoger, Shelley S.; Hu, Frank B.; Rimm, Eric] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gong, Jian; Curtis, Keith R.; Harrison, Tabitha A.; Hsu, Li; Jiao, Shuo; Potter, John D.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Giovannucci, Edward L.; Ogino, Shuji; Fuchs, Charles S.; Hunter, David J.; Tworoger, Shelley S.; Hu, Frank B.; Rimm, Eric; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Giovannucci, Edward L.; Ogino, Shuji; Fuchs, Charles S.; Hunter, David J.; Tworoger, Shelley S.; Hu, Frank B.; Rimm, Eric; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Consortium Translat Canc Res DKTK, Heidelberg, Germany. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Hsu, Li] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Potter, John D.; White, Emily; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org RI Hoffmeister, Michael/B-5745-2012; Song, Mingyang/M-6701-2013; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Song, Mingyang/0000-0002-1324-0316; Brenner, Hermann/0000-0002-6129-1572; Tworoger, Shelley/0000-0002-6986-7046; Potter, John/0000-0001-5439-1500 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045, R01 CA60987, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, P50 CA 127003, R01 CA042182, R37 CA54281, P01 CA033619, R01 CA63464, K05 CA154337, K24 DK098311]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; Harvard Transdisciplinary Research Center on Energetics and Cancer (TREC) [1U54CA155626] FX Grant sponsor: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; Grant numbers: U01 CA137088, R01 CA059045, R01 CA60987, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, P50 CA 127003, R01 CA042182, R37 CA54281, P01 CA033619, R01 CA63464, K05 CA154337, K24 DK098311; Grant sponsor: German Research Council (Deutsche Forschungsgemeinschaft); Grant numbers: BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1; Grant sponsor: German Federal Ministry of Education and Research; Grant numbers: 01KH0404, 01ER0814; Grant sponsor: Harvard Transdisciplinary Research Center on Energetics and Cancer (TREC); Grant number: 1U54CA155626 NR 50 TC 2 Z9 2 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2015 VL 137 IS 1 BP 154 EP 164 DI 10.1002/ijc.29360 PG 11 WC Oncology SC Oncology GA CG4ZH UT WOS:000353297600015 PM 25431318 ER PT J AU Ferder, IC Wang, N AF Ferder, Ianina C. Wang, Ning TI Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression SO ONCOTARGET LA English DT Article DE spermatogonial stem cell; aging; Plzf; mTORC1; differentiation ID CELL SELF-RENEWAL; MALE GERM-CELLS; STEM-CELLS; LIFE-SPAN; RETINOIC ACID; DROSOPHILA; DIFFERENTIATION; MICE; TOR; INITIATION AB Like stem cells in other tissues, spermatogonia, including spermatogonial stem cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays an essential role in spermatogonia maintenance by preventing their differentiation. To evaluate whether there is an age-related change in Plzf expression, we found that aged mouse testes exhibited a robust "Plzf overexpression" phenotype, in that they showed not only a higher frequency of Plzf-expressing cells but also an increased level of Plzf expression in these cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly appeared in the differentiating spermatogonia compartment, which is usually low or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for meiosis initiation. These data, together with our observation of a lack of meiosis-initiating spermatocytes associated with high Plzf-expressing spermatogonia in the aged testes, particularly in the degenerative seminiferous tubules, suggest that age-related increase in Plzf expression represents a novel molecular signature of spermatogonia aging by functionally arresting their differentiation. C1 [Ferder, Ianina C.; Wang, Ning] Massachusetts Gen Hosp, MGH Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Ferder, Ianina C.; Wang, Ning] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Wang, N (reprint author), Massachusetts Gen Hosp, MGH Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM nwang3@mgh.harvard.edu FU NIH; National Institute on Aging [K99/R00-AG039512]; Vincent Department of Obstetrics and Gynecology at Massachusetts General Hospital FX We would like to thank HSCI flow cytometry core facility for assistance with FACS analysis. N.W. is a recipient of an NIH Pathway-to-Independence Award from National Institute on Aging (K99/R00-AG039512). This work was also supported by the Vincent Department of Obstetrics and Gynecology at Massachusetts General Hospital. NR 35 TC 1 Z9 2 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 30 PY 2015 VL 6 IS 18 BP 15891 EP 15901 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO2UL UT WOS:000359012000035 PM 25986924 ER PT J AU Ma, WH Yu, J Qi, XL Liang, L Zhang, Y Ding, Y Lin, XS Li, GX Ding, YQ AF Ma, Wenhui Yu, Jiang Qi, Xiaolong Liang, Li Zhang, Yan Ding, Yi Lin, Xiaoshan Li, Guoxin Ding, Yanqing TI Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells by down-regulating Rb SO ONCOTARGET LA English DT Article DE radiosensitivity; microRNA-622; apoptosis; RB1; Rb ID TUMOR-SUPPRESSOR; RECTAL-CANCER; PREOPERATIVE CHEMORADIOTHERAPY; ONCOGENIC RESISTANCE; EXPRESSION; APOPTOSIS; PROTEIN; IDENTIFICATION; REGRESSION; SIGNATURE AB The standard treatment for patients with locally advanced rectal cancer is preoperative 5-fluorouracil-based chemoradiotherapy followed by total mesorectal excision. However, tumor response to standard dose radiation varies. In this study, we found that miR-622 was increased significantly in ionizing radiation-treated colorectal cancer (CRC) cells compared to the cells cultured with irradiated medium, and persisted stably in surviving cells treated with continuous low-dose radiation. Overexpression of miR-622 induced the radioresistance in vitro. In addition, miR-622 inhibited Rb expression by directly targeting RB1-3'UTR. Overexpression of Rb reversed miR-622-induced radioresistance in vitro. In response to ionizing radiation, the Rb-E2F1-P/CAF complex activated proapoptotic genes. Importantly, miR-622 was highly expressed in tumors of rectal cancer patients with non-regression after standard dose radiotherapy. In conclusion, miR-622 overexpressing cells are induced or selected by radiotherapy, causing in turn radioresistance and poor response to further therapy. MiR-622 is a potential biomarker of responders for radiotherapy and a potential therapeutic target. C1 [Ma, Wenhui; Yu, Jiang; Zhang, Yan; Li, Guoxin] Southern Med Univ, Dept Gen Surg, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. [Yu, Jiang; Liang, Li; Ding, Yanqing] Southern Med Univ, Dept Pathol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. [Qi, Xiaolong] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Qi, Xiaolong] Harvard Univ, Sch Med, Boston, MA USA. [Ding, Yi; Lin, Xiaoshan] Southern Med Univ, Dept Radiat Oncol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. [Qi, Xiaolong] Tongji Univ, Dept Gastroenterol, Tongji Hosp, Sch Med, Shanghai 200092, Peoples R China. RP Ding, YQ (reprint author), Southern Med Univ, Dept Pathol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. EM gzliguoxin@163.com; dyqgz@126.com FU National Natural Science Foundation of China [81071735]; Major projects of National Natural Science Foundation of China [81090422]; State Key Program of National Natural Science Foundation of China [U1201226]; National Basic Research Program of China (973 Program) [2010CB529402, 2010CB529403]; Science and Technology Innovation Foundation of Guangdong Higher Education [GXZD1016]; Key Program of Science and Technology Foundation of Guangzhou City, China [201300000056]; Natural Science Foundation of Guangdong Province [S2011010005301]; Key Clinical Specialty Discipline Construction Program FX This work was supported by the National Natural Science Foundation of China (No. 81071735), Major projects of National Natural Science Foundation of China (No. 81090422), State Key Program of National Natural Science Foundation of China (U1201226), National Basic Research Program of China (973 Program, No. 2010CB529402 and 2010CB529403), Science and Technology Innovation Foundation of Guangdong Higher Education (GXZD1016), Key Program of Science and Technology Foundation of Guangzhou City, China (201300000056), Natural Science Foundation of Guangdong Province (No. S2011010005301), and Key Clinical Specialty Discipline Construction Program. NR 38 TC 9 Z9 10 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 30 PY 2015 VL 6 IS 18 BP 15984 EP 15994 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO2UL UT WOS:000359012000041 PM 25961730 ER PT J AU Shin, M Yang, EG Song, HK Jeon, H AF Shin, Miyoung Yang, Eun Gyeong Song, Hyun Kyu Jeon, Hyesung TI Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells SO BMB REPORTS LA English DT Article DE EGFR activation; IGF-1R interaction; Insulin; MDA-MB-436; Triple-negative breast cancer cells ID GROWTH-FACTOR RECEPTOR; FACTOR-I-RECEPTOR; NEGATIVE BREAST-CANCER; RESISTANCE; INHIBITOR; NEOPLASIA; ERLOTINIB; THERAPY; NETWORK; PATHWAY AB The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC)cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFR-expressing MDA-MB-436 cells show high sensitivity to insulin-stimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. C1 [Shin, Miyoung; Song, Hyun Kyu] Korea Univ, Div Life Sci, Seoul 136701, South Korea. [Shin, Miyoung; Yang, Eun Gyeong; Jeon, Hyesung] Korea Inst Sci & Technol, Biomed Res Inst, Ctr Theragnosis, Seoul 136791, South Korea. [Jeon, Hyesung] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Song, HK (reprint author), Korea Univ, Div Life Sci, Seoul 136701, South Korea. EM hksong@korea.ac.kr; hjeon@red.dfci.harvard.edu RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU Intramural Research Program of the Korea Institute of Science and Technology (KIST); Korea University Grant; National Research Foundation of Kore agrant - Korean government [NRF 2011-0028168] FX We are grateful to Dr. Yosef Yarden (Weizmann Institute of Science, Israel) for his gift of the full-length EGFR plasmid. This study was supported by the Intramural Research Program of the Korea Institute of Science and Technology (KIST) and a Korea University Grant. This work was also supported by a National Research Foundation of Korea (NRF 2011-0028168) grant funded by the Korean government. NR 26 TC 2 Z9 2 U1 0 U2 3 PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG, KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA SN 1976-6696 EI 1976-670X J9 BMB REP JI BMB Rep. PD JUN 30 PY 2015 VL 48 IS 6 BP 342 EP 347 DI 10.5483/BMBRep.2015.48.6.157 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CN3YA UT WOS:000358363200008 PM 25341922 ER PT J AU Konishi, M McLaren, DG Engen, H Smallwood, J AF Konishi, Mahiko McLaren, Donald George Engen, Haakon Smallwood, Jonathan TI Shaped by the Past: The Default Mode Network Supports Cognition that Is Independent of Immediate Perceptual Input SO PLOS ONE LA English DT Article ID EVENT-RELATED FMRI; FUNCTIONAL CONNECTIVITY; SOCIAL COGNITION; WORKING-MEMORY; BRAIN-FUNCTION; FUTURE; MIND; THOUGHT; SELF; PROSPECTION AB Although many different accounts of the functions of the default mode network (DMN) have been proposed, few can adequately account for the spectrum of different cognitive functions that utilize this network. The current study used functional magnetic resonance imaging (fMRI) to explore the hypothesis that the role of the DMN in higher order cognition is to allow cognition to be shaped by information from stored representations rather than information in the immediate environment. Using a novel task paradigm, we observed increased BOLD activity in regions of the medial prefrontal cortex and posterior cingulate cortex when individuals made decisions on the location of shapes from the prior trial and decreased BOLD activity when individuals made decisions on the location of shapes on the current trial. These data are inconsistent with views of the DMN as a task-negative system or one that is sensitive only to stimuli with strong personal or emotional ties. Instead the involvement of the DMN when people make decisions about where a shape was, rather than where it is now, supports the hypothesis that the core hubs of the DMN allow cognition to be guided by information other than the immediate perceptual input. We propose that a variety of different forms of higher order thought (such as imagining the future or considering the perspective of another person) engage the DMN because these more complex introspective forms of higher order thought all depend on the capacity for cognition to be shaped by representations that are not present in the external environment. C1 [Konishi, Mahiko; Smallwood, Jonathan] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England. [Konishi, Mahiko; Smallwood, Jonathan] Univ York, York Neuroimaging Ctr, York YO10 5DD, N Yorkshire, England. [McLaren, Donald George] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald George] Harvard Univ, Sch Med, Boston, MA USA. [Engen, Haakon] Max Plank Inst Human Cognit Brain Sci, Dept Social Neurosci, Leipzig, Germany. RP Konishi, M (reprint author), Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England. EM mk947@york.ac.uk OI McLaren, Donald/0000-0002-0566-4610 NR 73 TC 15 Z9 15 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 30 PY 2015 VL 10 IS 6 AR e0132209 DI 10.1371/journal.pone.0132209 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CN1BR UT WOS:000358151300069 PM 26125559 ER PT J AU Sampson, JF Hasegawa, E Mulki, L Suryawanshi, A Jiang, SH Chen, WS Rabinovich, GA Connor, KM Panjwani, N AF Sampson, James F. Hasegawa, Eiichi Mulki, Lama Suryawanshi, Amol Jiang, Shuhong Chen, Wei-Sheng Rabinovich, Gabriel A. Connor, Kip M. Panjwani, Noorjahan TI Galectin-8 Ameliorates Murine Autoimmune Ocular Pathology and Promotes a Regulatory T Cell Response SO PLOS ONE LA English DT Article ID LEISHMANIA-MAJOR INFECTION; STEM-CELLS; IN-VIVO; DISEASE; UVEITIS; UVEORETINITIS; TH17; INFLAMMATION; SUPPRESSES; TOLERANCE AB Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103. Treg cells in the retina of Gal-8-treated mice were primarily inducible Treg cells that lack the expression of neuropilin-1. In addition, Gal-8 treatment blunted production of inflammatory cytokines by retinal T helper type (T-H) 1 and T(H)17 cells. The effect of Gal-8 on T cell differentiation and/or function was specific for tissues undergoing an active immune response, as Gal-8 treatment had no effect on T cell populations in the spleen. Given the need for rational therapies for managing human uveitis, Gal-8 emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other T(H)1-and T(H)17-mediated inflammatory disorders. C1 [Sampson, James F.; Panjwani, Noorjahan] Tufts Univ, Sackler Sch Grad Biomed Sci, Program Immunol, Boston, MA 02111 USA. [Hasegawa, Eiichi; Mulki, Lama; Connor, Kip M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA. [Suryawanshi, Amol; Panjwani, Noorjahan] Tufts Univ, Sch Med, New England Eye Ctr, Dept Ophthalmol, Boston, MA 02111 USA. [Jiang, Shuhong] Tufts Univ, JM USDA HNRCA, Lab Nutr & Vis Res, Boston, MA 02111 USA. [Jiang, Shuhong; Panjwani, Noorjahan] Peoples Hosp Inner Mongolia, Dept Ophthalmol, Hohhot, Peoples R China. [Chen, Wei-Sheng] Tufts Univ, Sackler Sch Grad Biomed Sci, Cell Mol & Dev Biol, Boston, MA 02111 USA. [Rabinovich, Gabriel A.] Consejo Nacl Invest Cient & Tecn, Lab Inmunopatol, IBYME, RA-1033 Buenos Aires, DF, Argentina. RP Connor, KM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA. EM kip_connor@meei.harvard.edu; Noorjahan.panjwani@tufts.edu OI Connor, Kip/0000-0002-2048-9080 FU National Eye Institute [R01EY007088, R01EY009349, R01EY022084-01/S1]; Mass Lions Eye Research fund; New England Corneal Transplant Fund; Research to Prevent Blindness FX This work was generously supported by National Eye Institute (https://www.nei.nih.gov/) Grants R01EY007088 (NP), R01EY009349 (NP), R01EY022084-01/S1 (KMC), Mass Lions Eye Research fund (NP), New England Corneal Transplant Fund (NP) and an unrestricted award from Research to Prevent Blindness (http://www.rpbusa.org/rpb/NP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 3 Z9 3 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 30 PY 2015 VL 10 IS 6 AR e0130772 DI 10.1371/journal.pone.0130772 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CN1BR UT WOS:000358151300025 PM 26126176 ER PT J AU Goodman, A AF Goodman, Annekathryn TI HPV testing as a screen for cervical cancer SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Review ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; RISK HUMAN-PAPILLOMAVIRUS; POPULATION-BASED COHORT; LIQUID-BASED CYTOLOGY; INTRAEPITHELIAL NEOPLASIA; FOLLOW-UP; COST-EFFECTIVENESS; UNITED-STATES; POOLED ANALYSIS AB Human papillomavirus (HPV) has been identified as a necessary factor in the development of pre-invasive and invasive cancers of the lower genital tract, of which cervical cancer is the most prevalent. A molecular understanding of malignant transformation and epidemiologic information has led to the development of many strategies for detection and early intervention. Newer tests for oncogenic subtypes of HPV have made it possible to predict the risk of future development of cervical cancer. This review summarizes the current understanding of HPV related disease and examines the role of HPV testing as a screening tool for cervical cancer. It summarizes the data from prospective and randomized controlled trials on HPV screening from Europe and North America and includes smaller studies from low and middle income countries where cervical cancer is the most common cancer in women. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02114 USA. EM agoodman@partners.org NR 75 TC 9 Z9 13 U1 5 U2 16 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 JUN 30 PY 2015 VL 350 AR h2372 DI 10.1136/bmj.h2372 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CM3TN UT WOS:000357607400001 PM 26126623 ER PT J AU Nipp, RD Currow, DC Cherny, NI Strasser, F Abernethy, AP Zafar, SY AF Nipp, R. D. Currow, D. C. Cherny, N. I. Strasser, F. Abernethy, A. P. Zafar, S. Y. TI Best supportive care in clinical trials: review of the inconsistency in control arm design SO BRITISH JOURNAL OF CANCER LA English DT Article DE research design; health services research; randomized controlled trial; palliative care; symptom assessment ID PHASE-III TRIAL; CELL LUNG-CANCER; MALIGNANT PLEURAL MESOTHELIOMA; RANDOMIZED CONTROLLED-TRIAL; EARLY PALLIATIVE CARE; COLORECTAL-CANCER; AMERICAN SOCIETY; PEMETREXED PLUS; GASTRIC-CANCER; OPEN-LABEL AB Background: Best supportive care (BSC) as a control arm in clinical trials is poorly defined. We conducted a review to evaluate clinical trials' concordance with published, consensus-based framework for BSC delivery in trials. Methods: A consensus-based Delphi panel previously identified four key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. We reviewed trials including BSC control arms from 2002 to 2014 to assess concordance to BSC standards and to selected items from the CONSORT 2010 guidelines. Results: Of 408 articles retrieved, we retained 18 after applying exclusion criteria. Overall, trials conformed to the CONSORT guidelines better than the BSC standards (28% vs 16%). One-third of articles offered a detailed description of BSC, 61% reported regular symptom assessment, and 44% reported using validated symptom assessment measures. One-third reported symptom assessment at identical intervals in both arms. None documented evidence-based symptom management. No studies reported educating patients about symptom management or goals of therapy. No studies reported offering access to palliative care specialists. Conclusions: Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such studies risk systematically over-estimating the net clinical effect of the comparator arms. C1 [Nipp, R. D.] Massachusetts Gen Hosp, Dept Med, Div Med Oncol, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. [Currow, D. C.] Flinders Univ S Australia, Sch Hlth Sci, Discipline Palliat & Support Serv, Adelaide, SA 5001, Australia. [Cherny, N. I.] Canc Pain & Palliat Med Unit, Dept Oncol, IL-91031 Jerusalem, Israel. [Strasser, F.] Cantonal Hosp, Dept Internal Med, CH-9007 St Gallen, Switzerland. [Strasser, F.] Cantonal Hosp, Palliat Care Ctr, Div Oncol, Oncol Palliat Med, CH-9007 St Gallen, Switzerland. [Abernethy, A. P.; Zafar, S. Y.] Duke Univ, Med Ctr, Div Med Oncol, Dept Med, Durham, NC 27710 USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, Dept Med, Div Med Oncol, Dana Farber Harvard Canc Ctr, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rnipp@mgh.harvard.edu OI Currow, David/0000-0003-1988-1250 NR 33 TC 4 Z9 4 U1 0 U2 1 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 JUN 30 PY 2015 VL 113 IS 1 BP 6 EP 11 DI 10.1038/bjc.2015.192 PG 6 WC Oncology SC Oncology GA CL7YJ UT WOS:000357188500002 PM 26068397 ER PT J AU Yoon, C Lee, HJ Park, DJ Lee, YJ Tap, WD Eisinger-Mathason, TSK Hart, CP Choy, E Simon, MC Yoon, SS AF Yoon, C. Lee, H-J Park, D. J. Lee, Y-J Tap, W. D. Eisinger-Mathason, T. S. K. Hart, C. P. Choy, E. Simon, M. C. Yoon, S. S. TI Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas SO BRITISH JOURNAL OF CANCER LA English DT Article DE VEGF-A; radiation; sarcoma; hypoxia ID SOFT-TISSUE SARCOMA; ENDOTHELIAL GROWTH-FACTOR; ANTI-ANGIOGENIC THERAPY; PRODRUG TH-302; COMBINATION THERAPY; TUMOR ANGIOGENESIS; MOUSE MODEL; CANCER; RADIOTHERAPY; RESISTANCE AB Background: Human sarcomas with a poor response to vascular endothelial growth factor-A (VEGF-A) inhibition and radiation therapy (RT) have upregulation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and HIF-1 alpha target genes. This study examines the addition of the hypoxia-activated chemotherapy TH-302 to VEGF-A inhibition and RT (a.k.a. trimodality therapy). Methods: Trimodality therapy was examined in two xenograft models and in vitro in tumour endothelial cells and sarcoma cell lines. Results: In both mouse models, VEGF-A inhibition and radiation showed greater efficacy than either therapy alone in slowing sarcoma growth. When TH-302 was added, this trimodality therapy completely blocked tumour growth with tumours remaining dormant for over 3 months after cessation of therapy. Trimodality therapy caused 2.6- to 6.2-fold more endothelial cell-specific apoptosis than bimodality therapies, and microvessel density and HIF-1 alpha activity were reduced to 11-13% and 13-20% of control, respectively. When trimodality therapy was examined in vitro, increases in DNA damage and apoptosis were much more pronounced in tumour endothelial cells compared with that in sarcoma cells, especially under hypoxia. Conclusions: The combination of TH-302, VEGF-A inhibition, and RT is highly effective in preclinical models of sarcoma and is associated with increased DNA damage and apoptosis in endothelial cells and decreased HIF-1 alpha activity. C1 [Yoon, C.; Park, D. J.; Yoon, S. S.