FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tree-McGrath, CAF Mutchler, J Perez, GK Canenguez, K Park, ER AF Tree-McGrath, Cheyenne A. Fox Mutchler, Jan Perez, Giselle K. Canenguez, Katia Park, Elyse R. TI JOB SATISFACTION AS A RESILIENCY FACTORAMONG MEDICAL INTERPRETERS: A QUALITATIVE STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tree-McGrath, Cheyenne A. Fox; Mutchler, Jan; Canenguez, Katia] Univ Massachusetts Boston, Bedford, MA 01730 USA. [Tree-McGrath, Cheyenne A. Fox; Perez, Giselle K.; Canenguez, Katia; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cheyenne.foxtreem001@umb.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S5 EP S5 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300017 ER PT J AU Trevino, KM Naik, A Walder, A Moye, J AF Trevino, Kelly M. Naik, Aanand Walder, Annette Moye, Jennifer TI THE BENEFITS OF RELIGIOUS/SPIRITUAL CHANGE DUE TO CANCER: LONGITUDINAL ANALYSES IN CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Trevino, Kelly M.] Rowan Univ, Glassboro, NJ 08028 USA. [Naik, Aanand; Walder, Annette] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Moye, Jennifer] VA Boston Healthcare Syst, Brockton, MA USA. EM trevino.kelly@gmail.com 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 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S185 EP S185 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300705 ER PT J AU Tucker-Seeley, RD Mitchell, J Shires, D Modlin, C AF Tucker-Seeley, Reginald D. Mitchell, Jamie Shires, Deirdre Modlin, Charles TI FINANCIAL HARDSHIP AND CONFIDENCE IN THE ABILITY TO TAKE CARE OF YOUR HEALTH AMONG AFRICAN AMERICAN MEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tucker-Seeley, Reginald D.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Tucker-Seeley, Reginald D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mitchell, Jamie; Shires, Deirdre] Wayne State, Detroit, MI USA. [Modlin, Charles] Cleveland Clin, Cleveland, OH 44106 USA. EM reginald_tucker-seeley@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S125 EP S125 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300480 ER PT J AU Sahin, I Moschetta, M Mishima, Y Glavey, SV Tsang, B Azab, F Manier, S Zhang, Y Maiso, P Sacco, A Azab, AK Roccaro, AM Ghobrial, IM AF Sahin, I. Moschetta, M. Mishima, Y. Glavey, S. V. Tsang, B. Azab, F. Manier, S. Zhang, Y. Maiso, P. Sacco, A. Azab, A. K. Roccaro, A. M. Ghobrial, I. M. TI Distinct roles of class I PI3K isoforms in multiple myeloma cell survival and dissemination SO BLOOD CANCER JOURNAL LA English DT Letter ID TRANSFORMATION; PATHWAY; DISEASE; CANCER; TARGET; LINE C1 [Sahin, I.; Moschetta, M.; Mishima, Y.; Glavey, S. V.; Tsang, B.; Azab, F.; Manier, S.; Zhang, Y.; Maiso, P.; Sacco, A.; Azab, A. K.; Roccaro, A. M.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Azab, F.; Azab, A. K.] Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, St Louis, MO USA. RP Sahin, I (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [R01 CA154648] NR 15 TC 5 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD APR PY 2014 VL 4 AR e204 DI 10.1038/bcj.2014.24 PG 5 WC Oncology SC Oncology GA AG6GI UT WOS:000335516700006 PM 24769645 ER PT J AU Siegel, DS Richardson, P Dimopoulos, M Moreau, P Mitsiades, C Weber, D Houp, J Gause, C Vuocolo, S Eid, J Graef, T Anderson, KC AF Siegel, D. S. Richardson, P. Dimopoulos, M. Moreau, P. Mitsiades, C. Weber, D. Houp, J. Gause, C. Vuocolo, S. Eid, J. Graef, T. Anderson, K. C. TI Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (vol 4, e182, 2014) SO BLOOD CANCER JOURNAL LA English DT Correction C1 [Siegel, D. S.; Mitsiades, C.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Myeloma Div, Hackensack, NJ 07601 USA. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dimopoulos, M.] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Moreau, P.] Univ Hosp, Nantes, France. [Weber, D.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Houp, J.; Gause, C.; Vuocolo, S.; Eid, J.] Merck & Co Inc, Whitehouse Stn, NJ USA. [Graef, T.] Pharmacyclics Inc, Sunnyvale, CA USA. [Anderson, K. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Kraft Family Blood Ctr, Boston, MA 02115 USA. RP Siegel, DS (reprint author), Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Myeloma Div, Hackensack, NJ 07601 USA. EM DSiegel@HackensackUMC.org RI richard, chrystelle/K-8595-2015 FU NCI NIH HHS [P01 CA155258, P50 CA100707] NR 1 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD APR PY 2014 VL 4 AR e202 DI 10.1038/bcj.2014.23 PG 1 WC Oncology SC Oncology GA AG6GI UT WOS:000335516700004 PM 24727998 ER PT J AU Lowery, JT Horick, N Kinney, AY Finkelstein, DM Garrett, K Haile, RW Lindor, NM Newcomb, PA Sandler, RS Burke, C Hill, DA Ahnen, DJ AF Lowery, Jan T. Horick, Nora Kinney, Anita Y. Finkelstein, Dianne M. Garrett, Kathleen Haile, Robert W. Lindor, Noralane M. Newcomb, Polly A. Sandler, Robert S. Burke, Carol Hill, Deirdre A. Ahnen, Dennis J. TI A Randomized Trial to Increase Colonoscopy Screening in Members of High-Risk Families in the Colorectal Cancer Family Registry and Cancer Genetics Network SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MISMATCH-REPAIR GENES; COLON-CANCER; 1ST-DEGREE RELATIVES; MUTATION CARRIERS; LYNCH SYNDROME; SURVEILLANCE; BEHAVIOR; HISTORY; INTERVENTIONS; MODEL AB Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial. Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months. Participants were randomized to receive a tailored telephone intervention grounded in behavioral theory or a mailed packet with general information about screening. Colonoscopy status was assessed through follow-up surveys and endoscopy reports. Cox proportional hazards models were used to assess intervention effect. Results: Of the 632 participants (ages 25-80), 60% were female, the majority were White, non-Hispanic, educated, and had health insurance. Colonoscopy adherence increased 11 percentage points in the tailored telephone intervention group, compared with no significant change in the mailed group. The telephone intervention was associated with a 32% increase in screening adherence compared with the mailed intervention (HR, 1.32; P = 0.01). Conclusions: A tailored telephone intervention can effectively increase colonoscopy adherence in high-risk persons. This intervention has the potential for broad dissemination to healthcare organizations or other high-risk populations. Impact: Increasing adherence to colonoscopy among persons with increased colorectal cancer risk could effectively reduce incidence and mortality from this disease. (C) 2014 AACR. C1 [Lowery, Jan T.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Lowery, Jan T.; Garrett, Kathleen] Univ Colorado, Ctr Canc, Div Canc Prevent & Control, Aurora, CO 80045 USA. [Ahnen, Dennis J.] Dept Vet Affairs Eastern Colorado Hlth Care Syst, Dept Med, Denver, CO USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO USA. [Horick, Nora; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Finkelstein, Dianne M.] Harvard Univ, Boston, MA 02115 USA. [Kinney, Anita Y.] Univ New Mexico, Div Epidemiol Biostat & Prevent, Albuquerque, NM 87131 USA. [Kinney, Anita Y.; Hill, Deirdre A.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Kinney, Anita Y.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Haile, Robert W.] Stanford Univ, Stanford, CA 94305 USA. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Sandler, Robert S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Burke, Carol] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. RP Lowery, JT (reprint author), Univ Colorado, Sch Publ Hlth, 13001 E 17th Pl,MS F-538, Aurora, CO 80045 USA. EM jan.lowery@ucdenver.edu FU NCI [5R01CA68099, HHSN2612007440000C]; University of Colorado Cancer Center Core [P30CA046934]; NIH under RFA [CA-95-011]; Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; cooperative agreements [U01CA078284, U24CA078164, U24CA078174] FX This study was funded by the NCI, grant #5R01CA68099 (to D.J. Ahnen), and supported by the University of Colorado Cancer Center Core Grant #P30CA046934 (to D. Theodorescu). The C-CFR was supported by the NCI, NIH under RFA #CA-95-011 and through cooperative agreements with members of the C-CFR and Principal Investigators: Familial Colorectal Neoplasia Collaborative Group (U01 CA074799; to R. Haile); Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800; to L. Lindor); Seattle Colorectal Cancer Family Registry (U01 CA074794; to P. Newcomb). The Cancer Genetics Network was supported through cooperative agreements (U01CA078284, to D. Finkelstein; U24CA078164, D Bowen; U24CA078174, to G. Mineau) and a contract (HHSN2612007440000C; to D Finkelstein) from the NCI.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 48 TC 15 Z9 15 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2014 VL 23 IS 4 BP 601 EP 610 DI 10.1158/1055-9965.EPI-13-1085 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZR UT WOS:000335145000005 PM 24501379 ER PT J AU Chen, BB Coon, TA Glasser, JR Zou, CB Ellis, B Das, T McKelvey, AC Rajbhandari, S Lear, T Kamga, C Shiva, S Li, CJ Pilewski, JM Callio, J Chu, CT Ray, A Ray, P Tyurina, YY Kagan, VE Mallampalli, RK AF Chen, Bill B. Coon, Tiffany A. Glasser, Jennifer R. Zou, Chunbin Ellis, Bryon Das, Tuhin McKelvey, Alison C. Rajbhandari, Shristi Lear, Travis Kamga, Christelle Shiva, Sruti Li, Chenjian Pilewski, Joseph M. Callio, Jason Chu, Charleen T. Ray, Anuradha Ray, Prabir Tyurina, Yulia Y. Kagan, Valerian E. Mallampalli, Rama K. TI E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia SO CELL REPORTS LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; NECROSIS-FACTOR-ALPHA; SCF UBIQUITIN LIGASE; PARKINSONS-DISEASE; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; OXYGEN DELIVERY; ORGAN FAILURE; SEPTIC SHOCK; CYTOCHROME-C AB Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial- specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S. aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S. aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S. aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. C1 [Chen, Bill B.; Coon, Tiffany A.; Glasser, Jennifer R.; Zou, Chunbin; Ellis, Bryon; Das, Tuhin; McKelvey, Alison C.; Rajbhandari, Shristi; Lear, Travis; Pilewski, Joseph M.; Ray, Anuradha; Ray, Prabir; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Kamga, Christelle; Shiva, Sruti] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. [Callio, Jason; Chu, Charleen T.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Tyurina, Yulia Y.; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA. [Li, Chenjian] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, 930 Scaife Hall, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu OI Chu, Charleen/0000-0002-5052-8271; Lear, Travis/0000-0001-9156-0844 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health R01 grant [HL096376, HL097376, HL098174, HL081784, P01HL114453, HL116472, NS065789, 12SDG12040330] FX This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376, HL098174, HL081784, and P01HL114453 (to R.K.M.); HL116472 (to B.B.C.); NS065789 (to C.T.C.); and 12SDG12040330 (to C.Z.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 65 TC 12 Z9 13 U1 0 U2 3 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 APR PY 2014 VL 7 IS 2 BP 476 EP 487 PG 12 WC Cell Biology SC Cell Biology GA AG5EO UT WOS:000335442300017 PM 24703837 ER PT J AU Kumar, V Alt, FW Oksenych, V AF Kumar, Vipul Alt, Frederick W. Oksenych, Valentyn TI Functional overlaps between XLF and the ATM-dependent DNA double strand break response SO DNA REPAIR LA English DT Article DE Cernunnos; ATM; DNA-PKcs; NHEJ; V(D)J recombination; 53BP1 ID CLASS-SWITCH RECOMBINATION; SIGNAL JOINT FORMATION; INCREASED GENOMIC INSTABILITY; LEAKY SCID PHENOTYPE; V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; LIGASE-IV; PROTEIN-KINASE; HISTONE H2AX; DAMAGE-RESPONSE AB Developing B and T lymphocytes generate programmed DNA double strand breaks (DSBs) during the V(D)J recombination process that assembles exons that encode the antigen-binding variable regions of antibodies. In addition, mature B lymphocytes generate programmed DSBs during the immunoglobulin heavy chain (IgH) class switch recombination (CSR) process that allows expression of different antibody heavy chain constant regions that provide different effector functions. During both V(D)J recombination and CSR, DSB intermediates are sensed by the ATM-dependent DSB response (DSBR) pathway, which also contributes to their joining via classical non-homologous end-joining (C-NHEJ). The precise nature of the interplay between the DSBR and C-NHEJ pathways in the context of DSB repair via C-NHEJ remains under investigation. Recent studies have shown that the XLF C-NHEJ factor has functional redundancy with several members of the ATM-dependent DSBR pathway in C-NHEJ, highlighting unappreciated major roles for both XLF as well as the DSBR in V(D)J recombination, CSR and C-NHEJ in general. In this review, we discuss current knowledge of the mechanisms that contribute to the repair of DSBs generated during B lymphocyte development and activation with a focus on potential functionally redundant roles of XLF and ATM-dependent DSBR factors. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kumar, Vipul; Alt, Frederick W.; Oksenych, Valentyn] Harvard Univ, Sch Med, Boston Childrens Hosp,Howard Hughes Med Inst, Program Cellular & Mol Med,Dept Genet, Boston, MA 02215 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp,Howard Hughes Med Inst, Program Cellular & Mol Med,Dept Genet, Boston, MA 02215 USA. EM alt@enders.tch.harvard.edu OI Oksenych, Valentyn/0000-0002-5088-3791 FU NIH [GM007226-38, A1076210] FX V.K. is supported by an NIH T32 training grant GM007226-38. F.W.A. is supported by NIH grant A1076210. F.W.A. is an Investigator of the Howard Hughes Medical Institute. NR 148 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD APR PY 2014 VL 16 BP 11 EP 22 DI 10.1016/j.dnarep.2014.01.010 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA AG0KW UT WOS:000335105400003 PM 24674624 ER PT J AU Wang, BCM Wong, ES Alfonso-Cristancho, R He, H Flum, DR Arterburn, DE Garrison, LP Sullivan, SD AF Wang, Bruce C. M. Wong, Edwin S. Alfonso-Cristancho, Rafael He, Hao Flum, David R. Arterburn, David E. Garrison, Louis P. Sullivan, Sean D. TI Cost-effectiveness of bariatric surgical procedures for the treatment of severe obesity SO EUROPEAN JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Obesity; Bariatric surgery; Cost-effectiveness; QALY ID BODY-MASS INDEX; GASTRIC BYPASS-SURGERY; MORBID-OBESITY; US ADULTS; ECONOMIC-IMPACT; MORTALITY; WEIGHT; POPULATION; METAANALYSIS; ASSOCIATION AB Objective One-third of Americans are obese and an increasing number opt for bariatric surgery. This study estimates the cost-effectiveness of common bariatric surgical procedures from a healthcare system perspective. Methods We evaluated the three most common bariatric surgical procedures in the US: laparoscopic gastric bypass (LRYGB), conventional (open) Roux-en-Y gastric bypass (ORYGB), and laparoscopic adjustable gastric banding (LAGB) compared to no surgery. The reference case was defined as a 53-year old female with body mass index (BMI) of 44 kg/m(2). We developed a two-part model using a deterministic approach for the first 5-year period postsurgery and separate empirical forecasts for the natural history of BMI, costs and outcomes in the remaining years. We used a combination of datasets including Medicare and MarketScan (R) together with estimates from the literature to populate the model. Results Bariatric surgery produced additional life expectancy (80-81 years) compared to no surgery (78 years). The incremental cost-effectiveness ratios (ICERs) of the surgical procedures were US $ 6,600 per quality-adjusted life expectancy (QALY) gained for LRYGB, US $ 6,200 for LAGB, and US $ 17,300 for ORYGB (3 % discount rate for cost and QALYs). ICERs varied according to choice of BMI forecasting method and clinically plausible variation in parameter estimates. In most scenarios, the ICER did not exceed a threshold of US $ 50,000 per QALY gained. C1 [Wang, Bruce C. M.; Wong, Edwin S.; Alfonso-Cristancho, Rafael; Garrison, Louis P.; Sullivan, Sean D.] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Wong, Edwin S.] VA Puget Sound, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Alfonso-Cristancho, Rafael; He, Hao; Flum, David R.] Univ Washington, Surg Outcomes Res Ctr, Seattle, WA 98195 USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA 98101 USA. RP Sullivan, SD (reprint author), Univ Washington, Pharmaceut Outcomes Res & Policy Program, 1959 NE Pacific Ave,H375Q, Seattle, WA 98195 USA. EM sdsull@uw.edu FU NIDDK NIH HHS [1R21DK069677] NR 47 TC 8 Z9 8 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1618-7598 EI 1618-7601 J9 EUR J HEALTH ECON JI Eur. J. Health Econ. PD APR PY 2014 VL 15 IS 3 BP 253 EP 263 DI 10.1007/s10198-013-0472-5 PG 11 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AF8XI UT WOS:000334998500004 PM 23526126 ER PT J AU Emadi, A Ju, SA Tsukamoto, T Fathi, AT Minden, MD Dang, CV AF Emadi, Ashkan Ju, Sung Ah Tsukamoto, Takashi Fathi, Amir T. Minden, Mark D. Dang, Chi V. TI Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ISOCITRATE-DEHYDROGENASE 1; CANCER; METABOLISM; ASPARAGINASE; THERAPY AB The incidence of mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) in de novo acute myeloid leukemia (AML) is approximately 20%. These mutations result in distinct metabolic characteristics including dependency of cancer cells on glutamine as the main source for alpha-ocketoglutarate, which is consumed by leukemia cells to produce a cancer-derived metabolite, 2-hydroxyglutarate. We sought to exploit this glutamine addiction therapeutically in mutant IDH primary AML cells from patients by measuring cell growth after exposure to a small molecule glutaminase inhibitor, BPTES. We found that BPTES only suppressed the growth of AML cells expressing mutant IDH compared with those expressing wild type IDH. This study lays the groundwork for strategies to target a specific subtype of AML metabolically with IDH mutations with a unique reprogramming of intermediary metabolism that culminates in glutamine dependency of cancer cells for survival. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Emadi, Ashkan] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA. [Ju, Sung Ah] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Tsukamoto, Takashi] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Med Oncol, Boston, MA USA. [Minden, Mark D.] Univ Toronto, Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Dang, Chi V.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Emadi, A (reprint author), Univ Maryland, Greenebaum Med Ctr, 22 S Greene St,S9D04C, Baltimore, MD 21201 USA. EM aemadi@umm.edu FU National Institutes of Health Grant [NIH R21NS074151]; Leukemia and Lymphoma Society Translational Research Grant [6175-08K23] FX We thank Brandon Carter-Cooper from the University of Maryland Translational Core and Translational Genomic Laboratories for resequencing and validating the primary AML samples mutational status. This work was supported by National Institutes of Health Grant NIH R21NS074151 (to T.T.) and Leukemia and Lymphoma Society Translational Research Grant 6175-08K23 (to C.V.D.). NR 22 TC 35 Z9 37 U1 3 U2 14 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 APR PY 2014 VL 42 IS 4 BP 247 EP 251 DI 10.1016/j.exphem.2013.12.001 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA AG2ZV UT WOS:000335286500002 PM 24333121 ER PT J AU Ueno, S Lu, JY He, J Li, AL Zhang, XX Ritz, J Silberstein, LE Chai, L AF Ueno, Shikiko Lu, Jiayun He, Jie Li, Ailing Zhang, XiaoXian Ritz, Jerome Silberstein, Leslie E. Chai, Li TI Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: Mechanism, function, and implication for a potential novel therapeutic target SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID EARLY EMBRYONIC-DEVELOPMENT; ACUTE MYELOID-LEUKEMIA; YOLK-SAC TUMORS; HEPATOCELLULAR-CARCINOMA; DIAGNOSTIC UTILITY; OKIHIRO-SYNDROME; GENE SALL4; STEM-CELLS; MARKER; TRANSCRIPTION AB Treatment for high-risk pediatric and adult acute B cell lymphoblastic leukemia (B-ALL) remains challenging. Exploring novel pathways in B-ALL could lead to new therapy. Our previous study has shown that stem cell factor SALL4 is aberrantly expressed in B-ALL, but its functional roles and the mechanism that accounts for its upregulation in B-ALL remain unexplored. To address this question, we first surveyed the existing B-ALL cell lines and primary patient samples for SALL4 expression. We then selected the B-ALL cell lines with the highest SALL4 expression for functional studies. RNA interference was used to downregulate SALL4 expression in these cell lines. When compared with control cells, SALL4 knockdown cells exhibited decreased cell proliferation, increased apoptosis in vitro, and decreased engraftment in a xenotransplant model in vivo. Gene expression analysis showed that in SALL4 knockdown B-ALL cells, multiple caspase members involved in cell apoptosis pathway were upregulated. Next, we explored the mechanisms of aberrant SALL4 expression in B-ALL. We found that hypomethylation of the SALL4 CpG islands was correlated with its high expression. Furthermore, treatment of low SALL4-expressing B-ALL cell lines with DNA methylation inhibitor led to demethylation of the SALL4 CpG and increased SALL4 expression. In summary, to our knowledge, we are the first to show that the aberrant expression of SALL4 in B-ALL is associated with hypomethylation, and that SALL4 plays a key role in B-ALL cell survival and could be a potential novel target in B-ALL treatment. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Ueno, Shikiko; Lu, Jiayun; He, Jie; Li, Ailing; Zhang, XiaoXian; Silberstein, Leslie E.; Chai, Li] Brigham & Womens Hosp, Dept Pathol, Blood Bank, Joint Program Transfus Med, Boston, MA 02115 USA. [Ueno, Shikiko; Lu, Jiayun; He, Jie; Li, Ailing; Zhang, XiaoXian; Silberstein, Leslie E.; Chai, Li] Harvard Univ, Sch Med, Children Hosp Boston, Boston, MA 02115 USA. [Ritz, Jerome] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Chai, L (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchai@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [RO1HL092437, DK080665, PO1HL095489] FX We thank Xi Tian for assisting with animal work and Kol Jia Young, Lihua Qi, Joline Lim, and Nicole Tenen for help with editing of the manuscript. This work was supported in part through the National Institutes of Health grants RO1HL092437 and DK080665 (to L.C.) and PO1HL095489 (to L.E.S). NR 30 TC 8 Z9 9 U1 0 U2 3 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 APR PY 2014 VL 42 IS 4 BP 307 EP 316 DI 10.1016/j.exphem.2014.01.005 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA AG2ZV UT WOS:000335286500008 PM 24463278 ER PT J AU Hideshima, H Yoshida, Y Ikeda, H Hide, M Iwasaki, A Anderson, KC Hideshima, T AF Hideshima, Hiromasa Yoshida, Yasuhiro Ikeda, Hiroshi Hide, Maya Iwasaki, Akinori Anderson, Kenneth C. Hideshima, Teru TI IKK similar to inhibitor in combination with bortezomib induces cytotoxicity in breast cancer cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE bortezomib; NF-B; IKK inhibitor; breast cancer ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; THERAPEUTIC IMPLICATIONS; SOLID TUMORS; PHASE-I/II; PS-341; RESISTANCE; PHOSPHORYLATION; DOXORUBICIN; MECHANISMS AB Bortezomib is a proteasome inhibitor with remarkable clinical antitumor activity in multiple myeloma (MM) and is under evaluation in clinical trials in various types of cancer including breast cancer. Although the initial rationale for its use in cancer treatment was the inhibition of NF-B activity by blocking proteasomal degradation of IB, direct evidence indicating inhibition of constitutive NF-B activity by bortezomib in tumor cells in patients has not yet been reported. Moreover, recent studies have shown that bortezomib activates constitutive NF-B activity via stimulating the canonical pathway in MM cells. In this study, we first examined protein expression of IB after bortezomib treatment. We observed that bortezomib upregulated the phosphorylation and downregulated IB protein expression in a dose- and time-dependent manner in MCF7 and T47D cells, associated with phosphorylation of IKK. Since IB is an inhibitor of nuclear translocation of NF-B, we further examined alteration of NF-B activity by bortezomib. Importantly, bortezomib significantly upregulates NF-B activity in both MCF7 and T47D in a dose-dependent fashion, demonstrated by electrophoretic mobility shift analysis (EMSA). Furthermore, immunocytochemical analysis confirmed enhanced nuclear translocation of p65 NF-B (RelA) by bortezomib treatment. Supershift assay showed supershifted bands by anti-p65 and -p50 antibodies. Taken together, these results indicate that bortezomib activates the canonical NF-B pathway in both cell lines. Finally, we demonstrated that IKK inhibitor enhanced cytotoxicity, associated with inhibition of NF-B activity induced by bortezomib in MCF7 and T47D breast cancer cells. C1 [Hideshima, Hiromasa; Yoshida, Yasuhiro; Ikeda, Hiroshi; Hide, Maya; Anderson, Kenneth C.; Hideshima, Teru] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Yoshida, Yasuhiro; Iwasaki, Akinori] Fukuoka Univ, Fac Med, Dept Thorac Endocrine & Pediat Surg, Jonan Ku, Fukuoka 81401, Japan. [Ikeda, Hiroshi] Sapporo Med Univ, Dept Internal Med, Sch Med, Chuo Ku, Sapporo, Hokkaido 0608543, Japan. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM teru_hideshima@dfci.harvard.edu FU National Institute of Health [SPORE-P50100707, P01 CA78378, R01 CA50947] FX This study was supported by the National Institute of Health Grants (SPORE-P50100707, P01 CA78378 and R01 CA50947; to K.C.A.). NR 32 TC 4 Z9 4 U1 1 U2 5 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 2014 VL 44 IS 4 BP 1171 EP 1176 DI 10.3892/ijo.2014.2273 PG 6 WC Oncology SC Oncology GA AE9EI UT WOS:000334307100018 PM 24481412 ER PT J AU Prasad, R Katiyar, SK AF Prasad, Ram Katiyar, Santosh K. TI Ultraviolet radiation- induced inflammation activates similar to- catenin signaling in mouse skin and skin tumors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cyclooxygenase-2; prostaglandins; ultraviolet radiation; -catenin; skin tumor; inflammation ID BETA-CATENIN; IMMUNE SUPPRESSION; CANCER; EXPRESSION; PHOTOCARCINOGENESIS; CARCINOGENESIS; MODELS; ALPHA; EP2 AB UVB-induced inflammation, in particular the overexpression of cyclooxygenase-2 (COX-2) and prostaglandin (PG) E2, has been implicated in photocarcinogenesis. UVB-induced COX-2 has been associated with -catenin signaling in keratinocytes. However, a definitive role for COX-2 in the activation of -catenin signaling as well as its role in UVB-induced skin tumors has not been established. We report that exposure of the skin to UVB resulted in a time- and dose-dependent activation of -catenin in C3H/HeN mice. This response was COX-2-dependent as UVB-exposed COX-2-deficient mice exhibited significantly lower levels of UVB-induced activation of -catenin. Moreover, treatment of mice with indomethacin, a COX-2 inhibitor, and an EP2 antagonist inhibited UVB-induced -catenin signaling. Exposure of SKH-1 hairless mice to UVB radiation (180 mJ/cm(2)) 3 times a week for 24 weeks resulted in activation of -catenin signaling in UVB-irradiated skin as well as UVB-induced skin tumors. Concomitantly, the levels of CK1 and GSK-3, which are responsible for -catenin signaling, were reduced while the levels of c-Myc and cyclin D1, which are downstream targets of -catenin, were increased. To further verify the role of UVB-induced inflammation in activation of -catenin signaling, a high-fat-diet model was used. Administration of high-fat diet exacerbated UVB-induced inflammation. Administration of the high-fat diet enhanced -catenin signaling and the levels of its downstream targets (c-Myc, cyclin D1, cyclin D2, MMP-2 and MMP-9) in UVB-exposed skin and skin tumors in SKH-1 mice. These data suggest that UV-induced COX-2/PGE(2) stimulates -catenin signaling, and that -catenin activation may contribute to skin carcinogenesis. C1 [Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU BLRD VA [I01 BX001410] NR 24 TC 6 Z9 7 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 2014 VL 44 IS 4 BP 1199 EP 1206 DI 10.3892/ijo.2014.2275 PG 8 WC Oncology SC Oncology GA AE9EI UT WOS:000334307100022 PM 24481495 ER PT J AU Wehner, MR Chren, MM Nameth, D Choudhry, A Gaskins, M Nead, KT Boscardin, WJ Linos, E AF Wehner, Mackenzie R. Chren, Mary-Margaret Nameth, Danielle Choudhry, Aditi Gaskins, Matthew Nead, Kevin T. Boscardin, W. John Linos, Eleni TI International Prevalence of Indoor Tanning A Systematic Review and Meta-analysis SO JAMA DERMATOLOGY LA English DT Review ID CUTANEOUS MALIGNANT-MELANOMA; NONMELANOMA SKIN-CANCER; HIGH-SCHOOL-STUDENTS; VITAMIN-D STATUS; SUNBED USE; COLLEGE-STUDENTS; UNITED-STATES; RISK-FACTORS; BED USE; SWEDISH ADOLESCENTS AB IMPORTANCE Indoor tanning is a known carcinogen, but the scope of exposure to this hazard is not known. OBJECTIVE To summarize the international prevalence of exposure to indoor tanning. DATA SOURCES Studies were identified through systematic searches of PubMed (1966 to present), Scopus (1823 to present), and Web of Science (1898 to present) databases, last performed on March 16, 2013. We also hand searched reference lists to identify records missed by database searches and publicly available data not yet published in the scientific literature. STUDY SELECTION Records reporting a prevalence of indoor tanning were eligible for inclusion. We excluded case-control studies, reports with insufficient study information, and reports of groups recruited using factors related to indoor tanning. Two independent investigators performed searches and study selection. Our search yielded 1976 unique records. After exclusions, 161 records were assessed for eligibility in full text, and 88 were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted data on characteristics of study participants, inclusion/exclusion criteria, data collection format, outcomes, and statistical methods. Random-effects meta-analyses were used to summarize the prevalence of indoor tanning in different age categories. We calculated the population proportional attributable risk of indoor tanning in the United States, Europe, and Australia for nonmelanoma skin cancer (NMSC) and melanoma. MAIN OUTCOMES AND MEASURES Ever and past-year exposure to indoor tanning. RESULTS The summary prevalence of ever exposure was 35.7% (95% Cl, 27.5% 44.0%) for adults, 55.0% (33.0%-77.1%) for university students, and 19.3% (14.7%-24.0%) for adolescents. The summary prevalence of past-year exposure was 14.0% (95% Cl, 11.5%-16.5%) for adults, 43.1% (21.7%-64.5%) for university students, and 18.3% (12.6%-24.0%) for adolescents. These results included data from 406 696 participants. The population proportional attributable risk were 3.0% to 21.8% for NMSC and 2.6% to 9.4% for melanoma, corresponding to more than 450 000 NMSC cases and more than 10 000 melanoma cases each year attributable to indoor tanning in the United States, Europe, and Australia. CONCLUSIONS AND RELEVANCE Exposure to indoor tanning is common in Western countries, especially among young persons. Given the large number of skin cancer cases attributable to indoor tanning, these findings highlight a major public health issue. C1 [Wehner, Mackenzie R.; Chren, Mary-Margaret; Linos, Eleni] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Wehner, Mackenzie R.; Nead, Kevin T.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Wehner, Mackenzie R.; Gaskins, Matthew] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA USA. [Nameth, Danielle] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Choudhry, Aditi] John Muir Med Ctr, Dept Internal Med, Walnut Creek, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Linos, E (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Mail Code 0808,Room N421, San Francisco, CA 94143 USA. EM linose@derm.ucsf.edu OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU Doris Duke Charitable Foundation; Dermatology Foundation; National Center for Research Resources of the National Institutes of Health [KL2RR024130]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [RO1AR 054983, K24 AR052667] FX This study was supported in part by the Doris Duke Charitable Foundation (grants to Ms Wehner); the Dermatology Foundation (grant to Dr Linos); the National Center for Research Resources of the National Institutes of Health (grant KL2RR024130 to Dr Linos); and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (grants RO1AR 054983 and K24 AR052667 to Dr Chren). NR 106 TC 72 Z9 74 U1 2 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2014 VL 150 IS 4 BP 390 EP 400 DI 10.1001/jamadermatol.2013.6896 PG 11 WC Dermatology SC Dermatology GA AF4HJ UT WOS:000334672300011 PM 24477278 ER PT J AU Jalian, HR Jalian, CA Avram, MM AF Jalian, H. Ray Jalian, Chris A. Avram, Mathew M. TI Increased Risk of Litigation Associated With Laser Surgery by Nonphysician Operators SO JAMA DERMATOLOGY LA English DT Article ID DERMATOLOGY AB IMPORTANCE Controversy exists regarding the role of nonphysicians performing laser surgery and the increased risk of injury associated with this practice. OBJECTIVE To identify the incidence of medical professional liability claims stemming from cutaneous laser surgery performed by nonphysician operators (NPOs). DESIGN, SETTING, AND PARTICIPANTS Search of an online national database of public legal documents involving laser surgery by NPOs. EXPOSURE Laser surgery by nonphysicians. MAIN OUTCOMES AND MEASURES Frequency and nature of cases, including year of litigation, certification of provider and operator, type of procedure performed, clinical setting of injury, and cause of legal action. RESULTS From January 1999, to December 2012, we identified 175 cases related to injury secondary to cutaneous laser surgery. Of these, 75(42.9%) were cases involving an NPO. From 2008 to 2011, the percentage of cases with NPOs increased from 36.3% to 77.8%. Laser hair removal was the most commonly performed procedure. Despite the fact that approximately only one-third of laser hair removal procedures are performed by NPOs, 75.5% of hair removal lawsuits from 2004 to 2012 were performed by NPOs. From 2008 to 2012, this number increased to 85.7%. Most cases (64.0%) by NPOs were performed outside of a traditional medical setting. CONCLUSIONS AND RELEVANCE Claims related to cutaneous laser surgery by NPOs, particularly outside of a traditional medical setting, are increasing. Physicians and other laser operators should be aware of their state laws, especially in regard to physician supervision of NPOs. C1 [Jalian, H. Ray] Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. [Jalian, H. Ray; Avram, Mathew M.