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Lee, H-J; Lee, Y-J] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, H-J; Lee, Y-J] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, H-J; Lee, Y-J] Korea Inst Radiol & Med Sci, Div Radiat Effects, Seoul, South Korea. [Park, D. J.] Seoul Natl Univ, Bundang Hosp, Dept Surg, Songnam, South Korea. [Tap, W. D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Eisinger-Mathason, T. S. K.; Simon, M. C.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Hart, C. P.] Threshold Pharmaceut, San Francisco, CA 94080 USA. [Choy, E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Choy, E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Simon, M. C.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Yoon, SS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, H 1209,1275 York Ave, New York, NY 10021 USA. EM yoons@mskcc.org OI Hart, Charles/0000-0003-4440-726X FU NIH [1R21 CA117128-02, 1R01 CA158301-01]; Society for Surgical Oncology Clinical Investigator Award FX This work was supported by NIH Grants 1R21 CA117128-02 (SSY) and 1R01 CA158301-01 (SSY and MCS), and the Society for Surgical Oncology Clinical Investigator Award (SSY). NR 37 TC 4 Z9 4 U1 1 U2 19 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 JUN 30 PY 2015 VL 113 IS 1 BP 46 EP 56 DI 10.1038/bjc.2015.186 PG 11 WC Oncology SC Oncology GA CL7YJ UT WOS:000357188500007 PM 26010414 ER PT J AU Wang, LL Teshiba, R Ikegaki, N Tang, XX Naranjo, A London, WB Hogarty, MD Gastier-Foster, JM Look, AT Park, JR Maris, JM Cohn, SL Seeger, RC Asgharzadeh, S Shimada, H AF Wang, L. L. Teshiba, R. Ikegaki, N. Tang, X. X. Naranjo, A. London, W. B. Hogarty, M. D. Gastier-Foster, J. M. Look, A. T. Park, J. R. Maris, J. M. Cohn, S. L. Seeger, R. C. Asgharzadeh, S. Shimada, H. TI Augmented expression of MYC and/or MYCN protein defines highly aggressive MYC-driven neuroblastoma: a Children's Oncology Group study SO BRITISH JOURNAL OF CANCER LA English DT Article DE neuroblastoma; MYCN protein; MYC protein; immunohistochemistry; prognosis ID N-MYC; PATHOLOGY CLASSIFICATION; C-MYC; AMPLIFICATION; TUMORS; CELLS; DIFFERENTIATION; SUPPRESSION; PHENOTYPE; COMMITTEE AB Background: MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. Methods: Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers. Results: Sixty-seven (19%) tumours were MYCN(+), 38 (11%) were MYC(+), and one(0.3%) had both proteins(+). MYCN(+) tumours and MYC(+) tumours were more likely diagnosed in children > 18months with stage4-disease. MYCN(+) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis-Karyorrhexis Index). MYC(+) tumours were also frequently UH but not associated with MYCN amplification, and more likely to have low-/intermediate-MKI. Favourable Histology patients without MYC/MYCN expressions exhibited the best survival (N = 167, 89.7 +/- 5.5% 3-year EFS, 97.0 +/- 3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N = 84, 63.1 +/- 13.6% 3-year EFS, 83.5 +/- 9.4% 3-year OS). MYCN(+) patients and MYC(+) patients had similar and significantly low (P<0.0001) survivals (46.2 +/- 12.0% 3-year EFS, 63.2 +/- 12.1% 3-year OS and 43.4 +/- 23.1% 3-year EFS, 63.5 +/- 19.2% 3-year OS, respectively). Notably, the prognostic impact imparted by MYC expression was independent from other markers. Conclusions: In this series, similar to 30% of neuroblastomas had augmented MYCN or MYC expression with dismal survivals. Prospective study of MYC/MYCN protein expression signature as a new biomarker for high-risk neuroblastomas should be conducted. C1 [Wang, L. L.; Teshiba, R.; Shimada, H.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. [Ikegaki, N.] Univ Illinois, Coll Med, Dept Anat & Cell Biol, Chicago, IL 60612 USA. [Ikegaki, N.] Univ Florida, Dept Biostat, Childrens Oncol Grp Stat, Gainesville, FL 32607 USA. [Naranjo, A.] Univ Florida, Ctr Data, Gainesville, FL 32607 USA. [London, W. B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. [London, W. B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Hogarty, M. D.; Maris, J. M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Hogarty, M. D.; Maris, J. M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Gastier-Foster, J. M.] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43210 USA. [Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. [Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Look, A. T.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Park, J. R.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98105 USA. [Park, J. R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98105 USA. [Cohn, S. L.] Univ Chicago, Dept Pediat, Div Hematol Oncol, Chicago, IL 60637 USA. [Seeger, R. C.; Asgharzadeh, S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. RP Shimada, H (reprint author), Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. EM hshimada@chla.usc.edu OI Cohn, Susan/0000-0001-5749-7650 FU NIH [U10CA98413, U10CA98543, PO1CA081403, R01CA127571] FX This work was in part supported by NIH grants: U10CA98413, U10CA98543, PO1CA081403, and R01CA127571. NR 32 TC 9 Z9 9 U1 0 U2 3 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 JUN 30 PY 2015 VL 113 IS 1 BP 57 EP 63 DI 10.1038/bjc.2015.188 PG 7 WC Oncology SC Oncology GA CL7YJ UT WOS:000357188500008 PM 26035700 ER PT J AU Menger, KE James, AM Cocheme, HM Harbour, ME Chouchani, ET Ding, SJ Fearnley, IM Partridge, L Murphy, MP AF Menger, Katja E. James, Andrew M. Cocheme, Helena M. Harbour, Michael E. Chouchani, Edward T. Ding, Shujing Fearnley, Ian M. Partridge, Linda Murphy, Michael P. TI Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster SO CELL REPORTS LA English DT Article ID DIETARY RESTRICTION; OXIDATIVE STRESS; IN-VIVO; THIOL; ANTIOXIDANT; PROTEOMICS; ROLES; LIFE AB Altering the redox state of cysteine residues on protein surfaces is an important response to environmental challenges. Although aging and fasting alter many redox processes, the role of cysteine residues is uncertain. To address this, we used a redox proteomic technique, oxidative isotope-coded affinity tags (OxICAT), to assess cysteine-residue redox changes in Drosophila melanogaster during aging and fasting. This approach enabled us to simultaneously identify and quantify the redox state of several hundred cysteine residues in vivo. Cysteine residues within young flies had a bimodal distribution with peaks at similar to 10% and similar to 85% reversibly oxidized. Surprisingly, these cysteine residues did not become more oxidized with age. In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized. We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster. C1 [Menger, Katja E.; James, Andrew M.; Harbour, Michael E.; Chouchani, Edward T.; Ding, Shujing; Fearnley, Ian M.; Murphy, Michael P.] MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England. [Menger, Katja E.] UCL, Inst Ophthalmol, London EC1V 9EL, England. [Cocheme, Helena M.; Partridge, Linda] UCL, Inst Hlth Ageing, London WC1E 6BT, England. [Cocheme, Helena M.; Partridge, Linda] UCL, GEE, London WC1E 6BT, England. [Cocheme, Helena M.; Partridge, Linda] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany. [Cocheme, Helena M.] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, London W12 0NN, England. [Chouchani, Edward T.] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England. [Chouchani, Edward T.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Chouchani, Edward T.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Murphy, MP (reprint author), MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England. EM mpm@mrc-mbu.cam.ac.uk RI James, Andrew/A-2639-2015 OI James, Andrew/0000-0002-0515-9649 FU Medical Research Council UK [MC-A070-5PS30]; Biotechnology and Biological Sciences Research Council UK [BB/D020786/1] FX This work was supported by the Medical Research Council UK (MC-A070-5PS30) and the Biotechnology and Biological Sciences Research Council UK (BB/D020786/1). We are grateful to Alan Robinson for assistance with data analysis algorithms. NR 24 TC 8 Z9 8 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JUN 30 PY 2015 VL 11 IS 12 BP 1856 EP 1865 DI 10.1016/j.celrep.2015.05.033 PG 10 WC Cell Biology SC Cell Biology GA CM0UF UT WOS:000357393500002 PM 26095360 ER PT J AU Begun, J Lassen, KG Jijon, HB Baxt, LA Goel, G Heath, RJ Ng, A Tam, JM Kuo, SY Villablanca, EJ Fagbami, L Oosting, M Kumar, V Schenone, M Carr, SA Joosten, LAB Vyas, JM Daly, MJ Netea, MG Brown, GD Wijmenga, C Xavier, RJ AF Begun, Jakob Lassen, Kara G. Jijon, Humberto B. Baxt, Leigh A. Goel, Gautam Heath, Robert J. Ng, Aylwin Tam, Jenny M. Kuo, Szu-Yu Villablanca, Eduardo J. Fagbami, Lola Oosting, Marije Kumar, Vinod Schenone, Monica Carr, Steven A. Joosten, Leo A. B. Vyas, Jatin M. Daly, Mark J. Netea, Mihai G. Brown, Gordon D. Wijmenga, Cisca Xavier, Ramnik J. TI Integrated Genomics of Crohn's Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy SO CELL REPORTS LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; HOST-DEFENSE; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; GENETIC ARCHITECTURE; SUSCEPTIBILITY LOCI; REGULATORY NETWORKS; EXPRESSION DATA; INFECTION AB The polymorphism ATG16L1 T300A, associated with increased risk of Crohn's disease, impairs pathogen defense mechanisms including selective autophagy, but specific pathway interactions altered by the risk allele remain unknown. Here, we use perturbational profiling of human peripheral blood cells to reveal that CLEC12A is regulated in an ATG16L1-T300A-dependent manner. Antibacterial autophagy is impaired in CLEC12A-deficient cells, and this effect is exacerbated in the presence of the ATG16L1*300A risk allele. Clec12a(-/-) mice are more susceptible to Salmonella infection, supporting a role for CLEC12A in antibacterial defense pathways in vivo. CLEC12A is recruited to sites of bacterial entry, bacteria-autophagosome complexes, and sites of sterile membrane damage. Integrated genomics identified a functional interaction between CLEC12A and an E3-ubiquitin ligase complex that functions in antibacterial autophagy. These data identify CLEC12A as early adaptor molecule for antibacterial autophagy and highlight perturbational profiling as a method to elucidate defense pathways in complex genetic disease. C1 [Begun, Jakob; Jijon, Humberto B.; Ng, Aylwin; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Begun, Jakob; Lassen, Kara G.; Jijon, Humberto B.; Baxt, Leigh A.; Goel, Gautam; Heath, Robert J.; Ng, Aylwin; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Begun, Jakob; Lassen, Kara G.; Jijon, Humberto B.; Baxt, Leigh A.; Goel, Gautam; Heath, Robert J.; Ng, Aylwin; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Begun, Jakob] Univ Queensland, Mater Res Inst, Brisbane, Qld 4101, Australia. [Lassen, Kara G.; Heath, Robert J.; Ng, Aylwin; Kuo, Szu-Yu; Villablanca, Eduardo J.; Fagbami, Lola; Schenone, Monica; Carr, Steven A.; Daly, Mark J.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Jijon, Humberto B.] Univ Calgary, Dept Med, Div Gastroenterol, Calgary, AB T2N 4N1, Canada. [Tam, Jenny M.; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Tam, Jenny M.; Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Oosting, Marije; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands. [Oosting, Marije; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 GA Nijmegen, Netherlands. [Kumar, Vinod; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Brown, Gordon D.] Univ Aberdeen, Inst Med Sci, CLSM, Div Appl Med,Aberdeen Fungal Grp, Aberdeen AB25 2ZD, Scotland. RP Lassen, KG (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM klassen@broadinstitute.org; xavier@molbio.mgh.harvard.edu RI Netea, Mihai/N-5155-2014; Oosting, Marije/H-7437-2015; Begun, Jakob/J-6793-2014; OI Begun, Jakob/0000-0001-5256-7672; Villablanca, Eduardo/0000-0001-9522-9729 FU Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis Foundation of America; NIH [AI109725, DK097485]; European Research Council under the European Union [2012-322698]; ERC Consolidator Grant [310372]; Wellcome Trust; Alberta Innovates-Health Solutions (AIHS), Alberta, Canada FX We thank Mathieu Platteel (UMCG) for microarray experiments and Natalia Nedelsky for editorial assistance. R.J.X. was supported by the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn's and Colitis Foundation of America, and grants AI109725 and DK097485 from the NIH. C.W. is supported by funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Advanced grant agreement 2012-322698). M.G.N was supported by an ERC Consolidator Grant (no. 310372). G.D.B. was supported by the Wellcome Trust. H.B.J. was supported by a clinical fellowship from Alberta Innovates-Health Solutions (AIHS), Alberta, Canada. NR 72 TC 5 Z9 5 U1 4 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JUN 30 PY 2015 VL 11 IS 12 BP 1905 EP 1918 DI 10.1016/j.celrep.2015.05.045 PG 14 WC Cell Biology SC Cell Biology GA CM0UF UT WOS:000357393500007 PM 26095365 ER PT J AU Barac, A Murtagh, G Carver, JR Chen, MH Freeman, AM Herrmann, J Iliescu, C Ky, B Mayer, EL Okwuosa, TM Plana, JC Ryan, TD Rzeszut, AK Douglas, PS AF Barac, Ana Murtagh, Gillian Carver, Joseph R. Chen, Ming Hui Freeman, Andrew M. Herrmann, Joerg Iliescu, Cezar Ky, Bonnie Mayer, Erica L. Okwuosa, Tochi M. Plana, Juan Carlos Ryan, Thomas D. Rzeszut, Anne K. Douglas, Pamela S. TI Cardiovascular Health of Patients With Cancer and Cancer Survivors A Roadmap to the Next Level SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cancer survivorship; cardiooncology; cardiovascular risk prevention; cardiovascular toxicity ID DOXORUBICIN-INDUCED CARDIOTOXICITY; VENTRICULAR SYSTOLIC DYSFUNCTION; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; HEART-FAILURE; EUROPEAN ASSOCIATION; EJECTION FRACTION; AMERICAN SOCIETY; EXPERT CONSENSUS; CARDIO-ONCOLOGY AB Many existing and emerging cancer therapies have a significant effect on the cardiovascular health of patients with cancer and cancer survivors. This paper examines current aspects of interdisciplinary cardio-oncology clinical care delivery and education in the United States and outlines how these data provide a platform for future development of the field. We present the results of the nationwide survey on cardio-oncology services, practices, and opinions, conducted among chiefs of cardiology and program directors, which demonstrate ranges of clinical activities and identify significant interest for increased educational opportunities and expert training of cardiovascular physicians in this field. The survey respondents recognized clinical relevance but emphasized lack of national guidelines, lack of funds, and limited awareness and infrastructure as the main challenges for development and growth of cardio-oncology. We discuss potential solutions to unmet needs through interdisciplinary collaboration and the active roles of professional societies and other stakeholders. (C) 2015 by the American College of Cardiology Foundation. C1 [Barac, Ana] MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC 20010 USA. [Murtagh, Gillian] NW Mem Hosp, Chicago, IL 60611 USA. [Carver, Joseph R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Chen, Ming Hui] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Chen, Ming Hui] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Freeman, Andrew M.] Natl Jewish Hlth, Denver, CO USA. [Herrmann, Joerg] Mayo Clin, Rochester, MN USA. [Herrmann, Joerg] Coll Med, Rochester, MN USA. [Iliescu, Cezar] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ky, Bonnie] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mayer, Erica L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Okwuosa, Tochi M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Plana, Juan Carlos] Baylor Coll Med, Houston, TX 77030 USA. [Ryan, Thomas D.] Inst Heart, Cincinnati, OH USA. [Rzeszut, Anne K.] Amer Coll Cardiol, Washington, DC USA. [Douglas, Pamela S.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. RP Barac, A (reprint author), MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, 110 Irving St Northwest,Suite 1F1222, Washington, DC 20010 USA. EM Ana.Barac@medstar.net FU National Institutes of Health; Cell Therapeutics, Inc.; Pfizer; PA Cure Health; Eisai; Myriad; National Cancer Institute; University of South Florida; [NIH/5KL2TR000102-04] FX This work was supported in part by NIH/5KL2TR000102-04 (to Dr. Barac). Dr. Barac has received research support from the National Institutes of Health; research support and honoraria for lectures from Genentech, Inc.; and consultancy fees from Cell Therapeutics, Inc. Dr. Murtagh will be an employee of Abbott Diagnostics in July 2015 but was not affiliated with this company at the time this paper was written. Dr. Freeman has served as a consultant to Gilead; and has served as a speaker for Medtronic. Dr. Hermann has served as a consultant to ARIAD Pharmaceuticals and Bristol-Myers Squibb; and as a member of advisory boards for ARIAD Pharmaceuticals and Bristol-Myers Squibb. Dr. Ky has received research support from Pfizer, the National Institutes of Health, and PA Cure Health. Dr. Mayer has received research support from Pfizer, Eisai, and Myriad. Dr. Douglas has received research grants from the National Cancer Institute and the University of South Florida. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 43 TC 10 Z9 10 U1 1 U2 7 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 JUN 30 PY 2015 VL 65 IS 25 BP 2739 EP 2746 DI 10.1016/j.jacc.2015.04.059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL2LJ UT WOS:000356775100011 PM 26112199 ER PT J AU Horton, LE Tarbox, SI Olino, TM Haas, GL AF Horton, Leslie E. Tarbox, Sarah I. Olino, Thomas M. Haas, Gretchen L. TI Trajectories of premorbid childhood and adolescent functioning in schizophrenia-spectrum psychoses: A first-episode study SO PSYCHIATRY RESEARCH LA English DT Article DE Premorbid adjustment; Social amotivation; First-episode schizophrenia (FEP); Psychosis; Schizophrenia-spectrum ID NEGATIVE SYMPTOMS; NONAFFECTIVE PSYCHOSIS; EPISODE SCHIZOPHRENIA; UNTREATED PSYCHOSIS; ADJUSTMENT SCALE; DISORDERS; PATTERNS; ONSET; DETERIORATION; ANHEDONIA AB Evidence of social and behavioral problems preceding the onset of schizophrenia-spectrum psychoses is consistent with a neurodevelopmental model of these disorders. Here we predict that individuals with a first episode of schizophrenia-spectrum psychoses will evidence one of three patterns of premorbid adjustment: an early deficit, a deteriorating pattern, or adequate or good social adjustment. Participants were 164(38% female; 31% black) individuals ages 15-50 with a first episode of schizophrenia-spectrum psychoses. Premorbid adjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. We compared the fit of a series of growth mixture models to examine premorbid adjustment trajectories, and found the following 3-class model provided the best fit with: a "stable-poor" adjustment class (54%), a "stable-good" adjustment class (39%), and a "deteriorating" adjustment class (7%). Relative to the "stable-good" class, the "stable-poor" class experienced worse negative symptoms at 1-year follow-up, particularly in the social amotivation domain. This represents the first known growth mixture modeling study to examine premorbid functioning patterns in first-episode schizophrenia-spectrum psychoses. Given that the stable-poor adjustment pattern was most prevalent, detection of social and academic maladjustment as early as childhood may help identify people at increased risk for schizophrenia-spectrum psychoses, potentially increasing feasibility of early interventions. Published by Elsevier Ireland Ltd. C1 [Horton, Leslie E.; Olino, Thomas M.; Haas, Gretchen L.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Horton, Leslie E.; Haas, Gretchen L.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Tarbox, Sarah I.] Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Dept Psychiat, New Haven, CT 06159 USA. [Olino, Thomas M.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Haas, GL (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM hortonle2@upmc.edu; sarah.tarbox@yale.edu; thomas.olino@temple.edu; haasgl@upmc.edu FU NIMH [MH48492]; NIH [UL1 RR024153, UL1 TR000005]; NIH/NCRR/GCRC [M01 RR00056] FX This publication was supported by funds received MH48492 (NIMH; PI: G L. Haas) and the NIH-funded UL1 RR024153, UL1 TR000005, and NIH/NCRR/GCRC Grant M01 RR00056. NR 58 TC 2 Z9 2 U1 2 U2 10 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 JUN 30 PY 2015 VL 227 IS 2-3 BP 339 EP 346 DI 10.1016/j.psychres.2015.02.013 PG 8 WC Psychiatry SC Psychiatry GA CK0GU UT WOS:000355884500033 PM 25829134 ER PT J AU Fulford, D Eisner, LR Johnson, SL AF Fulford, Daniel Eisner, Lori R. Johnson, Sheri L. TI Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity SO PSYCHIATRY RESEARCH LA English DT Article DE Bipolar disorder; Borderline personality disorder; Goal regulation; Impulsivity; Approach/avoidance motivation ID BIPOLAR SPECTRUM DISORDERS; BEHAVIORAL-APPROACH SYSTEM; BIS-BAS SCALES; HYPOMANIC PERSONALITY; AFFECTIVE INSTABILITY; II-DISORDER; ACTIVATION SYSTEM; COMMUNITY SAMPLE; BIS/BAS SCALES; 4-FACTOR MODEL AB Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Fulford, Daniel] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Fulford, Daniel] Palo Alto Med Fdn Res Inst, Mountain View, CA 94040 USA. [Eisner, Lori R.] Harvard Univ, Sch Med, Dept Psychiat, Bipolar Clin,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eisner, Lori R.] Harvard Univ, Sch Med, Dept Psychiat, Res Program,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Johnson, Sheri L.