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Jalian, Chris A.] Paul Hastings LLC, New York, NY USA. [Avram, Mathew M.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Jalian, HR (reprint author), Univ Calif Los Angeles, Div Dermatol, 2020 Santa Monica Blvd,Ste 570, Santa Monica, CA 90404 USA. EM hjalian@partners.org NR 9 TC 10 Z9 10 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2014 VL 150 IS 4 BP 407 EP 411 DI 10.1001/jamadermatol.2013.7117 PG 5 WC Dermatology SC Dermatology GA AF4HJ UT WOS:000334672300014 PM 24132614 ER PT J AU Paul, LA Price, M Gros, DF Gros, KS McCauley, JL Resnick, HS Acierno, R Ruggiero, KJ AF Paul, Lisa A. Price, Matthew Gros, Daniel F. Gros, Kirstin Stauffacher McCauley, Jenna L. Resnick, Heidi S. Acierno, Ron Ruggiero, Kenneth J. TI The Associations between Loss and Posttraumatic Stress and Depressive Symptoms Following Hurricane Ike SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE depression; loss of resources; hurricane; disaster; PTSD ID MENTAL-HEALTH PROBLEMS; PSYCHOLOGICAL DISTRESS; TRAUMATIC STRESS; NATURAL DISASTER; SOCIAL SUPPORT; RESOURCE LOSS; CONSERVATION; KATRINA; COMMUNITY; IMPACT AB Disasters can have wide-ranging effects on individuals and their communities. Loss of specific resources (e.g., household contents, job) following a disaster has not been well studied, despite the implications for preparedness efforts and postdisaster interventions. Objective To provide information about the effects of loss on postdisaster distress, the present study assessed associations between disaster-related variables, including the loss of specific resources, and postdisaster distress. Method Random-digit dialing methodology was used to recruit hurricane-affected adults from Galveston and Chambers, TX, counties one year after Hurricane Ike. Data from 1,249 survivors were analyzed to identify predictors of distress. Results Variables that were significantly associated with posttraumatic stress disorder symptoms included sustained losses, hurricane exposure, and sociodemographic characteristics; similar results were obtained for depressive symptoms. Conclusions Together, these findings suggest risk factors that may be associated with the development of posthurricane distress that can inform preparedness efforts and posthurricane interventions. C1 [Paul, Lisa A.; Price, Matthew; Gros, Daniel F.; Gros, Kirstin Stauffacher; McCauley, Jenna L.; Resnick, Heidi S.; Acierno, Ron; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC USA. [Paul, Lisa A.] No Illinois Univ, De Kalb, IL 60115 USA. [Price, Matthew; Gros, Daniel F.; Gros, Kirstin Stauffacher; Acierno, Ron; Ruggiero, Kenneth J.] Ralph H Johnson VAMC, Charleston, SC USA. RP Paul, LA (reprint author), No Illinois Univ, Dept Psychol, Psychol Comp Sci Bldg,Rm 400, De Kalb, IL 60115 USA. EM lpaul1@niu.edu FU NIDA NIH HHS [K12 DA031794]; NIMH NIH HHS [T32 MH018869, R34 MH077149, R01 MH081056, P60 MH082598] NR 43 TC 4 Z9 4 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD APR PY 2014 VL 70 IS 4 BP 322 EP 332 DI 10.1002/jclp.22026 PG 11 WC Psychology, Clinical SC Psychology GA AC4BN UT WOS:000332465700003 PM 23852826 ER PT J AU Jeon, HJ Woo, JM Lee, SH Kim, EJ Chung, S Ha, JH Fava, M Mischoulon, D Kim, JH Heo, JY Yu, BH AF Jeon, Hong Jin Woo, Jong-Min Lee, Seung-Hwan Kim, Eui-Joong Chung, Seockhoon Ha, Jee Hyun Fava, Maurizio Mischoulon, David Kim, Ji-Hae Heo, Jung-Yoon Yu, Bum-Hee TI Improvement in Subjective and Objective Neurocognitive Functions in Patients With Major Depressive Disorder A 12-Week, Multicenter, Randomized Trial of Tianeptine Versus Escitalopram, the CAMPION Study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE neurocognitive; major depressive disorder; tianeptine; escitalopram ID SEROTONIN-REUPTAKE INHIBITOR; LATE-LIFE DEPRESSION; ANTIDEPRESSANT TREATMENT; ALZHEIMERS-DISEASE; MEMORY; CITALOPRAM; COGNITION; SYMPTOMS; DEFICITS; PERFORMANCE AB Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini-Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini-Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration. C1 [Jeon, Hong Jin; Kim, Ji-Hae; Heo, Jung-Yoon; Yu, Bum-Hee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul 135710, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Woo, Jong-Min] Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. [Lee, Seung-Hwan] Inje Univ, Sch Med, Ilsan Paik Hosp, Dept Psychiat, Ilsan, South Korea. [Kim, Eui-Joong] Eulji Univ, Sch Med, Dept Psychiat, Eulji Gen Hosp, Taejon, South Korea. [Chung, Seockhoon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Ulsan, South Korea. [Ha, Jee Hyun] Konkuk Univ, Sch Med, Dept Psychiat, Seoul, South Korea. RP Yu, BH (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, 50 Irwon Dong, Seoul 135710, South Korea. EM bhyu@skku.edu FU Korean Society of Ginseng and Samsung Display; Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly Company; EnVivo Pharmaceuticals, Inc; Forest Pharmaceuticals Inc; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc; Synthelabo; Wyeth-Ayerst Laboratories; Bowman Family Foundation; Bristol-Myers Squibb Co; Cederroth; FisherWallace; Lichtwer Pharma; Nordic Naturals; Laxdale (Amarin); Methylation Sciences, Inc (MSI); SwissMedica FX Dr Yu has received research support from Korean Society of Ginseng and Samsung Display. He has received honoraria for consulting and speaking from Lundbeck Singapore Pte. Ltd. and Korea OIAA Co, Ltd. Dr Fava has received research support from Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly & Company; EnVivo Pharmaceuticals, Inc; Forest Pharmaceuticals Inc; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc; Synthelabo; and Wyeth-Ayerst Laboratories. He has served as an advisor and consultant to Abbott Laboratories; Affectis Pharmaceuticals AG; Amarin; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc; BioMarin Pharmaceuticals, Inc; Biovail Pharmaceuticals, Inc; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trials Solutions, LLC; CNS Response; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; Eisai, Inc; Eli Lilly & Company; EPIX Pharmaceuticals; Euthymics Bioscience, Inc; Fabre-Kramer, Pharmaceuticals, Inc; Forest Pharmaceuticals Inc; GlaxoSmithKline; Grunenthal GmBH; Janssen Pharmaceutica; Jazz Pharmaceuticals; J & J Pharmaceuticals; Knoll Pharmaceutical Company; Labopharm; Lorex Pharmaceuticals; Lundbeck, MedAvante Inc; Merck; Methylation Sciences; Neuronetics; Novartis; Nutrition 21; Organon Inc; PamLab, LLC; Pfizer Inc; PharmaStar; Pharmavite; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc; PsychoGenics; Psylin Neurosciences, Inc; Ridge Diagnostics, Inc; Roche; Sanofi-Aventis; Sepracor; Schering-Plough; Solvay Pharmaceuticals, Inc; Somaxon; Somerset Pharmaceuticals; Synthelabo; Takeda; Tetragenex; TransForm Pharmaceuticals; Inc; Transcept Pharmaceuticals; Vanda Pharmaceuticals Inc; and Wyeth-Ayerst Laboratories. He has received speaking and publishing honoraria from Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir; Boehringer-Ingelheim; Bristol-Myers Squibb Company; Cephalon; Eli Lilly & Company; Forest Pharmaceuticals Inc; GlaxoSmithKline; Imedex; Novartis; Organon Inc; Pfizer Inc; PharmaStar; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed-Elsevier; UBC; and Wyeth-Ayerst Laboratories. He holds equity in Compellis. He currently holds a patent for SPCD and a patent application for a combination of azapirones and bupropion in MDD and has received copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire, SFI, ATRQ, DESS, and SAFER diagnostic instruments. Dr Mischoulon has received research support from the Bowman Family Foundation; Bristol-Myers Squibb Co; Cederroth; FisherWallace; Ganeden; Lichtwer Pharma; Nordic Naturals; Laxdale (Amarin); Methylation Sciences, Inc (MSI); and SwissMedica. He has received honoraria for consulting, speaking, and writing from Pamlab, Bristol-Myers Squibb Co, Nordic Naturals, Virbac, Pfizer, Reed Medical Education, and the Massachusetts General Hospital Psychiatry Academy. He has received royalties from Back Bay Scientific for PMS Escape and from Lippincott Williams & Wilkins for the published book "Natural Medications for Psychiatric Disorders: Considering the Alternatives." No payment has exceeded $10,000. Other authors have no conflicts of interest. NR 48 TC 5 Z9 5 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2014 VL 34 IS 2 BP 218 EP 225 DI 10.1097/JCP.0000000000000072 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AG3OC UT WOS:000335328000008 PM 24525660 ER PT J AU Mancino, MJ McGaugh, J Chopra, MP Guise, JB Cargile, C Williams, DK Thostenson, J Kosten, TR Sanders, N Oliveto, A AF Mancino, Michael J. McGaugh, Janette Chopra, Mohit P. Guise, Joseph B. Cargile, Christopher Williams, D. Keith Thostenson, Jeff Kosten, Thomas R. Sanders, Nichole Oliveto, Alison TI Clinical Efficacy of Sertraline Alone and Augmented With Gabapentin in Recently Abstinent Cocaine-Dependent Patients With Depressive Symptoms SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE placebo control; randomized clinical trial; cognitive behavioral therapy; sertraline; gabapentin; cocaine dependence; relapse prevention ID PLACEBO-CONTROLLED TRIAL; CONTINGENCY MANAGEMENT; FLUOXETINE TREATMENT; ABUSE; DESIPRAMINE; OUTPATIENTS; IMPAIRMENT; CITALOPRAM; ADDICTION; SEROTONIN AB Background Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. Methods Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. Results Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. Conclusions Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy. C1 [Mancino, Michael J.; McGaugh, Janette; Guise, Joseph B.; Cargile, Christopher; Sanders, Nichole; Oliveto, Alison] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Chopra, Mohit P.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA. [Williams, D. Keith; Thostenson, Jeff] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Kosten, Thomas R.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Mancino, MJ (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Slot 848,4301 W,Markham St, Little Rock, AR 72205 USA. EM mjmancino@uams.edu RI Mancino, Michael/O-9696-2016 OI Mancino, Michael/0000-0002-7234-6305 FU National Institute on Drug Abuse [P50-DA12762, K05-DA00454, T32 DA022981]; National Institute of General Medical Services [GM103425-09] FX This study was funded by grants P50-DA12762 and K05-DA00454 (T. R. K.) and T32 DA022981 (N.S.) from the National Institute on Drug Abuse and GM103425-09 (M.J.M.) from the National Institute of General Medical Services. NR 39 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2014 VL 34 IS 2 BP 234 EP 239 DI 10.1097/JCP.0000000000000062 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AG3OC UT WOS:000335328000011 PM 24525654 ER PT J AU Deligiannidis, KM Byatt, N Freeman, MP AF Deligiannidis, Kristina M. Byatt, Nancy Freeman, Marlene P. TI Pharmacotherapy for Mood Disorders in Pregnancy A Review of Pharmacokinetic Changes and Clinical Recommendations for Therapeutic Drug Monitoring SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review DE pharmacokinetics; antidepressants; mood stabilizers; pregnancy ID SEROTONIN REUPTAKE INHIBITORS; FLUOXETINE N-DEMETHYLATION; PLASMA-CONCENTRATIONS; BIPOLAR DISORDER; IN-VITRO; ANTIEPILEPTIC DRUGS; HUMAN PLACENTA; BUPROPION HYDROXYLATION; TRANSPLACENTAL TRANSFER; POSTPARTUM PERIOD AB Objective Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments. The objectives of this review are to summarize the evidence for change in perinatal pharmacokinetics of commonly used pharmacotherapies for mood disorders, discuss the implications for clinical and therapeutic drug monitoring (TDM), and make clinical recommendations. Methods The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period. Results Pregnancy-associated changes in absorption, distribution, metabolism, and elimination may result in lowered psychotropic drug levels and possible treatment effects, particularly in late pregnancy. Mechanisms include changes in both phase 1 hepatic cytochrome P450 and phase 2 uridine diphosphate glucuronosyltransferase enzyme activities, changes in hepatic and renal blood flow, and glomerular filtration rate. Therapeutic drug monitoring, in combination with clinical monitoring, is indicated for tricyclic antidepressants and mood stabilizers during the perinatal period. Conclusions Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers. Dose increases may be indicated for antidepressants including citalopram, clomipramine, imipramine, fluoxetine, fluvoxamine, nortriptyline, paroxetine, and sertraline, especially late in pregnancy. Antenatal dose increases may also be needed for lithium, lamotrigine, and valproic acid because of perinatal changes in metabolism. Close clinical monitoring of perinatal mood disorders and TDM of tricyclic antidepressants and mood stabilizers are recommended. C1 [Deligiannidis, Kristina M.] Univ Massachusetts, UMass Mem Med Ctr, Sch Med, Dept Psychiat & Obstet & Gynecol, Worcester, MA 01655 USA. [Deligiannidis, Kristina M.] Univ Massachusetts, UMass Mem Med Ctr, Sch Med, Depress Specialty Clin, Worcester, MA 01655 USA. [Deligiannidis, Kristina M.; Byatt, Nancy] Univ Massachusetts, Womens Mental Hlth Specialty Clin, Ctr Psychopharmacol Res & Treatment, Med Sch,UMass Mem Med Ctr, Worcester, MA 01655 USA. [Byatt, Nancy] Univ Massachusetts, Womens Mental Hlth Specialty Clin, Sch Med, UMass Mem Med Ctr, Worcester, MA 01655 USA. [Freeman, Marlene P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Perinatal & Reprod Psychiat Program, Boston, MA USA. RP Deligiannidis, KM (reprint author), Univ Massachusetts, Womens Mental Hlth Specialty Clin, Ctr Psychopharmacol Res & Treatment, Med Sch,UMass Mem Med Ctr, 55 Lake Ave N, Worcester, MA 01655 USA. EM kristina.deligiannidis@umassmemorial.org RI Deligiannidis, Kristina/C-3654-2014; OI Deligiannidis, Kristina/0000-0001-7439-2236; Byatt, Nancy/0000-0002-4010-8919 FU UMass Medical School [NIHUL1RR031982]; NIH [NIMH 1K23MH097794]; Worcester Foundation for Biomedical Research; Forest Research Institute; Massachusetts Department of Mental Health for the Massachusetts Child Psychiatry Access Program for Moms; Meyers Primary Care Institute; Rosalie Wolf Interdisciplinary Geriatric Healthcare Research Center Small Grants Initiative; National Center for Research Resources; National Center for Advancing Translational Sciences of the National Institutes of Health [KL2TR000160]; GlaxoSmithKline; Lilly; Forest FX Dr Deligiannidis has received research support from UMass Medical School (NIHUL1RR031982), NIH (NIMH 1K23MH097794), Worcester Foundation for Biomedical Research, and Forest Research Institute and royalties from an employee invention (National Institutes of Health/National Institute of Child Health and Human Development). Dr Byatt has also received grant/funding support from the Massachusetts Department of Mental Health for the Massachusetts Child Psychiatry Access Program for Moms, Meyers Primary Care Institute and the Rosalie Wolf Interdisciplinary Geriatric Healthcare Research Center Small Grants Initiative. Dr Byatt's work was on this project supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through grant number KL2TR000160. Dr Freeman has received research support from GlaxoSmithKline, Lilly, and Forest, has served on advisory boards or consulted for Johnson & Johnson, Genentech, Takeda and Lundbeck, Otsuka, and Pamab, and has received a stipend for medical editing from DSM Nutritionals. NR 166 TC 23 Z9 23 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2014 VL 34 IS 2 BP 244 EP 255 DI 10.1097/JCP.0000000000000087 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AG3OC UT WOS:000335328000013 PM 24525634 ER PT J AU Goetz, M Surman, CBH AF Goetz, Michal Surman, Craig Bruce Hackett TI Prolonged Penile Erections Associated With the Use of Atomoxetine and Aripiprazole in an 11-Year-Old Boy SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID ATYPICAL ANTIPSYCHOTIC MEDICATIONS; PRIAPISM; CHILD C1 [Goetz, Michal] Charles Univ Prague, Fac Med 2, Dept Paediat Psychiat, Prague, Czech Republic. [Goetz, Michal] Motol Univ Hosp, Prague, Czech Republic. [Surman, Craig Bruce Hackett] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA USA. RP Goetz, M (reprint author), Charles Univ Prague, Fac Med 2, Dept Paediat Psychiat, Prague, Czech Republic. EM michal.goetz@lfmotol.cuni.cz NR 8 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2014 VL 34 IS 2 BP 275 EP 276 DI 10.1097/01.jcp.0000445185.90518.84 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AG3OC UT WOS:000335328000021 PM 24577257 ER PT J AU Ren, B Ramakrishnan, DP Chen, Y Best, B Silverstein, RL Ren, B Silverstein, RL Walcott, B Storz, P AF Ren, B. Ramakrishnan, D. P. Chen, Y. Best, B. Silverstein, R. L. Ren, B. Silverstein, R. L. Walcott, B. Storz, P. TI SIGNALING KINASE PKD-1 REGULATES ENDOTHELIAL CELL CD36 TRANSCRIPTION AND STIMULATES ARTERIOGENIC RESPONSES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Ren, B.; Ramakrishnan, D. P.; Chen, Y.; Best, B.; Silverstein, R. L.] Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53233 USA. [Ren, B.; Silverstein, R. L.] Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Walcott, B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Walcott, B.] Harvard Univ, Sch Med, Charlestown, MA USA. [Storz, P.] Mayo Clin, Dept Canc Biol, Ctr Comprehens Canc, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 736 EP 737 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300121 ER PT J AU Alex, AM Verhulst, S Sundareshan, V Mclafferty, R AF Alex, A. M. Verhulst, S. Sundareshan, V. Mclafferty, R. TI FACTORS THAT INFLUENCE WOUND HEALING OF DIABETIC FOOT ULCERS (DFU) TREATED WITH SKIN SUBSTITUTES (SS) SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Alex, A. M.; Verhulst, S.; Sundareshan, V.] So Illinois Univ, Springfield, IL USA. [Mclafferty, R.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 738 EP 739 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300127 ER PT J AU Deng, WJ Buonanno, FS Lopez, M Beecher, C Burant, C De Jong, F Palacios, I Inglessis, I Silverman, S Feeney, K Elia, M Wickham, TR McMullin, D Dec, W Lo, E Ning, MM AF Deng, Wenjun Buonanno, Ferdinando S. Lopez, Mary Beecher, Christopher Burant, Charles De Jong, Frank Palacios, Igor Inglessis, Ignacio Silverman, Scott Feeney, Kathleen Elia, Mikaela Wickham, Thomas R. McMullin, David Dec, William Lo, Engh. Ning, Mingming TI METABOLOMIC ANALYSIS REVEALS LONG-TERM DECREASE OF HOMOCYSTEINE POST PFO CLOSURE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Deng, Wenjun; Buonanno, Ferdinando S.; Lopez, Mary; Beecher, Christopher; Burant, Charles; De Jong, Frank; Palacios, Igor; Inglessis, Ignacio; Silverman, Scott; Feeney, Kathleen; Elia, Mikaela; Wickham, Thomas R.; McMullin, David; Dec, William; Lo, Engh.; Ning, Mingming] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 766 EP 767 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300179 ER PT J AU Wickham, T Feeney, K Deng, W Chen, L Inglessis, I Palacios, I McMullin, D Lo, EH Buonanno, F Ning, MM AF Wickham, T. Feeney, K. Deng, W. Chen, L. Inglessis, I. Palacios, I. McMullin, D. Lo, E. H. Buonanno, F. Ning, MingMing TI TRAVEL RELATED STROKE DISPARITY IN PATENT FORAMEN OVALE PATIENTS AND PLANS FOR A TRIAL FOR INTERVENTION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Wickham, T.; Feeney, K.; Deng, W.; Chen, L.; Inglessis, I.; Palacios, I.; McMullin, D.; Lo, E. H.; Buonanno, F.; Ning, MingMing] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 766 EP 766 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300178 ER PT J AU Deng, WJ Beecher, C Lopez, M De Jong, F Palacios, I Inglessis, I Feeney, K Elia, M McMullin, D Dec, W Burant, C Lo, EH Buonanno, FS Ning, MM AF Deng, Wenjun Beecher, Christopher Lopez, Mary De Jong, Frank Palacios, Igor Inglessis, Ignacio Feeney, Kathleen Elia, Mikaela McMullin, David Dec, William Burant, Charles Lo, Eng H. Buonanno, Ferdinando S. Ning, Mingming TI PERSONALIZED METABOLOMICS OF IDENTICAL TWINS VS GENERAL STROKE POPULATION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Deng, Wenjun; Beecher, Christopher; Lopez, Mary; De Jong, Frank; Palacios, Igor; Inglessis, Ignacio; Feeney, Kathleen; Elia, Mikaela; McMullin, David; Dec, William; Burant, Charles; Lo, Eng H.; Buonanno, Ferdinando S.; Ning, Mingming] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 767 EP 767 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300180 ER PT J AU Feeney, K Deng, W Wickham, T Inglessis, I Palacios, I Calvanio, R Lo, EH Buonanno, F Ning, MM AF Feeney, K. Deng, W. Wickham, T. Inglessis, I. Palacios, I. Calvanio, R. Lo, E. H. Buonanno, F. Ning, MingMing TI EFFECT OF ENDOVASCULAR CLOSURE PROCEDURE ON THE QUALITY OF LIFE IN STROKE PATIENTS WITH PATENT FORAMEN OVALE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Feeney, K.; Deng, W.; Wickham, T.; Inglessis, I.; Palacios, I.; Calvanio, R.; Lo, E. H.; Buonanno, F.; Ning, MingMing] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 772 EP 772 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300197 ER PT J AU Lendon, JP Silverstein, M Giarrusso, R AF Lendon, Jessica P. Silverstein, Merril Giarrusso, Roseann TI Ambivalence in Older Parent-Adult Child Relationships: Mixed Feelings, Mixed Measures SO JOURNAL OF MARRIAGE AND FAMILY LA English DT Article DE intergenerational relationships; ambivalence; quantitative methodology ID INTERGENERATIONAL SOLIDARITY; LATER-LIFE; AMERICAN FAMILIES; CONFLICT; PERSPECTIVES; TIES AB This research compared direct and indirect measures of ambivalence, 2 commonly used strategies for measuring intergenerational ambivalence between older parents and their adult children. Directly and indirectly measured ambivalence, corresponding to felt and potential manifestations of the construct, were contrasted with each other and across generations. Data were derived from 253 older parent-adult child dyads participating in the Longitudinal Study of Generations in 2005. Direct and indirect measures of ambivalence were moderately correlated with each other within each generation. Children expressed greater indirect ambivalence than their parents but were no different than their mothers or fathers in their levels of direct ambivalence. Multivariate regression analyses examining the relationship between each type of ambivalence with individual and relationship characteristics found differences in associations across equations. The results suggest that direct and indirect measures are related but represent 2 distinct conceptions of ambivalence. This research highlights the challenges in understanding the full complexity of intergenerational relations and suggests that both generational perspectives be considered in future research. C1 [Lendon, Jessica P.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev, Los Angeles, CA 90073 USA. [Silverstein, Merril] Syracuse Univ, Aging Studies Inst, Syracuse, NY 13244 USA. [Giarrusso, Roseann] Calif State Univ Los Angeles, Dept Sociol, Los Angeles, CA 90032 USA. RP Lendon, JP (reprint author), VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jessicapenn@gmail.com FU NIA NIH HHS [R01 AG007977] NR 37 TC 9 Z9 9 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-2445 EI 1741-3737 J9 J MARRIAGE FAM JI J. Marriage Fam. PD APR PY 2014 VL 76 IS 2 BP 272 EP 284 DI 10.1111/jomf.12101 PG 13 WC Family Studies; Sociology SC Family Studies; Sociology GA AC0DH UT WOS:000332164500003 PM 25378714 ER PT J AU Tran, K Kuo, B Zibaitis, A Bhattacharya, S Cote, C Belkind-Gerson, J AF Khoa Tran Kuo, Brad Zibaitis, Audrius Bhattacharya, Somaletha Cote, Charles Belkind-Gerson, Jaime TI Effect of Propofol on Anal Sphincter Pressure During Anorectal Manometry SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE constipation; propofol; anorectal manometry; anal sphincter pressure ID BOTULINUM TOXIN; SMOOTH-MUSCLE; CHRONIC CONSTIPATION; CHILDREN; ANESTHESIA; VOLUNTEERS; MECHANISMS; ACHALASIA; SEDATION; KETAMINE AB We evaluated the effect of propofol on resting anal sphincter pressure (RP) during anorectal manometry performed under general anesthesia in 20 children with chronic constipation. After propofol bolus administration, there was a significant decrease in the RP in 95% of children from a mean of 51.5 +/- 15.3 to a mean nadir of 21.7 +/- 10.5 mmHg (P < 0.001). The new postpropofol RP of 47.0 +/- 12.4 mmHg was significantly lower compared with prepropofol RP (P < 0.0001). Propofol should be used with caution as an anesthetic agent for anorectal manometry, given the potential for confounding RP measurements. C1 [Khoa Tran] Harvard Univ, Sch Med, New England Med Ctr, Dept Pediat Gastroenterol, Boston, MA 02114 USA. [Kuo, Brad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Zibaitis, Audrius; Bhattacharya, Somaletha; Cote, Charles] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. [Belkind-Gerson, Jaime] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Div Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. RP Belkind-Gerson, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Div Gastroenterol Hepatol & Nutr, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM jbelkindgerson@mgh.harvard.edu NR 19 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD APR PY 2014 VL 58 IS 4 BP 495 EP 497 DI 10.1097/MPG.0000000000000190 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AG3VJ UT WOS:000335347700031 PM 24121151 ER PT J AU Gerber, MR Iverson, KM Dichter, ME Klap, R Latta, RE AF Gerber, Megan R. Iverson, Katherine M. Dichter, Melissa E. Klap, Ruth Latta, Rachel E. TI Women Veterans and Intimate Partner Violence: Current State of Knowledge and Future Directions SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CARDIOVASCULAR-DISEASE; HIGH-RISK; QUITLINES; HEALTH AB Intimate partner violence (IPV) is a serious public health concern for all; however, women who experience IPV are more likely to sustain injury and report adverse health consequences. An expanding body of research suggests that experience of IPV is common in women veterans (WV), particularly those who access Veterans Health Administration (VA) services. With unprecedented numbers of women serving in the military and subsequently becoming veterans, it is critical that clinicians and advocates caring for WV understand the impact of IPV on this population. WV have unique risk factors for experiencing IPV, including high rates of premilitary trauma, as well as military sexual trauma and posttraumatic stress disorder (PTSD). Correlates of IPV, traumatic brain injury (TBI) and homelessness, are common among this group. Although research on WV health and IPV is emergent, evidence suggests that IPV results in multiple health sequelae and increased healthcare utilization. In this context, we next discuss clinical and policy implications for VA. A number of targeted interventions and treatments are available for WV who experience IPV, including evidence-based mental health services. VA is well situated to implement screening programs for WV to facilitate referral to needed services and treatments available both within and outside its facilities. As the population of WV expands, future research will be needed to determine best practices; many avenues of inquiry exist. Finally, WV are strong and resilient; it is crucial that those who work with them recognize evidence of IPV and refer to needed services and evidence-based treatment to enable strength-based recovery. C1 [Gerber, Megan R.] VA Boston Healthcare Syst, Women Vet Hlth Program, Boston, MA USA. [Gerber, Megan R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, VA Ctr Hlth Equ Res & Promot CHERP, Philadelphia, PA USA. [Klap, Ruth] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Latta, Rachel E.] Edith Nourse Rogers Mem Vet Adm Hosp, New England Mental Illness Res Educ & Clin Ctr MI, Bedford, MA 01730 USA. RP Gerber, MR (reprint author), VA Boston Healthcare Syst, Women Vet Hlth Program, 150 South Huntington Ave PC11, Jamaica Plain, MA 01230 USA. EM Megan.gerber@va.gov OI Gerber, Megan/0000-0002-8444-5554 FU VA Health Services Research and Development (HSRD) [CDA-10-029]; VA HSR&D Career Development Award [CDA-10-202]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSRD SDR [10-012]; Department of Veterans Affairs, Patient Care Services, Women's Health Services FX Funding was provided by VA Health Services Research and Development (HSR&D) Career Development Award CDA-10-029 (KI); VA HSR&D Career Development Award CDA-10-202 (MD); and Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSR&D SDR 10-012 (RK). This work was also supported in part by the Department of Veterans Affairs, Patient Care Services, Women's Health Services (RK). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. NR 20 TC 12 Z9 12 U1 3 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2014 VL 23 IS 4 BP 302 EP 309 DI 10.1089/jwh.2013.4513 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AE4EO UT WOS:000333934900132 PM 24506440 ER PT J AU Shek, SYN Yeung, CK Chan, JCY Chan, HHL AF Shek, Samantha Y. N. Yeung, Chi K. Chan, Johnny C. Y. Chan, Henry H. L. TI Efficacy of High-Intensity Focused Ultrasonography for Noninvasive Body Sculpting in Chinese Patients SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE high-intensity focused ultrasound; noninvasive; body sculpting; Chinese ID LASER-ASSISTED DELIVERY; CARBON-DIOXIDE LASER; BASAL-CELL CARCINOMAS; ERBIUM-YAG LASER; PHOTODYNAMIC THERAPY; TRANSDERMAL DELIVERY; FRACTIONAL LASER; DRUG-DELIVERY; TOPICAL DELIVERY; METHYL AMINOLEVULINATE AB Background and Objectives: High-intensity focused ultrasound (HIFU) is a noninvasive technology for body contouring. HIFU is focused within the subcutaneous adipose tissue, causing coagulative necrosis and cell death. The objective of this study is to evaluate the effectiveness of a HIFU device for sculpting of the abdomen. Materials and Methods: The system has a set focal depth of 1.3 cm. Twelve subjects with adipose thickness no less than 2.5cm who met the screening criteria were recruited. Each subject received one treatment to the abdomen. The total fluence used per site was 150-165 J/cm(2) with a mean of 161 J/cm(2). The waist circumference at iliac crest and the point of maximum circumference were recorded at baseline, 4, 8, and 12 weeks post-treatment, as well as their weight and BMI. Subjects' rating on comfort level and satisfaction were collected via questionnaires at every follow-up. Standardized photographs were also taken with the Canfield System(R) at each visit. Results: Seven out of 12 subjects were satisfied with the outcome and 9 out of 12 would recommend this treatment to their friends and family. There was statistically significant improvement in the waist circumference measured at both the iliac crest (P-value 0.013, 0.002, 0.005) and maximum waistline (P-value 0.003, 0.034, 0.023) at 4, 8, 12 weeks post-treatment. Spearman's rho for correlation of energy level versus improvement showed that at 12 weeks post-treatment follow-up, the improvement significantly correlated with the total fluence per treatment (P-value 0.041). The higher the total fluence delivered, the larger the decrease in waist circumference. Conclusions: High-intensity focused ultrasound effectively decreases waist circumference in Chinese. The higher the total fluence delivered, the larger the decrease in waist circumference was observed. Lasers Surg. Med. 46:263-269, 2014. (C) 2014 Wiley Periodicals, Inc. C1 [Shek, Samantha Y. N.; Yeung, Chi K.; Chan, Johnny C. Y.; Chan, Henry H. L.