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Fulford, D (reprint author), Univ Calif San Francisco, Dept Psychiat, 795 El Camino Real, Palo Alto, CA 94301 USA. EM daniel.fulford@ucsf.edu FU [2T32MH018261-27]; [1K12HS021700-01] FX Preparation of this manuscript was supported in part by the following grants to Dr. Fulford: 2T32MH018261-27, 1K12HS021700-01. NR 73 TC 5 Z9 5 U1 2 U2 13 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 JUN 30 PY 2015 VL 227 IS 2-3 BP 347 EP 352 DI 10.1016/j.psychres.2015.02.001 PG 6 WC Psychiatry SC Psychiatry GA CK0GU UT WOS:000355884500034 PM 25892256 ER PT J AU Goldstein, JM Lacaster, K Longenecker, JM Abbs, B Holsen, LM Cherkerzian, S Whitfield-Gabrieli, S Makris, N Tsuang, MT Buka, SL Seidman, LJ Klibanski, A AF Goldstein, Jill M. Lacaster, Katie Longenecker, Julia M. Abbs, Brandon Holsen, Laura M. Cherkerzian, Sara Whitfield-Gabrieli, Susan Makris, Nicolas Tsuang, Ming T. Buka, Stephen L. Seidman, Larry J. Klibanski, Anne TI Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Schizophrenia; Sex differences; HPA axis; HPG axis; Stress response; Negative valence affect ID ESTROGEN-RECEPTOR-ALPHA; FACIAL EMOTION DISCRIMINATION; POSITRON-EMISSION-TOMOGRAPHY; NEW-ENGLAND FAMILY; ADULT HUMAN BRAIN; GENDER-DIFFERENCES; PARAVENTRICULAR NUCLEUS; AMYGDALA ACTIVITY; SCHIZOPHRENIC OUTPATIENTS; AROUSAL CIRCUITRY AB Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactiviLy in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F=7.00, p=0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry -hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Goldstein, Jill M.; Lacaster, Katie; Longenecker, Julia M.; Abbs, Brandon; Holsen, Laura M.; Cherkerzian, Sara] Brigham & Womens Hosp, Div Womens Hlth, Connors Ctr Women Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Holsen, Laura M.; Makris, Nicolas; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.; Holsen, Laura M.; Makris, Nicolas; Klibanski, Anne] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, Jill M.; Holsen, Laura M.; Makris, Nicolas; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr, Div Psychiat Neurosci, Boston, MA 02114 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA USA. [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, OBC, 3rd Floor,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu; katie.lancaster@virginia.edu; longenecker.julia@gmail.com; brandon.abbs@gmail.com; lholsen@partners.org; scherkerzian@partners.org; swg@mit.edu; nmakris@partners.org; mtsuang@ucsd.edu; stephen_buka@brown.edu; lseidman@bidmc.harvard.edu; aklibanski@partners.org FU National Institute of Mental Health (NIMH) [RO1 MH56956]; Stanley Medical Research Institute, United States; NARSAD; NIMH [R01MH63951]; Harvard Catalyst I Harvard Clinical and Translational Science Center (CTSC) [UL1 RR025758] FX This study was supported by National Institute of Mental Health (NIMH) RO1 MH56956 (JMG, P.I.). In addition, original sample ascertainment was in part also supported by Grants from the Stanley Medical Research Institute, United States (SLB & JMG, US 1994-1997), NARSAD (LJS) and NIMH R01MH63951 (LJS, RI) and with support from the Harvard Catalyst I Harvard Clinical and Translational Science Center (CTSC) (NIH Award UL1 RR025758). NR 122 TC 3 Z9 3 U1 4 U2 22 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUN 30 PY 2015 VL 232 IS 3 BP 226 EP 236 DI 10.1016/j.pscychresns.2015.03.006 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CI2CQ UT WOS:000354552900005 PM 25914141 ER PT J AU Yehia, BR Stewart, L Momplaisir, F Mody, A Holtzman, CW Jacobs, LM Hines, J Mounzer, K Glanz, K Metlay, JP Shea, JA AF Yehia, Baligh R. Stewart, Leslie Momplaisir, Florence Mody, Aaloke Holtzman, Carol W. Jacobs, Lisa M. Hines, Janet Mounzer, Karam Glanz, Karen Metlay, Joshua P. Shea, Judy A. TI Barriers and facilitators to patient retention in HIV care SO BMC INFECTIOUS DISEASES LA English DT Article DE Retention; Engagement; HIV; Care; Barriers; Facilitators ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; MEDICAL-CARE; INFECTED PERSONS; POSITIVE WOMEN; RANDOMIZED-TRIAL; SEXUAL-ABUSE; RISK-FACTORS; HEALTH-CARE; ENGAGEMENT AB Background: Retention in HIV care improves survival and reduces the risk of HIV transmission to others. Multiple quantitative studies have described demographic and clinical characteristics associated with retention in HIV care. However, qualitative studies are needed to better understand barriers and facilitators. Methods: Semi-structured interviews were conducted with 51 HIV-infected individuals, 25 who were retained in care and 26 not retained in care, from 3 urban clinics. Interview data were analyzed for themes using a modified grounded theory approach. Identified themes were compared between the two groups of interest: patients retained in care and those not retained in care. Results: Overall, participants identified 12 barriers and 5 facilitators to retention in HIV care. On average, retained individuals provided 3 barriers, while persons not retained in care provided 5 barriers. Both groups commonly discussed depression/mental illness, feeling sick, and competing life activities as barriers. In addition, individuals not retained in care commonly reported expensive and unreliable transportation, stigma, and insufficient insurance as barriers. On average, participants in both groups referenced 2 facilitators, including the presence of social support, patient-friendly clinic services (transportation, co-location of services, scheduling/reminders), and positive relationships with providers and clinic staff. Conclusions: In our study, patients not retained in care faced more barriers, particularly social and structural barriers, than those retained in care. Developing care models where social and financial barriers are addressed, mental health and substance abuse treatment is integrated, and patient-friendly services are offered is important to keeping HIV-infected individuals engaged in care. C1 [Yehia, Baligh R.; Stewart, Leslie; Mody, Aaloke; Hines, Janet; Mounzer, Karam; Shea, Judy A.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Momplaisir, Florence] Drexel Univ, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Holtzman, Carol W.] Temple Univ, Dept Pharm Practice, Sch Pharm, Philadelphia, PA 19122 USA. [Jacobs, Lisa M.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mounzer, Karam] Philadelphia FIGHT, Jonathan Lax Ctr, Philadelphia, PA USA. [Glanz, Karen] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Glanz, Karen] Univ Penn, Sch Nursing, Dept Biobehav Hlth Sci, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Yehia, Baligh R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Yehia, BR (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM byehia@upenn.edu FU National Institutes of Health [K23-MH097647] FX This work was supported by the National Institutes of Health (K23-MH097647 to BRY). NR 61 TC 11 Z9 11 U1 4 U2 17 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 JUN 28 PY 2015 VL 15 AR 246 DI 10.1186/s12879-015-0990-0 PG 10 WC Infectious Diseases SC Infectious Diseases GA CL6IX UT WOS:000357071900001 PM 26123158 ER PT J AU Matlis, S Boric, K Chu, CJ Kramer, MA AF Matlis, Sean Boric, Katica Chu, Catherine J. Kramer, Mark A. TI Robust disruptions in electroencephalogram cortical oscillations and large-scale functional networks in autism SO BMC NEUROLOGY LA English DT Article DE ASD; EEG; Functional networks; Biomarker; Classification; Autism; Power spectra; Validation ID COMPLEX BRAIN NETWORKS; SPECTRUM QUOTIENT AQ; INFANT EEG ACTIVITY; SENTENCE COMPREHENSION; PHASE-SYNCHRONIZATION; PROMISING APPROACH; ASPERGERS-SYNDROME; VOLUME-CONDUCTION; EVOKED-POTENTIALS; OCCIPITAL CORTEX AB Background: Autism spectrum disorders (ASD) are increasingly prevalent and have a significant impact on the lives of patients and their families. Currently, the diagnosis is determined by clinical judgment and no definitive physiological biomarker for ASD exists. Quantitative biomarkers obtainable from clinical neuroimaging data - such as the scalp electroencephalogram (EEG) - would provide an important aid to clinicians in the diagnosis of ASD. The interpretation of prior studies in this area has been limited by mixed results and the lack of validation procedures. Here we use retrospective clinical data from a well-characterized population of children with ASD to evaluate the rhythms and coupling patterns present in the EEG to develop and validate an electrophysiological biomarker of ASD. Methods: EEG data were acquired from a population of ASD (n = 27) and control (n = 55) children 4-8 years old. Data were divided into training (n = 13 ASD, n = 24 control) and validation (n = 14 ASD, n = 31 control) groups. Evaluation of spectral and functional network properties in the first group of patients motivated three biomarkers that were computed in the second group of age-matched patients for validation. Results: Three biomarkers of ASD were identified in the first patient group: (1) reduced posterior/anterior power ratio in the alpha frequency range (8-14 Hz), which we label the "peak alpha ratio", (2) reduced global density in functional networks, and (3) a reduction in the mean connectivity strength of a subset of functional network edges. Of these three biomarkers, the first and third were validated in a second group of patients. Using the two validated biomarkers, we were able to classify ASD subjects with 83 % sensitivity and 68 % specificity in a post-hoc analysis. Conclusions: This study demonstrates that clinical EEG can provide quantitative biomarkers to assist diagnosis of autism. These results corroborate the general finding that ASD subjects have decreased alpha power gradients and network connectivities compared to control subjects. In addition, this study demonstrates the necessity of using statistical techniques to validate EEG biomarkers identified using exploratory methods. C1 [Matlis, Sean] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA. [Boric, Katica; Chu, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Boric, Katica; Chu, Catherine J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat, 111 Cummington Mall, Boston, MA 02215 USA. EM mak@bu.edu FU National Institutes of Health [NIH-5K12NS066225-02]; Career Award at the Scientific Interface from the Burroughs Wellcome Fund FX This work was supported by the National Institutes of Health through grant NIH-5K12NS066225-02, and by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (MAK, SM). NR 104 TC 2 Z9 2 U1 6 U2 14 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 JUN 27 PY 2015 VL 15 AR 97 DI 10.1186/s12883-015-0355-8 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA CL9ON UT WOS:000357308100001 PM 26111798 ER PT J AU Abazari, A Meimetis, LG Budin, G Bale, SS Weissleder, R Toner, M AF Abazari, Alireza Meimetis, Labros G. Budin, Ghyslain Bale, Shyam Sundhar Weissleder, Ralph Toner, Mehmet TI Engineered Trehalose Permeable to Mammalian Cells SO PLOS ONE LA English DT Article ID RED-BLOOD-CELLS; INTRACELLULAR TREHALOSE; DESICCATION TOLERANCE; PHASE-SEPARATION; PRESERVATION; PROTECTION; LIPOSOMES; ACCUMULATION; MITOCHONDRIA; DEHYDRATION AB Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies. C1 [Abazari, Alireza; Bale, Shyam Sundhar; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Engn Med, Boston, MA 02114 USA. [Abazari, Alireza; Bale, Shyam Sundhar; Toner, Mehmet] Shriners Hosp Children, Boston, MA USA. [Meimetis, Labros G.; Budin, Ghyslain; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Meimetis, Labros G.; Budin, Ghyslain; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Engn Med, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu FU Natural Sciences and Engineering Research Council (NSERC) of Canada; NIH [2 R01 DK046270-14A1, R01 EB010011.] FX Alireza Abazari held a Postdoctoral Fellowship from The Natural Sciences and Engineering Research Council (NSERC) of Canada. This research was also funded by NIH grants 2 R01 DK046270-14A1 and R01 EB010011. NR 37 TC 9 Z9 9 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2015 VL 10 IS 6 AR e0130323 DI 10.1371/journal.pone.0130323 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CN1AM UT WOS:000358147500066 PM 26115179 ER PT J AU Zhang, WQ Yu, Y Hertwig, F Thierry-Mieg, J Zhang, WW Thierry-Mieg, D Wang, J Furlanello, C Devanarayan, V Cheng, J Deng, YP Hero, B Hong, HX Jia, MW Li, L Lin, SM Nikolsky, Y Oberthuer, A Qing, T Su, ZQ Volland, R Wang, C Wang, MD Ai, JM Albanese, D Asgharzadeh, S Avigad, S Bao, WJ Bessarabova, M Brilliant, MH Brors, B Chierici, M Chu, TM Zhang, JB Grundy, RG He, MM Hebbring, S Kaufman, HL Lababidi, S Lancashire, LJ Li, Y Lu, XX Luo, H Ma, XW Ning, BT Noguera, R Peifer, M Phan, JH Roels, F Rosswog, C Shao, SS Shen, J Theissen, J Tonini, GP Vandesompele, J Wu, PY Xiao, WZ Xu, JS Xu, WH Xuan, JK Yang, Y Ye, Z Dong, ZR Zhang, KK Yin, Y Zhao, C Zheng, YT Wolfinger, RD Shi, TL Malkas, LH Berthold, F Wang, J Tong, WD Shi, LM Peng, ZY Fischer, M AF Zhang, Wenqian Yu, Ying Hertwig, Falk Thierry-Mieg, Jean Zhang, Wenwei Thierry-Mieg, Danielle Wang, Jian Furlanello, Cesare Devanarayan, Viswanath Cheng, Jie Deng, Youping Hero, Barbara Hong, Huixiao Jia, Meiwen Li, Li Lin, Simon M. Nikolsky, Yuri Oberthuer, Andre Qing, Tao Su, Zhenqiang Volland, Ruth Wang, Charles Wang, May D. Ai, Junmei Albanese, Davide Asgharzadeh, Shahab Avigad, Smadar Bao, Wenjun Bessarabova, Marina Brilliant, Murray H. Brors, Benedikt Chierici, Marco Chu, Tzu-Ming Zhang, Jibin Grundy, Richard G. He, Min Max Hebbring, Scott Kaufman, Howard L. Lababidi, Samir Lancashire, Lee J. Li, Yan Lu, Xin X. Luo, Heng Ma, Xiwen Ning, Baitang Noguera, Rosa Peifer, Martin Phan, John H. Roels, Frederik Rosswog, Carolina Shao, Susan Shen, Jie Theissen, Jessica Tonini, Gian Paolo Vandesompele, Jo Wu, Po-Yen Xiao, Wenzhong Xu, Joshua Xu, Weihong Xuan, Jiekun Yang, Yong Ye, Zhan Dong, Zirui Zhang, Ke K. Yin, Ye Zhao, Chen Zheng, Yuanting Wolfinger, Russell D. Shi, Tieliu Malkas, Linda H. Berthold, Frank Wang, Jun Tong, Weida Shi, Leming Peng, Zhiyu Fischer, Matthias TI Comparison of RNA-seq and microarray-based models for clinical endpoint prediction SO GENOME BIOLOGY LA English DT Article ID EXPRESSION-BASED CLASSIFICATION; GENE-EXPRESSION; NEUROBLASTOMA PATIENTS; RISK STRATIFICATION; PROSTATE-CANCER; BREAST-CANCER; TRANSCRIPTOME; SIGNATURE; DIFFERENTIATION; REPRODUCIBILITY AB Background: Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. Results: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. Conclusions: We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice. C1 [Zhang, Wenqian; Zhang, Wenwei; Zhang, Jibin; Dong, Zirui; Yin, Ye; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China. [Yu, Ying; Jia, Meiwen; Qing, Tao; Zhao, Chen; Zheng, Yuanting; Shi, Leming] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Yu, Ying; Jia, Meiwen; Qing, Tao; Zhao, Chen; Zheng, Yuanting; Shi, Leming] Fudan Univ, Sch Life Sci, MOE Key Lab Contemporary Anthropol, Shanghai 201203, Peoples R China. [Yu, Ying; Jia, Meiwen; Qing, Tao; Zhao, Chen; Zheng, Yuanting; Shi, Leming] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China. [Hertwig, Falk; Hero, Barbara; Oberthuer, Andre; Volland, Ruth; Roels, Frederik; Rosswog, Carolina; Theissen, Jessica; Berthold, Frank; Fischer, Matthias] Univ Childrens Hosp Cologne, Dept Pediat Oncol & Hematol, D-50924 Cologne, Germany. [Hertwig, Falk; Peifer, Martin; Roels, Frederik; Berthold, Frank; Fischer, Matthias] Univ Cologne, Fac Med, Ctr Mol Med CMMC, D-50924 Cologne, Germany. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH NCBI, Bethesda, MD 20894 USA. [Wang, Jian; Yang, Yong] Eli Lilly & Co Res Informat, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Furlanello, Cesare; Chierici, Marco] FBK, I-38123 Trento Povo, TN, Italy. [Devanarayan, Viswanath] AbbVie Inc, Global Pharmaceut R&D, Souderton, PA 18964 USA. [Cheng, Jie] GlaxoSmithKline, Discovery Analyt, Collegeville, PA 19426 USA. [Deng, Youping; Ai, Junmei; Kaufman, Howard L.; Li, Yan] Rush Univ, Ctr Canc, Dept Internal Med, Chicago, IL 60612 USA. [Hong, Huixiao; Su, Zhenqiang; Luo, Heng; Ning, Baitang; Shen, Jie; Xu, Joshua; Xuan, Jiekun; Tong, Weida; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Li, Li; Bao, Wenjun; Chu, Tzu-Ming; Shao, Susan; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Lin, Simon M.; He, Min Max; Ye, Zhan] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI 54449 USA. [Nikolsky, Yuri; Bessarabova, Marina; Lancashire, Lee J.] Thomson Reuters IP & Sci, Carlsbad, CA 92008 USA. [Wang, Charles] Loma Linda Univ, Ctr Genom, Loma Linda, CA 92350 USA. [Wang, Charles] Loma Linda Univ, Sch Med, Div Microbiol & Mol Genet, Loma Linda, CA 92350 USA. [Wang, May D.; Phan, John H.] GeorgiaTech, Dept Biomed Engn, Atlanta, GA 30332 USA. [Wang, May D.; Phan, John H.] Emory Univ, Atlanta, GA 30332 USA. [Albanese, Davide] CRI CBC, Fdn Edmund Mach, San Michele All Adige, TN, Italy. [Asgharzadeh, Shahab] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Avigad, Smadar] Schneider Childrens Med Ctr Israel, Felsenstein Med Res Ctr, Dept Pediat Hematol Oncol, Mol Oncol, IL-49202 Petah Tiqwa, Israel. [Brilliant, Murray H.; Hebbring, Scott] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI 54449 USA. [Brors, Benedikt] German Canc Res Ctr, Dept Theoret Bioinformat, D-69120 Heidelberg, Germany. [Grundy, Richard G.] Univ Nottingham, Queens Med Ctr, Childrens Brain Tumour Res Ctr, Nottingham NG7 2UH, England. [Lababidi, Samir] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lu, Xin X.] AbbVie Inc, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA. [Luo, Heng] Univ Arkansas, UALR UAMS Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Ma, Xiwen] Eli Lilly & Co, Lilly Corp Ctr, Discovery Stat, Indianapolis, IN 46285 USA. [Noguera, Rosa] Univ Valencia, Sch Med, Dept Pathol, Valencia 46010, Spain. [Peifer, Martin] Univ Cologne, Dept Translat Genom, D-50924 Cologne, Germany. [Tonini, Gian Paolo] Univ Padua, Pediat Res Inst, SDB Dept, Neuroblastoma Lab,Onco Hematol Lab, Padua, Italy. [Vandesompele, Jo] Univ Ghent, Ctr Med Genet, Dept Pediat & Genet, B-9000 Ghent, Belgium. [Wu, Po-Yen] Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA. [Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Xu, Weihong] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Zhang, Ke K.] Univ N Dakota, Sch Med, Dept Pathol, Grand Forks, ND 58202 USA. [Shi, Tieliu] E China Normal Univ, Ctr Bioinformat & Computat Biol, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China. [Shi, Tieliu] Sch Life Sci, Shanghai 200241, Peoples R China. [Malkas, Linda H.] City Hope Comprehens Canc Ctr, Beckman Res Inst, Dept Mol & Cellular Biol, Duarte, CA 91010 USA. [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [Wang, Jun] King Abdulaziz Univ, Jeddah 21589, Saudi Arabia. [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark. [Peng, Zhiyu] Guangzhou Higher Educ Mega Ctr, BGI Guangzhou, Guangzhou 510006, Guangdong, Peoples R China. RP Shi, LM (reprint author), Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. EM lemingshi@fudan.edu.cn; pengzhiyu@genomics.org.cn; matthias.fischer@uk-koeln.de RI Brors, Benedikt/E-5620-2013; Wang, Jun/C-8434-2016; Luo, Heng/D-3616-2016; THIERRY-MIEG, Jean/F-1975-2017; Wang, Jun/B-9503-2016; OI Brors, Benedikt/0000-0001-5940-3101; Grundy, Richard/0000-0002-2585-2539; Wang, Jun/0000-0002-8540-8931; Luo, Heng/0000-0001-5192-8878; THIERRY-MIEG, Jean/0000-0002-0396-6789; Chierici, Marco/0000-0001-9791-9301; Wang, Jun/0000-0002-2113-5874; Hertwig, Falk/0000-0003-4784-6516 FU National High Technology Research and Development Program of China - 863 Program [2015AA020104, 2012AA02A201]; National Science Foundation of China [31471239]; Intramural Research Program of the NIH, National Library of Medicine (USA); Cologne Center for Molecular Medicine; Bundesministerium fur Bildung und Forschung (BMBF) through the National Genome Research Network plus (NGFNplus) [01GS0895]; German Cancer Aid (Deutsche Krebshilfe) [110122]; Fordergesellschaft Kinderkrebs-Neuroblastom-Forschung e.V.; National Institutes of Health [U54CA119338, 1RC2CA148265, R01CA163256]; Georgia Cancer Coalition; BMBF through the Competence Network Pediatric Oncology and Hematology (KPOH); Italian Neuroblastoma Foundation; China National Supercomputing Center in Guangzhou; China National Supercomputing Center in Tianjin FX We are grateful to Yvonne Kahlert, Anne Engesser, and Simona Coco for technical assistance. This work was supported by grants from the National High Technology Research and Development Program of China - 863 Program (2015AA020104 to LS and 2012AA02A201 to TS), the National Science Foundation of China (31471239 to LS), the Intramural Research Program of the NIH, National Library of Medicine (USA), the Cologne Center for Molecular Medicine (to MF), the Bundesministerium fur Bildung und Forschung (BMBF) through the National Genome Research Network plus (NGFNplus, grant 01GS0895 to MF), the German Cancer Aid (Deutsche Krebshilfe, grant 110122 to MF), the Fordergesellschaft Kinderkrebs-Neuroblastom-Forschung e.V. (to FB and MF), and the National Institutes of Health (U54CA119338, 1RC2CA148265, and R01CA163256) and Georgia Cancer Coalition (to MDW). Tumor sample collection was supported by the BMBF through the Competence Network Pediatric Oncology and Hematology (KPOH) and by the Italian Neuroblastoma Foundation. We gratefully acknowledge support by China's National Supercomputing Centers in Guangzhou and Tianjin. NR 39 TC 12 Z9 12 U1 3 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JUN 25 PY 2015 VL 16 AR 133 DI 10.1186/s13059-015-0694-1 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CN0PZ UT WOS:000358117100001 PM 26109056 ER PT J AU Flynn, R Allen, JL Luznik, L MacDonald, KP Paz, K Alexander, KA Vulic, A Du, J Panoskaltsis-Mortari, A Taylor, PA Poe, JC Serody, JS Murphy, WJ Hill, GR Maillard, I Koreth, J Cutler, CS Soiffer, RJ Antin, JH Ritz, J Chao, NJ Clynes, RA Sarantopoulos, S Blazar, BR AF Flynn, Ryan Allen, Jessica L. Luznik, Leo MacDonald, Kelli P. Paz, Katelyn Alexander, Kylie A. Vulic, Ante Du, Jing Panoskaltsis-Mortari, Angela Taylor, Patricia A. Poe, Jonathan C. Serody, Jonathan S. Murphy, William J. Hill, Geoffrey R. Maillard, Ivan Koreth, John Cutler, Corey S. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome Chao, Nelson J. Clynes, Raphael A. Sarantopoulos, Stefanie Blazar, Bruce R. TI Targeting Syk-activated B cells in murine and human chronic graft-versus-host disease SO BLOOD LA English DT Article ID TOLL-LIKE RECEPTORS; CHRONIC GVHD; BRONCHIOLITIS OBLITERANS; SIGNALING PATHWAY; TYROSINE KINASE; BAFF; TRANSPLANTATION; RESPONSES; SURVIVAL; ANTIBODY AB Novel therapies for chronic graft-versus-host disease (cGVHD) are needed. Aberrant B-cell activation has been demonstrated in mice and humans with cGVHD. Having previously found that human cGVHD B cells are activated and primed for survival, we sought to further evaluate the role of the spleen tyrosine kinase (Syk) in cGVHD in multiple murine models and human peripheral blood cells. In a murine model of multiorgan system, non-sclerodermatous disease with bronchiolitis obliterans where cGVHD is dependent on antibody and germinal center (GC) B cells, we found that activation of Syk was necessary in donor B cells, but not T cells, for disease progression. Bone marrow-specific Syk deletion in vivo was effective in treating established cGVHD, as was a small-molecule inhibitor of Syk, fostamatinib, which normalized GC formation and decreased activated CD80/86(+) dendritic cells. In multiple distinct models of sclerodermatous cGVHD, clinical and pathological disease manifestations were not eliminated when mice were therapeutically treated with fostamatinib, though both clinical and immunologic effects could be observed in one of these scleroderma models. We further demonstrated that Syk inhibition was effective at inducing apoptosis of human cGVHD B cells. Together, these data demonstrate a therapeutic potential of targeting B-cell Syk signaling in cGVHD. C1 [Flynn, Ryan; Paz, Katelyn; Du, Jing; Panoskaltsis-Mortari, Angela; Taylor, Patricia A.; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Masonic Canc Ctr, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Allen, Jessica L.; Poe, Jonathan C.; Chao, Nelson J.; Sarantopoulos, Stefanie] Duke Univ, Dept Med, Duke Canc Inst, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA. [Luznik, Leo; Vulic, Ante] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [MacDonald, Kelli P.; Alexander, Kylie A.; Hill, Geoffrey R.] Queensland Inst Med Res, Dept Immunol, Brisbane, Qld 4006, Australia. [Serody, Jonathan S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA. [Murphy, William J.] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA. [Maillard, Ivan] Univ Michigan, Dept Internal Med, Inst Life Sci, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Clynes, Raphael A.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. [Clynes, Raphael A.] Columbia Univ, Dept Microbiol, New York, NY 10032 USA. RP Blazar, BR (reprint author), Univ Minnesota, Dept Pediat, Masonic Canc Ctr, 420 Delaware St SE,MMC 109, Minneapolis, MN 55455 USA. EM blaza001@umn.edu RI Hill, Geoffrey/O-2630-2016; MacDonald, Kelli/O-2722-2016; Alexander, Kylie /P-2666-2016; OI Hill, Geoffrey/0000-0003-2994-0429; MacDonald, Kelli/0000-0003-3451-4221; Alexander, Kylie /0000-0001-5772-0277; Serody, Jonathan/0000-0003-4568-1092; Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health National Cancer Institute [P01 CA142106-06A1, 5P01-CA047741-20]; National Heart, Lung, and Blood Institute [R01 HL126530, K08HL107756]; National Institute of Allergy and Infectious Diseases [P01 AI 056299, T32 AI 007313]; Leukemia and Lymphoma Society [6458-15, 6462-15]; Children's Cancer Research Fund, Minneapolis, MN FX The authors thank Rigel Pharmaceuticals for providing fostamatinib (R788/R406). This work was supported in part by National Institutes of Health National Cancer Institute grants P01 CA142106-06A1 and 5P01-CA047741-20; National Heart, Lung, and Blood Institute grants R01 HL126530 and K08HL107756; National Institute of Allergy and Infectious Diseases grants P01 AI 056299, and T32 AI 007313; and Leukemia and Lymphoma Society translational research grants 6458-15 and 6462-15. R.F. is supported by the Children's Cancer Research Fund, Minneapolis, MN. NR 36 TC 17 Z9 18 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 25 PY 2015 VL 125 IS 26 BP 4085 EP 4094 DI 10.1182/blood-2014-08-595470 PG 10 WC Hematology SC Hematology GA CL9GF UT WOS:000357284300020 PM 25852057 ER PT J AU Leveroni, CL Leveroni, CL Tanaka, N Emerton, BC Cole, AC Reinsberger, C Stufflebeam, SM AF Douw, Linda Leveroni, Catherine L. Tanaka, Naoaki Emerton, Britt C. Cole, Andrew C. Reinsberger, Claus Stufflebeam, Steven M. TI Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; FUNCTIONAL BRAIN NETWORKS; DEFAULT MODE NETWORK; CONNECTIVITY; SCALE; ORGANIZATION; PERFORMANCE; SYSTEM; FMRI; MRI AB The association between cognition and resting-state fMRI (rs-fMRI) has been the focus of many recent studies, most of which use stationary connectivity. The dynamics or flexibility of connectivity, however, may be seminal for understanding cognitive functioning. In temporal lobe epilepsy (TLE), stationary connectomic correlates of impaired memory have been reported mainly for the hippocampus and posterior cingulate cortex (PCC). We therefore investigate resting-state and task-based hippocampal and PCC flexibility in addition to stationary connectivity in left TLE (LTLE) patients. Sixteen LTLE patients were analyzed with respect to rs-fMRI and task-based fMRI (t-fMRI), and underwent clinical neuropsychological testing. Flexibility of connectivity was calculated using a sliding-window approach by determining the standard deviation of Fisher-transformed Pearson correlation coefficients over all windows. Stationary connectivity was also calculated. Disturbed memory was operationalized as having at least one memory subtest score equal to or below the 5th percentile compared to normative data. Lower PCC flexibility, particularly in the contralateral (i.e. right) hemisphere, was found in memory-disturbed LTLE patients, who had up to 22% less flexible connectivity. No significant group differences were found with respect to hippocampal flexibility, stationary connectivity during both rs-fMRI and t-fMRI, or flexibility during t-fMRI. Contralateral resting-state PCC flexibility was able to classify all but one patient with respect to their memory status (94% accuracy). Flexibility of the PCC during rest relates to memory functioning in LTLE patients. Loss of flexible connectivity to the rest of the brain originating from the PCC, particularly contralateral to the seizure focus, is able to discern memory disturbed patients from their preserved counterparts. This study indicates that the dynamics of resting-state connectivity are associated with cognitive status of LTLE patients, rather than stationary connectivity. C1 [Douw, Linda; Tanaka, Naoaki; Reinsberger, Claus; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Douw, Linda; Tanaka, Naoaki; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Douw, Linda] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Leveroni, Catherine L.; Emerton, Britt C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Cole, Andrew C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Reinsberger, Claus] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Reinsberger, Claus] Univ Paderborn, Fac Sci, Inst Sports Med, D-33098 Paderborn, Germany. RP Leveroni, CL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM douw@nmr.mgh.harvard.edu FU NCRR [S10RR014978]; NIH [5R01-NS060918, U01MH093765, 1S10RR023043, R01-NS069696]; Dutch Organization for Scientific Research Rubicon [825.11.002, Veni 016.146.086]; Society in Science-Branco Weiss Fellowship FX This study was supported by the following grants: NCRR S10RR014978 (http://www.nih.gov/about/almanac/organization/NCRR.htm;SMS), NIH 5R01-NS060918, U01MH093765, 1S10RR023043, R01-NS069696 (http://www.nih.gov/;SMS), the Dutch Organization for Scientific Research Rubicon 825.11.002 and Veni 016.146.086 (http://www.nwo.nl/en; LD), and a Society in Science-Branco Weiss Fellowship (http://www.society-in-science.org/;LD). NR 39 TC 0 Z9 0 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 JUN 25 PY 2015 VL 10 IS 6 DI 10.1371/journal.pone.0131209 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL4OY UT WOS:000356933800130 ER PT J AU Caskey, M Klein, F Lorenzi, JCC Seaman, MS West, AP Buckley, N Kremer, G Nogueira, L Braunschweig, M Scheid, JF Horwitz, JA Shimeliovich, I Ben-Avraham, S Witmer-Pack, M Platten, M Lehmann, C Burke, LA Hawthorne, T Gorelick, RJ Walker, BD Keler, T Gulick, RM Fatkenheuer, G Schlesinger, SJ Nussenzweig, MC AF Caskey, Marina Klein, Florian Lorenzi, Julio C. C. Seaman, Michael S. West, Anthony P., Jr. Buckley, Noreen Kremer, Gisela Nogueira, Lilian Braunschweig, Malte Scheid, Johannes F. Horwitz, Joshua A. Shimeliovich, Irina Ben-Avraham, Sivan Witmer-Pack, Maggi Platten, Martin Lehmann, Clara Burke, Leah A. Hawthorne, Thomas Gorelick, Robert J. Walker, Bruce D. Keler, Tibor Gulick, Roy M. Faetkenheuer, Gerd Schlesinger, Sarah J. Nussenzweig, Michel C. TI Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 SO NATURE LA English DT Article ID MONOCLONAL-ANTIBODIES; HIV-1 NEUTRALIZATION; GENETIC-DETERMINANTS; PASSIVE TRANSFER; IN-VIVO; THERAPY; VIRUS; IMMUNOTHERAPY; VACCINE; MICE AB HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned(1-3). However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated(6-10). Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody(11), in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log(10) and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure. C1 [Caskey, Marina; Klein, Florian; Lorenzi, Julio C. C.; Buckley, Noreen; Nogueira, Lilian; Braunschweig, Malte; Scheid, Johannes F.; Horwitz, Joshua A.; Shimeliovich, Irina; Ben-Avraham, Sivan; Witmer-Pack, Maggi; Burke, Leah A.; Schlesinger, Sarah J.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Seaman, Michael S.] Harvard Univ, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [West, Anthony P., Jr.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Kremer, Gisela; Platten, Martin; Lehmann, Clara; Faetkenheuer, Gerd] Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany. [Kremer, Gisela] Univ Cologne, Clin Trials Ctr Cologne, ZKS Koln, D-50931 Cologne, Germany. [Braunschweig, Malte] Univ Freiburg, D-79085 Freiburg, Germany. [Platten, Martin; Lehmann, Clara; Faetkenheuer, Gerd] Partner Site Bonn Cologne, German Ctr Infect Res DZIF, Cologne, Germany. [Burke, Leah A.; Gulick, Roy M.] Cornell Univ, Div Infect Dis, Weill Med Coll, New York, NY 10065 USA. [Hawthorne, Thomas; Keler, Tibor] Celldex Therapeut Inc, Hampton, NJ 08827 USA. [Gorelick, Robert J.] Frederick Natl Lab Canc Res, Leidos Biomed Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Walker, Bruce D.] Massachusetts Gen Hosp, Radon Inst MGH MIT & Harvard, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Walker, Bruce D.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@rockefeller.edu RI Cetrulo Lorenzi, Julio Cesar/B-5264-2008; OI Cetrulo Lorenzi, Julio Cesar/0000-0003-2492-3961; Ben-Avraham, Sivan/0000-0002-9130-0062 FU CNPq "Ciencia sem Fronteiras" Brazil [248676/2013-0]; Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) [OPP1033115, OPP1092074, OPP1040753, OPP1032144]; Cooperative Centers on Human Immunology from NIH [U19A1111825-01]; National Center for Advancing Translational Sciences (NCATS) [UL1 TR000043]; Robertson Foundation; NCI/NIH [HHSN261200800001E]; German Center for Infection Research (DZIF) [3BNC117]; Mark and Lisa Schwartz Foundation; CAVD [43307] FX We thank all individuals who participated in this study. We thank the Rockefeller University Hospital Clinical Research Support Office and nursing staff, as well as T. Kummerle, C. Wyen, and L. Siegel for help with recruitment; S. Kiss for ophthalmologic assessments; F. Maldarelli and J. Lifson for single-copy analysis and B. Freemire for technical assistance; J. Pring, A. Almaktari, C. Unsen, S. Hadrigan, E. Thomas, H. Gruell, D. Gillor, and U. Sandaradura de Silva for sample processing and study coordination, and N. Rodziewicz for help with HIV-1 culturing. We thank A. Louie and C. Conrad for help with regulatory submissions; L. Thomas for IND-enabling studies, L Vitale for cell line and anti-idiotype antibody development, B. Riordan, A. Rayo and J. Andreozzi for anti-idiotype ELISA method development and sample analysis, R. Hammond for process development, and S. DiSciullo for 3BNC117 manufacturing; J. Perry for performing neutralization assays. We thank M. Suarez-Farinas for support with statistical analysis; P. Fast and H. Park for clinical monitoring; and E. Gotschlich and B. Caller for input on study design. J.C.C.L. is supported by an award from CNPq "Ciencia sem Fronteiras" Brazil (248676/2013-0). This work was supported in part by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) Grants OPP1033115 (M.C.N.), OPP1092074 (M.C.N.), OPP1040753 (A.P.W.) and OPP1032144 (M.S.S.), and U19A1111825-01 Cooperative Centers on Human Immunology from NIH to M.C.N., by grant #UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), by a grant from the Robertson Foundation to M.C.N., in part with Federal funds from the NCI/NIH, under Contract No. HHSN261200800001E, and a grant from the German Center for Infection Research (DZIF) to G.F. 3BNC117 was generated from a subject in the International HIV Controller Study, supported by the Mark and Lisa Schwartz Foundation and CAVD Grant 43307. M.C.N. and B.D.W. are Howard Hughes Medical Institute Investigators. The authors declare no competing financial interests. NR 40 TC 142 Z9 144 U1 9 U2 53 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 JUN 25 PY 2015 VL 522 IS 7557 BP 487 EP + DI 10.1038/nature14411 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL2OC UT WOS:000356782900052 PM 25855300 ER PT J AU Roumiantsev, S Shah, U Westra, SJ Misdraji, J AF Roumiantsev, Serguei Shah, Uzma Westra, Sjirk J. Misdraji, Joseph TI Case 20-2015: A Newborn Girl with Hypotension, Coagulopathy, Anemia, and Hyperbilirubinemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALLOIMMUNE LIVER-DISEASE; NEONATAL HEMOCHROMATOSIS; MITOCHONDRIAL HEPATOPATHIES; FAILURE; EXPERIENCE; MANAGEMENT; METABOLISM; DIAGNOSIS; HEPATITIS; INFANTS C1 [Roumiantsev, Serguei] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Roumiantsev, Serguei] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Westra, Sjirk J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Misdraji, Joseph] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roumiantsev, S (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 29 TC 1 Z9 1 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 25 PY 2015 VL 372 IS 26 BP 2542 EP 2553 DI 10.1056/NEJMcpc1404334 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CL2QD UT WOS:000356788200011 PM 26107055 ER PT J AU Phimister, EG AF Phimister, Elizabeth G. TI TREM2 and Risk of Alzheimer's Disease - Friend or Foe? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Phimister, Elizabeth G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Phimister, Elizabeth G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Phimister, EG (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 8 TC 2 Z9 2 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 25 PY 2015 VL 372 IS 26 BP 2564 EP 2565 DI 10.1056/NEJMcibr1503954 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CL2QD UT WOS:000356788200014 ER PT J AU Vaduganathan, M Johnson, JH AF Vaduganathan, Muthiah Johnson, Jacob H. TI Ping-Pong Gaze SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Vaduganathan, Muthiah; Johnson, Jacob H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vaduganathan, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mvaduganathan@partners.org NR 0 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 JUN 25 PY 2015 VL 372 IS 26 BP E34 EP E34 DI 10.1056/NEJMicm1408161 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CL2QD UT WOS:000356788200001 PM 26107068 ER PT J AU Rashidian, M Keliher, EJ Dougan, M Juras, PK Cavallari, M Wojtkiewicz, GR Jacobsen, JT Edens, JG Tas, JMJ Victora, G Weissleder, R Ploegh, H AF Rashidian, Mohammad Keliher, Edmund J. Dougan, Michael Juras, Patrick K. Cavallari, Marco Wojtkiewicz, Gregory R. Jacobsen, Johanne T. Edens, Jerre G. Tas, Jeroen M. J. Victora, Gabriel Weissleder, Ralph Ploegh, Hidde TI Use of F-18-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer SO ACS CENTRAL SCIENCE LA English DT Article ID COLORECTAL-CANCER; PET; SORTASE; LIGATION; PROTEINS; NANOBODY; CELLS; BIOCONJUGATION; CONJUGATION AB We generated F-18-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans-cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-F-18-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of F-18-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon-fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to F-18-labeled antibodies and their fragments at a level of molecular specificity that complements conventional F-18-FDG imaging. C1 [Rashidian, Mohammad; Dougan, Michael; Juras, Patrick K.; Cavallari, Marco; Jacobsen, Johanne T.; Edens, Jerre G.; Tas, Jeroen M. J.; Victora, Gabriel; Ploegh, Hidde] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Keliher, Edmund J.; Wojtkiewicz, Gregory R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol Dept, Boston, MA 02114 USA. [Keliher, Edmund J.; Wojtkiewicz, Gregory R.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dougan, Michael] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Rashidian, Mohammad; Juras, Patrick K.; Ploegh, Hidde] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Ploegh, H (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM ploegh@wi.mit.edu FU NCI NIH HHS [P01 CA117969, P50 CA086355]; NIAID NIH HHS [R01 AI087879, R21 AI117373]; NIBIB NIH HHS [R01 EB010011]; NIGMS NIH HHS [DP1 GM106409, R01 GM100518] NR 38 TC 14 Z9 14 U1 4 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2374-7943 EI 2374-7951 J9 ACS CENTRAL SCI JI ACS Central Sci. PD JUN 24 PY 2015 VL 1 IS 3 BP 142 EP 147 DI 10.1021/acscentsci.5b00121 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA CX8QB UT WOS:000365967600009 PM 26955657 ER PT J AU Martinet, LE Ahmed, OJ Lepage, KQ Cash, SS Kramer, MA AF Martinet, Louis-Emmanuel Ahmed, Omar J. Lepage, Kyle Q. Cash, Sydney S. Kramer, Mark A. TI Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome SO JOURNAL OF NEUROSCIENCE LA English DT Article DE epilepsy; focal seizure; intracranial EEG; seizure propagation; seizure spread ID INDUCED EPILEPTIFORM ACTIVITY; TEMPORAL-LOBE SEIZURES; SMALL-WORLD NETWORKS; INTRACRANIAL EEG; ONSET PATTERNS; FOCAL EPILEPSY; GAP-JUNCTIONS; EVOKED-RESPONSES; PROPAGATION TIME; BRAIN-SLICES AB Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment-how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of similar to 30 s for a broad area of cortex (8 x 8 cm) to be recruited into the seizure, at an estimated speed of similar to 4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure. C1 [Martinet, Louis-Emmanuel; Lepage, Kyle Q.; Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ahmed, Omar J.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat, 111 Cummington Mall, Boston, MA 02215 USA. EM mak@bu.edu FU National Institute of Neurological Disorders and Stroke Award [R01NS072023, SNS062092]; Epilepsy Foundation [222178] FX This research is supported by National Institute of Neurological Disorders and Stroke Award R01NS072023 (to M.A.K. and S.S.C.) and Grant SNS062092 (to S.S.C.) and by the Epilepsy Foundation Grant 222178. We thank the patients who participated in this study and the nursing and physician staff. We also thank Jason Naftulin for technical assistance. NR 93 TC 5 Z9 5 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 24 PY 2015 VL 35 IS 25 BP 9477 EP 9490 DI 10.1523/JNEUROSCI.0049-15.2015 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CN2LG UT WOS:000358252000022 PM 26109670 ER PT J AU Tseng, JC Kung, AL AF Tseng, Jen-Chieh Kung, Andrew L. TI In vivo imaging of endogenous enzyme activities using luminescent 1,2-dioxetane compounds SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE In vivo imaging; Luminescence; Fluorescence; 1,2-dioxetane; CIEEL energy transfer ID INTESTINAL ALKALINE-PHOSPHATASE; FLUORESCENT COMPOUNDS; HUMAN-GRANULOCYTES; HYDROGEN-PEROXIDE; CHEMILUMINESCENCE; BIOLUMINESCENCE; ABILITY; CDNA AB Background: Here we present a non-invasive imaging method for visualizing endogenous enzyme activities in living animals. This optical imaging method is based on an energy transfer principle termed chemically initiated electron exchange luminescence (CIEEL). The light energy is provided by enzymatic activation of metastable 1,2-dioxetane substrates, whose protective groups are removed by hydrolytic enzymes such as beta-galactosidase and alkaline phosphatase. In the presence of a nearby fluorescent recipient, the chemical energy within the activated substrate is then transferred via formation of a charge-transfer complex with the fluorophore, a mechanism closely related to glow stick chemistry. Results: Efficient CIEEL energy transfer requires close proximity between the trigger enzyme and the fluorescent recipient. Using cells stained with fluorescent dialkylcarbocyanines as the energy recipients, we demonstrated CIEEL imaging of cellular beta-galactosidase or alkaline phosphatase activity. In living animals, we used a similar approach to non-invasively image alkaline phosphatase activity in the peritoneal cavity. Conclusions: In this report, we provide proof-of-concept for CIEEL imaging of in vivo enzymatic activity. In addition, we demonstrate the use of CIEEL energy transfer for visualizing elevated alkaline phosphatase activity associated with tissue inflammation in living animals. C1 [Tseng, Jen-Chieh] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA. [Kung, Andrew L.] Columbia Univ, Med Ctr, New York, NY 10032 USA. RP Tseng, JC (reprint author), PerkinElmer Inc, 68 Elm St, Hopkinton, MA 01748 USA. EM jct223@gmail.com OI Kung, Andrew/0000-0002-9091-488X FU Nancy Lurie Marks Foundation FX This work was supported by the Nancy Lurie Marks Foundation. NR 28 TC 1 Z9 1 U1 4 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 EI 1423-0127 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUN 24 PY 2015 VL 22 DI 10.1186/s12929-015-0155-x PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CL0TU UT WOS:000356656800002 ER PT J AU Cornelissen, L Kim, SE Purdon, PL Brown, EN Berde, CB AF Cornelissen, Laura Kim, Seong-Eun Purdon, Patrick L. Brown, Emery N. Berde, Charles B. TI Age-dependent electroencephalogram (EEG) patterns during sevoflurane general anesthesia in infants SO ELIFE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PROPOFOL-INDUCED UNCONSCIOUSNESS; NERVOUS-SYSTEM MYELINATION; INDUCED ALPHA-RHYTHM; PEDIATRIC ANESTHESIA; CONNECTIVITY CHANGES; COHERENCE ANALYSIS; BRAIN-DEVELOPMENT; CONSCIOUSNESS; CHILDREN AB Electroencephalogram (EEG) approaches may provide important information about developmental changes in brain-state dynamics during general anesthesia. We used multi-electrode EEG, analyzed with multitaper spectral methods and video recording of body movement to characterize the spatio-temporal dynamics of brain activity in 36 infants 0-6 months old when awake, and during maintenance of and emergence from sevoflurane general anesthesia. During maintenance: (1) slow-delta oscillations were present in all ages; (2) theta and alpha oscillations emerged around 4 months; (3) unlike adults, all infants lacked frontal alpha predominance and coherence. Alpha power was greatest during maintenance, compared to awake and emergence in infants at 4-6 months. During emergence, theta and alpha power decreased with decreasing sevoflurane concentration in infants at 4-6 months. These EEG dynamic differences are likely due to developmental factors including regional differences in synaptogenesis, glucose metabolism, and myelination across the cortex. We demonstrate the need to apply age-adjusted analytic approaches to develop neurophysiologic-based strategies for pediatric anesthetic state monitoring. C1 [Cornelissen, Laura; Berde, Charles B.