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Shek, SYN (reprint author), 11-F,Silver Fortune Plaza,1 Wellington St, Hong Kong, Hong Kong, Peoples R China. EM samantha@hhlchan.com RI Chan, Henry Hin Lee/L-2267-2013 NR 48 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2014 VL 46 IS 4 BP 263 EP 269 DI 10.1002/lsm.22232 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA AF4KE UT WOS:000334679900002 PM 24585511 ER PT J AU Kositratna, G Welford, D Jaspan, M Hibert, ML Manstein, D AF Kositratna, Garuna Welford, David Jaspan, Martin Hibert, Matthew Louis Manstein, Dieter TI EFFECTS OF POWER DENSITY AND PULSE MODULATION ON ABLATIVE FRACTIONAL LESION GEOMETRY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Endeavour Laser Technol Inc, Hathorne, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2014 VL 46 IS 4 BP 346 EP 346 DI 10.1002/lsm.22257 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AF4KE UT WOS:000334679900013 ER PT J AU Chagin, AS Vuppalapati, KK Kobayashi, T Guo, J Hirai, T Chen, M Offermanns, S Weinstein, LS Kronenberg, HM AF Chagin, Andrei S. Vuppalapati, Karuna K. Kobayashi, Tatsuya Guo, Jun Hirai, Takao Chen, Min Offermanns, Stefan Weinstein, Lee S. Kronenberg, Henry M. TI G-protein stimulatory subunit alpha and Gq/11 alpha G-proteins are both required to maintain quiescent stem-like chondrocytes SO NATURE COMMUNICATIONS LA English DT Article ID GROWTH-PLATE CHONDROGENESIS; PARATHYROID-HORMONE; IN-VIVO; ENDOCHONDRAL OSSIFICATION; SIGNALING PATHWAYS; PHOSPHOLIPASE-C; KINASE-A; RECEPTOR; DIFFERENTIATION; HYPERTROPHY AB Round chondrocytes in the resting zone of the growth plate provide precursors for columnar chondrocytes and have stem-like properties. Here we demonstrate that these stem-like chondrocytes undergo apoptosis in the absence of the receptor (PPR) for parathyroid hormone-related protein. We examine the possible roles of heterotrimeric G-proteins activated by the PPR. Inactivation of the G-protein stimulatory alpha-subunit (G(s)alpha) leads to accelerated differentiation of columnar chondrocytes, as seen in the PPR knockout, but a remnant of growth cartilage remains, in contrast to disappearance of the growth cartilage in the PPR knockout. Stem-like chondrocytes lose their quiescence and proliferate upon Gsa ablation. Inactivation of Gsa in mice with a mutant PPR that cannot activate G proteins, Gq and G11, leads to a PPR knockout-like phenotype. Thus, G(s)alpha is the major mediator of the anti-differentiation action of the PPR, while activation of both Gsa and Gq/11 alpha is required for quiescence of stem-like chondrocytes. C1 [Chagin, Andrei S.; Vuppalapati, Karuna K.] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. [Chagin, Andrei S.; Kobayashi, Tatsuya; Guo, Jun; Hirai, Takao; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Chagin, Andrei S.; Kobayashi, Tatsuya; Guo, Jun; Hirai, Takao; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, Min; Weinstein, Lee S.] Natl Inst Diabet Digest & Kidney Dis, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Offermanns, Stefan] Max Planck Inst Heart & Lung Res, Dept Pharmacol, D-61231 Bad Nauheim, Germany. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org RI Chagin, Andrei/F-4080-2014 OI Chagin, Andrei/0000-0002-2696-5850 FU National Institutes of Health [DK56246]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease; National Institutes of Health in Bethesda, Maryland; Sallskapet Barnavard Foundation in Stockholm; Swedish Research Council [2007-8037]; Swedish Society for Medical Research FX We thank Murat Bastepe and Shigeki Nishimori for helpful suggestions. This work was funded by National Institutes of Health Grant DK56246, the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health in Bethesda, Maryland, and the Sallskapet Barnavard Foundation in Stockholm. ASC was supported by postdoctoral fellowships from The Swedish Research Council (Dnr. 2007-8037) and The Swedish Society for Medical Research. NR 29 TC 10 Z9 10 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2014 VL 5 AR 3673 DI 10.1038/ncomms4673 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2CA UT WOS:000335221800004 PM 24781502 ER PT J AU Colman, RJ Beasley, TM Kemnitz, JW Johnson, SC Weindruch, R Anderson, RM AF Colman, Ricki J. Beasley, T. Mark Kemnitz, Joseph W. Johnson, Sterling C. Weindruch, Richard Anderson, Rozalyn M. TI Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys SO NATURE COMMUNICATIONS LA English DT Article ID DIETARY RESTRICTION; LIFE-SPAN; BODY-COMPOSITION; CANCER; HEALTH; MICE AB Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR's effects in primates. Here we show that CR significantly improves age-related and allcause survival in monkeys on a long-term similar to 30% restricted diet since young adulthood. These data contrast with observations in the 2012 NIA intramural study report, where a difference in survival was not detected between control-fed and CR monkeys. A comparison of body weight of control animals from both studies with each other, and against data collected in a multi-centred relational database of primate ageing, suggests that the NIA control monkeys were effectively undergoing CR. Our data indicate that the benefits of CR on ageing are conserved in primates. C1 [Colman, Ricki J.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Beasley, T. Mark] Birmingham Atlanta Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA. [Beasley, T. Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Kemnitz, Joseph W.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53706 USA. [Johnson, Sterling C.; Weindruch, Richard; Anderson, Rozalyn M.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Johnson, Sterling C.; Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Anderson, RM (reprint author), Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. EM rmanderson@medicine.wisc.edu RI Biguzzi, Felipe/E-4724-2015 FU NIH [P01AG011915, R01AG040178, R01AG037000]; Department of Medicine, School of Medicine and Public Health UW Madison; NCRR/ORIP [P51RR000167, P51OD011106] FX Funding for this study was provided by NIH grants P01AG011915, R01AG040178 and R01AG037000, and the Department of Medicine, School of Medicine and Public Health UW Madison. This publication was made possible in part by NCRR/ORIP grants P51RR000167/P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin- Madison. The study was conducted with the use of resources and facilities at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA. NR 21 TC 126 Z9 126 U1 15 U2 74 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2014 VL 5 AR 3557 DI 10.1038/ncomms4557 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BI UT WOS:000335219800005 PM 24691430 ER PT J AU Lopez-Serra, P Marcilla, M Villanueva, A Ramos-Fernandez, A Palau, A Leal, L Wahi, JE Setien-Baranda, F Szczesna, K Moutinho, C Martinez-Cardus, A Heyn, H Sandoval, J Puertas, S Vidal, A Sanjuan, X Martinez-Balibrea, E Vinals, F Perales, JC Bramsem, JB Orntoft, TF Andersen, CL Tabernero, J McDermott, U Boxer, MB Vander Heiden, MG Albar, JP Esteller, M AF Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucia Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Vinals, Francesc Perales, Jose C. Bramsem, Jesper B. Orntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Vander Heiden, Matthew G. Pablo Albar, Juan Esteller, Manel TI A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect SO NATURE COMMUNICATIONS LA English DT Article ID PYRUVATE-KINASE M2; UNFOLDED PROTEIN RESPONSE; CANCER METABOLISM; GLUCOSE-TRANSPORTER; CELL-METABOLISM; TUMOR-GROWTH; METHYLATION; LACTATE; PKM2; ER AB Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis. C1 [Lopez-Serra, Paula; Palau, Anna; Leal, Lucia; Wahi, Jessica E.; Setien-Baranda, Fernando; Szczesna, Karolina; Moutinho, Catia; Martinez-Cardus, Anna; Heyn, Holger; Sandoval, Juan; Esteller, Manel] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. [Marcilla, Miguel; Pablo Albar, Juan] CSIC, Spanish Natl Biotechnol Ctr CNB, Prote Unit, E-28049 Madrid, Spain. [Villanueva, Alberto; Puertas, Sara; Vinals, Francesc] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Translat Res Lab, Barcelona 08908, Catalonia, Spain. [Ramos-Fernandez, Antonio] Proteobotics SL, Spanish Natl Biotechnol Ctr CNB, Madrid 28049, Spain. [Vidal, August; Sanjuan, Xavier] Bellvitge Univ Hosp, Dept Pathol, Bellvitge Biomed Res Inst IDIBELL, Barcelona 08908, Catalonia, Spain. [Martinez-Balibrea, Eva] Hosp Badalona Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, Catalan Inst Oncol ICO, Med Oncol Serv, Barcelona 08916, Catalonia, Spain. [Vinals, Francesc; Perales, Jose C.; Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, E-08036 Barcelona, Spain. [Bramsem, Jesper B.; Orntoft, Torben F.; Andersen, Claus L.] Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark. [Tabernero, Josep] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Catalonia, Spain. [McDermott, Ultan] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20891 USA. [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Esteller, Manel] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Catalonia, Spain. RP Esteller, M (reprint author), Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. EM mesteller@idibell.cat RI Marcilla, Miguel/B-8430-2013; Andersen, Claus Lindbjerg/A-9217-2012; PERALES, JOSE C./D-5586-2012; Esteller, Manel/L-5956-2014; Lopez-Serra, Paula/M-6835-2015; Vidal, August/N-4662-2016; Andersen, Claus/C-1477-2017; OI Heyn, Holger/0000-0002-3276-1889; Marcilla, Miguel/0000-0001-9171-5076; McDermott, Ultan/0000-0001-9032-4700; Andersen, Claus Lindbjerg/0000-0002-7406-2103; PERALES, JOSE C./0000-0001-7363-2226; Esteller, Manel/0000-0003-4490-6093; Lopez-Serra, Paula/0000-0001-7231-3426; Vidal, August/0000-0001-5727-2099; Andersen, Claus/0000-0002-7406-2103; Martinez-Balibrea, Eva/0000-0002-4501-7100 FU European Community's Seventh Framework Programme [HEALTH-F2-2011-259015-COLTHERES, HEALTH-F5-2010-258236SYSCOL]; Cellex Foundation; Olga Torres Foundation; ERC grant [268626-EPINORC]; Spanish Ministry of Economy and Competitiveness (MINECO Project) [SAF2011-22803]; Institute of Health Carlos III (ISCIII) RTICC Grant [RD12/0036/0039]; Health and Science Departments of the Generalitat de Catalunya FX This work was supported by the European Community's Seventh Framework Programme HEALTH-F2-2011-259015-COLTHERES and HEALTH-F5-2010-258236SYSCOL Grants, Cellex Foundation, Olga Torres Foundation, ERC grant agreement no. 268626-EPINORC project, Spanish Ministry of Economy and Competitiveness (MINECO Project no. SAF2011-22803), the Institute of Health Carlos III (ISCIII) RTICC Grant RD12/0036/0039 and the Health and Science Departments of the Generalitat de Catalunya. We thank the Scientific and Technological Centre (CCiTUB) of the University of Barcelona for the cell cytometry and sorter technical support. NR 50 TC 10 Z9 10 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2014 VL 5 AR 3608 DI 10.1038/ncomms4608 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BQ UT WOS:000335220700013 PM 24699711 ER PT J AU Colman, MW Lozano-Calderon, S Raskin, KA Hornicek, FJ Gebhardt, M AF Colman, Matthew W. Lozano-Calderon, Santiago Raskin, Kevin A. Hornicek, Francis J. Gebhardt, Mark TI Non-neoplastic Soft Tissue Masses That Mimic Sarcoma SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Sarcoma; Imitator; Mimic; Soft tissue ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; MYOSITIS-OSSIFICANS; HETEROTOPIC OSSIFICATION; HIP-ARTHROPLASTY; TUMOR; PSEUDOTUMORS; DIAGNOSIS; LESION; BONE; SIZE AB Non-neoplastic soft tissue masses may mimic soft tissue sarcoma in a wide variety of clinical settings. Systematic and thorough review of patient history, physical examination, imaging, laboratory results, and biopsy will allow the clinician to differentiate between the two in most cases. We describe several common non-neoplastic entities that may mimic soft tissue sarcoma in case presentation format along with the characteristics that help distinguish them. C1 [Colman, Matthew W.; Lozano-Calderon, Santiago; Raskin, Kevin A.; Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Colman, Matthew W.; Lozano-Calderon, Santiago; Gebhardt, Mark] Dept Orthoped Surg, Boston, MA 02215 USA. [Colman, Matthew W.; Lozano-Calderon, Santiago; Gebhardt, Mark] Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Colman, MW (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. EM matthewcolman@gmail.com NR 40 TC 1 Z9 1 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 0030-5898 EI 1558-1373 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD APR PY 2014 VL 45 IS 2 BP 245 EP + DI 10.1016/j.ocl.2013.12.006 PG 12 WC Orthopedics SC Orthopedics GA AG0RB UT WOS:000335122200014 PM 24684918 ER PT J AU Becker, SJE Ring, D AF Becker, S. J. E. Ring, D. TI "A prospective randomized comparison of neoprene vs thermoplast hand-based thumb spica splinting for trapeziometacarpal arthrosis" reply SO OSTEOARTHRITIS AND CARTILAGE LA English DT Letter ID CONTROLLED-TRIALS C1 [Becker, S. J. E.; Ring, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. RP Becker, SJE (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM sjebecker@gmail.com RI Becker, Stephanie/N-5761-2014 NR 2 TC 0 Z9 0 U1 1 U2 4 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 APR PY 2014 VL 22 IS 4 BP 603 EP 604 DI 10.1016/j.joca.2014.02.001 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AG1WT UT WOS:000335207600011 PM 24530279 ER PT J AU Bajpayee, AG Scheu, AM Porter, RM Grodzinsky, AJ AF Bajpayee, A. G. Scheu, A. M. Porter, R. M. Grodzinsky, A. J. TI ELECTROSTATIC INTERACTIONS ENABLE RAPID PENETRATION, ENHANCED UPTAKE & RETENTION OF INTRA-ARTICULAR INJECTED AVIDIN IN RAT KNEE JOINTS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) CY APR 24-27, 2014 CL Paris, FRANCE SP Osteoarthritis Res Soc Int C1 [Bajpayee, A. G.; Grodzinsky, A. J.] MIT, Cambridge, MA 02139 USA. [Scheu, A. M.; Porter, R. M.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 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 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2014 VL 22 SU S BP S472 EP S473 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AG4XX UT WOS:000335424800883 ER PT J AU Alam, MM Aktar, A Afrin, S Rahman, MA Aktar, S Uddin, T Rahman, MA Al Mahbuba, D Chowdhury, F Khan, AI Bhuiyan, TR Begum, YA Ryan, ET Calderwood, SB Svennerholm, AM Qadri, F AF Alam, Mohammad Murshid Aktar, Amena Afrin, Sadia Rahman, Mohammad Arif Aktar, Sarmin Uddin, Taher Rahman, M. Arifur Al Mahbuba, Deena Chowdhury, Fahima Khan, Ashraful Islam Bhuiyan, Taufiqur Rahman Begum, Yasmin Ara Ryan, Edward T. Calderwood, Stephen B. Svennerholm, Ann-Mari Qadri, Firdausi TI Antigen-Specific Memory B-cell Responses to Enterotoxigenic Escherichia coli Infection in Bangladeshi Adults SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID COLONIZATION FACTOR ANTIGENS; VIBRIO-CHOLERAE O1; IMMUNE-RESPONSES; PROTECTIVE IMMUNOGENICITY; IMMUNOLOGICAL MEMORY; ANTIBODY-RESPONSES; HETEROLOGOUS CFAS; ETEC VACCINE; DIARRHEA; DISEASE AB Background Multiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. However, the precise mechanism of protection against ETEC infection is still unknown. Therefore, memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection. Methodology In this study, we investigated the heat labile toxin B subunit (LTB) and colonization factor antigens (CFA/I and CS6) specific IgA and IgG memory B cell responses in Bangladeshi adults (n = 52) who were infected with ETEC. We also investigated the avidity of IgA and IgG antibodies that developed after infection to these antigens. Principal Findings Patients infected with ETEC expressing LT or LT+heat stable toxin (ST) and CFA/I group or CS6 colonization factors developed LTB, CFA/I or CS6 specific memory B cell responses at day 30 after infection. Similarly, these patients developed high avidity IgA and IgG antibodies to LTB, CFA/I or CS6 at day 7 that remained significantly elevated at day 30 when compared to the avidity of these specific antibodies at the acute stage of infection (day 2). The memory B cell responses, antibody avidity and other immune responses to CFA/I not only developed in patients infected with ETEC expressing CFA/I but also in those infected with ETEC expressing CFA/I cross-reacting epitopes. We also detected a significant positive correlation of LTB, CFA/I and CS6 specific memory B cell responses with the corresponding increase in antibody avidity. Conclusion This study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to LTB and colonization factor CFA/I and CS6 antigens that could mediate anamnestic responses on re-exposure to ETEC and may help in understanding the requirements to design an effective vaccination strategies. Author Summary Enterotoxigenic Escherichia coli (ETEC) is a non-invasive pathogen causing diarrhea in children as well as in adults and travelers in developing countries. After colonizing the intestine using colonization factors, the organisms secrete heat-stable (ST) and/or heat-labile (LT) enterotoxin to cause watery diarrhea. Natural infection with ETEC provides protection against subsequent infection; however, the precise mechanism is unknown. In this study, we have shown that adult patients with diarrhea infected with ETEC develop toxin (LTB) and colonization factor (CFA/I and CS6) specific memory B cell responses as well as highly avid antigen-specific antibodies. The antibody avidity indices were shown to be positively associated with memory B cell responses, suggesting that these processes may occur in concert. This study encourages further evaluation of such responses in children as well as in vaccinees. C1 [Alam, Mohammad Murshid; Aktar, Amena; Afrin, Sadia; Rahman, Mohammad Arif; Aktar, Sarmin; Uddin, Taher; Rahman, M. Arifur; Al Mahbuba, Deena; Chowdhury, Fahima; Khan, Ashraful Islam; Bhuiyan, Taufiqur Rahman; Begum, Yasmin Ara; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Svennerholm, Ann-Mari] Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg Univ Vaccine Res Inst GUVAX, Gothenburg, Sweden. RP Alam, MM (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b); Swedish Sida (SIDA) [INT-ICDDR, B-HN-01-AV]; Swedish collaborative grant [SIDA-SWE2009-023]; European Union [261472-STOPENTERICS]; National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI077883, AI106878, AI058935]; Fogarty International Center [TW005572] FX This work was supported by the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), the Swedish Sida (SIDA) (grant INT-ICDDR, B-HN-01-AV) and Swedish collaborative grant SIDA-SWE2009-023 as well as from the European Union's Seventh Framework Programme for research, technological development and demonstration under Grant Agreement no 261472-STOPENTERICS. This study is also supported by grants from the National Institutes of Health, including grants from the National Institute of Allergy and Infectious Diseases (AI077883 [ETR and FQ], AI106878, AI058935 [SBC, ETR, and FQ], a Training Grant in Vaccine Development from the Fogarty International Center (TW005572 [TU, MMA and FQ]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 7 Z9 7 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2014 VL 8 IS 4 DI 10.1371/journal.pntd.0002822 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AG3TK UT WOS:000335342400007 PM 24762744 ER PT J AU Nishino, M Hatabu, H Johnson, BE McLoud, TC AF Nishino, Mizuki Hatabu, Hiroto Johnson, Bruce E. McLoud, Theresa C. TI State of the Art: Assessment in Lung Cancer in the Era of Genomic Medicine SO RADIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; SOLITARY PULMONARY NODULES; GROWTH-FACTOR RECEPTOR; EML4-ALK FUSION GENE; RESPONSE EVALUATION CRITERIA; TYROSINE KINASE INHIBITORS; STANDARDIZED UPTAKE VALUE; DIFFUSION-WEIGHTED MRI; CONTRAST-ENHANCED MRI; GUIDELINE VERSION 1.1 AB Tumor response assessment has been a foundation for advances in cancer therapy. Recent discoveries of effective targeted therapy for specific genomic abnormalities in lung cancer and their clinical application have brought revolutionary advances in lung cancer therapy and transformed the oncologist's approach to patients with lung cancer. Because imaging is a major method of response assessment in lung cancer both in clinical trials and practice, radiologists must understand the genomic alterations in lung cancer and the rapidly evolving therapeutic approaches to effectively communicate with oncology colleagues and maintain the key role in lung cancer care. This article describes the origin and importance of tumor response assessment, presents the recent genomic discoveries in lung cancer and therapies directed against these genomic changes, and describes how these discoveries affect the radiology community. The authors then summarize the conventional Response Evaluation Criteria in Solid Tumors and World Health Organization guidelines, which continue to be the major determinants of trial endpoints, and describe their limitations particularly in an era of genomic-based therapy. More advanced imaging techniques for lung cancer response assessment are presented, including computed tomography tumor volume and perfusion, dynamic contrast material-enhanced and diffusion-weighted magnetic resonance imaging, and positron emission tomography with fluorine 18 fluorodeoxyglucose and novel tracers. State-of-art knowledge of lung cancer biology, treatment, and imaging will help the radiology community to remain effective contributors to the personalized care of lung cancer patients. (C) RSNA, 2014 C1 [Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Nishino, Mizuki; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [McLoud, Theresa C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU National Cancer Institute [1K23CA157631, 5R21 CA11627- 02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578- 06] FX Supported by the National Cancer Institute (grant 1K23CA157631 [M.N.]), the National Institutes of Health ( grants 1RO1CA114465- 01 [B.E.J.] and 5R21 CA11627- 02 [H.H.], and the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer ( grant 2P50CA090578- 06 [B.E. J.]). NR 115 TC 24 Z9 24 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2014 VL 271 IS 1 BP 6 EP 27 DI 10.1148/radiol.14122524 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG0XN UT WOS:000335139200002 PM 24661292 ER PT J AU Chen, X Qin, L Pan, D Huang, YQ Yan, LF Wang, GY Liu, YB Liang, CH Liu, ZY AF Chen, Xin Qin, Lei Pan, Dan Huang, Yanqi Yan, Lifen Wang, Guangyi Liu, Yubao Liang, Changhong Liu, Zaiyi TI Liver Diffusion-weighted MR Imaging: Reproducibility Comparison of ADC Measurements Obtained with Multiple Breath-hold, Free-breathing, Respiratory-triggered, and Navigator-triggered Techniques SO RADIOLOGY LA English DT Article ID COEFFICIENTS; LESIONS; TUMORS; RELIABILITY; MODELS; VALUES AB To prospectively compare the reproducibility of normal liver apparent diffusion coefficient (ADC) measurements by using different respiratory motion compensation techniques with multiple breath-hold (MBH), free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) diffusion-weighted (DW) imaging and to compare the ADCs at different liver anatomic locations. The study protocol was approved by the institutional review board, and written informed consent was obtained from each participant. Thirty-nine volunteers underwent liver DW imaging twice. Imaging was performed with a 1.5-T MR imager with MBH, FB, RT, and NT techniques (b = 0, 100, and 500 sec/mm(2)). Three representative sections-superior, central, and inferior-were selected on left and right liver lobes, respectively. On each selected section, three regions of interest were drawn, and ADCs were measured. Analysis of variance was used to assess ADCs among the four techniques and various anatomic locations. Reproducibility of ADCs was assessed with the Bland-Altman method. ADCs obtained with MBH (range: right lobe, [1.641-1.662] Chi 10(-3)mm(2)/sec; left lobe, [2.034-2.054] Chi 10(-3)mm(2)/sec) were higher than those obtained with FB (right, [1.349-1.391] Chi 10(-3)mm(2)/sec; left, [1.630-1.700] Chi 10(-3)mm(2)/sec), RT (right, [1.439-1.455] Chi 10(-3)mm(2)/sec; left, [1.720-1.755] Chi 10(-3)mm(2)/sec), or NT (right, [1.387-1.400] Chi 10(-3)mm(2)/sec; left, [1.661-1.736] Chi 10(-3)mm(2)/sec) techniques (P < .001); however, no significant difference was observed between ADCs obtained with FB, RT, and NT techniques (P = .130 to P > . 99). ADCs showed a trend to decrease moving from left to right. Reproducibility in the left liver lobe was inferior to that in the right, and the central middle segment in the right lobe had the most reproducible ADC. Statistical differences in ADCs were observed in the left-right direction in the right lobe (P < .001), but they were not observed in the superior-inferior direction (P = .144-.450). However, in the left liver lobe, statistical differences existed in both directions (P = .001 to P = .016 in the left-right direction, P < .001 in the superior-inferior direction). Both anatomic location and DW imaging technique influence liver ADC measurements and their reproducibility. FB DW imaging is recommended for liver DW imaging because of its good reproducibility and shorter acquisition time compared with that of MBH, RT, and NT techniques. (C) RSNA, 2014 C1 [Chen, Xin; Pan, Dan; Huang, Yanqi; Yan, Lifen; Wang, Guangyi; Liu, Yubao; Liang, Changhong; Liu, Zaiyi] Guangdong Acad Med Sci, Dept Radiol, Guangdong Gen Hosp, Guangzhou 510080, Guangdong, Peoples R China. [Chen, Xin; Pan, Dan] Southern Med Univ, Grad Coll, Guangzhou, Guangdong, Peoples R China. [Qin, Lei] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Liu, ZY (reprint author), Guangdong Acad Med Sci, Dept Radiol, Guangdong Gen Hosp, 106 Zhongshan Er Rd, Guangzhou 510080, Guangdong, Peoples R China. EM zyliu@163.com NR 29 TC 25 Z9 29 U1 0 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2014 VL 271 IS 1 BP 113 EP 125 DI 10.1148/radiol.13131572 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG0XN UT WOS:000335139200012 PM 24475860 ER PT J AU Bierry, G Simeone, FJ Borg-Stein, JP Clavert, P Palmer, WE AF Bierry, Guillaume Simeone, F. Joseph Borg-Stein, Joanne P. Clavert, Philippe Palmer, William E. TI Sacrotuberous Ligament: Relationship to Normal, Torn, and Retracted Hamstring Tendons on MR Images SO RADIOLOGY LA English DT Article ID SURGICAL REPAIR; PROXIMAL ORIGIN; MUSCLE COMPLEX; WATER SKIERS; INJURIES; RUPTURE; TENDINOPATHY; PATHOPHYSIOLOGY; MANAGEMENT; DIAGNOSIS AB Purpose: To evaluate continuity of the sacrotuberous ligament (STL) in normal and abnormal hamstring (HS) tendons on magnetic resonance (MR) images and to test the hypothesis that greater degrees of HS retraction are correlated with STL discontinuity. Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Control cohort comprised 33 patients (mean age, 54.1 years) without HS abnormalities at hip MR arthrography. Study cohort comprised 100 patients (mean age, 55.3 years) with HS abnormalities at pelvic or hip MR imaging. Two musculoskeletal radiologists independently assessed STL continuity with the ischium and semimembranosus (SM) and conjoined biceps femoris and semitendinosus (BF-ST) tendons and evaluated these tendons for tendinopathy, partial tear, or rupture. A third musculoskeletal radiologist measured retraction of ruptured tendons. Inter- and intraobserver agreement was calculated with weighted kappa or intraclass correlation coefficients. HS abnormalities in the cohorts were compared with Mann-Whitney test. In patients with tendon rupture, relationships between qualitative (STL and HS attachments) and quantitative (tendon retraction measurements) data were analyzed with analysis of variance and linear regression with Bonferroni correction. Results: STL was continuous with ischium in all patients. In control patients, STL was always continuous with BF-ST but never continuous with SM. In study patients, BF-ST tendon alone, SM tendon alone, and both BF-ST and SM tendons showed abnormalities in 17, six, and 77 patients, respectively. HS rupture occurred in 24 patients; it involved BF-ST tendon alone in 13 patients and both BF-ST and SM tendons in 11. STL was continuous with BF-ST tendon in 12 patients and discontinuous in 12 patients. Retraction of BF-ST tendon (mean, 33 mm; range, 5-81 mm) was independently correlated with STL continuity with BF-ST (P =.0001) and SM (P =.0004) tendon rupture. Retraction was significantly greater (P < .0.01) when STL was discontinuous and SM tendon was ruptured. Inter- and intraobserver agreement was very good or excellent in categorization of HS abnormalities and measurement of retraction. Conclusion: STL showed continuity with both ischium and BF-ST tendon but not SM tendon. In HS rupture, tendon retraction was significantly less when STL remained attached to BF-ST tendon. (C) RSNA, 2013 C1 [Bierry, Guillaume] Univ Hosp Strasbourg, Dept Radiol, Strasbourg, France. [Clavert, Philippe] Univ Hosp Strasbourg, Dept Orthoped Surg, Strasbourg, France. [Simeone, F. Joseph; Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Borg-Stein, Joanne P.] Newton Wellesley Hosp, Dept Phys Med & Rehabil, Newton, MA USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM wpalmer@partners.org NR 40 TC 9 Z9 9 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2014 VL 271 IS 1 BP 162 EP 171 DI 10.1148/radiol.13130702 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG0XN UT WOS:000335139200017 PM 24475819 ER PT J AU Stewart, L AF Stewart, Lygia TI latrogenic Biliary Injuries Identification, Classification, and Management SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Bile duct injury; Biliary stricture; Laparoscopic cholecystectomy; Management; Biliary-enteric anastomosis ID BILE-DUCT INJURIES; HEPATIC-ARTERY INJURY; QUALITY-OF-LIFE; LAPAROSCOPIC CHOLECYSTECTOMY; SURGICAL REPAIR; VASCULAR INJURIES; REFERRAL PATTERN; NATIONAL-SURVEY; RISK-FACTORS; FOLLOW-UP AB Because it offers several advantages over open cholecystectomy, laparoscopic cholecystectomy has largely replaced open cholecystectomy for the management of symptomatic gallstone disease. The only potential disadvantage is a higher incidence of major bile duct injury. Although prevention of these biliary injuries is ideal, when they do occur, early identification and appropriate treatment are critical to improving the outcomes of patients suffering a major bile duct injury. This report delineates the key factors in classification (and its relationship to mechanism and management), identification (intraoperative and postoperative), and management principles of these bile duct injuries. C1 [Stewart, Lygia] Univ Calif San Francisco, Dept Surg 112, San Francisco, CA 94121 USA. [Stewart, Lygia] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Dept Surg 112, San Francisco, CA 94121 USA. EM lygia.stewart@va.gov NR 85 TC 11 Z9 14 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD APR PY 2014 VL 94 IS 2 BP 297 EP + DI 10.1016/j.suc.2014.01.008 PG 15 WC Surgery SC Surgery GA AG4WM UT WOS:000335421100008 PM 24679422 ER PT J AU Zhang, XY Bailey, SD Lupien, M AF Zhang, Xiaoyang Bailey, Swneke D. Lupien, Mathieu TI Laying a solid foundation for Manhattan - 'setting the functional basis for the post-GWAS era' SO TRENDS IN GENETICS LA English DT Review DE GWAS; genetic risk variant; causal variant; missing heritability; functional genomic; non-coding ID GENOME-WIDE ASSOCIATION; TRANSCRIPTION FACTOR-BINDING; BREAST-CANCER RISK; SINGLE-NUCLEOTIDE POLYMORPHISMS; EXONIC SPLICING ENHANCERS; CORONARY-ARTERY-DISEASE; TERT PROMOTER MUTATIONS; PLURIPOTENT STEM-CELLS; LONG-RANGE INTERACTION; GENETIC-VARIATION AB Genome-wide association studies (GWAS) have identified more than 8900 genetic variants, mainly single-nucleotide polymorphisms (SNPs), associated with hundreds of human traits and diseases, which define risk-associated loci. Variants that map to coding regions can affect protein sequence, translation rate, and alternative splicing, all of which influence protein function. However, the vast majority of sequence variants map to noncoding intergenic and intronic regions, and it has been much more challenging to assess the functional nature of these variants. Recent work annotating the non-coding regions of the genome has contributed to post-GWAS studies by facilitating the identification of the functional targets of risk-associated loci. Many non-coding genetic variants within risk-associated loci alter gene expression by modulating the activity of cis-regulatory elements. We review here these recent findings, discuss their implication for the post-GWAS era, and relate their importance to the interpretation of disease-associated mutations identified through whole-genome sequencing. C1 [Zhang, Xiaoyang] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Genet, Lebanon, NH USA. [Bailey, Swneke D.; Lupien, Mathieu] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [Bailey, Swneke D.; Lupien, Mathieu] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Lupien, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. RP Zhang, XY (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM mlupien@uhnres.utoronto.ca FU National Cancer Institute (NCI) of the National Institutes of Health (NIH) [R01CA155004]; Princess Margaret Cancer Foundation; Ontario Institute for Cancer Research; Canadian Institute of Health Research (CIHR); Knudson postdoctoral fellowship from the Princess Margaret Cancer Centre FX The National Cancer Institute (NCI) of the National Institutes of Health (NIH) under Award Number R01CA155004 (M.L.) and the Princess Margaret Cancer Foundation (M.L.) supported the research reported in this publication. The research content reported is the sole responsibility of the authors and does not necessarily represent the official views of the funding sources. M.L holds a young investigator award from the Ontario Institute for Cancer Research and a new investigator salary award from the Canadian Institute of Health Research (CIHR). S.D.B. is supported by a Knudson postdoctoral fellowship from the Princess Margaret Cancer Centre. NR 153 TC 29 Z9 29 U1 3 U2 36 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2014 VL 30 IS 4 BP 140 EP 149 DI 10.1016/j.tig.2014.02.006 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AG4YM UT WOS:000335426300004 PM 24661571 ER PT J AU Benjamin, S Travis, MJ Cooper, JJ Dickey, CC Reardon, CL AF Benjamin, Sheldon Travis, Michael J. Cooper, Joseph J. Dickey, Chandlee C. Reardon, Claudia L. TI Neuropsychiatry and Neuroscience Education of Psychiatry Trainees: Attitudes and Barriers SO ACADEMIC PSYCHIATRY LA English DT Article DE Psychiatric residency education; Curriculum development; Neuropsychiatry; Next Accreditation System; Milestones ID NEUROLOGY; RESIDENTS; FUTURE AB Objective The American Association of Directors of Psychiatric Residency Training (AADPRT) Task Force on Neuropsychiatry and Neuroscience Education of Psychiatry Residents was established in 2011 with the charge to seek information about what the field of psychiatry considers the core topics in neuropsychiatry and neuroscience to which psychiatry residents should be exposed; whether there are any "competencies" in this area on which the field agrees; whether psychiatry departments have the internal capacity to teach these topics if they are desirable; and what the reception would be for "portable curricula" in neuroscience. Methods The task force reviewed the literature and developed a survey instrument to be administered nationwide to all psychiatry residency program directors. The AADPRT Executive Committee assisted with the survey review, and their feedback was incorporated into the final instrument. Results In 2011-2012, 226 adult and child and adolescent psychiatry residency program directors responded to the survey, representing over half of all US adult and child psychiatry training directors. About three quarters indicated that faculty resources were available in their departments but 39 % felt the lack of neuropsychiatry faculty and 36 % felt the absence of neuroscience faculty to be significant barriers. Respectively, 64 and 60 % felt that neuropsychiatry and psychiatric neuroscience knowledge were very important or critically important to the provision of excellent care. Ninety-two percent were interested in access to portable neuroscience curricula. Conclusions There is widespread agreement among training directors on the importance of neuropsychiatry and neuroscience knowledge to general psychiatrists but barriers to training exist, including some programs that lack faculty resources and a dearth of portable curricula in these areas. C1 [Benjamin, Sheldon] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Travis, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Cooper, Joseph J.] Univ Chicago, Chicago, IL 60637 USA. [Dickey, Chandlee C.] VA Boston Healthcare Syst, Brockton, MA USA. [Reardon, Claudia L.