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Kim, Seong-Eun; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cornelissen, L (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. EM laura.cornelissen@childrens.harvard.edu FU Sara Page Mayo Endowment for Pediatric Pain Research and Treatment; Boston Children's Hospital (BCH); National Institutes of Health (NIH) [R01-GM104948, DP2-OD006454]; Massachusetts General Hospital (MGH) FX Sara Page Mayo Endowment for Pediatric Pain Research and Treatment Laura Cornelissen, Charles B Berde; Boston Children's Hospital (BCH) Laura Cornelissen, Charles B Berde; National Institutes of Health (NIH) R01-GM104948; DP2-OD006454 Seong-Eun Kim, Patrick L Purdon, Emery N Brown; Massachusetts General Hospital (MGH) Patrick L Purdon, Emery N Brown NR 53 TC 1 Z9 1 U1 1 U2 1 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 23 PY 2015 VL 4 AR e06513 DI 10.7554/eLife.06513 PG 25 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DJ5MI UT WOS:000374252300001 PM 26102526 ER PT J AU Smucny, J Stevens, KE Olincy, A Tregellas, JR AF Smucny, J. Stevens, K. E. Olincy, A. Tregellas, J. R. TI Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation SO TRANSLATIONAL PSYCHIATRY LA English DT Review ID NICOTINIC ACETYLCHOLINE-RECEPTORS; DEFICIENT SENSORY INHIBITION; FREELY MOVING RATS; MEDIAL PREFRONTAL CORTEX; DRUG-INDUCED PSYCHOSIS; PURSUIT EYE-MOVEMENTS; PROOF-OF-CONCEPT; DBA/2 MICE; CIGARETTE-SMOKING; P50 SUPPRESSION AB Impaired gating of the auditory evoked P50 potential is one of the most pharmacologically well-characterized features of schizophrenia. This deficit is most commonly modeled in rodents by implanted electrode recordings from the hippocampus of the rodent analog of the P50, the P20-N40. The validity and effectiveness of this tool, however, has not been systematically reviewed. Here, we summarize findings from studies that have examined the effects of pharmacologic modulation on gating of the rodent hippocampal P20-N40 and the human P50. We show that drug effects on the P20-N40 are highly predictive of human effects across similar dose ranges. Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings. We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied. Overall, this review supports continued use of hippocampal P20-N40 gating as a translational tool for schizophrenia research. C1 [Smucny, J.; Tregellas, J. R.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Smucny, J.; Olincy, A.; Tregellas, J. R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Smucny, J.; Stevens, K. E.; Olincy, A.; Tregellas, J. R.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Tregellas, JR (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus,Bldg 500,MS 546, Aurora, CO 80045 USA. EM jason.tregellas@ucdenver.edu FU VA Biomedical Laboratory and Clinical Science Research and Development Service; Brain and Behavior Foundation; Blowitz-Ridgeway Foundation [MH-086383-01, 1F31-MH102879-01A1] FX This work was supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service, the Brain and Behavior Foundation, the Blowitz-Ridgeway Foundation, MH-086383-01 and 1F31-MH102879-01A1. NR 180 TC 4 Z9 5 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JUN 23 PY 2015 VL 5 AR e587 DI 10.1038/tp.2015.77 PG 13 WC Psychiatry SC Psychiatry GA DA2WZ UT WOS:000367659200002 PM 26101850 ER PT J AU Melman, YF Shah, R Danielson, K Xiao, JJ Simonson, B Barth, A Chakir, K Lewis, GD Lavender, Z Truong, QA Kleber, A Das, R Rosenzweig, A Wang, YY Kass, DA Singh, JP Das, S AF Melman, Yonathan F. Shah, Ravi Danielson, Kirsty Xiao, Junjie Simonson, Bridget Barth, Andreas Chakir, Khalid Lewis, Gregory D. Lavender, Zachary Truong, Quynh A. Kleber, Andre Das, Ranendra Rosenzweig, Anthony Wang, Yaoyu Kass, David A. Singh, Jagmeet P. Das, Saumya TI Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis A Translational Pilot Study SO CIRCULATION LA English DT Article DE biological markers; heart failure; microRNAs; stress; biological ID QRS DURATION; MADIT-CRT; DYSSYNCHRONY; OUTCOMES; TARGETS; TRIAL; EXPRESSION; BIOMARKERS; MORPHOLOGY; MYOCYTES AB Background Biomarkers that predict response to cardiac resynchronization therapy (CRT) in heart failure patients with dyssynchrony (HFDYS) would be clinically important. Circulating extracellular microRNAs (miRNAs) have emerged as novel biomarkers that may also play important functional roles, but their relevance as markers for CRT response has not been examined. Methods and Results Comprehensive miRNA polymerase chain reaction arrays were used to assess baseline levels of 766 plasma miRNAs in patients undergoing clinically indicated CRT in an initial discovery set (n=12) with and without subsequent echocardiographic improvement at 6 months after CRT. Validation of candidate miRNAs in 61 additional patients confirmed that baseline plasma miR-30d was associated with CRT response (defined as an increase in left ventricular ejection fraction 10%). MiR-30d was enriched in coronary sinus blood and increased in late-contracting myocardium in a canine model of HFDYS, indicating cardiac origin with maximal expression in areas of high mechanical stress. We examined the functional effects of miR-30d in cultured cardiomyocytes and determined that miR-30d is expressed in cardiomyocytes and released in vesicles in response to mechanical stress. Overexpression of miR-30d in cultured cardiomyocytes led to cardiomyocyte growth and protected against apoptosis by targeting the mitogen-associated kinase 4, a downstream effector of tumor necrosis factor. In HFDYS patients, miR-30d plasma levels inversely correlated with high-sensitivity troponin T, a marker of myocardial necrosis. Conclusions Baseline plasma miR-30d level is associated with response to CRT in HFDYS in this translational pilot study. MiR-30d increase in cardiomyocytes correlates with areas of increased wall stress in HFDYS and is protective against deleterious tumor necrosis factor signaling. C1 [Melman, Yonathan F.; Shah, Ravi; Danielson, Kirsty; Simonson, Bridget; Kleber, Andre; Rosenzweig, Anthony; Das, Saumya] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Shah, Ravi; Lewis, Gregory D.; Lavender, Zachary; Truong, Quynh A.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Xiao, Junjie] Shanghai Univ, Sch Life Sci, Expt Ctr Life Sci, Shanghai 200041, Peoples R China. [Xiao, Junjie] Shanghai Univ, Sch Life Sci, Regenerat Lab, Shanghai 200041, Peoples R China. [Barth, Andreas; Chakir, Khalid; Kass, David A.] Johns Hopkins Univ Med Inst, Baltimore, MD USA. [Das, Ranendra] Johns Hopkins Univ, Baltimore, MD USA. [Wang, Yaoyu] Dana Farber Canc Inst, Ctr Computat Biol, Boston, MA 02115 USA. RP Das, S (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 330 Brookline Ave,CLS 907, Boston, MA 02215 USA. EM sdas@bidmc.harvard.edu FU Klarman Scholars Foundation; National Institutes of Health Common Funds through Office of Strategic Coordination/Office of the National Institutes of Health [UH2-TR000901]; NHLBI [PO1: HL077180] FX Dr Das is funded by the Klarman Scholars Foundation and a grant from National Institutes of Health Common Funds UH2-TR000901 through the Office of Strategic Coordination/Office of the National Institutes of Health Director. Dr Kass received funding from NHLBI PO1: HL077180. NR 35 TC 23 Z9 26 U1 10 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 23 PY 2015 VL 131 IS 25 BP 2202 EP 2216 DI 10.1161/CIRCULATIONAHA.114.013220 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ3UG UT WOS:000360528400007 PM 25995320 ER PT J AU Pandarinath, C Gilja, V Blabe, CH Nuyujukian, P Sarma, AA Sorice, BL Eskandar, EN Hochberg, LR Henderson, JM Shenoy, KV AF Pandarinath, Chethan Gilja, Vikash Blabe, Christine H. Nuyujukian, Paul Sarma, Anish A. Sorice, Brittany L. Eskandar, Emad N. Hochberg, Leigh R. Henderson, Jaimie M. Shenoy, Krishna V. TI Neural population dynamics in human motor cortex during movements in people with ALS SO ELIFE LA English DT Article ID ARM MOVEMENTS; TETRAPLEGIA AB The prevailing view of motor cortex holds that motor cortical neural activity represents muscle or movement parameters. However, recent studies in non-human primates have shown that neural activity does not simply represent muscle or movement parameters; instead, its temporal structure is well-described by a dynamical system where activity during movement evolves lawfully from an initial pre-movement state. In this study, we analyze neuronal ensemble activity in motor cortex in two clinical trial participants diagnosed with Amyotrophic Lateral Sclerosis (ALS). We find that activity in human motor cortex has similar dynamical structure to that of non-human primates, indicating that human motor cortex contains a similar underlying dynamical system for movement generation. C1 [Pandarinath, Chethan; Gilja, Vikash; Blabe, Christine H.; Nuyujukian, Paul; Henderson, Jaimie M.] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Pandarinath, Chethan; Gilja, Vikash; Nuyujukian, Paul; Shenoy, Krishna V.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. [Pandarinath, Chethan; Nuyujukian, Paul; Henderson, Jaimie M.; Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Stanford, CA 94305 USA. [Gilja, Vikash; Sarma, Anish A.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Sarma, Anish A.; Hochberg, Leigh R.] Dept VA Med Ctr, Rehabil R&D Serv, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Sarma, Anish A.; Sorice, Brittany L.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Sarma, Anish A.; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Neurol, Boston, MA USA. [Shenoy, Krishna V.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA. RP Shenoy, KV (reprint author), Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. EM shenoy@stanford.edu OI Hochberg, Leigh/0000-0003-0261-2273; Pandarinath, Chethan/0000-0003-1241-1432; Blabe, Christine/0000-0003-4623-4251; Henderson, Jaimie/0000-0002-3276-2267 FU National Institutes of Health (NIH) [R01DC009899, N01HD53403, N01HD10018, R01-NS066311]; U.S. Department of Veterans Affairs [B6453R, B6310N]; Garlick Foundation; Craig H. Neilsen Foundation; Massachusetts General Hospital Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Stanford University Institute for Neuro-Innovation and Translational Neuroscience; Stanford University Stanford BioX/Neuroventures; Stanford University Stanford Office of Postdoctoral Affairs FX National Institutes of Health (NIH) R01DC009899 Leigh R Hochberg; National Institutes of Health (NIH) N01HD53403 Leigh R Hochberg; National Institutes of Health (NIH) N01HD10018 Leigh R Hochberg; National Institutes of Health (NIH) R01-NS066311 Jaimie M Henderson, Krishna V Shenoy; U.S. Department of Veterans Affairs B6453R, B6310N Leigh R Hochberg; Garlick Foundation Jaimie M Henderson, Krishna V Shenoy; Craig H. Neilsen Foundation Chethan Pandarinath; Massachusetts General Hospital Deane Institute for Integrated Research on Atrial Fibrillation and Stroke Leigh R Hochberg; Stanford University Institute for Neuro-Innovation and Translational Neuroscience Jaimie M Henderson, Krishna V Shenoy; Stanford University Stanford BioX/Neuroventures Jaimie M Henderson, Krishna V Shenoy; Stanford University Stanford Office of Postdoctoral Affairs Chethan Pandarinath; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 17 TC 4 Z9 4 U1 0 U2 5 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 23 PY 2015 VL 4 AR e07436 DI 10.7554/eLife.07436 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CL1QX UT WOS:000356720100001 PM 26099302 ER PT J AU Giugliano, RP Sabatine, MS AF Giugliano, Robert P. Sabatine, Marc S. TI Are PCSK9 Inhibitors the Next Breakthrough in the Cardiovascular Field? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE cholesterol; lipids; low-density lipoprotein ID DENSITY-LIPOPROTEIN CHOLESTEROL; SUBTILISIN/KEXIN TYPE 9; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; CORONARY-HEART-DISEASE; EVOLOCUMAB AMG 145; PLACEBO-CONTROLLED TRIAL; HIGH-RISK PATIENTS; RANDOMIZED CONTROLLED-TRIAL; STATIN-INTOLERANT PATIENTS AB Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. Both gain-of-function mutations in PCSK9 (causing marked increases in low-density lipoprotein cholesterol [LDL-C] concentration and premature atherosclerosis) and loss-of-function mutations (causing modest LDL-C reduction with low rates of coronary heart disease) have been described. Several monoclonal antibodies to PCSK9 have achieved LDL-C reductions of 50% to 70% across various patient populations and background lipid therapies. Phase 2/3 trials have demonstrated good tolerability without clear drug-related toxicity, although the number and duration of patients treated to date is modest. Currently, 4 phase 3 trials involving >70,000 patients are testing whether these drugs reduce cardiovascular events. The U.S. Food and Drug Administration is currently reviewing the existing data to determine whether these agents could be made available prior to the completion of these cardiovascular endpoint trials expected in 2018. (C) 2015 by the American College of Cardiology Foundation. C1 [Giugliano, Robert P.; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Off, 350 Longwood Ave,First Floor Offices, Boston, MA 02115 USA. EM rgiugliano@partners.org RI 刘, 李陆/H-8469-2015 FU Merck; AstraZeneca; Amgen; Daiichi-Sankyo; Bristol-Myers Squibb; CVS Caremark; Pfizer; Sanofi; Abbott Laboratories; Accumetrics; Critical Diagnostics; Eisai; Genzyme; Nanosphere; Roche Diagnostics; Takeda; Gilead; GlaxoSmithKline; Intarcia; Aegerion; Alnylam; Cubist; MyoKardia; Quest Diagnostics; Vertex; Zeus Scientific FX Dr. Giugliano has received grant support from Merck and AstraZeneca; grant support and personal fees from Amgen and Daiichi-Sankyo; and personal fees from Bristol-Myers Squibb, CVS Caremark, Pfizer, and Sanofi outside the submitted work. Dr. Sabatine has received grant support from Abbott Laboratories, Accumetrics, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, Nanosphere, Roche Diagnostics, Takeda, and Gilead; grant support and personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Intarcia, Merck, and Sanofi; and personal fees from Aegerion, Alnylam, Cubist, MyoKardia, Pfizer, Quest Diagnostics, Vertex, Zeus Scientific, and CVS Caremark outside of the submitted work. NR 78 TC 51 Z9 53 U1 6 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 23 PY 2015 VL 65 IS 24 BP 2638 EP 2651 DI 10.1016/j.jacc.2015.05.001 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK6CK UT WOS:000356315200010 PM 26088304 ER PT J AU Jiang, P Freedman, ML Liu, JS Liu, XS AF Jiang, Peng Freedman, Matthew L. Liu, Jun S. Liu, Xiaole Shirley TI Inference of transcriptional regulation in cancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE regulatory inference; tumor profiling; transcription factor; RNA-binding protein ID GENE-EXPRESSION; CHIP-SEQ; PROLIFERATION; REGRESSION; PROGNOSIS; PROFILES; DATABASE; REVEALS; SCREENS; PROJECT AB Despite the rapid accumulation of tumor-profiling data and transcription factor (TF) ChIP-seq profiles, efforts integrating TF binding with the tumor-profiling data to understand how TFs regulate tumor gene expression are still limited. To systematically search for cancer-associated TFs, we comprehensively integrated 686 ENCODE ChIP-seq profiles representing 150 TFs with 7484 TCGA tumor data in 18 cancer types. For efficient and accurate inference on gene regulatory rules across a large number and variety of datasets, we developed an algorithm, RABIT (regression analysis with background integration). In each tumor sample, RABIT tests whether the TF target genes from ChIP-seq show strong differential regulation after controlling for background effect from copy number alteration and DNA methylation. When multiple ChIP-seq profiles are available for a TF, RABIT prioritizes the most relevant ChIP-seq profile in each tumor. In each cancer type, RABIT further tests whether the TF expression and somatic mutation variations are correlated with differential expression patterns of its target genes across tumors. Our predicted TF impact on tumor gene expression is highly consistent with the knowledge from cancer-related gene databases and reveals many previously unidentified aspects of transcriptional regulation in tumor progression. We also applied RABIT on RNA-binding protein motifs and found that some alternative splicing factors could affect tumor-specific gene expression by binding to target gene 3'UTR regions. Thus, RABIT (rabit.dfci.harvard.edu) is a general platform for predicting the oncogenic role of gene expression regulators. C1 [Jiang, Peng; Liu, Xiaole Shirley] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Freedman, Matthew L.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Liu, XS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM xsliu@jimmy.harvard.edu FU NIH [NHGRI U41 HG7000, NCI U01 CA180980, R01 GM113242-01]; NSF [DMS1208771] FX We thank Myles Brown, David Louis, Mario Suva, Jing Mi, Di Wu, Bo Li, and Eric Severson for helpful discussions. The work was supported by NIH Grants NHGRI U41 HG7000, NCI U01 CA180980, R01 GM113242-01, and NSF DMS1208771. NR 47 TC 13 Z9 13 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 23 PY 2015 VL 112 IS 25 BP 7731 EP 7736 DI 10.1073/pnas.1424272112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL1UV UT WOS:000356731300065 PM 26056275 ER PT J AU Ballal, SA Veiga, P Fenn, K Michaud, M Kim, JH Gallini, CA Glickman, JN Quere, G Garault, P Beal, C Derrien, M Courtin, P Kulakauskas, S Chapot-Chartier, MP Vlieg, JV Garrett, WS AF Ballal, Sonia A. Veiga, Patrick Fenn, Kathrin Michaud, Monia Kim, Jason H. Gallini, Carey Ann Glickman, Jonathan N. Quere, Gaelle Garault, Peggy Beal, Chloe Derrien, Muriel Courtin, Pascal Kulakauskas, Saulius Chapot-Chartier, Marie-Pierre Vlieg, Johan van Hylckama Garrett, Wendy S. TI Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Lactococcus lactis; oxidative stress; lysozyme; colitis; probiotics ID INFLAMMATORY-BOWEL-DISEASE; GRAM-POSITIVE BACTERIA; FERMENTED MILK PRODUCT; ULCERATIVE-COLITIS; ANTIMICROBIAL PEPTIDES; PROPHAGE INDUCTION; EPITHELIAL-CELLS; TEICHOIC-ACIDS; KAPPA-B; PEPTIDOGLYCAN AB Beneficial microbes that target molecules and pathways, such as oxidative stress, which can negatively affect both host and microbiota, may hold promise as an inflammatory bowel disease therapy. Prior work showed that a five-strain fermented milk product (FMP) improved colitis in T-bet(-/-) Rag2(-/-) mice. By varying the number of strains used in the FMP, we found that Lactococcus lactis I-1631 was sufficient to ameliorate colitis. Using comparative genomic analyses, we identified genes unique to L. lactis I-1631 involved in oxygen respiration. Respiration of oxygen results in reactive oxygen species (ROS) generation. Also, ROS are produced at high levels during intestinal inflammation and cause tissue damage. L. lactis I-1631 possesses genes encoding enzymes that detoxify ROS, such as superoxide dismutase (SodA). Thus, we hypothesized that lactococcal SodA played a role in attenuating colitis. Inactivation of the sodA gene abolished L. lactis I-1631' s beneficial effect in the T-bet(-/-) Rag2(-/-) model. Similar effects were obtained in two additional colonic inflammation models, Il10(-/-) mice and dextran sulfate sodium-treated mice. Efforts to understand how a lipophobic superoxide anion (O-2(-)) can be detoxified by cytoplasmic lactoccocal SodA led to the finding that host antimicrobial-mediated lysis is a prerequisite for SodA release and SodA's extracytoplasmic O-2(-) scavenging. L. lactis I-1631 may represent a promising vehicle to deliver antioxidant, colitis-attenuating SodA to the inflamed intestinal mucosa, and host antimicrobials may play a critical role in mediating SodA's bioaccessibility. C1 [Ballal, Sonia A.] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Boston, MA 02115 USA. [Ballal, Sonia A.; Veiga, Patrick; Fenn, Kathrin; Michaud, Monia; Kim, Jason H.; Gallini, Carey Ann; Garrett, Wendy S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Ballal, Sonia A.; Veiga, Patrick; Fenn, Kathrin; Michaud, Monia; Kim, Jason H.; Gallini, Carey Ann; Garrett, Wendy S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Veiga, Patrick; Quere, Gaelle; Garault, Peggy; Beal, Chloe; Derrien, Muriel; Vlieg, Johan van Hylckama] Danone Nutr Res, F-91767 Palaiseau, France. [Glickman, Jonathan N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Glickman, Jonathan N.] Miraca Life Sci, Newton, MA 02464 USA. [Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre] INRA, UMR Micalis 1319, F-78352 Jouy En Josas, France. [Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre] AgroParisTech, UMR Micalis, F-78352 Jouy En Josas, France. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Garrett, WS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu RI Veiga, Patrick/A-9862-2011; OI Veiga, Patrick/0000-0001-6318-8547; Derrien, Muriel/0000-0001-8841-9153 FU Danone Nutricia Research; Searle Scholars Award; National Cancer Institute [R01CA154426]; National Institute of Allergy and Infectious Diseases [K08AI078942]; Burroughs Wellcome Career in Medical Sciences Award FX We thank members of the W.S.G. laboratory for discussions and advice. This study was supported by a grant from Danone Nutricia Research, R01CA154426 (National Cancer Institute), K08AI078942 (National Institute of Allergy and Infectious Diseases), a Burroughs Wellcome Career in Medical Sciences Award, and a Searle Scholars Award. NR 46 TC 10 Z9 10 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 JUN 23 PY 2015 VL 112 IS 25 BP 7803 EP 7808 DI 10.1073/pnas.1501897112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL1UV UT WOS:000356731300077 PM 26056274 ER PT J AU Gordon, WR Zimmerman, B He, L Miles, LJ Huang, JH Tiyanont, K McArthur, DG Aster, JC Perrimon, N Loparo, JJ Blacklow, SC AF Gordon, Wendy R. Zimmerman, Brandon He, Li Miles, Laura J. Huang, Jiuhong Tiyanont, Kittichoat McArthur, Debbie G. Aster, Jon C. Perrimon, Norbert Loparo, Joseph J. Blacklow, Stephen C. TI Mechanical Allostery: Evidence for a Force Requirement in the Proteolytic Activation of Notch SO DEVELOPMENTAL CELL LA English DT Article ID LIGAND ENDOCYTOSIS; REGULATORY REGION; VINCULIN BINDING; CLEAVAGE; RECEPTOR; TENSION; MUTATIONS; MOLECULES; INTEGRIN; LEUKEMIA AB Ligands stimulate Notch receptors by inducing regulated intramembrane proteolysis (RIP) to produce a transcriptional effector. Notch activation requires unmasking of a metalloprotease cleavage site remote from the site of ligand binding, raising the question of how proteolytic sensitivity is achieved. Here, we show that application of physiologically relevant forces to the Notch1 regulatory switch results in sensitivity to metalloprotease cleavage, and bound ligands induce Notch signal transduction in cells only in the presence of applied mechanical force. Synthetic receptor-ligand systems that remove the native ligand-receptor interaction also activate Notch by inducing proteolysis of the regulatory switch. Together, these studies show that mechanical force exerted by signal-sending cells is required for ligand-induced Notch activation and establish that force-induced proteolysis can act as a mechanism of cellular mechanotransduction. C1 [Gordon, Wendy R.; Zimmerman, Brandon; Miles, Laura J.; Loparo, Joseph J.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Gordon, Wendy R.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Zimmerman, Brandon; Miles, Laura J.; Tiyanont, Kittichoat; McArthur, Debbie G.; Blacklow, Stephen C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [He, Li; Huang, Jiuhong; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Aster, Jon C.; Blacklow, Stephen C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Perrimon, Norbert] Howard Hughes Med Inst, Boston, MA 02115 USA. [Huang, Jiuhong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. RP Loparo, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM joseph_loparo@hms.harvard.edu; stephen_blacklow@hms.harvard.edu FU American Heart Association (AHA); Damon Runyon Postdoctoral Fellowship; NIH [P01 CA119070, R01 CA092433]; Howard Hughes Medical Institute (HHMI); NIH FX We thank Benedikt Bauer and Anthony Nguyen for help in optimizing single molecule experiments and Adam17 expression, Scott Ficarro for mass spectrometry, and Kelly Arnett and Brian McMillan for helpful discussions. W.R.G. was supported by an American Heart Association (AHA) SDG grant. L.H. was supported by a Damon Runyon Postdoctoral Fellowship. This work was supported by NIH grants P01 CA119070 (J.J.L., J.C.A., and S.C.B.) and R01 CA092433 (J.C.A. and S.C.B.), the Howard Hughes Medical Institute (HHMI), and the NIH (N.P.). NR 27 TC 33 Z9 34 U1 1 U2 6 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 JUN 22 PY 2015 VL 33 IS 6 BP 729 EP 736 DI 10.1016/j.devcel.2015.05.004 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CL2KY UT WOS:000356773900012 PM 26051539 ER PT J AU Chandler, PD Giovannucci, EL Scott, JB Bennett, GG Ng, K Chan, AT Hollis, BW Rifai, N Emmons, KM Fuchs, CS Drake, BF AF Chandler, Paulette D. Giovannucci, Edward L. Scott, Jamil B. Bennett, Gary G. Ng, Kimmie Chan, Andrew T. Hollis, Bruce W. Rifai, Nader Emmons, Karen M. Fuchs, Charles S. Drake, Bettina F. TI Effects of Vitamin D Supplementation on C-peptide and 25-hydroxyvitamin D Concentrations at 3 and 6 Months SO SCIENTIFIC REPORTS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; INSULIN-RESISTANCE; GLUCOSE-INTOLERANCE; AFRICAN-AMERICANS; D INSUFFICIENCY; CELL FUNCTION; D DEFICIENCY; SECRETION; METAANALYSIS; WOMEN AB The link between African-Americans' disproportionate rates of diabetes, obesity and vitamin D deficiency may be marked by C-peptide as an indicator of insulin secretion. We hypothesize that vitamin D supplementation will increase C-peptide, a marker of insulin secretion. During 3 winters from 2007-2010, 328 healthy African-Americans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. The differences in non-fasting C-peptide between baseline and 3 months were -0.44 ng/mL for those receiving placebo, -0.10 ng/mL for those receiving 1000 IU/d, 0 ng/mL for those receiving 2000 IU/d, 1.24 ng/mL for those receiving 4000 IU/d (C-peptide increased 0.42 ng/mL for each additional 1000 IU/d of vitamin D3, p < 0.001). Vitamin D supplementation increased C-peptide in overweight African-Americans and may be compatible with other recommendations for diabetes prevention and management including weight loss and increased physical activity. C1 [Chandler, Paulette D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chandler, Paulette D.; Giovannucci, Edward L.; Ng, Kimmie; Chan, Andrew T.; Rifai, Nader; Emmons, Karen M.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Scott, Jamil B.] Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Hollis, Bruce W.] Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. [Rifai, Nader] Childrens Hosp, Div Lab Med, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Drake, Bettina F.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. RP Chandler, PD (reprint author), Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. EM pchandler@partners.org OI Drake, Bettina/0000-0001-9340-5848 FU National Cancer Institute [U01CA138962]; Department of Defense Prostate Cancer Research Program [PC081669]; American Society of Clinical Oncology Career Development Award; Pharmavite LLC (Mission Hill, CA); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University and its affiliated academic healthcare centers; Office of Dietary Supplements [3P50 CA127003]; [K07CA148894]; [K22CA126992]; [5K05CA124415]; [K24DK098311] FX This trial was funded by the National Cancer Institute (U01CA138962 [Dr. Chandler]; Office of Dietary Supplements (3P50 CA127003 [Dr. Scott]); K07CA148894 [Dr Ng]; K22CA126992; 5K05CA124415 [Dr Emmons]; K24DK098311 [Dr. Chan]), the Department of Defense Prostate Cancer Research Program (PC081669 [Dr Drake]), the American Society of Clinical Oncology Career Development Award (Dr Ng), and Pharmavite LLC (Mission Hill, CA). These funding sources had no role in the conception or conduct of the study, took no part in the data collection or analysis, and had no role in the drafting, review, or approval of the article. Pharmavite LLC provided vitamin D and the placebo: We would like to thank Cara Marcus, MSLIS, AHIP, Director of Library Services, Brigham and Women's Faulkner Hospital for facilitating access to reference articles and Yiqing Song, MD, ScD for reviewing the manuscript and Camille A. Clarke, MD for assistance with editing manuscript. 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 UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. NR 39 TC 1 Z9 1 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUN 22 PY 2015 VL 5 AR 10411 DI 10.1038/srep10411 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK9TI UT WOS:000356582000001 PM 26095242 ER PT J AU Preiss, D Campbell, RT Murray, HM Ford, I Packard, CJ Sattar, N Rahimi, K Colhoun, HM Waters, DD LaRosa, JC Amarenco, P Pedersen, TR Tikkanen, MJ Koren, MJ Poulter, NR Sever, PS Ridker, PM MacFadyen, JG Solomon, SD Davis, BR Simpson, LM Nakamura, H Mizuno, K Marfisi, RM Marchioli, R Tognoni, G Athyros, VG Ray, KK Gotto, AM Clearfield, MB Downs, JR McMurray, JJ AF Preiss, David Campbell, Ross T. Murray, Heather M. Ford, Ian Packard, Chris J. Sattar, Naveed Rahimi, Kazem Colhoun, Helen M. Waters, David D. LaRosa, John C. Amarenco, Pierre Pedersen, Terje R. Tikkanen, Matti J. Koren, Michael J. Poulter, Neil R. Sever, Peter S. Ridker, Paul M. MacFadyen, Jean G. Solomon, Scott D. Davis, Barry R. Simpson, Lara M. Nakamura, Haruo Mizuno, Kyoichi Marfisi, Rosa M. Marchioli, Roberto Tognoni, Gianni Athyros, Vasilios G. Ray, Kausik K. Gotto, Antonio M. Clearfield, Michael B. Downs, John R. McMurray, John J. TI The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials SO EUROPEAN HEART JOURNAL LA English DT Article DE Statin; Heart failure; Randomized trial; Prevention; Meta-analysis ID AVERAGE CHOLESTEROL LEVELS; PLACEBO-CONTROLLED TRIAL; ACUTE CORONARY SYNDROMES; HIGH-DOSE ATORVASTATIN; PRIMARY PREVENTION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; VASCULAR EVENTS; LDL CHOLESTEROL AB Aims The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. Methods and results We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first on-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR0.97,95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98). Conclusion In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not. C1 [Preiss, David; Campbell, Ross T.; Sattar, Naveed; McMurray, John J.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [Murray, Heather M.; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8TA, Lanark, Scotland. [Packard, Chris J.] Univ Glasgow, Western Infirm, Glasgow Clin Res Facil, Glasgow G11 6NT, Lanark, Scotland. [Rahimi, Kazem] Univ Oxford, George Inst Global Hlth, Oxford, England. [Colhoun, Helen M.] Univ Dundee, Med Res Inst, Dundee, Scotland. [Waters, David D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [LaRosa, John C.] SUNY Hlth Sci Ctr Brooklyn, New York, NY USA. [Amarenco, Pierre] Hop Xavier Bichat, Dept Neurol, Paris, France. [Amarenco, Pierre] Hop Xavier Bichat, Stroke Ctr, Paris, France. [Pedersen, Terje R.] Univ Oslo, Oslo, Norway. [Pedersen, Terje R.] Oslo Univ Hosp, Ctr Preventat Med, Oslo, Norway. [Tikkanen, Matti J.] Univ Helsinki, Helsinki, Finland. [Tikkanen, Matti J.] Univ Helsinki, Cent Hosp, Heart & Lung Ctr, Helsinki, Finland. [Tikkanen, Matti J.] Folkhalsan Res Ctr, Helsinki, Finland. [Koren, Michael J.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. [Poulter, Neil R.; Sever, Peter S.; Ray, Kausik K.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, London, England. [Ridker, Paul M.; MacFadyen, Jean G.; Solomon, Scott D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA USA. [Davis, Barry R.; Simpson, Lara M.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Nakamura, Haruo] Mitsukoshi Hlth & Welf Fdn, Shinjuku Ku, Tokyo, Japan. [Mizuno, Kyoichi] Nippon Med Sch, Dept Med, Bunkyo Ku, Tokyo 113, Japan. [Marfisi, Rosa M.; Marchioli, Roberto; Tognoni, Gianni] Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy. [Athyros, Vasilios G.] Aristotle Univ Thessaloniki, Hippokrat Hosp, Propedeut Dept Internal Med 2, Sch Med, GR-54006 Thessaloniki, Greece. [Gotto, Antonio M.] Weill Cornell Med Coll, New York, NY USA. [Clearfield, Michael B.] Touro Univ, Coll Osteopath Med, Vallejo, CA USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Downs, John R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Preiss, D (reprint author), Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland. EM david.preiss@glasgow.ac.uk RI Rahimi, Kazem/Q-1279-2015; OI Rahimi, Kazem/0000-0002-4807-4610; Preiss, David/0000-0003-3139-1836; Colhoun, Helen/0000-0002-8345-3288; Sattar, Naveed/0000-0002-1604-2593; mcmurray, john/0000-0002-6317-3975 FU BHF project [PG/13/17/30050]; National Institute for Health Research Senior Investigator Awards; Biomedical Research Centre; British Heart Foundation Research Centre Excellence Award; National Institute for Health Research Career Development Fellowship; Oxford Biomedical Research Centre; Oxford Martin School FX This project was not supported by external funding. R.T.C. is funded by a BHF project grant (PG/13/17/30050). N.R.P. is supported by the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. K.R. is supported by a National Institute for Health Research Career Development Fellowship and funding from the Oxford Biomedical Research Centre, and the Oxford Martin School. NR 38 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JUN 21 PY 2015 VL 36 IS 24 BP 1536 EP 1546 DI 10.1093/eurheartj/ehv072 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CM7LZ UT WOS:000357876100015 PM 25802390 ER PT J AU Han, X Pearson, E Pelizzari, C Al-Hallaq, H Sidky, EY Bian, JG Pan, XC AF Han, Xiao Pearson, Erik Pelizzari, Charles Al-Hallaq, Hania Sidky, Emil Y. Bian, Junguo Pan, Xiaochuan TI Algorithm-enabled exploration of image-quality potential of cone-beam CT in image-guided radiation therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE cone-beam CT; image reconstruction; optimization; iterative algorithm ID INTENSITY-MODULATED RADIOTHERAPY; TOTAL VARIATION REGULARIZATION; COMPUTED-TOMOGRAPHY; ASSURANCE PROGRAM; PROSTATE-CANCER; MICRO-CT; RECONSTRUCTION; IMRT AB Kilo-voltage (KV) cone-beam computed tomography (CBCT) unit mounted onto a linear accelerator treatment system, often referred to as on-board imager (OBI), plays an increasingly important role in image-guided radiation therapy. While the FDK algorithm is currently used for reconstructing images from clinical OBI data, optimization-based reconstruction has also been investigated for OBI CBCT. An optimization-based reconstruction involves numerous parameters, which can significantly impact reconstruction properties (or utility). The success of an optimization-based reconstruction for a particular class of practical applications thus relies strongly on appropriate selection of parameter values. In the work, we focus on tailoring the constrained-TVminimization- based reconstruction, an optimization-based reconstruction previously shown of some potential for CBCT imaging conditions of practical interest, to OBI imaging through appropriate selection of parameter values. In particular, for given real data of phantoms and patient collected with OBI CBCT, we first devise utility metrics specific to OBI-quality-assurance tasks and then apply them to guiding the selection of parameter values in constrained-TV-minimization-based reconstruction. The study results show that the reconstructions are with improvement, relative to clinical FDK reconstruction, in both visualization and quantitative assessments in terms of the devised utility metrics. C1 [Han, Xiao; Sidky, Emil Y.; Pan, Xiaochuan] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Pearson, Erik; Pelizzari, Charles; Al-Hallaq, Hania; Pan, Xiaochuan] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Bian, Junguo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Han, X (reprint author), Univ Chicago, Dept Radiol, 5801 S Ellis Ave, Chicago, IL 60637 USA. EM xpan@uchicago.edu FU National Institutes of Health (NIH) [R01s EB000225, CA158446, CA182264, EB018102] FX This work was supported in part by the National Institutes of Health (NIH) under grants R01s EB000225, CA158446, CA182264, and EB018102. NR 43 TC 5 Z9 6 U1 2 U2 12 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 JUN 21 PY 2015 VL 60 IS 12 BP 4601 EP 4633 DI 10.1088/0031-9155/60/12/4601 PG 33 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CK3DA UT WOS:000356095200004 PM 26020490 ER PT J AU Xiao, G Sun, PZ Wu, RH AF Xiao, Gang Sun, Phillip Zhe Wu, Renhua TI Fast simulation and optimization of pulse-train chemical exchange saturation transfer (CEST) imaging SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE Bloch-McConnell equations; chemical exchange saturation transfer (CEST); quantitative chemical exchange saturation transfer (qCEST); pulse-train ID PROTON FRACTION RATIO; PH-WEIGHTED MRI; RF IRRADIATION; IN-VIVO; CONTRAST AGENTS; CEREBRAL-ISCHEMIA; PARACEST AGENTS; HUMAN BRAIN; TISSUE PH; 7 T AB Chemical exchange saturation transfer (CEST) MRI has been increasingly applied to detect dilute solutes and physicochemical properties, with promising in vivo applications. Whereas CEST imaging has been implemented with continuous wave (CW) radio-frequency irradiation on preclinical scanners, pulse-train irradiation is often chosen on clinical systems. Therefore, it is necessary to optimize pulse-train CEST imaging, particularly important for translational studies. Because conventional Bloch-McConnell formulas are not in the form of homogeneous differential equations, the routine simulation approach simulates the evolving magnetization step by step, which is time consuming. Herein we developed a computationally efficient numerical solution using matrix iterative analysis of homogeneous Bloch-McConnell equations. The proposed algorithm requires simulation of pulse-train CEST MRI magnetization within one irradiation repeat, with 99% computation time reduction from that of conventional approach under typical experimental conditions. The proposed solution enables determination of labile proton ratio and exchange rate from pulse- train CEST MRI experiment, within 5% from those determined from quantitative CW-CEST MRI. In addition, the structural similarity index analysis shows that the dependence of CEST contrast on saturation pulse flip angle and duration between simulation and experiment was 0.98 +/- 0.01, indicating that the proposed simulation algorithm permits fast optimization and quantification of pulse-train CEST MRI. C1 [Xiao, Gang] Hanshan Normal Univ, Dept Math & Stat, Chaozhou, Guangdong, Peoples R China. [Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Biomarker & Metab Imaging Lab, Charlestown, MA 02129 USA. [Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wu, Renhua] Shantou Univ, Affiliated Hosp 2, Coll Med, Dept Radiol, Shantou 515041, Guangdong, Peoples R China. RP Xiao, G (reprint author), Hanshan Normal Univ, Dept Math & Stat, Chaozhou, Guangdong, Peoples R China. EM pzhesun@mgh.harvard.edu; rhwu@stu.edu.cn FU NSFGD [S2013010013372]; NSFC [30930027]; NIH/NIBIB [1K01EB009771]; NIH/NINDS [1R01NS083654] FX This study was supported in part by grants from NSFGD S2013010013372 (Xiao G), NSFC 30930027 (Wu RH), NIH/NIBIB 1K01EB009771 (Sun PZ) and NIH/NINDS 1R01NS083654 (Sun PZ). NR 49 TC 3 Z9 3 U1 1 U2 14 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 JUN 21 PY 2015 VL 60 IS 12 BP 4719 EP 4730 DI 10.1088/0031-9155/60/12/4719 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CK3DA UT WOS:000356095200010 PM 26020414 ER PT J AU Kagan, VE Tyurina, YY Tyurin, VA Mohammadyani, D Angeli, JPF Baranov, SV Klein-Seetharaman, J Friedlander, RM Mallampalli, RK Conrad, M Bayir, H AF Kagan, Valerian E. Tyurina, Yulia Y. Tyurin, Vladimir A. Mohammadyani, Dariush Angeli, Jose Pedro Friedmann Baranov, Sergei V. Klein-Seetharaman, Judith Friedlander, Robert M. Mallampalli, Rama K. Conrad, Marcus Bayir, Huelya TI Cardiolipin Signaling Mechanisms: Collapse of Asymmetry and Oxidation SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID MASS-SPECTROMETRIC CHARACTERIZATION; HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; CYTOCHROME-C; BARTH-SYNDROME; CELL-DEATH; INDUCED APOPTOSIS; PHOSPHATIDYLSERINE PEROXIDATION; MITOCHONDRIAL CARDIOLIPIN; STRUCTURAL TRANSITIONS; ANIONIC PHOSPHOLIPIDS AB Significance: An ancient anionic phospholipid, cardiolipin (CL), ubiquitously present in prokaryotic and eukaryotic membranes, is essential for several structural and functional purposes. Recent Advances: The emerging role of CLs in signaling has become the focus of many studies. Critical Issues: In this work, we describe two major pathways through which mitochondrial CLs may fulfill the signaling functions via utilization of their (i) asymmetric distribution across membranes and translocations, leading to the surface externalization and (ii) ability to undergo oxidation reactions to yield the signature products recognizable by the executionary machinery of cells. Future Directions: We present a concept that CLs and their oxidation/hydrolysis products constitute a rich communication language utilized by mitochondria of eukaryotic cells for diversified regulation of cell physiology and metabolism as well as for inter-cellular interactions. Antioxid. Redox Signal. 22, 1667-1680. C1 [Kagan, Valerian E.; Tyurina, Yulia Y.; Tyurin, Vladimir A.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15219 USA. [Kagan, Valerian E.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15219 USA. [Kagan, Valerian E.] Univ Pittsburgh, Dept Radiat Oncol, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15219 USA. [Kagan, Valerian E.] Univ Pittsburgh, Dept Chem, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15219 USA. [Mohammadyani, Dariush] Univ Pittsburgh, Dept Chem, Dept Bioengn, Pittsburgh, PA 15219 USA. [Angeli, Jose Pedro Friedmann; Conrad, Marcus] German Res Ctr Environm Hlth, Inst Dev Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Baranov, Sergei V.; Friedlander, Robert M.] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA 15219 USA. [Klein-Seetharaman, Judith] Univ Warwick, Sch Med, Div Metab & Vasc Hlth, Coventry CV4 7AL, W Midlands, England. [Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15219 USA. [Mallampalli, Rama K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bayir, Huelya] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15219 USA. RP Kagan, VE (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, Ctr Free Rad & Antioxidant Hlth, Bridgeside Point 100 Technol Dr, Pittsburgh, PA 15219 USA. EM kagan@pitt.edu RI Friedlander, Robert/A-2845-2016; Friedmann Angeli, Jose /C-9038-2014; OI Friedlander, Robert/0000-0003-4423-9219; Tyurin, Vladimir/0000-0002-3474-1697; Conrad, Marcus/0000-0003-1140-5612; Friedmann Angeli, Jose Pedro/0000-0001-7706-1379 FU NIH [PO1HL114453, CA165065, ES020693, U19AIO68021, NS076511, NS061817]; NIOSH [OH008282, HFSP-RGP0013/2014]; US Department of Veterans Affairs; Alexander von Humboldt Stiftung; Marie Curie Actions grant MPFP FP7-People-IIF [626470] FX This study was supported by NIH: PO1HL114453, CA165065, ES020693, U19AIO68021, NS076511, NS061817; NIOSH: OH008282, HFSP-RGP0013/2014, a Merit Review award from the US Department of Veterans Affairs and Alexander von Humboldt Stiftung (to AJPF) and Marie Curie Actions grant 626470 MPFP FP7-People-IIF. NR 104 TC 10 Z9 11 U1 1 U2 14 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN 20 PY 2015 VL 22 IS 18 BP 1667 EP 1680 DI 10.1089/ars.2014.6219 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CU9WA UT WOS:000363895900003 PM 25566681 ER PT J AU Awad, MM Hammerman, PS AF Awad, Mark M. Hammerman, Peter S. TI Durable Responses With PD-1 Inhibition in Lung and Kidney Cancer and the Ongoing Search for Predictive Biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MELANOMA; SAFETY; NIVOLUMAB; ANTI-PD-1; BLOCKADE; ANTIBODY C1 [Awad, Mark M.; Hammerman, Peter S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Awad, MM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM peter_hammerman@dfci.harvard.edu NR 21 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 1993 EP U6 DI 10.1200/JCO.2015.61.4172 PG 3 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800002 PM 25918290 ER PT J AU Bellon, JR AF Bellon, Jennifer R. TI Personalized Radiation Oncology for Breast Cancer: The New Frontier SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LOCOREGIONAL RECURRENCE; CONSERVING THERAPY; TUMOR RECURRENCE; TAMOXIFEN; NODE; RADIOTHERAPY; IRRADIATION; SURGERY; WOMEN; RISK C1 [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 24 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 1998 EP U15 DI 10.1200/JCO.2015.61.2069 PG 5 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800004 PM 25964251 ER PT J AU Gettinger, SN Horn, L Gandhi, L Spigel, DR Antonia, SJ Rizvi, NA Powderly, JD Heist, RS Carvajal, RD Jackman, DM Sequist, LV Smith, DC Leming, P Carbone, DP Pinder-Schenck, MC Topalian, SL Hodi, FS Sosman, JA Sznol, M McDermott, DF Pardoll, DM Sankar, V Ahlers, CM Salvati, M Wigginton, JM Hellmann, MD Kollia, GD Gupta, AK Brahmer, JR AF Gettinger, Scott N. Horn, Leora Gandhi, Leena Spigel, David R. Antonia, Scott J. Rizvi, Naiyer A. Powderly, John D. Heist, Rebecca S. Carvajal, Richard D. Jackman, David M. Sequist, Lecia V. Smith, David C. Leming, Philip Carbone, David P. Pinder-Schenck, Mary C. Topalian, Suzanne L. Hodi, F. Stephen Sosman, Jeffrey A. Sznol, Mario McDermott, David F. Pardoll, Drew M. Sankar, Vindira Ahlers, Christoph M. Salvati, Mark Wigginton, Jon M. Hellmann, Matthew D. Kollia, Georgia D. Gupta, Ashok K. Brahmer, Julie R. TI Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLATINUM-BASED CHEMOTHERAPY; RESPONSE CRITERIA; EGFR MUTATIONS; SOLID TUMORS; PHASE-III; B7 FAMILY; MELANOMA; GUIDELINES; DOCETAXEL; BLOCKADE AB Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients and Methods Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Results Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Conclusion Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing. C1 [Gettinger, Scott N.; Sznol, Mario] Yale Canc Ctr, New Haven, CT 06510 USA. [Spigel, David R.; Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [Spigel, David R.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Gandhi, Leena; Jackman, David M.; Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heist, Rebecca S.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Antonia, Scott J.; Pinder-Schenck, Mary C.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Rizvi, Naiyer A.; Carvajal, Richard D.; Hellmann, Matthew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Powderly, John D.] Carolina BioOncol Inst, Huntersville, NC USA. [Smith, David C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Leming, Philip] Christ Hosp Canc Ctr, Cincinnati, OH USA. [Topalian, Suzanne L.; Pardoll, Drew M.; Brahmer, Julie R.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sankar, Vindira; Ahlers, Christoph M.; Salvati, Mark; Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok K.] Bristol Myers Squibb Co, Princeton, NJ USA. RP Gettinger, SN (reprint author), Yale Canc Ctr, 333 Cedar St,FMP127, New Haven, CT 06510 USA. EM scott.gettinger@yale.edu OI Gandhi, Leena/0000-0002-2398-9179 FU Bristol-Myers Squibb; Ono Pharmaceutical FX Supported by Bristol-Myers Squibb, which also funded medical writing assistance, and by Ono Pharmaceutical. NR 42 TC 201 Z9 216 U1 6 U2 26 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 2004 EP U32 DI 10.1200/JCO.2014.58.3708 PG 12 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800006 PM 25897158 ER PT J AU McDermott, DF Drake, CG Sznol, M Choueiri, TK Powderly, JD Smith, DC Brahmer, JR Carvajal, RD Hammers, HJ Puzanov, I Hodi, FS Kluger, HM Topalian, SL Pardoll, DM Wigginton, JM Kollia, GD Gupta, A McDonald, D Sankar, V Sosman, JA Atkins, MB AF McDermott, David F. Drake, Charles G. Sznol, Mario Choueiri, Toni K. Powderly, John D. Smith, David C. Brahmer, Julie R. Carvajal, Richard D. Hammers, Hans J. Puzanov, Igor Hodi, F. Stephen Kluger, Harriet M. Topalian, Suzanne L. Pardoll, Drew M. Wigginton, Jon M. Kollia, Georgia D. Gupta, Ashok McDonald, Dan Sankar, Vindira Sosman, Jeffrey A. Atkins, Michael B. TI Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; SOLID TUMORS; PROGNOSTIC-FACTORS; ADVANCED MELANOMA; INTERFERON-ALPHA; IN-VITRO; CANCER; B7-H1; GUIDELINES; EVEROLIMUS AB Purpose Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. C1 [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Puzanov, Igor; Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drake, Charles G.; Brahmer, Julie R.; Hammers, Hans J.; Topalian, Suzanne L.; Pardoll, Drew M.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sznol, Mario] Yale Univ, Sch Med, New Haven, CT USA. [Sznol, Mario] Yale New Haven Med Ctr, Smilow Canc Ctr, New Haven, CT 06504 USA. [Powderly, John D.] Carolina BioOncol Inst, Huntersville, NC USA. [Smith, David C.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok; McDonald, Dan; Sankar, Vindira] Bristol Myers Squibb Co, Princeton, NJ USA. [Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Mailstop MASCO 428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU Bristol-Myers Squibb; StemScientific; Ono Pharmaceutical; National Cancer Institute of the National Institutes of Health; Specialized Programs of Research Excellence grant [P50CA101942] FX Supported by Bristol-Myers Squibb, which also funded writing assistance provided by StemScientific; by Ono Pharmaceutical; and by the National Cancer Institute of the National Institutes of Health, and a Specialized Programs of Research Excellence grant under award number P50CA101942 (D.F.M., T.K.C., M.B.A., and F.S.H). NR 38 TC 94 Z9 96 U1 3 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 2013 EP U42 DI 10.1200/JCO.2014.58.1041 PG 10 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800007 PM 25800770 ER PT J AU Menon, U Ryan, A Kalsi, J Gentry-Maharaj, A Dawnay, A Habib, M Apostolidou, S Singh, N Benjamin, E Burnell, M Davies, S Sharma, A Gunu, R Godfrey, K Lopes, A Oram, D Herod, J Williamson, K Seif, MW Jenkins, H Mould, T Woolas, R Murdoch, JB Dobbs, S Amso, NN Leeson, S Cruickshank, D Scott, I Fallowfield, L Widschwendter, M Reynolds, K McGuire, A Campbell, S Parmar, M Skates, SJ Jacobs, I AF Menon, Usha Ryan, Andy Kalsi, Jatinderpal Gentry-Maharaj, Aleksandra Dawnay, Anne Habib, Mariam Apostolidou, Sophia Singh, Naveena Benjamin, Elizabeth Burnell, Matthew Davies, Susan Sharma, Aarti Gunu, Richard Godfrey, Keith Lopes, Alberto Oram, David Herod, Jonathan Williamson, Karin Seif, Mourad W. Jenkins, Howard Mould, Tim Woolas, Robert Murdoch, John B. Dobbs, Stephen Amso, Nazar N. Leeson, Simon Cruickshank, Derek Scott, Ian Fallowfield, Lesley Widschwendter, Martin Reynolds, Karina McGuire, Alistair Campbell, Stuart Parmar, Mahesh Skates, Steven J. Jacobs, Ian TI Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTIGEN VELOCITY; PROSTATE; MORTALITY; LUNG; MULTICENTER; RECRUITMENT; IMPACT; ROCA AB Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. Results After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Conclusion Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded. (C) 2015 American Society of Clinical Oncology. C1 [Menon, Usha; Ryan, Andy; Kalsi, Jatinderpal; Gentry-Maharaj, Aleksandra; Habib, Mariam; Apostolidou, Sophia; Benjamin, Elizabeth; Burnell, Matthew; Davies, Susan; Gunu, Richard; Widschwendter, Martin; Parmar, Mahesh; Jacobs, Ian] UCL, London W1T 7DN, England. [Dawnay, Anne; Mould, Tim] Univ Coll London Hosp, London, England. [Singh, Naveena] Barts & London Queen Marys Sch Med & Dent, London, England. [Oram, David; Reynolds, Karina] St Bartholomews Hosp, London, England. [McGuire, Alistair] London Sch Econ, London, England. [Campbell, Stuart] Create Hlth Clin, Waterloo, ON, Canada. [Sharma, Aarti] Univ Wales Hosp, Cardiff, S Glam, Wales. [Amso, Nazar N.] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales. [Godfrey, Keith] Queen Elizabeth Hosp, Gateshead, England. [Lopes, Alberto] Royal Cornwall Hosp, Truro, England. [Herod, Jonathan] Liverpool Womens Hosp, Liverpool, Merseyside, England. [Williamson, Karin] City Hosp Nottingham, Nottingham, England. [Seif, Mourad W.] St Marys Hosp, Manchester, England. [Jenkins, Howard; Jacobs, Ian] Royal Derby Hosp, Derby, England. [Woolas, Robert] Queen Alexandra Hosp, Portsmouth, Hants, England. [Murdoch, John B.] St Michaels Hosp, Bristol, Avon, England. [Dobbs, Stephen] Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland. [Leeson, Simon] Llandudno Hosp, Ysbyty Gwynedd, England. [Cruickshank, Derek] James Cook Univ Hosp, Middlesbrough, Cleveland, England. [Fallowfield, Lesley] Univ Sussex, Falmer, England. [Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jacobs, Ian] UNSW Australia, Sydney, NSW, Australia. RP Menon, U (reprint author), UCL, Inst Womens Hlth, Womens Canc, Maple House,149 Tottenham Court Rd, London W1T 7DN, England. EM u.menon@ucl.ac.uk OI de Barros Lopes, Alberto/0000-0002-8796-3891 FU Medical Research Council, Cancer Research United Kingdom; Department of Health; Eve Appeal; NIHR Senior Investigator Award; Special Trustees of Bart's; London and Special Trustees of UCLH; National Cancer Institute Early Detection Research Network [CA152990] FX Supported by the Medical Research Council, Cancer Research United Kingdom, and the Department of Health, with additional support from the Eve Appeal, and by researchers at the National Institute for Health Research (NIHR) University College London Hospital (UCLH) Biomedical Research Centre. I.J. held an NIHR Senior Investigator Award. The United Kingdom Collaborative Trial of Ovarian Cancer Screening Biobank was funded in part by the Special Trustees of Bart's and the London and Special Trustees of UCLH. S.J.S. is supported by Grant No. CA152990 from the National Cancer Institute Early Detection Research Network. NR 27 TC 38 Z9 38 U1 4 U2 14 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 2062 EP U114 DI 10.1200/JCO.2014.59.4945 PG 14 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800013 PM 25964255 ER PT J AU Yuan, C Wolpin, BM AF Yuan, Chen Wolpin, Brian M. TI Diabetes Associated With Short Survival in Pancreatic Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Yuan, Chen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wolpin, Brian M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yuan, C (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 BP 2121 EP 2121 DI 10.1200/JCO.2015.61.4875 PG 1 WC Oncology SC Oncology GA CR9DG UT WOS:000361652800023 PM 25940723 ER PT J AU Brown, PD Asher, AL Ballman, KV Farace, E Cerhan, JH Anderson, SK Carrero, XW Barker, FG Deming, RL Burri, S Menard, C Chung, C Stieber, VW Pollock, BE Galanis, E Buckner, JC Jaeckle, KA AF Brown, Paul D. Asher, Anthony L. Ballman, Karla V. Farace, Elana Cerhan, Jane H. Anderson, S. Keith Carrero, Xiomara W. Barker, Frederick G. Deming, Richard L. Burri, Stuart Menard, Cynthia Chung, Caroline Stieber, Volker W. Pollock, Bruce E. Galanis, Evanthia Buckner, Jan C. Jaeckle, Kurt A. TI NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 29-JUN 02, 2015 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Carolinas Healthcare Syst Neurosci Inst, Charlotte, NC USA. Mayo Clin, Rochester, MN USA. Penn State Hershey Med Ctr, Hershey, PA USA. Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mercy Canc Ctr, Des Moines, IA USA. Levine Canc Inst Radiat Oncol, Charlotte, NC USA. Princess Maraget Hosp, Toronto, ON, Canada. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Novant Hlth Forsyth Med Ctr, Winston Salem, NC USA. Mayo Clin Florida, Jacksonville, FL USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 SU S MA LBA4 PG 1 WC Oncology SC Oncology GA DO9HQ UT WOS:000378096500005 ER PT J AU Sandler, HM Hu, C Rosenthal, SA Sartor, O Gomella, LG Amin, M Purdy, J Michalski, JM Garzotto, M Pervez, N Balogh, AG Rodrigues, G Souhami, L Reaume, MN Williams, SG Hannan, R Horwitz, EM Raben, A Paulus, R Shipley, WU AF Sandler, Howard M. Hu, Chen Rosenthal, Seth A. Sartor, Oliver Gomella, Leonard G. Amin, Mahul Purdy, James Michalski, Jeff M. Garzotto, Mark Pervez, Nadeem Balogh, Alexander G. Rodrigues, George Souhami, Luis Reaume, M. Neil Williams, Scott G. Hannan, Raquibul Horwitz, Eric M. Raben, Adam Paulus, Rebecca Shipley, William U. TI A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 29-JUN 02, 2015 CL Chicago, IL SP Amer Soc Clin Oncol C1 Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. Sutter Canc Ctr, Sacramento, CA USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Calif Davis, Sacramento, CA USA. Washington Univ, St Louis, MO USA. Portland VA Med Ctr, Portland, OR USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. London Reg Canc Program, Dept Radiat Oncol, London, ON, Canada. McGill Univ, Dept Radiat Oncol, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. Ottawa Hosp, Ctr Canc, Ottawa, ON, Canada. Peter MacCallum Canc Ctr, East Melbourne, Australia. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Helen F Graham Canc Ctr, Newark, DE USA. Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 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 JUN 20 PY 2015 VL 33 IS 18 SU S MA LBA5002 PG 1 WC Oncology SC Oncology GA DO9HQ UT WOS:000378096500011 ER PT J AU Schoffski, P Maki, RG Italiano, A Gelderblom, H Grignani, G De Camargo, VP Bauer, S Rha, SY Chawla, SP Blay, JY Hohenberger, P D'Adamo, DR Wang, B Chmielowski, B Le Cesne, A Demetri, GD Patel, S AF Schoffski, Patrick Maki, Robert G. Italiano, Antoine Gelderblom, Hans Grignani, Giovanni De Camargo, Veridiana Pires Bauer, Sebastian Rha, Sun Young Chawla, Sant P. Blay, Jean-Yves Hohenberger, Peter D'Adamo, David R. Wang, Benjamin Chmielowski, Bartosz Le Cesne, Axel Demetri, George D. Patel, Shreyaskumar TI Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 29-JUN 02, 2015 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Hosp Leuven, Leuven, Belgium. Mt Sinai Med Ctr, New York, NY 10029 USA. CLCC Inst Bergonie, Bordeaux, France. Leiden Univ, Med Ctr, Leiden, Netherlands. Fdn Piemonte Oncol IRCC, Candiolo, Italy. Hosp Sirio Libanes, Sao Paulo, Brazil. West German Canc Ctr, Essen, Germany. Severance Hosp, Seoul, South Korea. Sarcoma Oncol Ctr, Santa Monica, CA USA. Univ Lyon 1, F-69365 Lyon, France. Ctr Leon Berard, F-69373 Lyon, France. Univ Mannheim, Med Ctr, D-68131 Mannheim, Germany. Eisai Inc, Woodcliff Lake, NJ USA. Eisai, Woodcliff Lake, NJ USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Inst Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2015 VL 33 IS 18 SU S MA LBA10502 PG 1 WC Oncology SC Oncology GA DO9HQ UT WOS:000378096500018 ER PT J AU Seiwert, TY Haddad, RI Gupta, S Mehra, R Tahara, M Berger, R Lee, SH Burtness, B Le, DT Heath, K Blum, A Dolled-Filhart, M Emancipator, K Pathiraja, K Cheng, JD Chow, LQ AF Seiwert, Tanguy Y. Haddad, Robert I. Gupta, Shilpa Mehra, Ranee Tahara, Makoto Berger, Raanan Lee, Se-Hoon Burtness, Barbara Le, Dung T. Heath, Karl Blum, Amy Dolled-Filhart, Marisa Emancipator, Kenneth Pathiraja, Kumudu Cheng, Jonathan D. Chow, Laura Q. TI Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 29-JUN 02, 2015 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Seoul Natl Univ Hosp, Seoul 110744, South Korea. Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. JHU, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Merck & Co Inc, Kenilworth, NJ USA. Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 1 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 JUN 20 PY 2015 VL 33 IS 18 SU S MA LBA6008 PG 1 WC Oncology SC Oncology GA DO9HQ UT WOS:000378096500012 ER PT J AU Wolchok, JD Chiarion-Sileni, V Gonzalez, R Rutkowski, P Grob, JJ Cowey, CL Lao, CD Schadendorf, D Ferrucci, PF Smylie, M Dummer, R Hill, AG Haanen, JBAG Maio, M McArthur, GA Yang, A Rollin, L Horak, CE Larkin, JMG Hodi, FS AF Wolchok, Jedd D. Chiarion-Sileni, Vanna Gonzalez, Rene Rutkowski, Piotr Grob, Jean Jacques Cowey, Charles Lance Lao, Christopher D. Schadendorf, Dirk Ferrucci, Pier Francesco Smylie, Michael Dummer, Reinhard Hill, Andrew Graham Haanen, John B. A. G. Maio, Michele McArthur, Grant A. Yang, Arvin Rollin, Linda Horak, Christine E. Larkin, James M. G. Hodi, F. Stephen TI Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients (pts) with advanced melanoma (MEL) (CheckMate 067) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 29-JUN 02, 2015 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. IRCCS, Oncol Inst Veneto, Padua, Italy. Univ Colorado, Ctr Canc, Denver, CO 80202 USA. Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Warsaw, Poland. Hosp Timone, Marseille, France. Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. European Inst Oncol, Milan, Italy. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Spital, Zurich, Switzerland. Tasman Oncol Res, Brisbane, Qld, Australia. Netherlands Canc Inst, Amsterdam, Netherlands. Univ Hosp Siena, Siena, Italy. Peter MacCallum Canc Ctr, East Melbourne, Australia. Bristol Myers Squibb Co, Princeton, NJ USA. Bristol Myers Squibb Co, Wallingford, CT USA. Royal Marsden Hosp, London SW3 6JJ, England. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 JUN 20 PY 2015 VL 33 IS 18 SU S MA LBA1 PG 1 WC Oncology SC Oncology GA DO9HQ UT WOS:000378096500002 ER PT J AU Stary, G Olive, A Radovic-Moreno, AF Gondek, D Alvarez, D Basto, PA Perro, M Vrbanac, VD Tager, AM Shi, JJ Yethon, JA Farokhzad, OC Langer, R Starnbach, MN von Andrian, UH AF Stary, Georg Olive, Andrew Radovic-Moreno, Aleksandar F. Gondek, David Alvarez, David Basto, Pamela A. Perro, Mario Vrbanac, Vladimir D. Tager, Andrew M. Shi, Jinjun Yethon, Jeremy A. Farokhzad, Omid C. Langer, Robert Starnbach, Michael N. von Andrian, Ulrich H. TI A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells SO SCIENCE LA English DT Article ID CD103(+) DENDRITIC CELLS; ADAPTIVE IMMUNE-RESPONSES; MURINE GENITAL MUCOSA; 3 DOSAGE LEVELS; RESIDENT MEMORY; FIELD TRIAL; MEDIATED PROTECTION; ORAL TOLERANCE; SAUDI ARABIA; INFECTION AB Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-g-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T-RM cells). Optimal Ct clearance required both TRM seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties. C1 [Stary, Georg; Olive, Andrew; Gondek, David; Alvarez, David; Perro, Mario; Starnbach, Michael N.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Radovic-Moreno, Aleksandar F.; Basto, Pamela A.; Langer, Robert] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Radovic-Moreno, Aleksandar F.; Basto, Pamela A.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Vrbanac, Vladimir D.; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Yethon, Jeremy A.] Sanofi Pasteur, Cambridge, MA 02139 USA. [Shi, Jinjun; Farokhzad, Omid C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA. [Farokhzad, Omid C.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [von Andrian, Ulrich H.] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. EM georg_stary@hms.harvard.edu; uva@hms.harvard.edu OI Olive, Andrew/0000-0003-3441-3113 FU NIH [AI078897, AI069259, AI095261, AI111595, U54-CA119349, U54-CA151884, R37-EB000244, 1 R01-EB015419-01, R00 CA160350, T32 HL066987, P30-AI060354, R01 AI062827, R01 AI39558]; Harvard Innovation Award from Sanofi Pasteur; Ragon Institute of MGH, MIT and Harvard; David Koch Prostate Cancer Foundation; MGH Humanized Mouse Program by the Harvard University CFAR; Epidemiology and Prevention Interdisciplinary Center for Sexually Transmitted Diseases (NIH) [U19 AI113187]; Max Kade foundation; MIT Portugal Program; National Science Foundation (NSF-GRFP) FX We thank E. Nigro for secretarial assistance, L. B. Jones for technical support, and the members of the von Andrian laboratory for discussion. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. Supported by NIH grants AI078897, AI069259, AI095261, and AI111595, a Harvard Innovation Award from Sanofi Pasteur, and the Ragon Institute of MGH, MIT and Harvard (U.H.v.A.); NIH grants U54-CA119349, U54-CA151884, and R37-EB000244 and the David Koch Prostate Cancer Foundation (R.L. and O.C.F.); NIH grant 1 R01-EB015419-01 (O.C.F.); NIH grant R00 CA160350 (J.S.); NIH grant T32 HL066987 (D.A.); NIH grant P30-AI060354 and the MGH Humanized Mouse Program by the Harvard University CFAR (A.M.T.); and NIH grant R01 AI062827, NIH grant R01 AI39558, and the Epidemiology and Prevention Interdisciplinary Center for Sexually Transmitted Diseases (NIH grant U19 AI113187) (M.N.S.). G.S. is a Max Kade foundation postdoctoral research exchange grant recipient. A.F.R.-M. acknowledges support from the MIT Portugal Program and the National Science Foundation (NSF-GRFP). G.S., A.R.F.-M., P.A.B., M.N.S., R.L., O.C.F., and U.H.v.A. are inventors on a patent application entitled "Nanoparticle-Based Compositions" (U.S. Application number PCT2014/029000; International Publication No. WO2014/153087) filed by Harvard University together with MIT and Brigham and Women's Hospital (BWH) that relates to the use of cSAP for mucosal vaccination. A.R.F.-M., R.L., and O.C.F. are inventors on a patent application entitled "pH Sensitive Biodegradable Polymeric Particles for Drug Delivery" (U.S. Application no. PCT2011/0065807) filed by BWH together with MIT that relates to the engineering of charge-switching particles. O.C.F., R.L., and U.H.v.A. disclose financial interests in BIND Therapeutics, Selecta Biosciences, and Blend Therapeutics, three biotechnology companies developing nanocarrier technologies for medical applications. BIND, Selecta, and Blend did not support the research in this study. Selecta and Blend have obtained licenses to a portion of the intellectual property described in this study. O.C.F., R.L., and U.H.v.A. are scientific founders and members of the Scientific Advisory Board and O.C.F. and R.L. are directors of Selecta Biosciences. O.C.F., R.L. and U.H.v.A. are members of the Scientific Advisory Board and O.C.F. and R.L. are scientific founders and directors of Blend Therapeutics. The following reagents used in the paper are subject to MTA: NR-1 transgenic mice, cSAP, cSP, and SAP. All reasonable requests for collaboration involving materials used in the research will be fulfilled, provided that a written agreement is executed in advance between BWH, MIT, or Harvard Medical School and the requester (and his or her affiliated institution). Such inquiries or requests for additional data should be directed to the corresponding author. NR 64 TC 34 Z9 35 U1 5 U2 17 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 JUN 19 PY 2015 VL 348 IS 6241 AR aaa8205 DI 10.1126/science.aaa8205 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK7XK UT WOS:000356449500042 PM 26089520 ER PT J AU Ciaranello, AL Doherty, K Penazzato, M Lindsey, JC Harrison, L Kelly, K Walensky, RP Essajee, S Losina, E Muhe, L Wools-Kaloustian, K Ayaya, S Weinstein, MC Palumbo, P Freedberg, KA AF Ciaranello, Andrea L. Doherty, Kathleen Penazzato, Martina Lindsey, Jane C. Harrison, Linda Kelly, Kathleen Walensky, Rochelle P. Essajee, Shaffiq Losina, Elena Muhe, Lulu Wools-Kaloustian, Kara Ayaya, Samuel Weinstein, Milton C. Palumbo, Paul Freedberg, Kenneth A. TI Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African children less than 3 years of age SO AIDS LA English DT Article DE Africa; cost-effectiveness; first-line antiretroviral therapy; IMPAACT; P1060 trial; pediatric HIV AB Background:The International Maternal, Pediatric, and Adolescent Clinical Trials P1060 trial demonstrated superior outcomes for HIV-infected children less than 3 years old initiating antiretroviral therapy (ART) with lopinavir/ritonavir compared to nevirapine, but lopinavir/ritonavir is four-fold costlier.Design/methods:We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model, with published and P1060 data, to project outcomes under three strategies: no ART; first-line nevirapine (with second-line lopinavir/ritonavir); and first-line lopinavir/ritonavir (second-line nevirapine). The base-case examined South African children initiating ART at age 12 months; sensitivity analyses varied all key model parameters. Outcomes included life expectancy, lifetime costs, and incremental cost-effectiveness ratios [ICERs; dollars/year of life saved ($/YLS)]. We considered interventions with ICERs less than 1x per-capita gross domestic product (South Africa: $7500)/YLS as very cost-effective,' interventions with ICERs below 3x gross domestic product/YLS as cost-effective,' and interventions leading to longer life expectancy and lower lifetime costs as cost-saving'.Results:Projected life expectancy was 2.8 years with no ART. Both ART regimens markedly improved life expectancy and were very cost-effective, compared to no ART. First-line lopinavir/ritonavir led to longer life expectancy (28.8 years) and lower lifetime costs ($41350/person, from lower second-line costs) than first-line nevirapine (27.6 years, $44030). First-line lopinavir/ritonavir remained cost-saving or very cost-effective compared to first-line nevirapine unless: liquid lopinavir/ritonavir led to two-fold higher virologic failure rates or 15-fold greater costs than in the base-case, or second-line ART following first-line lopinavir/ritonavir was very ineffective.Conclusions:On the basis of P1060 data, first-line lopinavir/ritonavir leads to longer life expectancy and is cost-saving or very cost-effective compared to first-line nevirapine. This supports WHO guidelines, but increasing access to pediatric ART is critical regardless of the regimen used. C1 [Ciaranello, Andrea L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Doherty, Kathleen; Kelly, Kathleen; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Ciaranello, Andrea L.; Doherty, Kathleen; Kelly, Kathleen; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Penazzato, Martina] MRC, Clin Trials Unit, London, England. [Penazzato, Martina; Muhe, Lulu] WHO, CH-1211 Geneva, Switzerland. [Lindsey, Jane C.; Harrison, Linda] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Essajee, Shaffiq] Clinton Hlth Access Initiat, New York, NY USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wools-Kaloustian, Kara] Indiana Univ Sch Med, Dept Med, Div Infect Dis, Indianapolis, IN 46202 USA. [Ayaya, Samuel] Moi Univ, Dept Child Hlth & Pediat, Eldoret, Kenya. [Palumbo, Paul] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. [Palumbo, Paul] Dartmouth Hitchcock Med Ctr, Dept Pediat 16, Lebanon, NH 03766 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,Room 936, Boston, MA 02114 USA. EM aciaranello@partners.org FU WHO; National Institutes of Health through International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT); International Database to Evaluate AIDS (IeDEA); National Institute of Allergy and Infectious Diseases [K01 AI078754, R01 HD079214, K24 AI062476, R01 AI058736, R01 AI093269, U01 AI069911, U01AI09919]; Harvard Center for AIDS Research; March of Dimes Foundation; Massachusetts General Hospital Executive Committee on Research; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) (IMPAACT LOC) [UM1AI068632]; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) (IMPAACT SDMC) [UM1AI068616]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH); National Institute of Allergy and Infectious Diseases (NIAID); NICHD [N01-DK-9-001/HHSN 267200800001C]; National Cancer Institute FX Supported by the WHO; the National Institutes of Health through the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT), International Database to Evaluate AIDS (IeDEA), and National Institute of Allergy and Infectious Diseases (K01 AI078754, R01 HD079214, K24 AI062476, R01 AI058736, R01 AI093269, U01 AI069911, U01AI09919, and the Harvard Center for AIDS Research); the March of Dimes Foundation; and the Massachusetts General Hospital Executive Committee on Research. The funders had no role in study design, data analysis, interpretation of results, or decision to publish.; Overall support for IMPAACT was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN 267200800001C).; Overall support for the IeDEA network is provided by the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Cancer Institute. NR 0 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 19 PY 2015 VL 29 IS 10 BP 1247 EP 1259 DI 10.1097/QAD.0000000000000672 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4KX UT WOS:000368483000002 PM 25870982 ER PT J AU Shah, S Bellows, BA Adedipe, AA Totten, JE Backlund, BH Sajed, D AF Shah, Sachita Bellows, Blaise A. Adedipe, Adeyinka A. Totten, Jodie E. Backlund, Brandon H. Sajed, Dana TI Perceived barriers in the use of ultrasound in developing countries SO CRITICAL ULTRASOUND JOURNAL LA English DT Article DE Ultrasound; Global health; Public health ID ULTRASONOGRAPHY AB Background: Access to ultrasound has increased significantly in resource-limited settings, including the developing world; however, there remains a lack of sonography education and ultrasound-trained physician support in developing countries. To further investigate this potential knowledge gap, our primary objective was to assess perceived barriers to ultrasound use in resource-limited settings by surveying care providers who practice in low-and middle-income settings. Methods: A 25-question online survey was made available to health care providers who work with an ultrasound machine in low-and middle-income countries (LMICs), including doctors, nurses, technicians, and clinical officers. This was a convenience sample obtained from list-serves of ultrasound and radiologic societies. The survey was analyzed, and descriptive results were obtained. Results: One hundred and thirty-eight respondents representing 44 LMICs including countries from the continents of Africa, South America, and Asia completed the survey, with a response rate of 9.6 %. Ninety-one percent of the respondents were doctors, and 9 % were nurses or other providers. Applications for ultrasound were diverse, including obstetrics (75 %), DVT evaluation (51 %), abscess evaluation (54 %), cardiac evaluation (64 %), inferior vena cava (IVC) assessment (49 %), Focused Assessment Sonography for Trauma (FAST) exam (64 %), biliary tree assessment (54 %), and other applications. The respondents identified the following barriers to use of ultrasound: lack of training (60 %), lack of equipment (45 %), ultrasound machine malfunction (37 %), and lack of ultrasound maintenance capability (47 %). Seventy-four percent of the respondents wished to have further training in ultrasound, and 82 % were open to receiving distance learning or telesonography training. Subjects used communication tools including Skype, Dropbox, emailed photos, and picture archiving and communication system (PACS) as ways to communicate and receive feedback on ultrasound images. Conclusions: Health care providers in the developing world identify lack of training as a primary barrier to regular use of ultrasound in their practice. While equipment requirements including maintenance and cost of machines are also important factors, future research is warranted on best practices for training methods, including telesonography and distance learning to enhance ultrasound use in low-resource settings. C1 [Shah, Sachita; Bellows, Blaise A.; Adedipe, Adeyinka A.; Totten, Jodie E.; Backlund, Brandon H.] Univ Washington, Div Emergency Med, Seattle, WA 98104 USA. [Sajed, Dana] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Totten, JE (reprint author), Univ Washington, Div Emergency Med, Box 359702,1CT89,325 9th Ave, Seattle, WA 98104 USA. EM jet25@uw.edu NR 8 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 2036-3176 EI 2036-7902 J9 CRIT ULTRASOUND J JI Crit. Ultrasound J. PD JUN 19 PY 2015 VL 7 AR 11 DI 10.1186/s13089-015-0028-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CS7FU UT WOS:000362250300001 ER PT J AU Andrews, JR Ryan, ET AF Andrews, Jason R. Ryan, Edward T. TI Diagnostics for invasive Salmonella infections: Current challenges and future directions SO VACCINE LA English DT Review DE Salmonella; Invasive; Enteric fever; Typhoid; Paratyphoid; Non-typhoidal; Diagnostics ID ENTERICA SEROVAR TYPHI; MEDIATED ISOTHERMAL AMPLIFICATION; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; NON-TYPHOIDAL SALMONELLA; TARGET PRODUCT PROFILES; CLINICAL-FEATURES; WIDAL TEST; FEBRILE ILLNESS; TROPICAL DISEASES AB Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results infrequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics. (C) 2015 Published by Elsevier Ltd. C1 [Andrews, Jason R.] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Ryan, Edward T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Andrews, JR (reprint author), Stanford Univ, Sch Med, Div Infect Dis & Geog Med, 300 Pasteur Dr,Lane Bldg,L141, Stanford, CA 94305 USA. EM jandr@stanford.edu; etryan@mgh.harvard.edu FU Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene; U.S. National Institutes of Health [AI100023] FX This work was supported in part by awards from the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene (JRA), and the U.S. National Institutes of Health (AI100023; ETR). The funders had no role in decision to publish or preparation of the manuscript. NR 108 TC 11 Z9 12 U1 7 U2 34 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JUN 19 PY 2015 VL 33 SU 3 BP C8 EP C15 DI 10.1016/j.vaccine.2015.02.030 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CM1KI UT WOS:000357439400003 PM 25937611 ER PT J AU Zhang, W Cho, SY Xiang, G Min, KJ Yu, Q Jin, JO AF Zhang, Wei Cho, Si-Young Xiang, Gao Min, Kyung-Jin Yu, Qing Jin, Jun-O TI Ginseng Berry Extract Promotes Maturation of Mouse Dendritic Cells SO PLOS ONE LA English DT Article ID IMMUNE-RESPONSES; DIABETIC MICE; T-CELLS; IN-VIVO; POLYSACCHARIDES; LIPOPOLYSACCHARIDES; PATHWAYS; ANTIGEN; VACCINE; RG1 AB Ginseng extract has been shown to possess certain anti-virus, anti-tumor and immune-activating effects. However, the immunostimulatory effect of ginseng berry extract (GB) has been less well characterized. In this study, we investigated the effect of GB on the activation of mouse dendritic cells (DCs) in vitro and in vivo. GB treatment induced up-regulation of co-stimulatory molecules in bone marrow-derived DCs (BMDCs). Interestingly, GB induced a higher degree of co-stimulatory molecule up-regulation than ginseng root extract (GR) at the same concentrations. Moreover, in vivo administration of GB promoted up-regulation of CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-alpha in spleen DCs. GB also promoted the generation of Th1 and Tc1 cells. Furthermore, Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling pathway were essential for DC activation induced by GB. In addition, GB strongly prompted the proliferation of ovalbumin (OVA)-specific CD4 and CD8 T cells. Finally, GB induced DC activation in tumor-bearing mice and the combination of OVA and GB treatment inhibited B16-OVA tumor cell growth in C57BL/6 mice. These results demonstrate that GB is a novel tumor therapeutic vaccine adjuvant by promoting DC and T cell activation. C1 [Zhang, Wei; Jin, Jun-O] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China. [Cho, Si-Young] AmorePacific Corp, R&D Unit, Yongin, Gyeonggi Do, South Korea. [Xiang, Gao] Nanjing Univ, Model Anim Res Ctr, Nanjing 210008, Jiangsu, Peoples R China. [Min, Kyung-Jin] Inha Univ, Dept Biol Sci, Inchon, South Korea. [Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China. EM Junojin1@gmail.com FU Research fund for International Young Scientists from National Natural Science Foundation of China [81450110090]; AmorePacific Corporation FX This study was supported by Research fund for International Young Scientists from National Natural Science Foundation of China (81450110090). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AmorePacific Corporation provided support in the form of salary for author Si-Young Cho and research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the 'author contributions' section. NR 36 TC 5 Z9 5 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 19 PY 2015 VL 10 IS 6 AR e0130926 DI 10.1371/journal.pone.0130926 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL3FE UT WOS:000356835000160 PM 26090808 ER PT J AU Winter, GE Buckley, DL Paulk, J Roberts, JM Souza, A Dhe-Paganon, S Bradner, JE AF Winter, Georg E. Buckley, Dennis L. Paulk, Joshiawa Roberts, Justin M. Souza, Amanda Dhe-Paganon, Sirano Bradner, James E. TI Phthalimide conjugation as a strategy for in vivo target protein degradation SO SCIENCE LA English DT Article ID BET BROMODOMAINS; SELECTIVE-INHIBITION; THALIDOMIDE; MOLECULES; COMPLEX; UBIQUITINATION; ACTIVATION; LEUKEMIA; CANCER; CELLS AB The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem. In part, this is because many small-molecule antagonists disrupt the activity of only one domain in the target protein. We devised a chemical strategy that promotes ligand-dependent target protein degradation using as an example the transcriptional coactivator BRD4, a protein critical for cancer cell growth and survival. We appended a competitive antagonist of BET bromodomains to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The resultant compound, dBET1, induced highly selective cereblon-dependent BET protein degradation in vitro and in vivo and delayed leukemia progression in mice. A second series of probes resulted in selective degradation of the cytosolic protein FKBP12. This chemical strategy for controlling target protein stability may have implications for therapeutically targeting previously intractable proteins. C1 [Winter, Georg E.; Buckley, Dennis L.; Paulk, Joshiawa; Roberts, Justin M.; Souza, Amanda; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu FU EMBO long-term fellowship FX We thank W. Kaelin, S. Orkin, and R. Mazitschek for engaging discussions and W. Kaelin for cellular reagents; S.-H. Seo and S. Deangelo for assistance in the purification of BRD4; C. Ott for help with in vivo model studies; and N. Thoma for CRBN expression reagents. This research was supported by generous philanthropic gifts from Marc Cohen and Alain Cohen, the William Lawrence and Blanche Hughes Foundation, and the NIH (R01-CA176745 and P01-CA066996 to J.E.B.). G.E.W. is supported by an EMBO long-term fellowship. D.L.B. is a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2196-14). Atomic coordinates and structure factors have been deposited in the Protein Data Bank (accession code 4ZC9). Quantitative proteomics studies were performed by R. Kunz of the Thermo Fisher Scientific Center for Multiplexed Proteomics at Harvard Medical School. Dana-Farber Cancer Institute has filed patent applications (62/096,318; 62/128,457; 62/149,170) that include the dBET and dFKBP compositions described in this manuscript. J.E.B. is a Founder of Tensha Therapeutics, a biotechnology company that develops druglike derivatives of JQ1 as investigational cancer therapies. NR 29 TC 69 Z9 70 U1 30 U2 98 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 JUN 19 PY 2015 VL 348 IS 6241 BP 1376 EP 1381 DI 10.1126/science.aab1433 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK7XK UT WOS:000356449500055 PM 25999370 ER PT J AU Tacke, R Hilgendorf, I Garner, H Waterborg, C Park, K Nowyhed, H Hanna, RN Wu, RP Swirski, FK Geissmann, F Hedrick, CC AF Tacke, Robert Hilgendorf, Ingo Garner, Hannah Waterborg, Claire Park, Kiwon Nowyhed, Heba Hanna, Richard N. Wu, Runpei Swirski, Filip K. Geissmann, Frederic Hedrick, Catherine C. TI The transcription factor NR4A1 is essential for the development of a novel macrophage subset in the thymus SO SCIENTIFIC REPORTS LA English DT Article ID TISSUE MACROPHAGES; MONOCYTES; MOUSE; CELLS; HOMEOSTASIS; APOPTOSIS AB Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset. C1 [Tacke, Robert; Waterborg, Claire; Park, Kiwon; Nowyhed, Heba; Hanna, Richard N.; Wu, Runpei; Hedrick, Catherine C.] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA. [Garner, Hannah; Geissmann, Frederic] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London, England. [Hilgendorf, Ingo; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Hilgendorf, Ingo; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA USA. RP Hedrick, CC (reprint author), La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA. EM hedrick@lji.org RI Waterborg, Claire/P-9245-2015 FU NIH [R01 HL118765, P01 HL055798]; American Heart Association [13POST16990029] FX We would like to thank D. Yoakum, A. Blatchley, and the LJI microscopy and flow cytometry cores for excellent technical assistance. This work was supported by funding from NIH R01 HL118765 (to C.C.H.), NIH P01 HL055798 (to C.C.H.) and the American Heart Association 13POST16990029 (to R.T.). NR 25 TC 6 Z9 6 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUN 19 PY 2015 VL 5 AR 10055 DI 10.1038/srep10055 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK9AU UT WOS:000356532900001 PM 26091486 ER PT J AU Ray, JP Hacohen, N AF Ray, John P. Hacohen, Nir TI Impact of autoimmune risk alleles on the immune system SO GENOME MEDICINE LA English DT Editorial Material ID DISEASE AB Genetic analyses of autoimmune diseases have revealed hundreds of disease-associated DNA variants, but the identity and function of the causal variants are understudied and warrant deeper mechanistic studies. Here, we highlight methods for deciphering how alleles that are associated with autoimmune disease alter the human immune system, and suggest strategies for future autoimmune genetic research. C1 [Ray, John P.; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Ray, JP (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM johnray@broadinstitute.org; nhacohen@mgh.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD JUN 19 PY 2015 VL 7 AR 57 DI 10.1186/s13073-015-0182-y PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CK8HN UT WOS:000356479200001 PM 26089985 ER PT J AU Vardy, E Sassano, MF Rennekamp, AJ Kroeze, WK Mosier, PD Westkaemper, RB Stevens, CW Katritch, V Stevens, RC Peterson, RT Roth, BL AF Vardy, Eyal Sassano, Maria F. Rennekamp, Andrew J. Kroeze, Wesley K. Mosier, Philip D. Westkaemper, Richard B. Stevens, Craig W. Katritch, Vsevolod Stevens, Raymond C. Peterson, Randall T. Roth, Bryan L. TI Single Amino Acid Variation Underlies Species-Specific Sensitivity to Amphibian Skin-Derived Opioid-like Peptides SO CHEMISTRY & BIOLOGY LA English DT Article ID ZEBRAFISH DANIO-RERIO; PROTEIN-COUPLED RECEPTORS; NICOTINIC ACETYLCHOLINE-RECEPTOR; NEWT TARICHA-GRANULOSA; PHARMACOLOGICAL CHARACTERIZATION; BINDING-SITES; HETEROLOGOUS EXPRESSION; EXTRACELLULAR LOOPS; ANALGESIC POTENCY; ALPHA-NEUROTOXIN AB It has been suggested that the evolution of vertebrate opioid receptors (ORs) follow a vector of increased functionality. Here, we test this idea by comparing human and frog ORs. Interestingly, some of the most potent opioid peptides known have been isolated from amphibian skin secretions. Here we show that such peptides (dermorphin and deltorphin) are highly potent in the human receptors and inactive in frog ORs. The molecular basis for the insensitivity of the frog ORs to these peptides was studied using chimeras and molecular modeling. The insensitivity of the delta OR (DOR) to deltorphin was due to variation of a single amino acid, Trp7.35, which is a leucine in mammalian DORs. Notably, Trp7.35 is completely conserved in all known DOR sequences from lamprey, fish, and am