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Benjamin, S (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. EM sheldon.benjamin@umassmed.edu OI Benjamin, Sheldon/0000-0001-6279-1934 NR 23 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD APR PY 2014 VL 38 IS 2 BP 135 EP 140 DI 10.1007/s40596-014-0051-9 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA AF0OQ UT WOS:000334414300006 PM 24643397 ER PT J AU Dickey, CC Tarnavsky, T Khan, I Panych, LP AF Dickey, Chandlee C. Tarnavsky, Tetanya Khan, Ilea Panych, Lawrence P. TI Decreasing Inter-resident Conflict by Using Computer-generated On-call Schedules SO ACADEMIC PSYCHIATRY LA English DT Article DE Psychiatry residents; On-call; Chief resident ID HOUR RESTRICTIONS; SLEEP LOSS; WORK HOURS; PHYSICIANS; EDUCATION; BURNOUT AB Although significant attention has been paid to the number of hours worked by residents, little consideration has been given to how the hours are assigned. This project describes an alternative to having Chief Residents manually create on-call schedules. In order to enhance objectivity and transparency, reduce perceived inequities in the process, and reduce inter-resident conflict, Harvard South Shore Psychiatry Residency Training Program experimented with a computer-generated on-call schedule. A locally written MATLAB script generated an on-call schedule for academic year (AY) 2012-2013. Measurements to assess the manual scheduling method (from AY 2011-2012) and the computer-generated method included the balance in the total number of hours assigned to individual residents; the number of call switches over two six-month periods; and survey of the residents' perception of fairness of the two scheduling methods and preferences. A retrospective analysis of the AY 2011-2012 Chief Resident-generated call schedule found a range of differences of up to 25.8 % between total hours assigned to individual residents in a given year. In the AY 2012-2013 computer-generated schedule, the differences in total hours assigned were reduced to a maximum of 6.1 %. There were 63 % fewer call switches resulting from the computer-generated as compared to the Chief Resident-generated method. Resident survey response rate was 76 %. Seventy-seven percent of resident respondents (N = 22) perceived the computer-generated method to be fairer, and 90.9 % of residents preferred having a summary table of hours of call per resident. Residents perceived the computer-generated method as resulting in less inter-resident conflict. Methods for assigning duty hour schedules that are transparent, equitable, and require less Chief involvement may result in perceptions of greater fairness and less inter-resident conflict. C1 [Dickey, Chandlee C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Tarnavsky, Tetanya; Khan, Ilea] Harvard Univ, Sch Med, Boston, MA USA. [Panych, Lawrence P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Dickey, CC (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM Chandlee.Dickey@va.gov NR 20 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD APR PY 2014 VL 38 IS 2 BP 213 EP 216 DI 10.1007/s40596-014-0060-8 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA AF0OQ UT WOS:000334414300019 PM 24519802 ER PT J AU Courter, JR Madani, N Sodroski, J Schon, A Freire, E Kwong, PD Hendrickson, WA Chaiken, IM LaLonde, JM Smith, AB AF Courter, Joel R. Madani, Navid Sodroski, Joseph Schoen, Arne Freire, Ernesto Kwong, Peter D. Hendrickson, Wayne A. Chaiken, Irwin M. LaLonde, Judith M. Smith, Amos B., III TI Structure-Based Design, Synthesis and Validation of CD4-Mimetic Small Molecule Inhibitors of HIV-1 Entry: Conversion of a Viral Entry Agonist to an Antagonist SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN TRIMER; CD4 RECEPTOR-BINDING; CONFORMATIONAL-CHANGES; GP120; ANTIBODY AB CONSPECTUS: This Account provides an overview of a multidisciplinary consortium focused on structure-based strategies to devise small molecule antagonists of HIV-1 entry into human T-cells, which if successful would hold considerable promise for the development of prophylactic modalities to prevent HIV transmission and thereby alter the course of the AIDS pandemic. Entry of the human immunodeficiency virus (HIV) into target T-cells entails an interaction between CD4 on the host T-cell and gp120, a component of the trimeric envelope glycoprotein spike on the virion surface. The resultant interaction initiates a series of conformational changes within the envelope spike that permits binding to a chemokine receptor, formation of the gp41 fusion complex, and cell entry. A hydrophobic cavity at the CD4-gp120 interface, defined by X-ray crystallography, provided an initial site for small molecule antagonist design. This site however has evolved to facilitate viral entry. As such, the binding of prospective small molecule inhibitors within this gp120 cavity can inadvertently trigger an allosteric entry signal. Structural characterization of the CD4-gp120 interface, which provided the foundation for small molecule structure-based inhibitor design, will be presented first. An integrated approach combining biochemical, virological, structural, computational, and synthetic studies, along with a detailed analysis of ligand binding energetics, revealed that modestly active small molecule inhibitors of HIV entry can also promote viral entry into cells lacking the CD4 receptor protein; these competitive inhibitors were termed small molecule CD4 mimetics. Related congeners were subsequently identified with both improved binding affinity and more potent viral entry inhibition. Further assessment of the affinity-enhanced small molecule CD4 mimetics demonstrated that premature initiation of conformational change within the viral envelope spike, prior to cell encounter, can lead to irreversible deactivation of viral entry machinery. Related congeners, which bind the same gp120 site, possess different propensities to elicit the allosteric response that underlies the undesired enhancement of CD4-independent viral entry. Subsequently, key hotspots in the CD4-gp120 interface were categorized using mutagenesis and isothermal titration calorimetry according to the capacity to increase binding affinity without triggering the allosteric signal. This analysis, combined with cocrystal structures of small molecule viral entry agonists with gp120, led to the development of fully functional antagonists of HIV-1 entry. Additional structure-based design exploiting two hotspots followed by synthesis has now yielded low micromolar inhibitors of viral entry. C1 [Courter, Joel R.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Ragon Inst MGH MIT & Harvard, Dept Microbiol & Immunol,Med Sch,Dept Immunol & I, Boston, MA 02115 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Chaiken, Irwin M.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. RP Smith, AB (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. FU NIH [P01 GM 56550] FX The authors thank all previous co-workers who have helped advance this project. The research presented in this Account has been primarily supported for over 15 years through an NIH Program Project (P01 GM 56550). NR 42 TC 25 Z9 25 U1 2 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD APR PY 2014 VL 47 IS 4 BP 1228 EP 1237 DI 10.1021/ar4002735 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA AF4CE UT WOS:000334658200025 PM 24502450 ER PT J AU Pereira, MJN Sundback, CA Lang, N Cho, WK Pomerantseva, I Ouyang, B Tao, SL McHugh, K Mwizerwa, O Vemula, PK Mochel, MC Carter, DJ Borenstein, JT Langer, R Ferreira, LS Karp, JM Masiakos, PT AF Pereira, Maria J. N. Sundback, Cathryn A. Lang, Nora Cho, Woo Kyung Pomerantseva, Irina Ouyang, Ben Tao, Sarah L. McHugh, Kevin Mwizerwa, Olive Vemula, Praveen K. Mochel, Mark C. Carter, David J. Borenstein, Jeffrey T. Langer, Robert Ferreira, Lino S. Karp, Jeffrey M. Masiakos, Peter T. TI Combined Surface Micropatterning and Reactive Chemistry Maximizes Tissue Adhesion with Minimal Inflammation SO ADVANCED HEALTHCARE MATERIALS LA English DT Article DE wet tissue adhesives; microtextured surfaces; biodegradable glues; bioinspired; biocompatibility ID CYANOACRYLATE AB The use of tissue adhesives for internal clinical applications is limited due to a lack of materials that balance strong adhesion with biocompatibility. The use of substrate topography is explored to reduce the volume of a highly reactive and toxic glue without compromising adhesive strength. Micro-textured patches coated with a thin layer of cyanoacrylate glue achieve similar adhesion levels to patches employing large amounts of adhesive, and is superior to the level of adhesion achieved when a thin coating is applied to a non-textured patch. In vivo studies demonstrate reduced tissue inflammation and necrosis for patterned patches with a thinly coated layer of reactive glue, thus overcoming a significant challenge with existing tissue adhesives such as cyanoacrylate. Closure of surgical stomach and colon defects in a rat model is achieved without abdominal adhesions. Harnessing the synergy between surface topography and reactive chemistry enables controlled tissue adhesion with an improved biocompatibility profile without requiring changes in the chemical composition of reactive tissue glues. C1 [Pereira, Maria J. N.; Cho, Woo Kyung; Ouyang, Ben; Vemula, Praveen K.; Karp, Jeffrey M.] Harvard Univ, Harvard MIT Div Hlth Sci & Technol, Ctr Regenerat Therapeut,Div Biomed Engn,Sch Med, Harvard Stem Cell Inst,Brigham & Womens Hosp,Dept, Cambridge, MA 02139 USA. [Pereira, Maria J. N.; Ferreira, Lino S.] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Biocant Biotechnol Innovat Ctr, P-3004517 Coimbra, Portugal. [Sundback, Cathryn A.; Pomerantseva, Irina; Mwizerwa, Olive; Masiakos, Peter T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Lang, Nora] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiac Surg, Boston, MA 02115 USA. [Cho, Woo Kyung; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Cho, Woo Kyung; Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Cho, Woo Kyung] Chungnam Natl Univ, Dept Chem, Taejon 305764, South Korea. [Tao, Sarah L.; McHugh, Kevin; Carter, David J.; Borenstein, Jeffrey T.] Draper Lab Biomed Engn, Cambridge, MA 02139 USA. [Mochel, Mark C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ferreira, LS (reprint author), Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Biocant Biotechnol Innovat Ctr, P-3004517 Coimbra, Portugal. EM lino@biocant.pt; jkarp@rics.bwh.harvard.edu; pmasiakos@partners.org OI ferreira, lino/0000-0001-8985-9302 FU National Institutes of Health [GM086433, DE013023]; Portuguese Foundation for Science and Technology [SFR/BD/43013/2008] FX The authors would like to thank Admet Inc. for generously providing an eXpert 7601 mechanical tester that was critical for this work. This work was also supported by the National Institutes of Health grant GM086433 to J. M. K., and National Institutes of Health grant DE013023 to R. L. M. J. P. acknowledges the Portuguese Foundation for Science and Technology (fellowship SFR/BD/43013/2008) and the MIT-Portugal program (Bioengineering focus area). NR 18 TC 9 Z9 9 U1 4 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD APR PY 2014 VL 3 IS 4 BP 565 EP 571 DI 10.1002/adhm.201300264 PG 7 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA AE8VZ UT WOS:000334282400012 PM 24106240 ER PT J AU Jimenez, JJ Wikramanayake, TC Bergfeld, W Hordinsky, M Hickman, JG Hamblin, MR Schachner, LA AF Jimenez, Joaquin J. Wikramanayake, Tongyu C. Bergfeld, Wilma Hordinsky, Maria Hickman, Janet G. Hamblin, Michael R. Schachner, Lawrence A. TI Efficacy and Safety of a Low-level Laser Device in the Treatment of Male and Female Pattern Hair Loss: A Multicenter, Randomized, Sham Device-controlled, Double-blind Study SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID 2-PERCENT TOPICAL MINOXIDIL; ANDROGENETIC ALOPECIA; CLINICAL-TRIAL; ORAL MUCOSITIS; PART I; THERAPY; FINASTERIDE; LIGHT; MEN; INFLAMMATION AB Male and female pattern hair loss are common, chronic dermatologic disorders with limited therapeutic options. In recent years, a number of commercial devices using low-level laser therapy have been promoted, but there have been little peer-reviewed data on their efficacy. To determine whether treatment with a low-level laser device, the US FDA-cleared HairMax Lasercomb(A (R)), increases terminal hair density in both men and women with pattern hair loss. Randomized, sham device-controlled, double-blind clinical trials were conducted at multiple institutional and private practices. A total of 146 male and 188 female subjects with pattern hair loss were screened. A total of 128 male and 141 female subjects were randomized to receive either a lasercomb (one of three models) or a sham device in concealed sealed packets, and were treated on the whole scalp three times a week for 26 weeks. Terminal hair density of the target area was evaluated at baseline and at 16- and 26-week follow-ups, and analyzed to determine whether the hypothesis formulated prior to data collection, that lasercomb treatment would increase terminal hair density, was correct. The site investigators and the subjects remained blinded to the type of device they dispensed/received throughout the study. The evaluator of masked digital photographs was blinded to which trial arm the subject belonged. Seventy-eight, 63, 49, and 79 subjects were randomized in four trials of 9-beam lasercomb treatment in female subjects, 12-beam lasercomb treatment in female subjects, 7-beam lasercomb treatment in male subjects, and 9- and 12-beam lasercomb treatment in male subjects, compared with the sham device, respectively. Nineteen female and 25 male subjects were lost to follow-up. Among the remaining 122 female and 103 male subjects in the efficacy analysis, the mean terminal hair count at 26 weeks increased from baseline by 20.2, 20.6, 18.4, 20.9, and 25.7 per cm(2) in 9-beam lasercomb-treated female subjects, 12-beam lasercomb-treated female subjects, 7-beam lasercomb-treated male subjects, and 9- and 12-beam lasercomb-treated male subjects, respectively, compared with 2.8 (p < 0.0001), 3.0 (p < 0.0001), 1.6 (p = 0.0017), 9.4 (p = 0.0249), and 9.4 (p = 0.0028) in sham-treated subjects (95 % confidence interval). The increase in terminal hair density was independent of the age and sex of the subject and the lasercomb model. Additionally, a higher percentage of lasercomb-treated subjects reported overall improvement of hair loss condition and thickness and fullness of hair in self-assessment, compared with sham-treated subjects. No serious adverse events were reported in any subject receiving the lasercomb in any of the four trials. We observed a statistically significant difference in the increase in terminal hair density between lasercomb- and sham-treated subjects. No serious adverse events were reported. Our results suggest that low-level laser treatment may be an effective option to treat pattern hair loss in both men and women. Additional studies should be considered to determine the long-term effects of low-level laser treatment on hair growth and maintenance, and to optimize laser modality. C1 [Jimenez, Joaquin J.; Wikramanayake, Tongyu C.; Schachner, Lawrence A.] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Miami, FL 33136 USA. [Bergfeld, Wilma] Cleveland Clin Fdn, Dept Dermatol, Cleveland, OH 44195 USA. [Hordinsky, Maria] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Hickman, Janet G.] Educ & Res Fdn Inc, Lynchburg, VA 24501 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Jimenez, JJ (reprint author), Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Miami, FL 33136 USA. EM j.jimenez@med.miami.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Lexington International, LLC; Department of Dermatology at the University of Minnesota; NIH [R01AI050875] FX The authors would like to thank Zoe Draelos, MD (Dermatology Consulting Services, High Point), David Goldberg, MD (Skin Laser and Surgery Specialist, Hillsborough, NJ, USA; Hackensack, NJ, USA), Michael Jarratt, MD (DermaResearch, Inc., Austin, TX, USA), Abe Marcadis, MD (Palm Beach Research Center, West Palm Beach, FL, USA), and Jose Mendez, DO (International Dermatology Research, Inc., Miami, FL, USA) for their participation. Statistical analyses were contracted to Stat-Tech Services, LLC (Chapel Hill, NC, USA). Lexington International, LLC partially funded the study, and provided the treatment and sham devices and equipment (including the digital imaging system). M. R. Hamblin has received honorarium/consulting fees, and L. A. Schachner has received fees for participation from Lexington International, LLC. M. Hordinsky has received, on behalf of the Department of Dermatology at the University of Minnesota, a grant to conduct part of this study. J.J. Jimenez, T. C. Wikramanayake, W. F. Bergfeld, and J.G. Hickman have no conflicts of interest that are directly relevant to this study. M. R. Hamblin was supported by a NIH grant R01AI050875. The authors have full control of all primary data, and agree to allow the journal to review their data if requested. NR 39 TC 21 Z9 22 U1 1 U2 16 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 EI 1179-1888 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PD APR PY 2014 VL 15 IS 2 BP 115 EP 127 DI 10.1007/s40257-013-0060-6 PG 13 WC Dermatology SC Dermatology GA AF0VA UT WOS:000334431000006 PM 24474647 ER PT J AU Duncan, LE Pollastri, AR Smoller, JW AF Duncan, Laramie E. Pollastri, Alisha R. Smoller, Jordan W. TI Mind the Gap Why Many Geneticists and Psychological Scientists Have Discrepant Views About Gene-Environment Interaction (GXE) Research SO AMERICAN PSYCHOLOGIST LA English DT Article DE gene-environment interaction (GXE); genetics; depression; 5-HTTLPR; publication bias ID GENOME-WIDE ASSOCIATION; STRESSFUL LIFE EVENTS; DE-NOVO MUTATIONS; SEROTONIN TRANSPORTER POLYMORPHISM; DEFICIT HYPERACTIVITY DISORDER; RARE CHROMOSOMAL DELETIONS; BY-ENVIRONMENT INTERACTION; AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIANTS; PSYCHIATRIC-DISORDERS AB As our field seeks to elucidate the biopsychosocial etiologies of mental health disorders, many traditional psychological and social science researchers have added, or plan to add, genetic components to their programs of research. An understanding of the history, methods, and perspectives of the psychiatric genetics community is useful in this pursuit. In this article we provide a brief overview of psychiatric genetic methods and findings. This overview lays the groundwork for a more thorough review of gene-environment interaction (GXE) research and the candidate gene approach to GXE research that remains popular among many psychologists and social scientists. We describe the differences in perspective between psychiatric geneticists and psychological scientists that have contributed to a growing divide between the research cited and conducted by these two related disciplines. Finally, we outline a strategy for the future of research on gene-environment interactions that capitalizes on the relative strengths of each discipline. C1 [Duncan, Laramie E.] Harvard Univ, Sch Med, Broad Inst MIT & Harvard, Dept Psychiat,Stanley Ctr Psychiat Res, Cambridge, MA 02138 USA. [Duncan, Laramie E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pollastri, Alisha R.; Smoller, Jordan W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Pollastri, Alisha R.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Smoller, Jordan W.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Pollastri, AR (reprint author), Massachusetts Gen Hosp, 151 Merrimac St,5th Floor, Boston, MA 02114 USA. EM apollastri@mgh.harvard.edu NR 70 TC 29 Z9 29 U1 5 U2 38 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2014 VL 69 IS 3 BP 249 EP 268 DI 10.1037/a0036320 PG 20 WC Psychology, Multidisciplinary SC Psychology GA AF4LZ UT WOS:000334685500003 PM 24750075 ER PT J AU Baker, RR AF Baker, Rodney R. TI Jule Dewayne Moravec (1933-2013) OBITUARY SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 Dept Vet Affairs, San Antonio, TX USA. RP Baker, RR (reprint author), Dept Vet Affairs, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2014 VL 69 IS 3 BP 303 EP 303 DI 10.1037/a0035719 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF4LZ UT WOS:000334685500011 PM 24750082 ER PT J AU Locascio, JJ AF Locascio, Joseph J. TI The Reality of Racism Based on the Illusion of "Race" SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material C1 [Locascio, Joseph J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Locascio, Joseph J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Locascio, JJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren Bldg,Off 806,55 Fruit St, Boston, MA 02114 USA. EM jlocascio@partners.org NR 2 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2014 VL 69 IS 3 BP 310 EP 311 DI 10.1037/a0035694 PG 4 WC Psychology, Multidisciplinary SC Psychology GA AF4LZ UT WOS:000334685500019 PM 24750090 ER PT J AU Iezzoni, LI Ogg, M AF Iezzoni, Lisa I. Ogg, Michael TI Performance Metrics for Power Wheelchairs: A Pipe Dream? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article AB Power wheelchair (PWC) users depend on their equipment to reliably transport them throughout daily activities and allow them to participate fully in community life. However, as reported by Worobey and colleagues, PWCs frequently require repairs and cause users a variety of problems, which can range from annoying to catastrophic. These authors suggest that comparing the performance of individual PWC makes and models-a PWC Consumer Reports-might be helpful to inform users and others about the relative quality of different products. Although a comparative report is an appealing idea, we suggest that producing meaningful comparisons of specific PWCs, especially complex rehabilitation PWCs, confronts significant methodologic and practical hurdles. Challenges include dealing with small sample sizes for individual products, risk-adjusting outcomes to account for systematic differences in patterns of use, specifying meaningful outcome metrics, distinguishing the contributions of manufacturers and PWC suppliers to suboptimal performance, and disentangling the myriad components of complex rehabilitation PWCs, which often carry parts from multiple manufacturers. In any case, most users have little control over their PWC selections, with the policies of health insurers and other factors largely dictating equipment choices. Considering these various concerns, we argue that producing a valid and useful Consumer Reports for PWCs will be difficult and, at least for complex rehabilitation chairs, will be of limited value. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ogg, Michael] Carleton Univ, Dept Phys, Ottawa, ON K1S 5B6, Canada. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Rm 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2014 VL 95 IS 4 BP 604 EP 607 DI 10.1016/j.apmr.2014.01.002 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AF3YJ UT WOS:000334648300003 PM 24445090 ER PT J AU Williams, RM Turner, AP Green, M Norvell, DC Henderson, AW Hakimi, KN Blake, DJ Czerniecki, JM AF Williams, Rhonda M. Turner, Aaron P. Green, Monica Norvell, Daniel C. Henderson, Alison W. Hakimi, Kevin N. Blake, Donna J. Czerniecki, Joseph M. TI Changes in Cognitive Function From Presurgery to 4 Months Postsurgery in Individuals Undergoing Dysvascular Amputation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Amputation; Cognition; Postoperative period; Rehabilitation ID PERIPHERAL ARTERIAL-DISEASE; LOWER-LIMB AMPUTATION; SELF-RATED HEALTH; VASCULAR-DISEASE; NONCARDIAC SURGERY; DIABETES-MELLITUS; REHABILITATION; PERFORMANCE; DYSFUNCTION; PREDICTORS AB Objective: To describe cognition among individuals with new amputations at 3 time points: presurgical, 6 weeks postamputation, and 4 months postamputation. Design: Prospective cohort. Setting: Medical centers. Participants: Referred sample Veterans who were primarily men (N=80) experiencing their first lower extremity amputation as a result of complications of diabetes mellitus or peripheral arterial disease. Patients were screened for the absence of gross cognitive impairment using the Short Portable Mental Status Questionnaire (SPMSQ). Of those 87 individuals who were eligible, 64% enrolled; 29 were enrolled presurgically and have cognitive data for all 3 time points, and 58 were enrolled postamputation. Eighty of the 87 individuals enrolled by 6 weeks remained enrolled at 4 months. Interventions: Not applicable. Main Outcome Measures: Demographic and general health information, general mental status (SPMSQ), and 4 brief, well-established neuropsychological measures. Results: Most mean neuropsychological test scores fell in the low average or average range. For most participants, overall cognitive status improved from pre- to postsurgery and then remained stable between 6 weeks and 4 months. There were significant improvements between pre- and postsurgical test scores in verbal learning and memory, and these remained unchanged between 6 weeks and 4 months. Better 4 month cognitive performance was associated with higher perceived general health. Conclusions: Overall cognitive performance is poorest presurgically. Though there is improvement between pre- and postamputation, cognition appears generally stable between 6 weeks and 4 months. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Williams, Rhonda M.; Turner, Aaron P.; Green, Monica; Henderson, Alison W.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Williams, Rhonda M.; Turner, Aaron P.; Green, Monica; Henderson, Alison W.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. [Blake, Donna J.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Blake, Donna J.] Univ Colorado, Denver, CO 80202 USA. RP Williams, RM (reprint author), VA Puget Sound Hlth Care Syst, RCS-117,1660 S Columbian Way, Seattle, WA 98108 USA. EM Rhonda.Williams1@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU U.S. Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [A41241, B4927W] FX Supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (merit review no. A41241 and career development award no. B4927W). NR 54 TC 1 Z9 1 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2014 VL 95 IS 4 BP 663 EP 669 DI 10.1016/j.apmr.2013.11.013 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AF3YJ UT WOS:000334648300012 PM 24316326 ER PT J AU Lilly, SM Jacobs, DR Kronmal, R Bluemke, DA Criqui, M Lima, J Allison, M Duprez, D Segers, P Chirinos, JA AF Lilly, Scott M. Jacobs, David R., Jr. Kronmal, Richard Bluemke, David A. Criqui, Michael Lima, Joao Allison, Matthew Duprez, Daniel Segers, Patrick Chirinos, Julio A. TI Arterial compliance across the spectrum of ankle-brachial index: The multiethnic study of atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE Cardiovascular disease; Medial artery calcification; Vascular compliance; Atherosclerosis ID INCIDENT CARDIOVASCULAR EVENTS; CORONARY-HEART-DISEASE; CHRONIC KIDNEY-DISEASE; PULSE-WAVE VELOCITY; AORTIC STIFFNESS; INDEPENDENT PREDICTOR; HYPERTENSIVE PATIENTS; BLOOD-PRESSURE; RISK-FACTORS; ALL-CAUSE AB Objective: A low ankle-brachial index is associated with cardiovascular disease and reduced arterial compliance. A high ankle-brachial index is also associated with an increased risk of cardiovascular events. We tested the hypothesis that subjects with a high ankle-brachial index demonstrate a lower arterial compliance. In addition, we assessed whether pulse pressure amplification is increased among subjects with a high ankle-brachial index. Methods: We studied 6814 adults enrolled in the multiethnic study of atherosclerosis who were, by definition, free of clinical cardiovascular disease at baseline. Differences in total arterial compliance (ratio of stroke volume to pulse pressure), aortic and carotid distensibility (measured with magnetic resonance imaging and duplex ultrasound, respectively) were compared across ankle-brachial index subclasses (<= 0.90, 0.91-1.29; >= 1.30) with analyses adjusted for cardiovascular risk factors and subclinical atherosclerosis. Results: Peripheral arterial disease was detected in 230 (3.4%) and high ABI in 648 (9.6%) of subjects. Those with high ankle-brachial index demonstrated greater aortic/radial pulse pressure amplification than those with a normal ankle-brachial index. In adjusted models aortic and carotid distensibility as well as total arterial compliance, were lowest among those with ankle-brachial index <= 0.9 (p < 0.01 vs. all), but were not reduced in subjects with an ankle-brachial index >= 1.3. Conclusion: Lower aortic, carotid and total arterial compliance is not present in subjects free of overt cardiovascular disease and with a high ankle-brachial index. However, increased pulse pressure amplification contributes to a greater ankle-brachial index in the general population and may allow better characterization of individuals with this phenotype. Published by Elsevier Ireland Ltd. C1 [Lilly, Scott M.] Ohio State Univ, Heart & Vasc Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Bluemke, David A.; Lima, Joao] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Bluemke, David A.; Lima, Joao] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Criqui, Michael] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA. [Duprez, Daniel] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA. [Segers, Patrick] Univ Ghent, Inst Biomed Technol, B-9000 Ghent, Belgium. [Chirinos, Julio A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Chirinos, JA (reprint author), Room 8B111,5800 Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu OI Bluemke, David/0000-0002-8323-8086; Allison, Matthew/0000-0003-0777-8272 FU Multi-Ethnic Study of Atherosclerosis (MESA) FX The authors would like to thank the staff and investigators of the Multi-Ethnic Study of Atherosclerosis (MESA) for the support and contributions. NR 42 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2014 VL 233 IS 2 BP 691 EP 696 DI 10.1016/j.atherosclerosis.2014.01.029 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9OM UT WOS:000334337200057 PM 24583417 ER PT J AU Yukl, SA Kaiser, P Kim, P Li, PL Wong, JK AF Yukl, Steven A. Kaiser, Philipp Kim, Peggy Li, Peilin Wong, Joseph K. TI Advantages of using the QIAshredder instead of restriction digestion to prepare DNA for droplet digital PCR SO BIOTECHNIQUES LA English DT Article DE digital PCR; Droplet Digital PCR; DNA; QIAshredder; restriction enzyme; BsaJI; RsaI ID QUANTITATION; EXTRACTION AB The viscosity of genomic DNA can interfere with digital PCR systems that partition samples into oil droplets or microfluidic wells. Restriction digestion may reduce the viscosity, but the process is labor-intensive, and the buffer can alter the conditions for PCR. DNA fragmentation using the QIAshredder (a biopolymer spin column) is faster, may result in more predictable and uniformly-sized fragments, and avoids the need for restriction buffers that can inhibit downstream PCR. In 10 separate head-to-head experiments comparing aliquots of DNA processed using the QIAshredder to those digested with RsaI or BsaJI prior to droplet digital PCR, we found that the copy numbers measured from the QIAshredded DNA tended to be greater than those measured from the digested DNA (average of 1.35-fold compared with BsaJI; P < 0.0001), even for inputs as high as 1.8 mu g or dilution down to the single copy level. C1 [Yukl, Steven A.; Kaiser, Philipp; Li, Peilin; Wong, Joseph K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yukl, Steven A.; Kaiser, Philipp; Kim, Peggy; Li, Peilin; Wong, Joseph K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Yukl, SA (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM Steven.yukl@ucsf.edu FU U.S. Department of Veterans Affairs [1 IK2 CX000520-01, 101 BX000192]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573, U19AI096109]; Swiss National Science Foundation [PBZHP3_147260] FX The authors thank the blood donors and the Blood Systems Research Institute for PBMCs. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: 8E5/LAV from Dr. Thomas Folks. This work was supported by the U.S. Department of Veterans Affairs [1 IK2 CX000520-01 (to S.Y.), 101 BX000192 (to J.W.)], the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573 (J.W., S.Y.), U19AI096109 (to J.W.)], and the Swiss National Science Foundation [PBZHP3_147260 (to P.K.)]. This paper is subject to the NIH Public Access Policy. NR 9 TC 6 Z9 7 U1 1 U2 6 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2014 VL 56 IS 4 BP 194 EP 196 DI 10.2144/000114159 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG0SV UT WOS:000335126800008 PM 24724845 ER PT J AU Haq, R AF Haq, Rizwan TI Metabolic Dysregulation in Melanoma: Cause or Consequence? SO CANCER DISCOVERY LA English DT Editorial Material ID HYPOXIA; ADAPTATION; CANCER AB Parmenter and colleagues identify molecular pathways by which BRAF-MAPK signaling regulates glycolysis in melanoma, suggesting novel approaches to target these metabolic dependencies. Cancer Discov; 4(4); 390-1. (C) 2014 AACR. C1 [Haq, Rizwan] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. [Haq, Rizwan] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. RP Haq, R (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM rhaq@partners.org NR 10 TC 2 Z9 2 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2014 VL 4 IS 4 BP 390 EP 391 DI 10.1158/2159-8290.CD-14-0173 PG 2 WC Oncology SC Oncology GA AE9RT UT WOS:000334347300017 PM 24706656 ER PT J AU Zhu, ZH Aref, AR Cohoon, TJ Barbie, TU Imamura, Y Yang, SH Moody, SE Shen, RR Schinzel, AC Thai, TC Reibel, JB Tamayo, P Godfrey, JT Qian, ZR Page, AN Maciag, K Chan, EM Silkworth, W Labowsky, MT Rozhansky, L Mesirov, JP Gillanders, WE Ogino, S Hacohen, N Gaudet, S Eck, MJ Engelman, JA Corcoran, RB Wong, KK Hahn, WC Barbie, DA AF Zhu, Zehua Aref, Amir R. Cohoon, Travis J. Barbie, Thanh U. Imamura, Yu Yang, Shenghong Moody, Susan E. Shen, Rhine R. Schinzel, Anna C. Thai, Tran C. Reibel, Jacob B. Tamayo, Pablo Godfrey, Jason T. Qian, Zhi Rong Page, Asher N. Maciag, Karolina Chan, Edmond M. Silkworth, Whitney Labowsky, Mary T. Rozhansky, Lior Mesirov, Jill P. Gillanders, William E. Ogino, Shuji Hacohen, Nir Gaudet, Suzanne Eck, Michael J. Engelman, Jeffrey A. Corcoran, Ryan B. Wong, Kwok-Kin Hahn, William C. Barbie, David A. TI Inhibition of KRAS-Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit SO CANCER DISCOVERY LA English DT Article ID PANCREATIC DUCTAL ADENOCARCINOMA; BREAST-CANCER ONCOGENE; TUMOR-CELL SURVIVAL; MURINE LUNG-CANCER; BINDING KINASE 1; JAK2 INHIBITOR; RAS; ACTIVATION; TBK1; EXPRESSION AB Although the roles of mitogen-activated protein kinase ( MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, the inhibition of which are likely to be necessary for effective KRAS-directed therapy. Here, we show that the I kappa B kinase (IKK)related kinases Tank-binding kinase-1 (TBK1) and IKK epsilon promote KRAS-driven tumorigenesis by regulating autocrine CCL5 and interleukin(IL)-6 and identify CYT387 as a potent JAK/TBK1/IKK epsilon inhibitor. CYT387 treatment ablates RAS-associated cytokine signaling and impairs Kras-driven murine lung cancer growth. Combined CYT387 treatment and MAPK pathway inhibition induces regression of aggressive murine lung adenocarcinomas driven by Kras mutation and p53 loss. These observations reveal that TBK1/IKKe promote tumor survival by activating CCL5 and IL-6 and identify concurrent inhibition of TBK1/IKKe, Janus-activated kinase (JAK), and MEK signaling as an effective approach to inhibit the actions of oncogenic KRAS. SIGNIFICANCE: In addition to activating MAPK and PI3K, oncogenic KRAS engages cytokine signaling to promote tumorigenesis. CYT387, originally described as a selective JAK inhibitor, is also a potent TBK/ IKKe inhibitor that uniquely disrupts a cytokine circuit involving CCL5, IL-6, and STAT3. The efficacy of CYT387-based treatment in murine Kras-driven lung cancer models uncovers a novel therapeutic approach for these refractory tumors with immediate translational implications. Cancer Discov; 4( 4); 452-65. (c) 2014 AACR. C1 [Zhu, Zehua; Cohoon, Travis J.; Imamura, Yu; Yang, Shenghong; Moody, Susan E.; Shen, Rhine R.; Schinzel, Anna C.; Thai, Tran C.; Reibel, Jacob B.; Qian, Zhi Rong; Chan, Edmond M.; Labowsky, Mary T.; Rozhansky, Lior; Wong, Kwok-Kin; Hahn, William C.; Barbie, David A.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [Aref, Amir R.; Page, Asher N.; Gaudet, Suzanne; Eck, Michael J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Page, Asher N.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Yang, Shenghong; Thai, Tran C.; Tamayo, Pablo; Silkworth, Whitney; Mesirov, Jill P.; Hacohen, Nir; Hahn, William C.; Barbie, David A.] Broad Inst Harvard, Cambridge, MA USA. [Yang, Shenghong; Thai, Tran C.; Tamayo, Pablo; Maciag, Karolina; Chan, Edmond M.; Silkworth, Whitney; Mesirov, Jill P.; Hacohen, Nir; Hahn, William C.; Barbie, David A.] MIT, Cambridge, MA 02139 USA. [Godfrey, Jason T.; Engelman, Jeffrey A.; Corcoran, Ryan B.] Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA USA. [Maciag, Karolina; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Barbie, Thanh U.; Gillanders, William E.] Washington Univ, Dept Surg, Div Biol & Biomed Sci, St Louis, MO USA. RP Barbie, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D819, Boston, MA 02115 USA. EM kwong1@partners.org; William_Hahn@dfci.harvard.edu; dbarbie@partners.org OI wong, kwok kin/0000-0001-6323-235X FU U.S. NIH [K08 CA138918-01A1, P01 CA154303, R01 CA130988, R01 CA122794, R01 CA166480, R01 CA163896, R01CA140594, U01CA141576]; V Scholar; Gloria Spivak Faculty; GTM Fund for Lung Cancer Research; Friends of the Dana-Farber Cancer Institute Awards; Uniting Against Lung Cancer Grants FX This work is supported by U.S. NIH K08 CA138918-01A1 (to D. A. Barbie), P01 CA154303 and R01 CA130988 (to W. C. Hahn), and R01 CA122794, R01 CA166480, R01 CA163896, R01CA140594, and U01CA141576 (to K.-K. Wong). D. A. Barbie is supported by V Scholar, Gloria Spivak Faculty, GTM Fund for Lung Cancer Research, and Friends of the Dana-Farber Cancer Institute Awards. Z. Zhu and K.-K. Wong are supported by Uniting Against Lung Cancer Grants. NR 49 TC 38 Z9 38 U1 5 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2014 VL 4 IS 4 BP 452 EP 465 DI 10.1158/2159-8290.CD-13-0646 PG 14 WC Oncology SC Oncology GA AE9RT UT WOS:000334347300025 PM 24444711 ER PT J AU Wainger, BJ Kiskinis, E Mellin, C Wiskow, O Han, SSW Sandoe, J Perez, NP Williams, LA Lee, S Boulting, G Berry, JD Brown, RH Cudkowicz, ME Bean, BP Eggan, K Woolf, CJ AF Wainger, Brian J. Kiskinis, Evangelos Mellin, Cassidy Wiskow, Ole Han, Steve S. W. Sandoe, Jackson Perez, Numa P. Williams, Luis A. Lee, Seungkyu Boulting, Gabriella Berry, James D. Brown, Robert H., Jr. Cudkowicz, Merit E. Bean, Bruce P. Eggan, Kevin Woolf, Clifford J. TI Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons SO CELL REPORTS LA English DT Article ID AXONAL EXCITABILITY PROPERTIES; SPINAL MUSCULAR-ATROPHY; MOUSE MODEL; STEM-CELLS; HUMAN ES; DISEASE; ALS; MOTONEURONS; MICE; DPP6 AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates. C1 [Wainger, Brian J.; Mellin, Cassidy; Perez, Numa P.; Lee, Seungkyu; Woolf, Clifford J.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Wainger, Brian J.; Mellin, Cassidy; Perez, Numa P.; Lee, Seungkyu; Woolf, Clifford J.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kiskinis, Evangelos; Wiskow, Ole; Han, Steve S. W.; Sandoe, Jackson; Williams, Luis A.; Boulting, Gabriella; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kiskinis, Evangelos; Wiskow, Ole; Han, Steve S. W.; Sandoe, Jackson; Williams, Luis A.; Boulting, Gabriella; Eggan, Kevin] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02138 USA. [Han, Steve S. W.; Berry, James D.; Cudkowicz, Merit E.; Eggan, Kevin] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01655 USA. [Bean, Bruce P.; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Eggan, Kevin] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Eggan, K (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM eggan@mcb.harvard.edu; clifford.woolf@childrens.harvard.edu FU NIH [5 T32 GM007592-33, 5 R01 NS038253-10, 2 R01 NS038153-15]; Harvard NeuroDiscovery; ALS Association; American Brain Foundation Clinical Research Fellowship; Charles King Trust Postdoctoral Fellowship; American Brain Foundation/ALS Association; KL2 MeRIT fellowship/Harvard Catalyst; ALS Therapy Alliance; P2ALS; Angel Fund; Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable Foundation; NIH/NINDS [1R01NS050557]; NIH/NINDS (NINDS ARRA Award) [RC2-NS070342]; Project ALS; Target ALS; NINDS GO grant [5RC2NS069395-02]; NINDS R24 [1U24NS078736-01]; HHMI; New York Stem Cell Foundation; GlaxoSmithKline FX We thank W. David and S. Cash for comments, suggestions, and review of the manuscript, K. Kapur for assistance with statistical analysis, and K. Wainger for assistance with figures. This work was supported by NIH 5 T32 GM007592-33, Harvard NeuroDiscovery, ALS Association, and American Brain Foundation Clinical Research Fellowship (B.J.W.); Charles King Trust Postdoctoral Fellowship (E.K.); American Brain Foundation/ALS Association and KL2 MeRIT fellowship/Harvard Catalyst (S.S.W.H.); ALS Therapy Alliance, P2ALS, Angel Fund, Pierre L. de Bourgknecht ALS Research Foundation, Al-Athel ALS Research Foundation, ALS Family Charitable Foundation and NIH/NINDS (1R01NS050557 and NINDS ARRA Award RC2-NS070342) (R.H.B.); P2ALS, Project ALS, Target ALS, NINDS GO grant (5RC2NS069395-02), NINDS R24 (1U24NS078736-01) and HHMI (K.E.); NIH (5 R01 NS038253-10; 2 R01 NS038153-15), Target ALS and New York Stem Cell Foundation (C.J.W.). GlaxoSmithKline supports research distinct from this study as part of an alliance with the Harvard Stem Cell Institute, including the Woolf and Eggan labs. NR 48 TC 116 Z9 117 U1 9 U2 30 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 APR PY 2014 VL 7 IS 1 BP 1 EP 11 DI 10.1016/j.celrep.2014.03.019 PG 11 WC Cell Biology SC Cell Biology GA AE9BG UT WOS:000334298200001 PM 24703839 ER PT J AU Zeglis, BM Emmetiere, F Pillarsetty, N Weissleder, R Lewis, JS Reiner, T AF Zeglis, Brian M. Emmetiere, Fabien Pillarsetty, Nagavarakishore Weissleder, Ralph Lewis, Jason S. Reiner, Thomas TI Building Blocks for the Construction of Bioorthogonally Reactive Peptides via Solid-Phase Peptide Synthesis SO CHEMISTRYOPEN LA English DT Article DE bioorthogonal chemistry; click chemistry; positron emission tomography (PET); solid-phase peptide synthesis; zirconium-89 ID ALDER CLICK CHEMISTRY; TRANSPLANTED ISLETS; PROSTATE-CANCER; IN-VIVO; PET; RECEPTOR; ANALOGS; ANTAGONISTS; EXENDIN-4; STRATEGY AB The need for post-synthetic modifications and reactive prosthetic groups has long been a limiting factor in the synthesis and study of peptidic and peptidomimetic imaging agents. In this regard, the application of biologically and chemically orthogonal reactions to the design and development of novel radiotracers has the potential to have far-reaching implications in both the laboratory and the clinic. Herein, we report the synthesis and development of a series of modular and versatile building blocks for inverse electron-demand Diels-Alder copper-free click chemistry: tetrazine-functionalized artificial amino acids. Following the development of a novel peptide coupling protocol for peptide synthesis in the presence of tetrazines, we successfully demonstrated its effectiveness and applicability. This versatile methodology has the potential to have a transformational impact, opening the door for the rapid, facile, and modular synthesis of bioorthogonally reactive peptide probes. C1 [Zeglis, Brian M.; Emmetiere, Fabien; Pillarsetty, Nagavarakishore; Lewis, Jason S.; Reiner, Thomas] Mem Sloan Kettering Canc Ctr, Dept Radiol, Radiochem & Imaging Sci Serv, New York, NY 10065 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. RP Zeglis, BM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, Radiochem & Imaging Sci Serv, 1275 York Ave, New York, NY 10065 USA. EM lewisj2@mskcc.org; reinert@mskcc.org OI Reiner, Thomas/0000-0002-7819-5480 FU US National Institute of Health (NIH) [R01A138468, K25EB016673]; Brain Tumor Center of Memorial Sloan-Kettering Cancer Center FX The authors thank Dr. Wolfgang Weber (Memorial Sloan-Kettering Cancer Center) for helpful discussions. The authors also thank the US National Institute of Health (NIH) (JSL: R01A138468 and TR: K25EB016673) and the Brain Tumor Center of Memorial Sloan-Kettering Cancer Center (TR) for their generous funding. NR 26 TC 7 Z9 7 U1 2 U2 24 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 2191-1363 J9 CHEMISTRYOPEN JI ChemistryOpen PD APR PY 2014 VL 3 IS 2 BP 48 EP 53 DI 10.1002/open.201402000 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA AF4KM UT WOS:000334680800001 PM 24808990 ER PT J AU Stoddard, FJ AF Stoddard, Frederick J., Jr. TI Outcomes of Traumatic Exposure SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Childhood trauma; Posttraumatic sequelae; Resilience; Trauma and stressor-related disorders ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH OUTCOMES; CHILDHOOD SEXUAL-ABUSE; CONTROLLED-TRIAL; NATIONAL SAMPLE; RISK-FACTORS; CHILDREN; ADOLESCENTS; MALTREATMENT; PTSD AB There is a great need to recognize, prevent, reduce, or treat the immediate and long-term effects of childhood trauma. Most children affected by trauma will not develop long-term posttraumatic sequelae due to their resilience, but comorbid psychopathological outcomes occur and are more common after exposure to severe traumatic events. Factors influencing posttraumatic outcomes are numerous. Young dependent children tend to be more susceptible than older children; children with pain or injury are also more susceptible. Psychopathological effects may not be evident until adulthood. Awareness of the range of adverse outcomes underscores the importance of preventive interventions, accurate assessment, diagnosis and where possible, treatment. Advocacy and public policy initiatives are essential to improving outcomes. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, 55 Fruit St,SHC 610, Boston, MA 02114 USA. EM fstoddard@mgh.harvard.edu NR 96 TC 6 Z9 6 U1 3 U2 25 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2014 VL 23 IS 2 BP 243 EP + DI 10.1016/j.chc.2014.01.004 PG 15 WC Psychiatry SC Psychiatry GA AF3YK UT WOS:000334648400005 PM 24656578 ER PT J AU Malin, HM Saleh, FM Grudzinskas, AJ AF Malin, H. Martin Saleh, Fabian M. Grudzinskas, Albert J. TI Recent Research Related to Juvenile Sex Offending: Findings and Directions for Further Research SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Sex offender; Registration; Adam Walsh Act; Typologies; Recidivism; SORNA; Juvenile justice reform; Juvenile offender; Peer offenders; Child molesters; Mixed offenders; Offender subtypes; Callous-unemotional traits: Kernberg model: J-SOAP-II: ERASOR: SAVRY: PCL: YV; MACI; Polygraph: PPG; Emotional Stroop test: MnSOST-R: JRAS: Dissociation; Incest ID PREDICTIVE-VALIDITY; REGISTRATION; RISK; RECIDIVISM; OFFENSES; TYPOLOGY; SUPPORT; DOMAINS AB Serious scholarly inquiry into juvenile sex offending represents a relatively new field, dating from the mid 1940s. During the next 4 decades, a mere handful of articles exploring aspects of juvenile sex offending were added to the available literature. By the 1980s, however, the literature began to increase rapidly, a trend that continues today. The purpose of this article is a focused review of the juvenile sex offender literature cited in PubMed over the last 5 years (2009-2013). The authors have chosen studies that will bring readers up to date on research they believe impacts our current understanding of best practices in the management of juvenile sex offending. For convenience, our review is organized into topical categories including research into characteristics and typologies of juvenile sex offenders, risk assessment and recidivism, assessment and treatment, the ongoing debate about mandatory registration of sex offenders as it applies to juveniles, and other thought provoking studies that do not fit neatly into the aforementioned categories. The studies included contain findings that both reinforce and challenge currently held notions about best practices concerning treatment and public policy, suggesting that our knowledge of the field continues to evolve in important ways. C1 [Malin, H. Martin] Inst Adv Study Human Sexual, San Francisco, CA 94109 USA. [Saleh, Fabian M.] Harvard Univ, Sch Med, BIDMC, Sexual Violence Prevent & Risk Management Program, Boston, MA 02115 USA. [Grudzinskas, Albert J.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. RP Saleh, FM (reprint author), Harvard Univ, Sch Med, BIDMC, Sexual Violence Prevent & Risk Management Program, Boston, MA 02115 USA. EM malin@vptherapy.com; fsaleh@bidmc.harvard.edu; Albert.GrudzinskasJr@umassmed.edu NR 40 TC 1 Z9 1 U1 2 U2 32 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 EI 1535-1645 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD APR PY 2014 VL 16 IS 4 AR 440 DI 10.1007/s11920-014-0440-5 PG 7 WC Psychiatry SC Psychiatry GA AF0XF UT WOS:000334437400002 PM 24562765 ER PT J AU Lo, C Lui, M Ranasinha, S Teede, HJ Kerr, PG Polkinghorne, KR Nathan, DM Zheng, H Zoungas, S AF Lo, Clement Lui, Michelle Ranasinha, Sanjeeva Teede, Helena J. Kerr, Peter G. Polkinghorne, Kevan R. Nathan, David M. Zheng, Hui Zoungas, Sophia TI Defining the relationship between average glucose and HbA1c in patients with type 2 diabetes and chronic kidney disease SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes mellitus; Chronic kidney disease; Erythropoietin stimulating agent; Glycated haemoglobin ID GLOMERULAR-FILTRATION-RATE; HEMOGLOBIN A(1C) LEVELS; GLYCEMIC CONTROL; GLYCATED ALBUMIN; ERYTHROPOIETIN TREATMENT; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; INTENSIVE TREATMENT; OUTCOMES; MELLITUS AB Aims: To examine the relationship between average glucose (AG) and HbA(1c) in patients with and without chronic kidney disease (CKD) and type 2 diabetes. Materials and methods: 43 patients with diabetes and CKD (stages 3-5) with stable glycaemic control, and glucose-lowering and erythropoiesis stimulating agent (ESA) doses, were prospectively studied for 3 months and compared to 104 age-matched controls with diabetes, without CKD from the ADAG study. Over 3 months, AG was calculated from 7 to 8 point self-monitored blood glucose measurements (SMBG) and from continuous glucose monitoring (CGMS), and mean HbA(1c) was calculated from 4 measurements. AG and HbA(1c) relationships were determined using multivariable linear regression analyses. Results: The CKD and non-CKD groups were well matched for age and gender. Mean AG tended to be higher (p = 0.08) but HbA(1c) levels were similar (p = 0.68) in the CKD compared with non-CKD groups. A linear relationship between AG and HbA(1c) was observed irrespective of the presence and stage of CKD. The relationship was weaker in patients with stage 4-5 CKD (non-CKD R-2 = 0.75, stage 3 CKD R-2 = 0.79 and stage 4-5 CKD R-2 = 0.34, all p < 0.01). The inclusion of ESA use in the model rendered the effect of CKD stage insignificant (R-2 = 0.67, p < 0.01). Conclusions: In patients with type 2 diabetes and CKD there is a linear relationship between HbA(1c) and AG that is attenuated by ESA use, suggesting that ESA results in a systematic underestimation of AG derived from HbA1c. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Lo, Clement; Ranasinha, Sanjeeva; Teede, Helena J.; Zoungas, Sophia] Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic 3004, Australia. [Lo, Clement; Lui, Michelle; Teede, Helena J.; Zoungas, Sophia] Monash Hlth, Diabet & Vasc Med Unit, Melbourne, Vic, Australia. [Kerr, Peter G.; Polkinghorne, Kevan R.] Monash Med Ctr, Dept Nephrol, Clayton, Vic, Australia. [Kerr, Peter G.; Polkinghorne, Kevan R.] Monash Univ, Clayton, Vic, Australia. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA USA. [Nathan, David M.; Zheng, Hui] Harvard Univ, Sch Med, Boston, MA USA. [Zoungas, Sophia] George Inst Global Hlth, Sydney, NSW, Australia. RP Zoungas, S (reprint author), Monash Univ, Sch Publ Hlth & Prevent Med, Diabet & Cardiovasc Res Unit, 43-51 Kanooka Grove, Clayton, Vic 3168, Australia. EM sophia.zoungas@monash.edu FU Novo Nordisk; Pfizer FX This work was supported by research grants from Novo Nordisk and Pfizer. The investigators designed and conducted the study, analysed the data, and prepared the manuscript, independently of any funding sources. The investigators vouch for the completeness and accuracy of the data. NR 42 TC 5 Z9 6 U1 1 U2 2 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 APR PY 2014 VL 104 IS 1 BP 84 EP 91 DI 10.1016/j.diabres.2014.01.020 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF3AH UT WOS:000334583200015 PM 24573088 ER PT J AU Gendron, M Roberson, D van der Vyver, JM Barrett, LF AF Gendron, Maria Roberson, Debi van der Vyver, Jacoba Marietta Barrett, Lisa Feldman TI Perceptions of Emotion From Facial Expressions Are Not Culturally Universal: Evidence From a Remote Culture SO EMOTION LA English DT Article DE emotion; perception; facial expression; universality; culture ID FUNCTIONAL ARCHITECTURE; ACTION IDENTIFICATION; NEURAL SYSTEMS; RECOGNITION; BRAIN; LANGUAGE; BEHAVIOR; CONTEXT; MODEL; MIND AB It is widely believed that certain emotions are universally recognized in facial expressions. Recent evidence indicates that Western perceptions (e. g., scowls as anger) depend on cues to U. S. emotion concepts embedded in experiments. Because such cues are standard features in methods used in cross-cultural experiments, we hypothesized that evidence of universality depends on this conceptual context. In our study, participants from the United States and the Himba ethnic group from the Keunene region of northwestern Namibia sorted images of posed facial expressions into piles by emotion type. Without cues to emotion concepts, Himba participants did not show the presumed "universal" pattern, whereas U. S. participants produced a pattern with presumed universal features. With cues to emotion concepts, participants in both cultures produced sorts that were closer to the presumed "universal" pattern, although substantial cultural variation persisted. Our findings indicate that perceptions of emotion are not universal, but depend on cultural and conceptual contexts. C1 [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Affect Sci Inst, Boston, MA 02115 USA. [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Roberson, Debi] Univ Essex, Dept Psychol, Colchester CO4 3SQ, Essex, England. [van der Vyver, Jacoba Marietta] Univ Namibia, Sch Nursing & Publ Hlth, Windhoek, Namibia. [van der Vyver, Jacoba Marietta; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gendron, M (reprint author), Northeastern Univ, 125 Nightingale Hall, Boston, MA 02115 USA. EM m.gendron@neu.edu RI Roberson, Debi/C-1612-2009 OI Roberson, Debi/0000-0002-6778-8547 FU NIH HHS [DP1OD003312, DP1 OD003312] NR 59 TC 26 Z9 27 U1 2 U2 42 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD APR PY 2014 VL 14 IS 2 BP 251 EP 262 DI 10.1037/a0036052 PG 12 WC Psychology, Experimental SC Psychology GA AF2WT UT WOS:000334573900005 PM 24708506 ER PT J AU Lindquist, KA Gendron, M Barrett, LF Dickerson, BC AF Lindquist, Kristen A. Gendron, Maria Barrett, Lisa Feldman Dickerson, Bradford C. TI Emotion Perception, but not Affect Perception, Is Impaired With Semantic Memory Loss SO EMOTION LA English DT Article DE emotion perception; language; semantic dementia ID FACIAL EXPRESSIONS; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; CATEGORICAL PERCEPTION; CULTURAL-DIFFERENCES; BASIC EMOTIONS; HUMAN BRAIN; CORE AFFECT; RECOGNITION; LANGUAGE AB For decades, psychologists and neuroscientists have hypothesized that the ability to perceive emotions on others' faces is inborn, prelinguistic, and universal. Concept knowledge about emotion has been assumed to be epiphenomenal to emotion perception. In this article, we report findings from 3 patients with semantic dementia that cannot be explained by this "basic emotion" view. These patients, who have substantial deficits in semantic processing abilities, spontaneously perceived pleasant and unpleasant expressions on faces, but not discrete emotions such as anger, disgust, fear, or sadness, even in a task that did not require the use of emotion words. Our findings support the hypothesis that discrete emotion concept knowledge helps transform perceptions of affect (positively or negatively valenced facial expressions) into perceptions of discrete emotions such as anger, disgust, fear, and sadness. These findings have important consequences for understanding the processes supporting emotion perception. C1 [Lindquist, Kristen A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 28223 USA. [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Affect Sci Inst, Boston, MA USA. [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Boston, MA 02114 USA. RP Lindquist, KA (reprint author), Univ N Carolina, Dept Psychol, Davie 321, Chapel Hill, NC 28223 USA. EM kristen.lindquist@unc.edu FU NIA NIH HHS [R01AG029840, R21 AG029840]; NIH HHS [DP1 OD003312, DP1OD003312] NR 73 TC 13 Z9 13 U1 1 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD APR PY 2014 VL 14 IS 2 BP 375 EP 387 DI 10.1037/a0035293 PG 13 WC Psychology, Experimental SC Psychology GA AF2WT UT WOS:000334573900016 PM 24512242 ER PT J AU Yan, TD Cao, C D'Amico, TA Demmy, TL He, JX Hansen, H Swanson, SJ Walker, WS AF Yan, Tristan D. Cao, Christopher D'Amico, Thomas A. Demmy, Todd L. He, Jianxing Hansen, Henrik Swanson, Scott J. Walker, William S. CA Int VATS Lobectomy Consensus Grp TI Video-assisted thoracoscopic surgery lobectomy at 20 years: a consensus statement SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Video-assisted thoracoscopic surgery; Minimally invasive pulmonary resection; Lung resection; Non-small cell lung cancer; Consensus ID CELL LUNG-CANCER; THORACIC-SURGERY; DATABASE-ANALYSIS; DELPHI TECHNIQUE; THORACOTOMY AB OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) lobectomy has been gradually accepted as an alternative surgical approach to open thoracotomy for selected patients with non-small-cell lung cancer (NSCLC) over the past 20 years. The aim of this project was to standardize the perioperative management of VATS lobectomy patients through expert consensus and to provide insightful guidance to clinical practice. METHODS: A panel of 55 experts on VATS lobectomy was identified by the Scientific Secretariat and the International Scientific Committee of the '20th Anniversary of VATS Lobectomy Conference-The Consensus Meeting'. The Delphi methodology consisting of two rounds of voting was implemented to facilitate the development of consensus. Results from the second-round voting formed the basis of the current Consensus Statement. Consensus was defined a priori as more than 50% agreement among the panel of experts. Clinical practice was deemed 'recommended' if 50-74% of the experts reached agreement and 'highly recommended' if 75% or more of the experts reached agreement. RESULTS: Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of standardized questionnaires. No statistically significant differences in the responses between the two rounds of questioning were identified. Consensus was reached on 21 controversial points, outlining the current accepted definition of VATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSION: The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience. C1 [Yan, Tristan D.; Cao, Christopher] Collaborat Res CORE Grp, Sydney, NSW, Australia. [Yan, Tristan D.] Univ Sydney, Royal Prince Alfred Hosp, Dept Cardiothorac Surg, Sydney, NSW 2006, Australia. [D'Amico, Thomas A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA. [Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Demmy, Todd L.] SUNY Buffalo, Buffalo, NY 14260 USA. [He, Jianxing] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. [Hansen, Henrik] Rigshosp, DK-2100 Copenhagen, Denmark. [Swanson, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Swanson, Scott J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Walker, William S.] Royal Infirm Edinburgh NHS Trust, Dept Cardiothorac Surg, Edinburgh EH16 4SU, Midlothian, Scotland. RP Walker, WS (reprint author), Royal Infirm Edinburgh NHS Trust, Dept Cardiothorac Surg, Edinburgh EH16 4SU, Midlothian, Scotland. EM wsw@holyrood.ed.ac.uk RI Decaluwe, Herbert/A-2436-2009; OI Decaluwe, Herbert/0000-0002-0877-7717; Shackcloth, Michael/0000-0002-6494-9907; Wright, Gavin/0000-0002-7000-9305; Lee, Hyun-Sung/0000-0001-8259-046X NR 22 TC 37 Z9 39 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD APR PY 2014 VL 45 IS 4 BP 633 EP 639 DI 10.1093/ejcts/ezt463 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AF1UW UT WOS:000334500400017 PM 24130372 ER PT J AU Stepp, MA Zieske, JD Trinkaus-Randall, V Kyne, BM Pal-Ghosh, S Tadvalkar, G Pajoohesh-Ganji, A AF Stepp, Mary Ann Zieske, James D. Trinkaus-Randall, Vickery Kyne, Briana M. Pal-Ghosh, Sonali Tadvalkar, Gauri Pajoohesh-Ganji, Ahdeah TI Wounding the cornea to learn how it heals SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE cornea; wound healing; animal models; mouse strain; keratectomy; debridement ID LIMBAL EPITHELIAL-CELLS; GROWTH-FACTOR REGULATION; BASEMENT-MEMBRANE DYSTROPHY; HUMAN DIABETIC CORNEAS; HERPES-SIMPLEX-VIRUS; IN-VITRO MODEL; DELTA T-CELLS; C-MET GENE; OCULAR SURFACE; XENOPUS-LAEVIS AB Corneal wound healing studies have a long history and rich literature that describes the data obtained over the past 70 years using many different species of animals and methods of injury. These studies have lead to reduced suffering and provided clues to treatments that are now helping patients live more productive lives. In spite of the progress made, further research is required since blindness and reduced quality of life due to corneal scarring still happens. The purpose of this review is to summarize what is known about different types of wound and animal models used to study corneal wound healing. The subject of corneal wound healing is broad and includes chemical and mechanical wound models. This review focuses on mechanical injury models involving debridement and keratectomy wounds to reflect the authors' expertise. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stepp, Mary Ann; Kyne, Briana M.; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Pajoohesh-Ganji, Ahdeah] George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, Washington, DC 20037 USA. [Stepp, Mary Ann] George Washington Univ, Med Ctr, Dept Ophthalmol, Washington, DC 20037 USA. [Zieske, James D.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. [Trinkaus-Randall, Vickery] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Trinkaus-Randall, Vickery] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Stepp, MA (reprint author), George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, Washington, DC 20037 USA. EM mastepp@gwu.edu OI Stepp, Mary Ann/0000-0001-5623-2538 FU National Eye Institute FX We could not cite all of the studies done over the years that have moved this field forward. We ask our colleagues to understand that we did our best. We especially want to acknowledge our (MAS, VTR, and JDZ) shared mentor, Ilene K. Gipson, and the Schepens Eye Research Institute for getting us started studying the cornea. We are also grateful for our students, trainees, and staff over the years whose dedication and enthusiasm have kept us engaged and our labs productive. Funding for this work comes from the National Eye Institute. EY008512, EY021784, and EY023106 for MAS; EY06000 and EY06000S for VTR; EY005665, EY020886, EY003790 for JDZ. NR 223 TC 26 Z9 27 U1 2 U2 21 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2014 VL 121 BP 178 EP 193 DI 10.1016/j.exer.2014.02.007 PG 16 WC Ophthalmology SC Ophthalmology GA AG0LI UT WOS:000335106600022 PM 24607489 ER PT J AU Zhu, WT Li, QZ Bai, B Conti, PS Leahy, RM AF Zhu, Wentao Li, Quanzheng Bai, Bing Conti, Peter S. Leahy, Richard M. TI Patlak Image Estimation From Dual Time-Point List-Mode PET Data SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Dual time-point; dynamic positron emission tomography (PET); lesion detection; Patlak; standardized uptake value (SUV); whole body ID POSITRON-EMISSION-TOMOGRAPHY; DYNAMIC PET; F-18-FDG PET; FDG PET; RECONSTRUCTION ALGORITHM; PULMONARY NODULES; PARAMETRIC IMAGES; KINETIC-MODEL; RESOLUTION; CANCER AB We investigate using dual time-point PET data to perform Patlak modeling. This approach can be used for whole body dynamic PET studies in which we compute voxel-wise estimates of Patlak parameters using two frames of data for each bed position. Our approach directly uses list-mode arrival times for each event to estimate the Patlak parametric image. We use a penalized likelihood method in which the penalty function uses spatially variant weighting to ensure a count independent local impulse response. We evaluate performance of the method in comparison to fractional changes in SUV values (%DSUV) between the two frames using Cramer Rao analysis and Monte Carlo simulation. Receiver operating characteristic (ROC) curves are used to compare performance in differentiating tumors relative to background based on the dynamic data sets. Using area under the ROC curve as a performance metric, we show superior performance of Patlak relative to % DSUV over a range of dynamic data sets and parameters. These results suggest that Patlak analysis may be appropriate for analysis of dual time-point whole body PET data and could lead to superior detection of tumors relative to % DSUV metrics. C1 [Zhu, Wentao; Leahy, Richard M.] Univ So Calif, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. [Li, Quanzheng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bai, Bing; Conti, Peter S.] Univ So Calif, Dept Radiol, Los Angeles, CA 90089 USA. RP Leahy, RM (reprint author), Univ So Calif, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. EM leahy@sipi.usc.edu FU National Institutes of Health (NIH) [R01EB013293, R21 CA149587, R01EB010197] FX This work was supported by the National Institutes of Health (NIH) under Grant R01EB013293, Grant R21 CA149587, and Grant R01EB010197. Asterisk indicates corresponding author. NR 40 TC 6 Z9 6 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2014 VL 33 IS 4 BP 913 EP 924 DI 10.1109/TMI.2014.2298868 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA AF4FM UT WOS:000334667000011 PM 24710160 ER PT J AU Weissman, JS Lopez, L Schneider, EC Epstein, AM Lipsitz, S Weingart, SN AF Weissman, Joel S. Lopez, Lenny Schneider, Eric C. Epstein, Arnold M. Lipsitz, Stu Weingart, Saul N. TI The association of hospital quality ratings with adverse events SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE measurement of quality; quality indicators; adverse events; patient safety ID PATIENT-SATISFACTION; HEALTH-CARE; OF-CARE; MORTALITY AB To understand how patient-reported quality is related to adverse events (AEs). Random sample telephone survey. Sixteen acute care Massachusetts hospitals. Two thousand and five hundred and eight-two of 4163 (62 response rate) eligible adult patients. Patients hospitalized from 1 April 2003 to 1 October 2003 provided global quality ratings and whether they experienced AEs. Service recovery, defined as efforts by a service provider to return customers to a state of satisfaction after a lapse in service, was operationalized as high participation in ones care, timely discharge and disclosure of the circumstances of an AE. Of respondents, 82 rated the quality as high and 23 reported one or more AEs. Patients with no AEs gave higher quality ratings (85 vs. 77 or 62 for patients with 1 or 2 AEs, respectively, P 0.001). Patients were more likely to rate the quality high if they reported high participation (86 vs. 53), or felt discharge timing was just right (85 vs. 64); for those with AEs, ratings were higher among those reporting disclosure (82 vs. 66) (all P 0.01). In adjusted analyses, patients with AEs experiencing all three service recovery components rated their quality higher (86 vs. 68, P 0.01). Patients with AEs rate the quality of care lower than others. However, patients with AEs who experienced service recovery as we defined it rated their quality of care at levels similar to those who did not experience AEs. Hospitals seeking to improve quality ratings might consider efforts to ensure patient safety and to address AEs in a transparent and responsive way. C1 [Weissman, Joel S.; Lipsitz, Stu] Harvard Univ, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Sch Med, Boston, MA 02115 USA. [Weissman, Joel S.; Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Weissman, Joel S.; Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Weissman, Joel S.; Schneider, Eric C.; Epstein, Arnold M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Dept Healthcare Policy, Boston, MA USA. [Weingart, Saul N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Schneider, Eric C.] RAND Corp, Boston, MA USA. [Lopez, Lenny; Schneider, Eric C.] Harvard Univ, Brigham & Womens Hosp, Div Gen Med & Primary Care, Sch Med, Boston, MA 02115 USA. RP Weissman, JS (reprint author), Ctr Surg & Publ Hlth, Boston, MA 02120 USA. EM jweissman@partners.org OI Schneider, Eric/0000-0002-1132-5084 FU Agency for Healthcare Research and Quality FX The Agency for Healthcare Research and Quality funded the study. NR 18 TC 5 Z9 5 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 EI 1464-3677 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR PY 2014 VL 26 IS 2 BP 129 EP 135 DI 10.1093/intqhc/mzt092 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AF4MR UT WOS:000334687500004 PM 24481052 ER PT J AU Bamberg, F Hinkel, R Marcus, RP Baloch, E Hildebrandt, K Schwarz, F Hetterich, H Sandner, TA Schlett, CL Ebersberger, U Kupatt, C Hoffmann, U Reiser, MF Theisen, D Nikolaou, K AF Bamberg, Fabian Hinkel, Rabea Marcus, Roy P. Baloch, Elisabeth Hildebrandt, Kristof Schwarz, Florian Hetterich, Holger Sandner, Torleif A. Schlett, Christopher L. Ebersberger, Ullrich Kupatt, Christian Hoffmann, Udo Reiser, Maximilian F. Theisen, Daniel Nikolaou, Konstantin TI Feasibility of dynamic CT-based adenosine stress myocardial perfusion imaging to detect and differentiate ischemic and infarcted myocardium in an large experimental porcine animal model SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Cardiac CT; Myocardial perfusion; Ischemia; Infarct; Animal model; Coronary stenosis ID DUAL-SOURCE CT; PERCUTANEOUS CORONARY INTERVENTION; INITIAL-CLINICAL-EXPERIENCE; COMPUTED-TOMOGRAPHY; MULTISECTION CT; BLOOD-FLOW; ANGIOGRAPHY; HEART; MICROSPHERES; VALIDATION AB The purpose of the study is feasibility of dynamic CT perfusion imaging to detect and differentiate ischemic and infarcted myocardium in a large porcine model. 12 Country pigs completed either implantation of a 75 % luminal coronary stenosis in the left anterior descending coronary artery simulating ischemia or balloon-occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs), fluorescent microspheres, and histopathology were performed in all models. CT based myocardial blood flow (MBFCT), blood volume (MBVCT) and transit constant (K-trans), as well as microsphere's based myocardial blood flow (MBFMic) were derived for each myocardial segment. According to histopathology or microsphere measurements, 20 myocardial segments were classified as infarcted and 23 were ischemic (12 and 14 %, respectively). Across all perfusion states, MBFCT strongly predicted MBFMic (beta 0.88 +/- A 0.12, p < 0.0001). MBFCT, MBVCT, and K-trans were significantly lower in ischemic/infarcted when compared to reference myocardium (all p < 0.01). Relative differences of all CT parameters between affected and non-affected myocardium were higher for infarcted when compared to ischemic segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBFCT, MBVCT, respectively). Under stress, MBFCT was significantly lower in infarcted than in ischemic myocardium (67.8 +/- A 26 vs. 88.2 +/- A 22 ml/100 ml/min, p = 0.002). In a large animal model, CT-derived parameters of myocardial perfusion may enable detection and differentiation of ischemic and infarcted myocardium. C1 [Bamberg, Fabian; Marcus, Roy P.; Baloch, Elisabeth; Hildebrandt, Kristof; Schwarz, Florian; Hetterich, Holger; Sandner, Torleif A.; Reiser, Maximilian F.; Theisen, Daniel; Nikolaou, Konstantin] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany. [Bamberg, Fabian; Schlett, Christopher L.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiol,Cardiac MR PET CT Program, Boston, MA USA. [Bamberg, Fabian; Hinkel, Rabea; Schwarz, Florian; Hetterich, Holger; Kupatt, Christian; Reiser, Maximilian F.; Theisen, Daniel; Nikolaou, Konstantin] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany. [Hinkel, Rabea; Kupatt, Christian] Univ Munich, Klinikum Grosshadern, Dept Cardiol, D-81377 Munich, Germany. [Ebersberger, Ullrich] Munich Municipal Hosp Grp, Heart Ctr Bogenhausen, Munich, Germany. RP Bamberg, F (reprint author), Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM fbamberg@post.harvard.edu RI Hinkel, Rabea/I-9165-2014; OI Hinkel, Rabea/0000-0002-2936-0400; Nikolaou, Konstantin/0000-0003-2668-7325 FU Bayer Healthcare, Berlin, Germany; DZHK (German Centre for Cardiovascular Research); BMBF (German Ministry of Education and Research) FX This study supported by an unrestricted grant by Bayer Healthcare, Berlin, Germany and by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). NR 27 TC 7 Z9 8 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD APR PY 2014 VL 30 IS 4 BP 803 EP 812 DI 10.1007/s10554-014-0390-3 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AF1AJ UT WOS:000334446300016 PM 24570085 ER PT J AU Jung, M Bigman-Galimore, CA Viswanath, K AF Jung, Minsoo Bigman-Galimore, Cabral A. Viswanath, K. TI Contextual effects of community mobilization and communication capacity as a positive factor for self-rated health status: a multi-level analysis SO INTERNATIONAL JOURNAL OF PUBLIC HEALTH LA English DT Article DE Contextual effects; Community capacity; Health communication; South Korea ID LOCAL NEWS; MEDIA USE; PARTICIPATION; DETERMINANTS; NETWORK; KOREA; SEOUL AB We examined relationships between individual-level community participation, two types of contextual effectsaEuro center dot community capacity for mobilization and capacity for health communication-and residents' self-reported health status in order to explore the role health communication may play in community building for health. To estimate multi-level effects of the community participation and the two contextual indicators with self-rated health status, we applied hierarchical generalized linear regression to crosssectional data from the Korean National Health and Nutrition Examination Survey. After adjusting for individual- and community-level confounders, the likelihood of having high self-rated health status is significantly higher among those who live in a region with higher community capacity for mobilization, higher health communication capacity at the community level, and higher participation in community groups at the individual-level. Our findings suggest that living in a community characterized by higher levels of communication and mobilization capacity is beneficial to residents' self-rated health status-increasing the odds of high health status by up to 9 %. Thus, building community capacity in mobilization and health communication may help develop better health promotion campaigns. C1 [Jung, Minsoo; Bigman-Galimore, Cabral A.; Viswanath, K.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. [Bigman-Galimore, Cabral A.] Univ Illinois, Dept Commun, Urbana, IL USA. [Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM mj748@dongduk.ac.kr OI Jung, Minsoo/0000-0003-3317-6507 NR 38 TC 2 Z9 2 U1 1 U2 11 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 APR PY 2014 VL 59 IS 2 BP 289 EP 299 DI 10.1007/s00038-013-0532-8 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AE8RL UT WOS:000334269100009 PM 24362447 ER PT J AU Baliga, RR Nienaber, CA Bossone, E Oh, JK Isselbacher, EM Sechtem, U Fattori, R Raman, SV Eagle, KA AF Baliga, Ragavendra. R. Nienaber, Christoph A. Bossone, Eduardo Oh, Jae K. Isselbacher, Eric M. Sechtem, Udo Fattori, Rossella Raman, Subha V. Eagle, Kim A. TI The Role of Imaging in Aortic Dissection and Related Syndromes SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE acute aortic syndromes; aortic dissection; aortic intramural hematoma; aortic ulcer; cardiovascular imaging ID PENETRATING ATHEROSCLEROTIC ULCER; ANEURYSM DIAMETER MEASUREMENTS; DESCENDING THORACIC AORTA; ENHANCED MR-ANGIOGRAPHY; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; INTRAMURAL HEMATOMA; CT ANGIOGRAPHY; INTERNATIONAL REGISTRY; HELICAL CT AB Aortic aneurysm and acute aortic syndrome are not uncommon conditions. Management of acute aortic dissection and related syndromes requires a multidisciplinary approach with input from the patient, clinician, imager, surgeon, and anesthesiologist. This requires an integrated evaluation of pathophysiology, anatomy, and severity to enable appropriate therapy. This review includes discussion of essential anatomy of the aortic valve and the aorta that determines the candidacy for surgical repair. It also includes discussion of various imaging modalities, particularly echocardiography, cardiac computed tomography, and cardiac magnetic resonance angiography. The relative benefits and demerits of each of these techniques are reviewed. This paper is intended to help guide management decisions for patients with acute aortic dissection and related syndromes. (J Am Coll Cardiol lmg 2014;7:406-24) (C) 2014 by the American College of Cardiology Foundation C1 [Baliga, Ragavendra. R.] Ohio State Univ, Wexner Med Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA. [Nienaber, Christoph A.] Univ Rostock, Univ Heart Ctr, D-18055 Rostock, Germany. [Bossone, Eduardo] Univ Salerno, Heart Dept, Cava de Tirreni & Amalfi Coast Hosp, Div Cardiol, I-84100 Salerno, Italy. [Oh, Jae K.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Isselbacher, Eric M.] Harvard Univ, Sch Med, Boston, MA USA. [Sechtem, Udo] Robert Bosch Krankenhaus Stuttgart, Dept Cardiol, Stuttgart, Germany. [Fattori, Rossella] Osped Marche Nord, Intervent Cardiol Unit, Pesaro, Italy. [Raman, Subha V.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. [Eagle, Kim A.] Univ Michigan Hlth Syst, Sch Publ Hlth, Frankel Cardiovasc Ctr, Ann Arbor, MI USA. RP Baliga, RR (reprint author), Ohio State Univ, Wexner Med Ctr, Div Cardiovasc Med, 200 Davis Heart & Lung Res Inst HLRI, Columbus, OH 43210 USA. EM rrbaliga@gmail.com NR 74 TC 15 Z9 17 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2014 VL 7 IS 4 BP 406 EP 424 DI 10.1016/j.jcmg.2013.10.015 PG 19 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AG0GI UT WOS:000335093500009 PM 24742892 ER PT J AU Niesten, MEF Lookabaugh, S Curtin, H Merchant, SN McKenna, MJ Grolman, W Lee, DJ AF Niesten, Marlien E. F. Lookabaugh, Sarah Curtin, Hugh Merchant, Saumil N. McKenna, Michael J. Grolman, Wilko Lee, Daniel J. TI Familial Superior Canal Dehiscence Syndrome SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID BONE; MALFORMATION; VERTIGO AB IMPORTANCE The etiology of superior canal dehiscence (SCD) involving the arcuate eminence is not completely understood, but genetic factors may play a role. One hypothesis is that patients are born with a defect of the superior canal, and an acute event (such as head trauma) or progressive loss of bone (eg, due to dural pulsations) may result in the onset of SCD symptoms. Familial SCD has only been briefly mentioned in the literature to date. OBSERVATIONS We report 3 families that each had 2 members with SCD syndrome. We found that first-degree relatives presented with similar complaints and that temporal bone computed tomography scans between relatives showed very similar skull base topography and anatomic SCD defects. CONCLUSIONS AND RELEVANCE The presence of symptomatic SCD among first-degree relatives and similar skull base topography suggests that geneticsmay play a role in the etiology of SCD. C1 [Niesten, Marlien E. F.; Grolman, Wilko] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.; Grolman, Wilko] Brainctr Rudolf Magnus, Utrecht, Netherlands. [Niesten, Marlien E. F.; Merchant, Saumil N.; McKenna, Michael J.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Niesten, Marlien E. F.; Lookabaugh, Sarah; Merchant, Saumil N.; McKenna, Michael J.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Curtin, Hugh] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu OI Grolman, Wilko/0000-0002-3524-3526 NR 16 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD APR PY 2014 VL 140 IS 4 BP 363 EP 368 DI 10.1001/jamaoto.2013.6718 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AF4HV UT WOS:000334673500012 PM 24526223 ER PT J AU Bookman, MA Gilks, CB Kohn, EC Kaplan, KO Huntsman, D Aghajanian, C Birrer, MJ Ledermann, JA Oza, AM Swenerton, KD AF Bookman, Michael A. Gilks, C. Blake Kohn, Elise C. Kaplan, Karen O. Huntsman, David Aghajanian, Carol Birrer, Michael J. Ledermann, Jonathan A. Oza, Amit M. Swenerton, Kenneth D. TI Better Therapeutic Trials in Ovarian Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GRADE SEROUS CARCINOMA; OPEN-LABEL; LIPOSOMAL DOXORUBICIN; BREAST-CANCER; BRAF MUTATION; 2-TIER SYSTEM; STAGE-III; CELL-TYPE; PHASE-II; WOMEN AB The Ovarian Task Force of the Gynecologic Cancer Steering Committee convened a clinical trials planning meeting on October 28-29, 2011, with the goals to identify key tumor types, associated molecular pathways, and biomarkers for targeted drug intervention; review strategies to improve early-phase screening, therapeutic evaluation, and comparison of new agents; and optimize design of randomized trials in response to an evolving landscape of scientific, regulatory, and funding priorities. The meeting was attended by international clinical and translational investigators, pharmaceutical industry representatives, government regulators, and patient advocates. Panel discussions focused on disease types, early-phase trials, and randomized trials. A manuscript team summarized the discussions and assisted with formulating key recommendations. A more integrated and efficient approach for screening new agents using smaller selective randomized trials in specific disease-type settings was endorsed, together with collaborative funding models between industry and the evolving national clinical trials network, as well as efforts to enhance public awareness and study enrollment through advocacy. C1 [Bookman, Michael A.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA. [Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Kohn, Elise C.] NCI, Mol Signalling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kaplan, Karen O.] Prevent Canc Fdn, Alexandria, VA USA. [Huntsman, David] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Swenerton, Kenneth D.] Univ British Columbia, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada. [Aghajanian, Carol] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. [Birrer, Michael J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Ledermann, Jonathan A.] UCL, Inst Canc, CR UK UCL Canc Trials Ctr, London, England. [Oza, Amit M.] Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. RP Bookman, MA (reprint author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave,Rm 1903, Tucson, AZ 85724 USA. EM mbookman@email.arizona.edu NR 38 TC 19 Z9 19 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju029 DI 10.1093/jnci/dju029 PG 8 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500014 PM 24627272 ER PT J AU Dews, M Tan, GS Hultine, S Raman, P Choi, J Duperret, EK Lawler, J Bass, A Thomas-Tikhonenko, A AF Dews, Michael Tan, Grace S. Hultine, Stacy Raman, Pichai Choi, Jaewoo Duperret, Elizabeth K. Lawler, Jack Bass, Adam Thomas-Tikhonenko, Andrei TI Masking Epistasis Between MYC and TGF-beta Pathways in Antiangiogenesis-Mediated Colon Cancer Suppression SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MICROSATELLITE INSTABILITY; SIGNALING PATHWAYS; MICRORNA CLUSTER; TUMOR-GROWTH; C-MYC; CELLS; ANGIOGENESIS; RECEPTOR; THROMBOSPONDIN-1; SUPERFAMILY AB Background The c-Myc oncoprotein is activated in the majority of colorectal cancers (CRCs), whereas the TGF-beta pathway is frequently affected by loss-of-function mutations, for example in SMAD2/3/4 genes. The canonical model places Myc downstream of inhibitory TGF-beta signaling. However, we previously demonstrated that Myc also inhibits TGF-beta signaling through the miR-17 similar to 92 microRNA cluster, raising the question about functional relationships between these two pathways. Methods We engineered a series of genetically complex murine and human CRC cell lines in which Myc and TGF-beta activities could be manipulated simultaneously. This was achieved through retroviral expression of the Myc-estrogen receptor fusion protein and through Smad4 short hairpin RNA knockdown. Cell lines thus modified were injected subcutaneously in immunocompromised mice, and the resultant tumors (n = 5-10 per treatment group) were analyzed for overall growth and neovascularization. Additionally, the distribution of MYC and TGF-beta pathway mutations was analyzed in previously profiled human CRC samples. Results In kras-mutated/trp53-deleted murine colonocytes, either Myc activation or TGF-beta inactivation increased tumor sizes and microvascular densities approximately 1.5- to 2.5-fold, chiefly through downregulation of thrombospondin-1 and related type I repeat-containing proteins. Combining Myc activation with TGF-beta inactivation did not further accelerate tumorigenesis. This redundancy and the negative effect of TGF-beta signaling on angiogenesis were also demonstrated using xenografts of human CRC cell lines. Furthermore, the analysis of the Cancer Genome Atlas data revealed that in CRC without microsatellite instability, overexpression of Myc and inactivation of Smads (including acquired mutations in SMAD2) are mutually exclusive, with odds ratio less than 0.1. Conclusions In human CRC, gain-of-function alterations in Myc and loss-of-function alterations in TGF-beta exhibit a masking epistatic interaction and are functionally redundant. C1 [Dews, Michael; Tan, Grace S.; Hultine, Stacy; Thomas-Tikhonenko, Andrei] Childrens Hosp Philadelphia, Div Canc Pathobiol, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Raman, Pichai] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Choi, Jaewoo; Duperret, Elizabeth K.; Thomas-Tikhonenko, Andrei] Univ Penn, Perelman Sch Med, Canc Biol Grad Program, Philadelphia, PA 19104 USA. [Thomas-Tikhonenko, Andrei] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Lawler, Jack] Beth Israel Deaconess Med Ctr, Div Expt Pathol, Boston, MA 02215 USA. [Bass, Adam] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thomas-Tikhonenko, A (reprint author), 4056 Colket Translat Res Bldg,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM andreit@mail.med.upenn.edu RI Thomas-Tikhonenko, Andrei/E-5329-2011 OI Thomas-Tikhonenko, Andrei/0000-0002-2739-2206 FU National Institutes of Health [CA122334, T32 HL07915, CA130895, NS071197] FX This work was supported by grants from the National Institutes of Health (CA122334 to ATT; T32 HL07915 to GST; and CA130895 and NS071197 to JL). NR 37 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju043 DI 10.1093/jnci/dju043 PG 10 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500022 PM 24627270 ER PT J AU Mehta, RS Song, MY Bezawada, N Wu, KN Garcia-Albeniz, X Morikawa, T Fuchs, CS Ogino, S Giovannucci, EL Chan, AT AF Mehta, Raaj S. Song, Mingyang Bezawada, Navya Wu, Kana Garcia-Albeniz, Xabier Morikawa, Teppei Fuchs, Charles S. Ogino, Shuji Giovannucci, Edward L. Chan, Andrew T. TI A Prospective Study of Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) and Risk of Colorectal Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ASPIRIN; PLASMA; WOMEN; MEN; ASSOCIATIONS; NAG-1/GDF15; EXPRESSION; DIAGNOSIS; SULINDAC; MICE AB Background Chronic inflammation plays a role in the development of colorectal cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal carcinogenesis. Methods We conducted a prospective, nested, case-control study of incident CRC among men and women who provided a prediagnostic blood specimen. We used an enzyme-linked immunosorbent assay to measure MIC-1 and examined associations between quintiles of MIC-1 and CRC using logistic regression adjusted for matching factors (age and date of blood draw), risk factors, and other plasma inflammatory markers. We also assessed the relationship between MIC-1 levels and prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX-2) enzyme status in tumors with available tissue for analysis. All statistical tests were two-sided. Results Compared with men and women within the lowest quintile of plasma MIC-1, the multivariable relative risk (RR) for CRC was 1.93 (95% confidence interval [CI] = 1.27 to 2.94) for the highest quintile (P-linear trend = .004). In an exploratory analysis, we found that among individuals with high plasma MIC-1 levels (quintiles 2-5), compared with nonuse, regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.60; 95% confidence interval = 0.41 to 0.88) but not PTGS2-negative CRC (multivariable RR = 1.21; 95% CI = 0.71 to 2.07). In contrast, among individuals with low MIC-1 levels (quintile 1), aspirin and NSAID use was not associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.57; 95% CI = 0.21 to 1.54) or PTGS2-negative CRC (multivariable RR = 1.41; 95% CI = 0.47 to 4.23). Conclusions Our results support an association between higher levels of circulating MIC-1 (GDF15) and CRC. Aspirin/NSAID use appeared to lower risk of PTGS2-positive cancers, particularly among individuals with high levels of circulating MIC-1. C1 [Mehta, Raaj S.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Mehta, Raaj S.; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Bezawada, Navya] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Aberdeen, Scotland. [Garcia-Albeniz, Xabier; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Song, Mingyang; Wu, Kana; Garcia-Albeniz, Xabier; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Morikawa, Teppei] Univ Tokyo, Dept Pathol, Tokyo, Japan. [Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp GRJ 825C, Gastrointestinal Unit, Boston, MA 02114 USA. EM achan@mgh.harvard.edu RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU US National Institute of Health [P01 CA55075, UM1CA167552, P50CA127003, P01CA087969, R01CA151993, R01 CA137178, K24 DK098311]; ASISA; Sociedad Espanola de Oncologia Medica FX This work was supported by grants from the US National Institute of Health (P01 CA55075, UM1CA167552, P50CA127003, P01CA087969, R01CA151993, R01 CA137178, and K24 DK098311). ATC is a Damon Runyon Cancer Research Foundation Clinical Investigator. XGA is the recipient of an ASISA Fellowship and Sociedad Espanola de Oncologia Medica grant. NR 22 TC 1 Z9 1 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju010 DI 10.1093/jnci/dju016 PG 8 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500005 ER PT J AU Skates, SJ AF Skates, Steven J. TI A Statistical Challenge: Developing Tests for Biomarker Utility Specific to the Intended Use SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Ste 560, Boston, MA 02114 USA. EM sskates@mgh.harvard.edu FU NCI NIH HHS [CA152990, U01 CA152990] NR 11 TC 3 Z9 3 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju076 DI 10.1093/jnci/dju076 PG 2 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500034 PM 24681600 ER PT J AU Laird, JR Jain, A Zeller, T Feldman, R Scheinert, D Popma, JJ Armstrong, EJ Jaff, MR AF Laird, John R. Jain, Ash Zeller, Thomas Feldman, Robert Scheinert, Dierk Popma, Jeffrey J. Armstrong, Ehrin J. Jaff, Michael R. CA Complete SE Investigators TI Nitinol Stent Implantation in the Superficial Femoral Artery and Proximal Popliteal Artery: Twelve-Month Results From the Complete SE Multicenter Trial SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE angioplasty; nitinol stents; peripheral artery disease; multicenter trial; superficial femoral artery; popliteal artery; stenosis; occlusion; patency; restenosis; target; lesion revascularization; stent fracture ID PACLITAXEL-ELUTING STENTS; TRANSLUMINAL ANGIOPLASTY; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL; LIMB ISCHEMIA; SINGLE-CENTER; LESIONS; DISEASE; RESTENOSIS; FRACTURES AB Purpose: To determine the safety and efficacy of a new-generation nitinol stent with enhanced flexibility in arterial lesions in the superficial femoral artery (SFA) and proximal popliteal artery (PPA). Methods: The Complete Self-Expanding (SE) Multicenter Trial (ClinicalTrials.gov identifier NCT00814970) enrolled 196 patients (124 men; mean age 68.7 +/- 10.5 years) from 28 centers in the United States and Europe. The patients presented with intermittent claudication (193/196) or ischemic rest pain (3/196) and were treated with nitinol stents for obstructive lesions of the SFA or PPA. Over a quarter of lesions (29.9%) were chronic total occlusions. The mean lesion length was 60.7 mm. Moderate to severe calcification was present in 91.0% of lesions. Results: A total of 225 stents were successfully implanted in 213 (99.5%) of 214 lesions. Acute lesion success (<30% residual stenosis) was achieved in 90.0%. There were no inhospital major adverse events. Primary patency (defined as a peak systolic velocity ratio <2.0) at 12 months was 72.6%. Clinically-driven target lesion revascularization (TLR) was required in 8.4% of patients at 12 months. The mean ankle-brachial index increased from 0.7 at baseline to 0.9, and there was sustained improvement in the Rutherford category, with 83% of patients classified as Rutherford category 0 or 1 at 12-month follow-up. No stent fractures were detected through 12 months. Conclusion: In this multicenter trial, primary implantation of a new-generation selfexpanding nitinol stent in the SFA and PPA was associated with a low rate of TLR and sustained clinical benefit at 12 months without stent fracture. C1 [Laird, John R.; Armstrong, Ehrin J.] Univ Calif Davis Hlth Syst, Sacramento, CA USA. [Jain, Ash] Washington Hosp, Fremont, CA USA. [Zeller, Thomas] Heart Ctr Bad Krozingen, Bad Krozingen, Germany. [Feldman, Robert] Munroe Reg Med Ctr, Ocala, FL USA. [Scheinert, Dierk] Pk Hosp, Leipzig, Germany. [Scheinert, Dierk] Leipzig Heart Ctr, Leipzig, Germany. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laird, JR (reprint author), UC Davis Vasc Ctr, Lawrence J Ellison Ambulatory Care Ctr, 4860 Y St,Suite 3400, Sacramento, CA 95817 USA. EM john.laird@ucdmc.ucdavis.edu FU Medtronic Vascular FX This study was funded by Medtronic Vascular. NR 26 TC 14 Z9 14 U1 0 U2 2 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 EI 1545-1550 J9 J ENDOVASC THER JI J. Endovascular Ther. PD APR PY 2014 VL 21 IS 2 BP 202 EP 212 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AG0DH UT WOS:000335085000004 PM 24754279 ER PT J AU Kisu, I Mihara, M Banno, K Hara, H Masugi, Y Araki, J Iida, T Yamada, Y Kato, Y Shiina, T Suganuma, N Aoki, D AF Kisu, Iori Mihara, Makoto Banno, Kouji Hara, Hisako Masugi, Yohei Araki, Jun Iida, Takuya Yamada, Yohei Kato, Yojiro Shiina, Takashi Suganuma, Nobuhiko Aoki, Daisuke TI Uterus allotransplantation in cynomolgus macaque: A preliminary experience with non-human primate models SO JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH LA English DT Article DE cynomolgus macaque; immunosuppressants; indocyanine green; uterine factor infertility; uterus transplantation ID UTERINE AUTOTRANSPLANTATION; MULTIORGAN DONOR; TRANSPLANTATION; PREGNANCY AB AimUterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. MethodsUteri of two cynomolgus monkeys were simultaneously removed, cooled at 4 degrees C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. ResultsThe blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. ConclusionAllogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required. C1 [Kisu, Iori; Banno, Kouji; Aoki, Daisuke] Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1608582, Japan. [Masugi, Yohei] Keio Univ, Sch Med, Dept Pathol, Tokyo 1608582, Japan. [Mihara, Makoto; Hara, Hisako; Araki, Jun; Iida, Takuya] Univ Tokyo, Grad Sch Med, Dept Plast & Reconstruct Surg, Tokyo, Japan. [Shiina, Takashi] Tokai Univ, Sch Med, Dept Mol Life Sci, Div Basic Med Sci & Mol Med, Hiratsuka, Kanagawa 25912, Japan. [Suganuma, Nobuhiko] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Kyoto, Japan. [Yamada, Yohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. [Kato, Yojiro] Columbia Univ, Med Ctr, Dept Surg, New York, NY USA. RP Kisu, I (reprint author), Keio Univ, Sch Med, Dept Obstet & Gynecol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM iori71march@a7.keio.jp OI BANNO, KOUJI/0000-0003-2610-2833; Masugi, Yohei/0000-0002-6952-4043 FU Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT); Keio University; Kanzawa Medical Research Foundation; Akaeda Medical Research Foundation; Inamori Research Foundation; Program for the Next Generation of World-leading Research of the Japanese Cabinet Office [LS039] FX We are grateful to Dr Timothy Shim, Dr Kazuki Kikuchi and Dr Kensuke Tashiro (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo) for help with surgery; to Hirohito Kato, Nobuyoshi Yamashita, Yoshiro Nishida, Kotaro Hanaki, Ryuichi Katagiri, Tomoko Shimonosono and Syuzo Koyama (Shin Nippon Biomedical Laboratories) for experimental support; to Noriko Kagawa (the chief of Repro Self Bank, Japan) for her advice with hormonal examination; to Tomoharu Mine and Yuhei Shigeta (IMI) for technical assistance and to Hiroshi Suzuki (Department of Pathology, School of Medicine, Keio University) for technical assistance with the immunohistochemical analysis. This study was supported by the Strategic Research Foundation Grant-aided Project for Private Universities from Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT), a Keio University Grant-in-Aid for Encouragement of Young Medical Scientists, Kanzawa Medical Research Foundation, Akaeda Medical Research Foundation, Inamori Research Foundation and the Program for the Next Generation of World-leading Research of the Japanese Cabinet Office (LS039). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 15 TC 9 Z9 9 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1341-8076 EI 1447-0756 J9 J OBSTET GYNAECOL RE JI J. Obstet. Gynaecol. Res. PD APR PY 2014 VL 40 IS 4 BP 907 EP 918 DI 10.1111/jog.12302 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AD9WL UT WOS:000333615200002 PM 24612366 ER PT J AU Sudore, RL Knight, SJ McMahan, RD Feuz, M Farrell, D Miao, YH Barnes, DE AF Sudore, Rebecca L. Knight, Sara J. McMahan, Ryan D. Feuz, Mariko Farrell, David Miao, Yinghui Barnes, Deborah E. TI A Novel Website to Prepare Diverse Older Adults for Decision Making and Advance Care Planning: A Pilot Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Advance care planning; medical decision making; aging; technology ID HEALTH BEHAVIOR-CHANGE; ELDERLY-PATIENTS; LIFE; END; DIRECTIVES; LITERACY; BARRIERS; SKILLS; TRIAL; VIDEO AB Context. We have reconceptualized advance care planning (ACP) as a multistep process focused on preparing patients with skills needed for communication and in-the-moment decision making. Objectives. To operationalize this paradigm, we created an easy-to-use ACP website (prepareforyourcare. org) based on a theoretical framework of behavior change and pilot-tested its efficacy to engage older adults in ACP. Methods. At baseline and 1 week after viewing the PREPARE website, we assessed behavior change in ACP by using a validated survey that includes Process Measures (knowledge, contemplation, self-efficacy, and readiness, 5-point Likert scales) and Action Measures (yes/no whether an ACP behavior was completed). We also assigned participants into behavior change stages (i.e., precontemplation, contemplation, preparation, action, maintenance) and determined the percentage of participants who moved from precontemplation at baseline to higher stages at 1 week. We also assessed PREPARE ease-of-use (10-point scale, 10 being the easiest). Changes were assessed with Wilcoxon signed rank sum tests and McNemar's tests. Results. Mean age of the participants was 68.4 years (SD 6.6), and 65% were nonwhite. Behavior Change Process Measures average Likert scores increased from 3.1 (0.9) to 3.7 (0.7), P < 0.001. Action Measures did not change significantly. However, precontemplation significantly decreased for most actions (e. g., talking to doctor about desired medical care, 61% to 35%, P < 0.003), with a mean decrease of 21% (range, 16%-33%). PREPARE was rated a nine of ten (+/- 1.9) for ease-of-use. Conclusion. A new, patient-centered ACP website that focuses on preparing patients for communication and decision making significantly improves engagement in the process of ACP and behavior change. A clinical trial of PREPARE is currently underway. J Pain Symptom Manage 2014;47:674-686. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Sudore, Rebecca L.; McMahan, Ryan D.; Feuz, Mariko; Miao, Yinghui; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Sudore, Rebecca L.; McMahan, Ryan D.; Feuz, Mariko; Miao, Yinghui] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Knight, Sara J.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Knight, Sara J.] Vet Adm, Hlth Serv Res & Dev Serv, Washington, DC USA. [Farrell, David] People Designs Inc, Durham, NC USA. RP Sudore, RL (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM rebecca.sudore@ucsf.edu FU U.S. Department of Veterans Affairs; National Palliative Care Research Center Foundation FX This study was supported by the U.S. Department of Veterans Affairs and the National Palliative Care Research Center Foundation. The funding sources had no role in the creation of study materials, data collection, analysis, or interpretation of the data. No authors report any conflicts of interest. NR 32 TC 25 Z9 25 U1 3 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2014 VL 47 IS 4 BP 674 EP 686 DI 10.1016/j.jpainsymman.2013.05.023 PG 13 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AF3CC UT WOS:000334588100007 PM 23972574 ER PT J AU Di Salvo, DN Clarke, PD Cho, CH Alexander, EK AF Di Salvo, Donald N. Clarke, Peter D. Cho, Charles H. Alexander, Erik K. TI Redesign and Implementation of the Radiology Clerkship: From Traditional to Longitudinal and Integrative SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Medical education; radiology education; longitudinal radiology clerkship ID MEDICAL-STUDENTS AB Purpose: The authors discuss the evolution and application of 3 radiology teaching methods a fundamentals-of-imaging course, a combined clinical-radiology case conference, and a radiology objective structured clinical examination-to medical education at the Brigham and Women's Hospital site of Harvard Medical School. Methods: The evolution of the medical student radiology teaching program from content needs assessment to blueprint creation, through implementation, is outlined. Results: The 3 components of the teaching program are described. The changes in format in response to feedback and challenges faced in deploying this new curriculum are detailed.. Results from student surveys and the radiology objective structured clinical examination scores from recent years are also presented. Conclusions: As radiology assumes an increasingly central role in patient care and diagnosis, the need for effective integration of radiology teaching into medical education becomes more critical. The concepts presented here have been deemed to be successful by students and faculty members and may be applicable to other institutions. C1 [Di Salvo, Donald N.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Clarke, Peter D.; Cho, Charles H.; Alexander, Erik K.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Di Salvo, DN (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ddisalvo@partners.org NR 14 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2014 VL 11 IS 4 BP 413 EP 420 DI 10.1016/j.jacr.2013.05.018 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AF1NG UT WOS:000334480000021 PM 23993252 ER PT J AU Lumish, HS Sidhu, MS Kallianos, K Brady, TJ Hoffmann, U Ghoshhajra, BB AF Lumish, Heidi S. Sidhu, Manavjot S. Kallianos, Kimberly Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian B. TI Reporting Scan Time Reduces Cardiac MR Examination Duration SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID RADIOLOGY; PROGRESS; WASTE C1 [Lumish, Heidi S.; Sidhu, Manavjot S.; Kallianos, Kimberly; Brady, Thomas J.; Hoffmann, Udo; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Lumish, Heidi S.; Sidhu, Manavjot S.; Kallianos, Kimberly; Brady, Thomas J.; Hoffmann, Udo; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Lumish, Heidi S.; Sidhu, Manavjot S.; Kallianos, Kimberly; Brady, Thomas J.; Hoffmann, Udo; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Boston, MA USA. [Sidhu, Manavjot S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sidhu, Manavjot S.] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Sidhu, Manavjot S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lumish, HS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM manavjotsidhu@yahoo.co.in NR 13 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2014 VL 11 IS 4 BP 425 EP 428 DI 10.1016/j.jacr.2013.05.037 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AF1NG UT WOS:000334480000024 PM 23999473 ER PT J AU Soones, T Ahalt, C Garrigues, S Faigman, D Williams, BA AF Soones, Tacara Ahalt, Cyrus Garrigues, Sarah Faigman, David Williams, Brie A. TI "My Older Clients Fall Through Every Crack in the System": Geriatrics Knowledge of Legal Professionals SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE qualitative; geriatric; prisoners; attorneys ID HEALTH; CARE; RESIDENTS; ATTITUDES AB With the number of older adult arrestees and prisoners increasing rapidly, legal professionals increasingly provide front-line identification and response to age-related health conditions (including cognitive and physical impairments) that may affect legal outcomes, such as the ability to participate in one's defense or stay safe in jail. The goals of this study were to assess the ability of legal professionals to recognize and respond to age-related conditions that could affect legal outcomes and to identify recommendations to address important knowledge gaps. This was a mixed quantitative-qualitative study. Legal professionals (N=72) in the criminal justice system were surveyed to describe their demographic characteristics, expertise, and prior aging-related training and to inform the qualitative interview guide. Those surveyed included attorneys (district attorneys (25%), public defenders and legal advocates (58%)), judges (6%), and court-affiliated social workers (11%). In-depth qualitative interviews were then conducted with a subset of 10 legal professionals who worked with older adults at least weekly. Results from the surveys and interviews revealed knowledge deficits in four important areas: age-related health, identification of cognitive impairment, assessment of safety risk, and optimization of services upon release from jail. Four recommendations to close these gaps emerged: educate legal professionals about age-related health, train professionals to identify cognitive and sensory impairment, develop checklists to identify those at risk of poor health or safety, and improve knowledge of and access to transitional services for older adults. These findings suggest that geriatrics knowledge gaps of legal professionals exist that may contribute to adverse medical or legal outcomes for older adults involved in the criminal justice system and that partnerships between healthcare and legal professionals are needed to address these challenges. C1 [Soones, Tacara; Ahalt, Cyrus; Garrigues, Sarah; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94118 USA. [Faigman, David] Univ Calif San Francisco, Hastings Coll Law, San Francisco, CA 94102 USA. [Faigman, David] Univ Calif San Francisco, Univ Calif Hastings Consortium Law Sci & Hlth Pol, San Francisco, CA 94143 USA. [Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM brie.williams@ucsf.edu FU National Institute on Aging [K23AG033102]; Jacob and Valeria Langeloth Foundation; UCSF Program for the Aging Century FX Dr. Williams is supported by the National Institute on Aging (K23AG033102), the Jacob and Valeria Langeloth Foundation, and the UCSF Program for the Aging Century. The opinions expressed in this manuscript do not necessarily represent those of the Department of Veterans Affairs. NR 28 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2014 VL 62 IS 4 BP 734 EP 739 DI 10.1111/jgs.12751 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AE8YV UT WOS:000334289900021 PM 24611718 ER PT J AU Ghani, KR Sukumar, S Sammon, JD Rogers, CG Trinh, QD Menon, M AF Ghani, Khurshid R. Sukumar, Shyam Sammon, Jesse D. Rogers, Craig G. Quoc-Dien Trinh Menon, Mani TI Practice Patterns and Outcomes of Open and Minimally Invasive Partial Nephrectomy Since the Introduction of Robotic Partial Nephrectomy: Results from the Nationwide Inpatient Sample SO JOURNAL OF UROLOGY LA English DT Article DE kidney; nephrectomy; robotics; laparoscopy; complications ID RENAL-CELL CARCINOMA; LAPAROSCOPIC PARTIAL NEPHRECTOMY; ASSISTED PARTIAL NEPHRECTOMY; OPEN RADICAL PROSTATECTOMY; PROPENSITY-SCORE; TRENDS; SURGERY; COMPLICATIONS; DISPARITIES; TECHNOLOGY AB Purpose: We determined practice patterns and perioperative outcomes of open and minimally invasive partial nephrectomy in the United States since the introduction of a robot-assisted modifier in the Nationwide Inpatient Sample. Materials and Methods: We identified all patients with nonmetastatic disease treated with open, laparoscopic or robotic partial nephrectomy in the Nationwide Inpatient Sample between October 2008 and December 2010. Utilization rates were assessed by year, patient and hospital characteristics. We evaluated the perioperative outcomes of open vs robotic and open vs laparoscopic partial nephrectomy using binary logistic regression models adjusted for patient and hospital covariates. Results: In a weighted sample of 38,064 partial nephrectomies 66.9%, 23.9% and 9.2% of the procedures were open, robotic and laparoscopic operations, respectively. In 2010 the relative annual increase in open, robotic and laparoscopic partial nephrectomy was 7.9%, 45.4% and 6.1%, respectively. Compared to open partial nephrectomy patients treated with minimally invasive partial nephrectomy were less likely to receive blood transfusion (robotic vs laparoscopic OR 0.56, p < 0.001 vs OR 0.68, p = 0.016), postoperative complication (OR 0.63, p < 0.001 vs OR 0.78, p < 0.009) or prolonged length of stay (OR 0.27 vs OR 0.41, each p < 0.001). Only patients who underwent the robotic procedure were less likely to experience an intraoperative complication (robotic vs laparoscopic OR 0.69, p = 0.014 vs OR 0.67, p = 0.069). Excess hospital charges were higher after robotic surgery (OR 1.35, p < 0.001). Conclusions: The dissemination of robotic surgery for partial nephrectomy in the United States has been rapid and safe. Compared to open partial nephrectomy the robotic procedure had lower odds than laparoscopic partial nephrectomy for most study outcomes except hospital charges. Robotic partial nephrectomy has now supplanted laparoscopic partial nephrectomy as the most common minimally invasive approach for partial nephrectomy. C1 [Ghani, Khurshid R.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Sammon, Jesse D.; Rogers, Craig G.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Sukumar, Shyam] Univ Minnesota, Dept Urol, Minneapolis, MN USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ghani, KR (reprint author), Univ Michigan, Dept Urol, Bldg 16,1st Floor,Room 100S-19,2800 Plymouth Rd, Ann Arbor, MI 48109 USA. EM kghani@med.umich.edu FU Urology Foundation, United Kingdom (KRG) FX Supported by a Fellowship from The Urology Foundation, United Kingdom (KRG). NR 29 TC 43 Z9 44 U1 0 U2 4 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 APR PY 2014 VL 191 IS 4 BP 907 EP 912 DI 10.1016/j.juro.2013.10.099 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AF5OP UT WOS:000334763100007 PM 24184365 ER PT J AU Goss, PE Strasser-Weippl, K Lee-Bychkovsky, BL Fan, L Li, JJ Chavarri-Guerra, Y Liedke, PER Pramesh, CS Badovinac-Crnjevic, T Sheikine, Y Chen, Z Qiao, YL Shao, ZM Wu, YL Fan, DM Chow, LWC Wang, J Zhang, Q Yu, SY Shen, G He, J Purushotham, A Sullivan, R Badwe, R Banavali, SD Nair, R Kumar, L Parikh, P Subramanian, S Chaturvedi, P Iyer, S Shastri, SS Digumarti, R Soto-Perez-de-Celis, E Adilbay, D Semiglazov, V Orlov, S Kaidarova, D Tsimafeyeu, I Tatishchev, S Danishevskiy, KD Hurlbert, M Vail, C St Louis, J Chan, A AF Goss, Paul E. Strasser-Weippl, Kathrin Lee-Bychkovsky, Brittany L. Fan, Lei Li, Junjie Chavarri-Guerra, Yanin Liedke, Pedro E. R. Pramesh, C. S. Badovinac-Crnjevic, Tanja Sheikine, Yuri Chen, Zhu Qiao, You-lin Shao, Zhiming Wu, Yi-Long Fan, Daiming Chow, Louis W. C. Wang, Jun Zhang, Qiong Yu, Shiying Shen, Gordon He, Jie Purushotham, Arnie Sullivan, Richard Badwe, Rajendra Banavali, Shripad D. Nair, Reena Kumar, Lalit Parikh, Purvish Subramanian, Somasundarum Chaturvedi, Pankaj Iyer, Subramania Shastri, Surendra Srinivas Digumarti, Raghunadhrao Soto-Perez-de-Celis, Enrique Adilbay, Dauren Semiglazov, Vladimir Orlov, Sergey Kaidarova, Dilyara Tsimafeyeu, Ilya Tatishchev, Sergei Danishevskiy, Kirill D. Hurlbert, Marc Vail, Caroline St Louis, Jessica Chan, Arlene TI Challenges to effective cancer control in China, India, and Russia SO LANCET ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FORMER SOVIET-UNION; REPUBLIC-OF-CHINA; BREAST-CANCER; CERVICAL-CANCER; HEALTH-CARE; ALCOHOL-CONSUMPTION; AIR-POLLUTION; CLINICAL-TRIALS; GASTRIC-CANCER AB Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement. C1 [Goss, Paul E.; Lee-Bychkovsky, Brittany L.; Sheikine, Yuri] Harvard Univ, Sch Med, Boston, MA USA. [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, Vienna, Austria. [Lee-Bychkovsky, Brittany L.] Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. [Sheikine, Yuri] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Goss, Paul E.] Massachusetts Gen Hosp, Avon Breast Canc Ctr Excellence, Boston, MA 02114 USA. [Lee-Bychkovsky, Brittany L.; Fan, Lei; Chavarri-Guerra, Yanin; Liedke, Pedro E. R.; Badovinac-Crnjevic, Tanja; Vail, Caroline; St Louis, Jessica] Massachusetts Gen Hosp, Int Canc Res Program, Boston, MA 02114 USA. [Fan, Lei; Li, Junjie; Shao, Zhiming] Fudan Univ, Breast Surg Dept, Shanghai Med Coll, Ctr Canc, Shanghai 200433, Peoples R China. [Fan, Lei; Li, Junjie; Shao, Zhiming] Fudan Univ, Breast Surg Dept, Shanghai Med Coll, Inst Canc, Shanghai 200433, Peoples R China. [Chavarri-Guerra, Yanin; Soto-Perez-de-Celis, Enrique] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Hematooncol Dept, Mexico City, DF, Mexico. [Liedke, Pedro E. R.] Oncol Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Liedke, Pedro E. R.] Inst Canc Mae Deus, Porto Alegre, RS, Brazil. [Pramesh, C. S.] Tata Mem Hosp, Dept Surg Oncol Clin Res, Bombay, Maharashtra, India. [Badwe, Rajendra] Tata Mem Hosp, Bombay, Maharashtra, India. [Banavali, Shripad D.] Tata Mem Hosp, Dept Med & Pediat Oncol, Bombay, Maharashtra, India. [Chaturvedi, Pankaj] Tata Mem Hosp, Dept Head & Neck Surg, Bombay, Maharashtra, India. [Shastri, Surendra Srinivas] Tata Mem Hosp, Dept Prevent Oncol, Bombay, Maharashtra, India. [Badovinac-Crnjevic, Tanja] Univ Hosp Zagreb, Dept Oncol, Zagreb, Croatia. [Chen, Zhu] Shanghai Jiao Tong Univ, Sch Med, Key Lab Med Genom, Shanghai Inst Hematol,Rui Jin Hosp, Shanghai 200030, Peoples R China. [Qiao, You-lin] Chinese Acad Med Sci, Dept Canc Epidemiol, Beijing 100730, Peoples R China. [He, Jie] Chinese Acad Med Sci, Dept Thorac Surg, Beijing 100730, Peoples R China. [Wu, Yi-Long] Chinese Acad Med Sci, Natl Canc Ctr, Beijing 100730, Peoples R China. [Wu, Yi-Long] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Fan, Daiming] Fourth Mil Med Univ, State Key Lab Canc Biol, Xian 710032, Shaanxi Provinc, Peoples R China. [Fan, Daiming] Xijing Hosp Digest Dis, Xian, Shaanxi Provinc, Peoples R China. [Chow, Louis W. C.] Org Oncol & Translat Res, Hong Kong, Hong Kong, Peoples R China. [Chow, Louis W. C.] Comprehens Ctr Breast Dis, UNIMED Med Inst, Hong Kong, Hong Kong, Peoples R China. [Wang, Jun] Cent Univ Finance & Econ, Inst Publ Hlth Econ & Management, Beijing, Peoples R China. [Zhang, Qiong] Cent Univ Finance & Econ, Dept Econ, Sch Econ, Beijing, Peoples R China. [Yu, Shiying] Huazhong Univ Sci & Technol, Tongji Hosp, Ctr Canc, Tongji Med Coll, Wuhan 430074, Peoples R China. [Shen, Gordon] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Shen, Gordon] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Purushotham, Arnie; Sullivan, Richard] Guys Hosp, Kings Coll London, Kings Hlth Partners Canc Ctr, London SE1 9RT, England. [Sullivan, Richard] Guys Hosp, Kings Coll London, Inst Canc Policy, London SE1 9RT, England. [Nair, Reena] Tata Med Ctr, Dept Clin Hematol, Kolkata, W Bengal, India. [Kumar, Lalit] All India Inst Med Sci, Inst Rotary Canc Hosp, New Delhi, India. [Parikh, Purvish] BSES GH Municipal Hosp, Bombay, Maharashtra, India. [Subramanian, Somasundarum] Eurasian Federat Oncol Educ & Res Ctr, Moscow, Russia. [Iyer, Subramania] Amrita Inst Med Sci & Res Ctr, Kochi, Kerala, India. [Digumarti, Raghunadhrao] Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India. [Adilbay, Dauren] Astana Oncol Ctr, Astana, Kazakhstan. [Semiglazov, Vladimir] NN Petrov Oncol Res Inst, Reprod Syst Tumors Dept, St Petersburg, Russia. [Orlov, Sergey] St Petersburg Med Univ, Dept Thorac Oncol, St Petersburg, Russia. [Kaidarova, Dilyara] Almaty Oncol Ctr, Alma Ata, Kazakhstan. [Tsimafeyeu, Ilya] Kidney Canc Res Bur, Soc Clin Oncol, Moscow, Russia. [Tatishchev, Sergei] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Danishevskiy, Kirill D.] Higher Sch Econ, Dept Hlth Econ, Moscow, Russia. [Hurlbert, Marc] Avon Fdn Breast Canc, New York, NY USA. [Chan, Arlene] Breast Canc Res Ctr Western Australia, Perth, WA, Australia. [Chan, Arlene] Curtin Univ, Perth, WA 6845, Australia. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org RI Qiao, You-Lin/B-4139-2012; OI Qiao, You-Lin/0000-0001-6380-0871; Semiglazov, Vladimir/0000-0003-0077-9619; Hurlbert, Marc/0000-0003-3301-3572; Sullivan, Richard/0000-0002-6435-1825 FU Avon Foundation, New York FX PEG, JL, MH, CV, and JS are supported by the Avon Foundation, New York, through a grant to the International Cancer Program. NR 452 TC 83 Z9 89 U1 13 U2 87 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2014 VL 15 IS 5 BP 489 EP 538 PG 50 WC Oncology SC Oncology GA AE9CP UT WOS:000334302100005 PM 24731404 ER PT J AU Wang, X Yan, Z Fulciniti, M Li, Y Gkotzamanidou, M Amin, SB Shah, PK Zhang, Y Munshi, NC Li, C AF Wang, X. Yan, Z. Fulciniti, M. Li, Y. Gkotzamanidou, M. Amin, S. B. Shah, P. K. Zhang, Y. Munshi, N. C. Li, C. TI Transcription factor-pathway coexpression analysis reveals cooperation between SP1 and ESR1 on dysregulating cell cycle arrest in non-hyperdiploid multiple myeloma SO LEUKEMIA LA English DT Article DE coexpression; cell cycle arrest; multiple myeloma; hyperdiploid ID BREAST-CANCER CELLS; GENE-EXPRESSION; C-MYC; DIFFERENTIAL COEXPRESSION; MOLECULAR CLASSIFICATION; BINDING-SITES; UP-REGULATION; ESTROGEN; ACTIVATION; PROFILES AB Multiple myeloma is a hematological cancer of plasma B cells and remains incurable. Two major subtypes of myeloma, hyperdiploid MM (HMM) and non-hyperdiploid MM (NHMM), have distinct chromosomal alterations and different survival outcomes. Transcription factors (TrFs) have been implicated in myeloma oncogenesis, but their dysregulation in myeloma subtypes are less studied. Here, we developed a TrF-pathway coexpression analysis to identify altered coexpression between two sample types. We apply the method to the two myeloma subtypes and the cell cycle arrest pathway, which is significantly differentially expressed between the two subtypes. We find that TrFs MYC, nuclear factor-kB and HOXA9 have significantly lower coexpression with cell cycle arrest in HMM, co-occurring with their overactivation in HMM. In contrast, TrFs ESR1 (estrogen receptor 1), SP1 and E2F1 have significantly lower coexpression with cell cycle arrest in NHMM. SP1 chromatin immunoprecipitation targets are enriched by cell cycle arrest genes. These results motivate a cooperation model of ESR1 and SP1 in regulating cell cycle arrest, and a hypothesis that their overactivation in NHMM disrupts proper regulation of cell cycle arrest. Cotargeting ESR1 and SP1 shows a synergistic effect on inhibiting myeloma proliferation in NHMM cell lines. Therefore, studying TrF-pathway coexpression dysregulation in human cancers facilitates forming novel hypotheses toward clinical utility. C1 [Wang, X.; Li, Y.; Zhang, Y.; Li, C.] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Yan, Z.; Amin, S. B.; Shah, P. K.; Li, C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Yan, Z.; Amin, S. B.; Shah, P. K.; Li, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fulciniti, M.; Gkotzamanidou, M.; Munshi, N. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fulciniti, M.; Gkotzamanidou, M.; Munshi, N. C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Li, C (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM Nikhil_Munshi@dfci.harvard.edu; lch3000@gmail.com RI Zhang, Yong/B-4838-2011; OI Zhang, Yong/0000-0001-6316-2734; Amin, Samir/0000-0002-3207-9505 FU National Basic Research Program of China (973 Program) [2010CB944904]; NIH [R01 GM077122, RO1-124929, PO1-155258, P50-100007, PO1-78378]; Department of Veterans Affairs Merit Review Awards; Claudia Adams Barr Program in Innovative Basic Cancer Research; Multiple Myeloma Career Development award FX This work was supported by National Basic Research Program of China (973 Program; No. 2010CB944904) (XW, YL, YZ, CL) and NIH R01 GM077122 (CL, ZY). This work was also supported in part by NIH Grants RO1-124929, PO1-155258, P50-100007 and PO1-78378 (to NCM) and by the Department of Veterans Affairs Merit Review Awards (to NCM). PKS was supported by Claudia Adams Barr Program in Innovative Basic Cancer Research and the Multiple Myeloma Career Development award. We thank the reviewers and Cheng Li group members for constructive comments and discussion. NR 60 TC 8 Z9 8 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2014 VL 28 IS 4 BP 894 EP 903 DI 10.1038/leu.2013.233 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA AE9SU UT WOS:000334350900021 PM 23925045 ER PT J AU Huang, C Ackerman, JL Petibon, Y Brady, TJ El Fakhri, G Ouyang, JS AF Huang, Chuan Ackerman, Jerome L. Petibon, Yoann Brady, Thomas J. El Fakhri, Georges Ouyang, Jinsong TI MR-based motion correction for PET imaging using wired active MR microcoils in simultaneous PET-MR: Phantom study(a)) SO MEDICAL PHYSICS LA English DT Article DE brain PET; motion correction; active microcoil; PET-MR ID HEAD MOTION; EMISSION-TOMOGRAPHY; TRACKING; IMAGES; IMPLEMENTATION; REGISTRATION; ANESTHESIA; ALGORITHM; SYSTEM; COILS AB Purpose: Artifacts caused by head motion present a major challenge in brain positron emission tomography (PET) imaging. The authors investigated the feasibility of using wired active MR microcoils to track head motion and incorporate the measured rigid motion fields into iterative PET reconstruction. Methods: Several wired active MR microcoils and a dedicated MR coil-tracking sequence were developed. The microcoils were attached to the outer surface of an anthropomorphic F-18-filled Hoffman phantom to mimic a brain PET scan. Complex rotation/translation motion of the phantom was induced by a balloon, which was connected to a ventilator. PET list-mode and MR tracking data were acquired simultaneously on a PET-MR scanner. The acquired dynamic PET data were reconstructed iteratively with and without motion correction. Additionally, static phantom data were acquired and used as the gold standard. Results: Motion artifacts in PET images were effectively removed by wired active MR microcoil based motion correction. Motion correction yielded an activity concentration bias ranging from -0.6% to 3.4% as compared to a bias ranging from -25.0% to 16.6% if no motion correction was applied. The contrast recovery values were improved by 37%-156% with motion correction as compared to no motion correction. The image correlation (mean +/- standard deviation) between the motion corrected (uncorrected) images of 20 independent noise realizations and static reference was R-2 = 0.978 +/- 0.007 (0.588 +/- 0.010, respectively). Conclusions: Wired active MR microcoil based motion correction significantly improves brain PET quantitative accuracy and image contrast. (C) 2014 American Association of Physicists in Medicine. C1 [Huang, Chuan; Petibon, Yoann; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong] Massachusetts Gen Hosp, Dept Imaging, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Huang, Chuan; Ackerman, Jerome L.; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ackerman, Jerome L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Dept Imaging, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu RI Ackerman, Jerome/E-2646-2015; OI Ackerman, Jerome/0000-0001-5176-7496; Huang, Chuan/0000-0001-6052-0663 FU NIH [R21-EB012326, R01-CA165221]; Athinoula A. Martinos Center for Biomedical Imaging; Center for Functional Neuroimaging Technologies; NIH/NIBIB [P41-EB015896] FX This research was supported in part by NIH Grant Nos. R21-EB012326, R01-CA165221, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Functional Neuroimaging Technologies (funded by NIH/NIBIB Grant No. P41-EB015896). NR 36 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2014 VL 41 IS 4 AR 041910 DI 10.1118/1.4868457 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE8XT UT WOS:000334287000024 PM 24694141 ER PT J AU Petibon, Y Huang, C Ouyang, JS Reese, TG Li, QZ Syrkina, A Chen, YL El Fakhri, G AF Petibon, Yoann Huang, Chuan Ouyang, Jinsong Reese, Timothy G. Li, Quanzheng Syrkina, Aleksandra Chen, Yen-Lin El Fakhri, Georges TI Relative role of motion and PSF compensation in whole-body oncologic PET-MR imaging SO MEDICAL PHYSICS LA English DT Article DE motion correction; PSF modeling; oncologic PET-MRI ID RESPIRATORY MOTION; ATTENUATION CORRECTION; EMISSION-TOMOGRAPHY; SURFACE COILS; RECONSTRUCTION; SYSTEM; MODEL; QUANTIFICATION; REGISTRATION; FEASIBILITY AB Purpose: Respiratory motion and partial-volume effects are the two main sources of image degradation in whole-body PET imaging. Simultaneous PET-MR allows measurement of respiratory motion using MRI while collecting PET events. Improved PET images may be obtained by modeling respiratory motion and point spread function (PSF) within the PET iterative reconstruction process. In this study, the authors assessed the relative impact of PSF modeling and MR-based respiratory motion correction in phantoms and patient studies using a whole-body PET-MR scanner. Methods: An asymmetric exponential PSF model accounting for radially varying and axial detector blurring effects was obtained from point source acquisitions performed in the PET-MR scanner. A dedicated MRI acquisition protocol using single-slice steady state free-precession MR acquisitions interleaved with pencil-beam navigator echoes was developed to track respiratory motion during PET-MR studies. An iterative ordinary Poisson fully 3D OSEM PET reconstruction algorithm modeling all the physical effects of the acquisition (attenuation, scatters, random events, detectors efficiencies, PSF), as well as MR-based nonrigid respiratory deformations of tissues (in both emission and attenuation maps) was developed. Phantom and F-18-FDG PET-MR patient studies were performed to evaluate the proposed quantitative PET- MR methods. Results: The phantom experiment results showed that PSF modeling significantly improved contrast recovery while limiting noise propagation in the reconstruction process. In patients with soft-tissue static lesions, PSF modeling improved lesion contrast by 19.7%-109%, enhancing the detectability and assessment of small tumor foci. In a patient study with small moving hepatic lesions, the proposed reconstruction technique improved lesion contrast by 54.4%-98.1% and reduced apparent lesion size by 21.8%-34.2%. Improvements were particularly important for the smallest lesion undergoing large motion at the lung-liver interface. Heterogeneous tumor structures delineation was substantially improved. Enhancements offered by PSF modeling were more important when correcting for motion at the same time. Conclusions: The results suggest that the proposed quantitative PET-MR methods can significantly enhance the performance of tumor diagnosis and staging as compared to conventional methods. This approach may enable utilization of the full potential of the scanner in oncologic studies of both the lower abdomen, with moving lesions, as well as other parts of the body unaffected by motion. (c) 2014 American Association of Physicists in Medicine. C1 [Petibon, Yoann; Huang, Chuan; Ouyang, Jinsong; Reese, Timothy G.; Li, Quanzheng; Syrkina, Aleksandra; Chen, Yen-Lin; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Imaging, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Huang, Chuan; Ouyang, Jinsong; Reese, Timothy G.; Li, Quanzheng; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Reese, Timothy G.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Chen, Yen-Lin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Dept Imaging, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu OI Huang, Chuan/0000-0001-6052-0663 FU NIH [R21-EB012326, R01-CA165221] FX This work was supported in part by NIH R21-EB012326 and R01-CA165221. The authors would like to thank Dr. Ciprian Catana and Dr. Alexander Guimaraes for their help with the abdominal study, Dr. Xuping Zhu for her help preparing the point sources, and Grae Arabasz and Shirley Hsu for their help during the acquisitions. NR 42 TC 13 Z9 13 U1 1 U2 12 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2014 VL 41 IS 4 AR 042503-1 DI 10.1118/1.4868458 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE8XT UT WOS:000334287000039 PM 24694156 ER PT J AU Trattner, S Cheng, B Pieniazek, RL Hoffmann, U Douglas, PS Einstein, AJ AF Trattner, Sigal Cheng, Bin Pieniazek, Radoslaw L. Hoffmann, Udo Douglas, Pamela S. Einstein, Andrew J. TI Sample size requirements for estimating effective dose from computed tomography using solid-state metal-oxide-semiconductor field-effect transistor dosimetry SO MEDICAL PHYSICS LA English DT Article DE effective dose; MOSFET; computer tomography; dosimetry; sample size ID CORONARY CT ANGIOGRAPHY; PHANTOM; TECHNOLOGY; PATIENT AB Purpose: Effective dose (ED) is a widely used metric for comparing ionizing radiation burden between different imaging modalities, scanners, and scan protocols. In computed tomography (CT), ED can be estimated by performing scans on an anthropomorphic phantom in which metal-oxide-semiconductor field-effect transistor (MOSFET) solid-state dosimeters have been placed to enable organ dose measurements. Here a statistical framework is established to determine the sample size (number of scans) needed for estimating ED to a desired precision and confidence, for a particular scanner and scan protocol, subject to practical limitations. Methods: The statistical scheme involves solving equations which minimize the sample size required for estimating ED to desired precision and confidence. It is subject to a constrained variation of the estimated ED and solved using the Lagrange multiplier method. The scheme incorporates measurement variation introduced both by MOSFET calibration, and by variation in MOSFET readings between repeated CT scans. Sample size requirements are illustrated on cardiac, chest, and abdomen-pelvis CT scans performed on a 320-row scanner and chest CT performed on a 16-row scanner. Results: Sample sizes for estimating ED vary considerably between scanners and protocols. Sample size increases as the required precision or confidence is higher and also as the anticipated ED is lower. For example, for a helical chest protocol, for 95% confidence and 5% precision for the ED, 30 measurements are required on the 320-row scanner and 11 on the 16-row scanner when the anticipated ED is 4 mSv; these sample sizes are 5 and 2, respectively, when the anticipated ED is 10 mSv. Conclusions: Applying the suggested scheme, it was found that even at modest sample sizes, it is feasible to estimate ED with high precision and a high degree of confidence. As CT technology develops enabling ED to be lowered, more MOSFET measurements are needed to estimate ED with the same precision and confidence. (c) 2014 American Association of Physicists in Medicine. C1 [Trattner, Sigal; Einstein, Andrew J.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. [Trattner, Sigal; Pieniazek, Radoslaw L.; Einstein, Andrew J.] New York Presbyterian Hosp, New York, NY 10032 USA. [Cheng, Bin] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Pieniazek, Radoslaw L.] Columbia Univ, Med Ctr, Ctr Radiol Res, New York, NY 10032 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Douglas, Pamela S.] Duke Univ, Dept Med, Div Cardiol, Durham, NC 27715 USA. [Einstein, Andrew J.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10032 USA. RP Einstein, AJ (reprint author), Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. EM andrew.einstein@columbia.edu FU NIH-NHLBI [R01, HL109711, HL098237, HL098305]; Herbert Irving Associate Professorship; Victoria and Esther Aboodi Cardiology Researcher; Philips Healthcare; GE Healthcare and Philips Healthcare FX This work was supported by NIH-NHLBI R01 Grant Nos. HL109711, HL098237, and HL098305, by a Herbert Irving Associate Professorship, and as a Victoria and Esther Aboodi Cardiology Researcher (Dr. Einstein). Dr. Trattner and Mr. Pieniazek have received funding for other research from Philips Healthcare. Dr. Einstein has received funding for other research from GE Healthcare and Philips Healthcare. NR 17 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2014 VL 41 IS 4 AR 042102-1 DI 10.1118/1.4868693 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE8XT UT WOS:000334287000033 PM 24694150 ER PT J AU Zhu, MY Botticello, T Lu, HM Winey, B AF Zhu, Mingyao Botticello, Thomas Lu, Hsiao-Ming Winey, Brian TI Long-term stability and mechanical characteristics of kV digital imaging system for proton radiotherapy SO MEDICAL PHYSICS LA English DT Article DE digital imaging; patient positioning; protons; panel position; flex map ID BEAM COMPUTED-TOMOGRAPHY; GUIDED RADIATION-THERAPY; QUALITY-ASSURANCE; LINEAR-ACCELERATOR AB Purpose: To quantitatively evaluate the long-term image panel positioning stability and gantry angle dependence for gantry-mounted kV imaging systems. Methods: For patient setup digital imaging systems in isocentric rotating proton beam delivery facilities, physical crosshairs are commonly inserted into the snout to define the kV x-ray beam isocenter. Utilizing an automatic detection algorithm, the authors analyzed the crosshair center positions in 2744 patient setup kV images acquired with the four imagers in two treatment rooms from January 2012 to January 2013. The crosshair position was used as a surrogate for imaging panel position, and its long-term stability at the four cardinal angles and the panel flex dependency on gantry angle was investigated. Results: The standard deviation of the panel position distributions was within 0.32 mm (with the range of variation less than +/- 1.4 mm) in both the X-Z plane and Y direction. The mean panel inplane rotations were not more than 0.51 degrees for the four panels at the cardinal angles, with standard deviations <= 0.26 degrees. The panel position variations with gantry rotation due to gravity (flex) were within +/- 4 mm, and were panel-specific. Conclusions: The authors demonstrated that the kV image panel positions in our proton treatment system were highly reproducible at the cardinal angles over 13 months and also that the panel positions can be correlated to gantry angles. This result indicates that the kV image panel positions are stable over time; the amount of panel sag is predictable during gantry rotation and the physical crosshair for kV imaging may eventually be removed, with the imaging beam isocenter position routinely verified by adequate quality assurance procedures and measurements. (C) 2014 American Association of Physicists in Medicine. C1 [Zhu, Mingyao; Botticello, Thomas; Lu, Hsiao-Ming; Winey, Brian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zhu, MY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM mzhu4@mgh.harvard.edu FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06-CA059267]; IBA FX The authors would like to thank Thomas Madden for discussions on crosshair autodetection algorithms. This work was supported in part by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. Hsiao-Ming Lu received funding from IBA. Part of the work was presented at 2013 AAPM annual meeting. NR 12 TC 2 Z9 2 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2014 VL 41 IS 4 AR 041706 DI 10.1118/1.4868460 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE8XT UT WOS:000334287000009 PM 24694126 ER PT J AU Choi, PS Meyerson, M AF Choi, Peter S. Meyerson, Matthew TI Targeted genomic rearrangements using CRISPR/Cas technology SO NATURE COMMUNICATIONS LA English DT Article ID LUNG-CANCER; GENE FUSIONS; ZINC-FINGER; HUMAN-CELLS; CAS9; TRANSLOCATIONS; SPECIFICITY; RET; ADENOCARCINOMA; IDENTIFICATION AB Genomic rearrangements are frequently observed in cancer cells but have been difficult to generate in a highly specific manner for functional analysis. Here we report the application of CRISPR/Cas technology to successfully generate several types of chromosomal rearrangements implicated as driver events in lung cancer, including the CD74-ROS1 translocation event and the EML4-ALK and KIF5B-RET inversion events. Our results demonstrate that Cas9-induced DNA breaks promote efficient rearrangement between pairs of targeted loci, providing a highly tractable approach for the study of genomic rearrangements. C1 [Choi, Peter S.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Choi, Peter S.; Meyerson, Matthew] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM matthew_meyerson@dfci.harvard.edu FU International Association for the Study of Lung Cancer; NCI [R01CA109038]; DOD [W81XWH-12-1-0269] FX We thank Hideo Watanabe and other members of the Meyerson laboratory for helpful suggestions, and Feng Zhang for advice and reagents. P.S.C. is supported by a fellowship from the International Association for the Study of Lung Cancer. This research was supported by NCI R01CA109038 and DOD Grant W81XWH-12-1-0269 (M.M.). NR 23 TC 74 Z9 75 U1 3 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2014 VL 5 AR 3728 DI 10.1038/ncomms4728 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2CN UT WOS:000335223300002 PM 24759083 ER PT J AU Cooke, SL Shlien, A Marshall, J Pipinikas, CP Martincorena, I Tubio, JMC Li, Y Menzies, A Mudie, L Ramakrishna, M Yates, L Davies, H Bolli, N Bignell, GR Tarpey, PS Behjati, S Nik-Zainal, S Papaemmanuil, E Teixeira, VH Raine, K O'Meara, S Dodoran, MS Teague, JW Butler, AP Iacobuzio-Donahue, C Santarius, T Grundy, RG Malkin, D Greaves, M Munshi, N Flanagan, AM Bowtell, D Martin, S Larsimont, D Reis-Filho, JS Boussioutas, A Taylor, JA Hayes, DN Janes, SM Futreal, PA Stratton, MR McDermott, U Campbell, PJ AF Cooke, Susanna L. Shlien, Adam Marshall, John Pipinikas, Christodoulos P. Martincorena, Inigo Tubio, Jose M. C. Li, Yilong Menzies, Andrew Mudie, Laura Ramakrishna, Manasa Yates, Lucy Davies, Helen Bolli, Niccolo Bignell, Graham R. Tarpey, Patrick S. Behjati, Sam Nik-Zainal, Serena Papaemmanuil, Elli Teixeira, Vitor H. Raine, Keiran O'Meara, Sarah Dodoran, Maryam S. Teague, Jon W. Butler, Adam P. Iacobuzio-Donahue, Christine Santarius, Thomas Grundy, Richard G. Malkin, David Greaves, Mel Munshi, Nikhil Flanagan, Adrienne M. Bowtell, David Martin, Sancha Larsimont, Denis Reis-Filho, Jorge S. Boussioutas, Alex Taylor, Jack A. Hayes, D. Neil Janes, Sam M. Futreal, P. Andrew Stratton, Michael R. McDermott, Ultan Campbell, Peter J. CA ICGC Breast Cancer Grp TI Processed pseudogenes acquired somatically during cancer development SO NATURE COMMUNICATIONS LA English DT Article ID CELL LUNG CANCERS; 21 BREAST CANCERS; L1 RETROTRANSPOSITION; MUTATIONAL PROCESSES; GENE-EXPRESSION; HUMAN BRAIN; A549 CELLS; REARRANGEMENT; LANDSCAPE; GENOMES AB Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target- site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 50 truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context. C1 [Cooke, Susanna L.; Shlien, Adam; Marshall, John; Martincorena, Inigo; Tubio, Jose M. C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R.; Tarpey, Patrick S.; Behjati, Sam; Nik-Zainal, Serena; Papaemmanuil, Elli; Raine, Keiran; O'Meara, Sarah; Dodoran, Maryam S.; Teague, Jon W.; Butler, Adam P.; Martin, Sancha; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan; ICGC Breast Cancer Grp] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England. [Pipinikas, Christodoulos P.; Teixeira, Vitor H.; Janes, Sam M.] UCL, Lungs Living Res Ctr, Rayne Inst, London WC1E 6JF, England. [Bolli, Niccolo; Behjati, Sam] Univ Cambridge, Cambridge CB2 0XY, England. [Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Santarius, Thomas; McDermott, Ultan; Campbell, Peter J.] Addenbrookes NHS Fdn Trust, Cambridge CB2 0QQ, England. [Grundy, Richard G.] Univ Nottingham, Childrens Brain Tumour Res Ctr, Nottingham NG7 2UH, England. [Malkin, David] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Greaves, Mel] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Munshi, Nikhil] Dana Farber Canc Inst, Boston, MA 02215 USA. [Flanagan, Adrienne M.] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England. [Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Larsimont, Denis] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium. [Reis-Filho, Jorge S.; Campbell, Peter J.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Boussioutas, Alex] Univ Melbourne, Royal Melbourne Hosp, Dept Gastroenterol, Parkville, Vic 3050, Australia. [Taylor, Jack A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27713 USA. [Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Genome Campus, Hinxton CB10 1SA, Cambs, England. EM pc8@sanger.ac.uk RI Bolli, Niccolo/D-4057-2011; Sweep, C.G.J./H-8096-2014; Stunnenberg, Hendrik/D-6875-2012; Simpson, Peter/F-1225-2010; Tubio, Jose/H-5076-2015; Bowtell, David/H-1007-2016; Span, Paul/G-4710-2012; OI Martin, Sancha/0000-0001-6213-5259; Ehinger, Anna/0000-0001-9225-7396; taylor, jack/0000-0001-5303-6398; Boussioutas, Alex/0000-0002-8109-6897; Bolli, Niccolo/0000-0002-1018-5139; chin, suet-feung/0000-0001-5697-1082; Purdie, Colin/0000-0002-1258-4010; Simpson, Peter/0000-0002-4816-8289; McDermott, Ultan/0000-0001-9032-4700; Tubio, Jose/0000-0003-3540-2459; Bowtell, David/0000-0001-9089-7525; Span, Paul/0000-0002-1930-6638; Desmedt, Christine/0000-0002-5223-5579 FU Health Innovation Challenge Fund; Wellcome Trust [077012/Z/05/Z]; Kay Kendall Leukaemia Fund; Wellcome Trust Senior Clinical Research Fellowships; National Research Council Canada; EMBO fellowship; Cancer Research UK Clinician Scientist Fellowship; Academy of Medical Sciences; Lady Tata Memorial Trust; European Community's Seventh Framework Programme [242006]; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences; UCL/UCLH NIHR Biomedical Centre; Skeletal Cancer Action Trust; Rosetrees Trust FX This work was supported by the Health Innovation Challenge Fund, the Wellcome Trust (grant reference 077012/Z/05/Z), and the Kay Kendall Leukaemia Fund. P. J. C. and S. M. J. are personally funded through Wellcome Trust Senior Clinical Research Fellowships. A. S. is funded by the H. L. Holmes Award from the National Research Council Canada and an EMBO fellowship. UAM is personally supported by a Cancer Research UK Clinician Scientist Fellowship. NB was supported by a starter grant from the Academy of Medical Sciences and from Lady Tata Memorial Trust. The breast cancer sequencing was supported by the BASIS project. The BASIS project is a European research project funded by the European Community's Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We also acknowledge support for the sample banking and processing from UCL/UCLH NIHR Biomedical Centre, the Skeletal Cancer Action Trust (SCAT), especially Miss Dina Halai, and the Rosetrees Trust. NR 42 TC 19 Z9 19 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2014 VL 5 AR 3644 DI 10.1038/ncomms4644 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BV UT WOS:000335221300001 PM 24714652 ER PT J AU Warinner, C Rodrigues, JFM Vyas, R Trachsel, C Shved, N Grossmann, J Radini, A Hancock, Y Tito, RY Fiddyment, S Speller, C Hendy, J Charlton, S Luder, HU Salazar-Garcia, DC Eppler, E Seiler, R Hansen, LH Castruita, JAS Barkow-Oesterreicher, S Teoh, KY Kelstrup, CD Olsen, JV Nanni, P Kawai, T Willerslev, E von Mering, C Lewis, CM Collins, MJ Gilbert, MTP Ruhli, F Cappellini, E AF Warinner, Christina Rodrigues, Joao F. Matias Vyas, Rounak Trachsel, Christian Shved, Natallia Grossmann, Jonas Radini, Anita Hancock, Y. Tito, Raul Y. Fiddyment, Sarah Speller, Camilla Hendy, Jessica Charlton, Sophy Luder, Hans Ulrich Salazar-Garcia, Domingo C. Eppler, Elisabeth Seiler, Roger Hansen, Lars H. Castruita, Jose Alfredo Samaniego Barkow-Oesterreicher, Simon Teoh, Kai Yik Kelstrup, Christian D. Olsen, Jesper V. Nanni, Paolo Kawai, Toshihisa Willerslev, Eske von Mering, Christian Lewis, Cecil M., Jr. Collins, Matthew J. Gilbert, M. Thomas P. Ruehli, Frank Cappellini, Enrico TI Pathogens and host immunity in the ancient human oral cavity SO NATURE GENETICS LA English DT Article ID STABLE-ISOTOPE EVIDENCE; TANNERELLA-FORSYTHIA; ANTIBIOTIC-RESISTANCE; PERIODONTAL-DISEASES; PORPHYROMONAS-GINGIVALIS; FUNCTIONAL-ANALYSIS; SYSTEMIC-DISEASES; MICROBIOTA; DATABASE; BACTERIA AB Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past. C1 [Warinner, Christina; Shved, Natallia; Seiler, Roger; Ruehli, Frank] Univ Zurich, Ctr Evolutionary Med, Inst Anat, Zurich, Switzerland. [Warinner, Christina; Tito, Raul Y.; Lewis, Cecil M., Jr.] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Rodrigues, Joao F. Matias; Vyas, Rounak; von Mering, Christian] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland. [Rodrigues, Joao F. Matias; Vyas, Rounak; von Mering, Christian] Swiss Inst Bioinformat, Lausanne, Switzerland. [Trachsel, Christian; Grossmann, Jonas; Barkow-Oesterreicher, Simon; Nanni, Paolo] Univ Zurich, Swiss Fed Inst Technol ETH Zurich, Funct Genom Ctr Zurich, Zurich, Switzerland. [Radini, Anita; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Teoh, Kai Yik; Collins, Matthew J.] Univ York, BioArCh, Dept Archaeol, York YO10 5DD, N Yorkshire, England. [Radini, Anita] Univ Leicester, Univ Leicester Archaeol Serv, Sch Archaeol & Ancient Hist, Leicester, Leics, England. [Hancock, Y.] Univ York, Dept Phys, York YO10 5DD, N Yorkshire, England. [Luder, Hans Ulrich] Univ Zurich, Ctr Dent Med, Inst Oral Biol, Zurich, Switzerland. [Salazar-Garcia, Domingo C.] Max Planck Inst Evolutionary Anthropol, Res Grp Plant Foods Hominin Dietary Ecol, Leipzig, Germany. [Salazar-Garcia, Domingo C.] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, Leipzig, Germany. [Salazar-Garcia, Domingo C.] Univ Valencia, Dept Archaeol & Prehist, Valencia, Spain. [Eppler, Elisabeth] Univ Zurich, Inst Anat, Res Grp Neuroendocrine Immune Interact, Zurich, Switzerland. [Eppler, Elisabeth] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. [Hansen, Lars H.] Univ Copenhagen, Dept Biol Microbiol, Copenhagen, Denmark. [Hansen, Lars H.] Aarhus Univ, Dept Environm Sci, Roskilde, Denmark. [Castruita, Jose Alfredo Samaniego; Willerslev, Eske; Gilbert, M. Thomas P.; Cappellini, Enrico] Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, Copenhagen, Denmark. [Kelstrup, Christian D.; Olsen, Jesper V.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark. [Kawai, Toshihisa] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Gilbert, M. Thomas P.] Murdoch Univ, Ancient DNA Lab, Perth, WA, Australia. RP Warinner, C (reprint author), Univ Zurich, Ctr Evolutionary Med, Inst Anat, Zurich, Switzerland. EM twarinner@gmail.com; ecappellini@gmail.com RI Cappellini, Enrico/F-9346-2013; von Mering, Christian/B-3300-2008; Gilbert, Marcus/A-8936-2013; Samaniego Castruita, Jose Alfredo/B-9033-2015; Collins, Matthew/A-7534-2008; Speller, Camilla/D-2830-2014; OI Cappellini, Enrico/0000-0001-7885-7811; von Mering, Christian/0000-0001-7734-9102; Warinner, Christina/0000-0002-4528-5877; Salazar-Garcia, Domingo C./0000-0002-8017-0194; Gilbert, Marcus/0000-0002-5805-7195; Samaniego Castruita, Jose Alfredo/0000-0001-5904-1198; Collins, Matthew/0000-0003-4226-5501; Speller, Camilla/0000-0001-7128-9903; Matias Rodrigues, Joao F/0000-0001-8413-9920; feigelman, rounak/0000-0002-1830-9300; Olsen, Jesper/0000-0002-4747-4938; Kelstrup, Christian Dahl/0000-0003-4647-1425 FU Maxi Foundation Zurich,; Swiss Foundation for Nutritional Research; Danish Research Foundation [29396]; Danish Council for Independent Research [10-081390]; Lundbeck Foundation [R52-A5062, R44-A4384]; US National Institutes of Health [R01-HG005172, R01-GM089886, R01-DE018499, R21-DE018310,]; European Research Council [UMICIS/242870]; Wellcome Trust [097829]; Swiss National Science Foundation [31003A-135688]; Novartis Foundation; Novo Nordisk Foundation; Max Planck Society; University of York; [EUROTAST FP7-PEOPLE-2010 MC ITN]; [PALIMPSEST FP7-PEOPLE-2011-IEF 299101]; [ORCA FP7-PEOPLE-2011-IOF 299075] FX We thank the Kantonale Ethik- Kommission Zurich, the Functional Genomics Center Zurich, the Center for Microscopy and Image Analysis, and the Institute of Oral Biology at the University of Zurich; the PRIDE Team; G. Akgul, K. Alt, D. Ashford, P. Ashton, H. Barton, A. Bouwman, C. Burger, D. Coulthard, J. Hublin, V. Meskenaite, F. Najar, M. Richards, K. Sankaranarayanan, R. Schlapbach, L. Shillito, T. Stollner, O. Ullrich and H. Zbinden for assistance with data collection, analysis and management; and M. Carver, F. Dewhirst, A. Tanner, K. Hardy and A. Henry for helpful comments on early drafts and data analyses. This work was supported by the Maxi Foundation Zurich, the Swiss Foundation for Nutritional Research, Danish Research Foundation grant 29396, Danish Council for Independent Research grant 10-081390, Lundbeck Foundation grants R52-A5062 and R44-A4384, US National Institutes of Health grants R01-HG005172, R01-GM089886, R01-DE018499 and R21-DE018310, European Research Council grant UMICIS/242870, Marie Curie grants EUROTAST FP7-PEOPLE-2010 MC ITN, PALIMPSEST FP7-PEOPLE-2011-IEF 299101 and ORCA FP7-PEOPLE-2011-IOF 299075, a C2D2 Research Priming Fund grant partly funded by Wellcome Trust 097829, Swiss National Science Foundation grant 31003A-135688, the Novartis Foundation, the Novo Nordisk Foundation, the Max Planck Society and the University of York. NR 73 TC 77 Z9 78 U1 11 U2 101 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 2014 VL 46 IS 4 BP 336 EP + DI 10.1038/ng.2906 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AF1YP UT WOS:000334510100008 PM 24562188 ER PT J AU Flannick, J Thorleifsson, G Beer, NL Jacobs, SBR Grarup, N Burtt, NP Mahajan, A Fuchsberger, C Atzmon, G Benediktsson, R Blangero, J Bowden, DW Brandslund, I Brosnan, J Burslem, F Chambers, J Cho, YS Cho, YS Douglas, DA Duggirala, R Dymek, Z Farjoun, Y Fennell, T Fontanillas, P Forsen, T Gabriel, S Glaser, B Gudbjartsson, DF Hanis, C Hansen, T Hreidarsson, AB Hveem, K Ingelsson, E Isomaa, B Johansson, S Jorgensen, T Jorgensen, ME Kathiresan, S Kong, A Kooner, J Kravic, J Laakso, M Lee, JY Lind, L Lindgren, CM Linneberg, A Masson, G Meitinger, T Mohlke, KL Molven, A Morris, AP Potluri, S Rauramaa, R Ribel-Madsen, R Richard, AM Rolph, T Saloemaa, V Segre, AV Skarstrand, H Steinthorsdottir, V Stringham, HM Sulem, P Tai, ES Teo, YY Teslovich, T Thorsteinsdottir, U Trimmer, JK Tuomi, T Tuomilehto, J Vaziri-Sani, F Voight, BF Voight, BF Boehnke, M McCarthy, MI Njolstad, PR Pedersen, O Groop, L Cox, DR Stefansson, K Altshuler, D AF Flannick, Jason Thorleifsson, Gudmar Beer, Nicola L. Jacobs, Suzanne B. R. Grarup, Niels Burtt, Noel P. Mahajan, Anubha Fuchsberger, Christian Atzmon, Gil Benediktsson, Rafn Blangero, John Bowden, Don W. Brandslund, Ivan Brosnan, Julia Burslem, Frank Chambers, John Cho, Yoon Shin Christensen, Cramer Douglas, Desiree A. Duggirala, Ravindranath Dymek, Zachary Farjoun, Yossi Fennell, Timothy Fontanillas, Pierre Forsen, Tom Gabriel, Stacey Glaser, Benjamin Gudbjartsson, Daniel F. Hanis, Craig Hansen, Torben Hreidarsson, Astradur B. Hveem, Kristian Ingelsson, Erik Isomaa, Bo Johansson, Stefan Jorgensen, Torben Jorgensen, Marit Eika Kathiresan, Sekar Kong, Augustine Kooner, Jaspal Kravic, Jasmina Laakso, Markku Lee, Jong-Young Lind, Lars Lindgren, Cecilia M. Linneberg, Allan Masson, Gisli Meitinger, Thomas Mohlke, Karen L. Molven, Anders Morris, Andrew P. Potluri, Shobha Rauramaa, Rainer Ribel-Madsen, Rasmus Richard, Ann-Marie Rolph, Tim Salomaa, Veikko Segre, Ayellet V. Skaerstrand, Hanna Steinthorsdottir, Valgerdur Stringham, Heather M. Sulem, Patrick Tai, E. Shyong Teo, Yik Ying Teslovich, Tanya Thorsteinsdottir, Unnur Trimmer, Jeff K. Tuomi, Tiinamaija Tuomilehto, Jaakko Vaziri-Sani, Fariba Voight, Benjamin F. Wilson, James G. Boehnke, Michael McCarthy, Mark I. Njolstad, Pal R. Pedersen, Oluf Groop, Leif Cox, David R. Stefansson, Kari Altshuler, David CA Go-T2D Consortium T2D-Genes Consortium TI Loss-of-function mutations in SLC30A8 protect against type 2 diabetes SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ZINC TRANSPORTER ZNT8; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; COMMON VARIANTS; BETA-CELL; MICE; RARE; PATHOPHYSIOLOGY; EXPRESSION AB Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets1-3, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of -150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) 4 and harbors a common variant (p. Trp325Arg) associated with T2D risk and glucose and proinsulin levels5-7. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 x 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p. Lys34Serfs* 50) demonstrated reduced glucose levels (-0.17 s. d., P = 4.6 x 10(-4)). The two most common proteintruncating variants (p. Arg138* and p. Lys34Serfs* 50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk(8,9), and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts(10-15). In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention. C1 [Flannick, Jason; Beer, Nicola L.; Jacobs, Suzanne B. R.; Burtt, Noel P.; Dymek, Zachary; Farjoun, Yossi; Fennell, Timothy; Fontanillas, Pierre; Gabriel, Stacey; Kathiresan, Sekar; Lindgren, Cecilia M.; Segre, Ayellet V.; Voight, Benjamin F.; Njolstad, Pal R.; Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02141 USA. [Flannick, Jason; Segre, Ayellet V.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Thorleifsson, Gudmar; Gudbjartsson, Daniel F.; Kong, Augustine; Masson, Gisli; Steinthorsdottir, Valgerdur; Sulem, Patrick; Thorsteinsdottir, Unnur; Stefansson, Kari] Amgen Inc, deCODE Genet, Reykjavik, Iceland. [Beer, Nicola L.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Grarup, Niels; Hansen, Torben; Ribel-Madsen, Rasmus; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen, Denmark. [Mahajan, Anubha; Ingelsson, Erik; Lindgren, Cecilia M.; Morris, Andrew P.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Fuchsberger, Christian; Stringham, Heather M.; Teslovich, Tanya; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Atzmon, Gil] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Atzmon, Gil] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Benediktsson, Rafn; Hreidarsson, Astradur B.] Landspitali Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland. [Blangero, John; Duggirala, Ravindranath] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Bowden, Don W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Bowden, Don W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Diabet Res, Winston Salem, NC USA. [Bowden, Don W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC USA. [Bowden, Don W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC USA. [Brandslund, Ivan] Vejle Hosp, Dept Clin Biochem, Vejle, Denmark. [Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark. [Brosnan, Julia; Richard, Ann-Marie; Rolph, Tim; Trimmer, Jeff K.] Pfizer Inc, Cardiovasc & Metab Dis Res Unit, Cambridge, MA USA. [Burslem, Frank] Prescient Life Sci, Cardiovasc & Metab Dis Practice, London, England. [Chambers, John] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Chambers, John; Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Healthcare Natl Hlth Serv NHS Trust, London, England. [Chambers, John; Kooner, Jaspal] Ealing Hosp NHS Trust, Southall, Middx, England. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea. [Christensen, Cramer] Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark. [Douglas, Desiree A.; Skaerstrand, Hanna; Vaziri-Sani, Fariba] Lund Univ, Dept Clin Sci, Unit Diabet & Celiac Dis, Malmo, Sweden. [Forsen, Tom; Tuomi, Tiinamaija] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Forsen, Tom] Vaasa Hlth Care Ctr, Diabetes Care Unit, Vaasa, Finland. [Glaser, Benjamin] Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel. [Glaser, Benjamin] IDRG, Holon, Israel. [Hanis, Craig] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Hveem, Kristian] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, Levanger, Norway. [Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Johansson, Stefan; Molven, Anders; Njolstad, Pal R.] Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway. [Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Johansson, Stefan] Univ Bergen, Dept Biomed, Bergen, Norway. [Jorgensen, Torben; Linneberg, Allan] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Jorgensen, Torben; Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med, Copenhagen, Denmark. [Jorgensen, Torben; Linneberg, Allan] Aalborg Univ, Fac Med, Aalborg, Denmark. [Jorgensen, Marit Eika] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Kathiresan, Sekar; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; Altshuler, David] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, NHLI, London, England. [Kravic, Jasmina; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Lee, Jong-Young] Korea Natl Inst Hlth, Osong Hlth Technol, Ctr Genome Sci, Seoul, Chungcheongbuk, South Korea. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway. [Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Potluri, Shobha; Cox, David R.] Pfizer Inc, Appl Quantitat Genotherapeut, San Francisco, CA USA. [Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Salomaa, Veikko] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Tai, E. Shyong; Teo, Yik Ying] Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Tai, E. Shyong] Natl Univ Singapore, Natl Univ Hlth Syst, Dept Med, Singapore 117548, Singapore. [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Dept Med, Singapore, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Teo, Yik Ying] Genome Inst Singapore, Agcy Sci Technol & Res, Singapore, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabetes Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Phys & Biophys, Jackson, MS 39216 USA. [McCarthy, Mark I.] Churchill Hosp, Hlth Res NIHR Biomed Res Ctr, Oxford Natl Inst, Oxford, England. [Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Groop, Leif] Univ Helsinki, Finnish Inst Mol Med FIMM, Helsinki, Finland. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Altshuler, D (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02141 USA. EM kstefans@decode.is; altshuler@molbio.mgh.harvard.edu RI Vaziri-Sani, Fariba/J-6390-2014; Chen, Peng/E-5546-2015; Meitinger, Thomas/O-1318-2015; Johansson, Stefan/C-4394-2011; Grarup, Niels/K-2807-2015 OI Linneberg, Allan/0000-0002-0994-0184; Vaziri-Sani, Fariba/0000-0002-9953-2829; Chen, Peng/0000-0002-1422-4641; Fuchsberger, Christian/0000-0002-5918-8947; Jacobs, Suzanne/0000-0002-8103-1700; Johansson, Stefan/0000-0002-2298-7008; Tuomi, Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830; Tai, E Shyong/0000-0003-2929-8966; Grarup, Niels/0000-0001-5526-1070 FU US National Institutes of Health (NIH) Training [5-T32-GM007748-33]; Doris Duke Charitable Foundation [2006087]; Fulbright Diabetes UK Fellowship [BDA 11/0004348]; Broad Institute from Pfizer, Inc.; NIH [U01 DK085501, U01 DK085524, U01 DK085545, U01 DK085584]; Swedish Research Council [Dnr 521-2010-3490, Dnr 349-2006-237]; European Research Council (ERC) [GENETARGET T2D, GA269045]; ENGAGE [2007-201413]; CEED3 [2008-223211]; Sigrid Juselius Foundation; Folkh lsan Research Foundation; ERC [AdG 293574]; Research Council of Norway [197064/V50]; KG Jebsen Foundation; University of Bergen; Western Norway Health Authority; Lundbeck Foundation; Novo Nordisk Foundation; Wellcome Trust [WT098017, WT064890, WT090532, WT090367, WT098381]; Uppsala University; Swedish Research Council and the Swedish Heart- Lung Foundation; Academy of Finland [124243, 102318, 123885, 139635]; Finnish Heart Foundation; Finnish Diabetes Foundation, Tekes [1510/31/06]; Commission of the European Community [HEALTH-F2-2007-201681]; Ministry of Education and Culture of Finland; European Commission Framework Programme 6 Integrated Project [LSHM-CT-2004-005272]; City of Kuopio and Social Insurance Institution of Finland; Finnish Foundation for Cardiovascular Disease; NIH/NIDDK [U01-DK085545]; National Heart, Lung, and Blood Institute (NHLBI); National Institute on Minority Health and Health Disparities [N01 HC-95170, N01 HC-95171, N01 HC-95172]; European Union Seventh Framework Programme, DIAPREPP; Swedish Child Diabetes Foundation (Barndiabetesfonden); [5U01DK085526]; [DK088389]; [U54HG003067]; [R01DK072193]; [R01DK062370]; [Z01HG000024] FX This manuscript is dedicated to the memory of David R. Cox, our dear friend and colleague, who was relentlessly supportive of this work-and more generally, of the use of human genetics to improve human health. He is missed, but his legacy goes on. We gratefully acknowledge the contribution of all similar to 150,000 participants from the various population studies that contributed to this work. J.F. was supported in part by US National Institutes of Health (NIH) Training Grant 5-T32-GM007748-33. D. A. was supported by funding from the Doris Duke Charitable Foundation (2006087). N. L. B. was supported by a Fulbright Diabetes UK Fellowship (BDA 11/0004348). This work was supported in part by funding to the Broad Institute (principal investigator D. A.) from Pfizer, Inc. Funding for the GoT2D and T2D-GENES studies was provided by grants 5U01DK085526 (NIH/NIDDK; Multiethnic Study of Type 2 Diabetes Genes), DK088389 (NIH/NIDDK; Low-Pass Sequencing and High-Density SNP Genotyping for Type 2 Diabetes) and U54HG003067 (National Human Genome Research Institute (NHGRI); Large-Scale Sequencing and Analysis of Genomes), as well as by NIH grants U01 DK085501, U01 DK085524, U01 DK085545 and U01 DK085584. The Malm Preventive Project and the Scania Diabetes Registry were supported by grants from the Swedish Research Council (Dnr 521-2010-3490 to L. G. and Dnr 349-2006-237 to the Lund University Diabetes Centre), as well as by a European Research Council (ERC) grant (GENETARGET T2D, GA269045) and two European Union grants (ENGAGE (2007-201413) and CEED3 (2008-223211)) to L. G. The Botnia study was supported by funding from the Sigrid Juselius Foundation and the Folkh lsan Research Foundation. P. R. N. was funded by the ERC (AdG 293574), the Research Council of Norway (197064/V50), the KG Jebsen Foundation, the University of Bergen, the Western Norway Health Authority, the European Association for the Study of Diabetes Sabbatical Leave Programme and Innovest. The Danish studies were supported by the Lundbeck Foundation (Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp); http://www.lucamp.org/) and the Danish Council for Independent Research. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk/). The PIVUS/ ULSAM cohort was supported by Wellcome Trust grants WT098017, WT064890 and WT090532, Uppsala University, the Uppsala University Hospital, the Swedish Research Council and the Swedish Heart- Lung Foundation. The METSIM study was supported by the Academy of Finland (contract 124243), the Finnish Heart Foundation, the Finnish Diabetes Foundation, Tekes (contract 1510/31/06), the Commission of the European Community (HEALTH-F2-2007-201681) and grants R01DK062370 and R01DK072193 (NIH/NIDDK) and grant (NHGRI). The FUSION study was supported by grants R01DK062370 and R01DK072193 (NIH/NIDDK) and grant Z01HG000024 (NHGRI). The DR's EXTRA Study was supported by the Ministry of Education and Culture of Finland (627; 2004-2011), the Academy of Finland (102318; 123885), Kuopio University Hospital, the Finnish Diabetes Association, the Finnish Heart Association and the P ivikki and Sakari Sohlberg Foundation and by grants from the European Commission Framework Programme 6 Integrated Project (EXGENESIS); LSHM-CT-2004-005272, City of Kuopio and Social Insurance Institution of Finland (4/26/2010). V.; Salomaa is funded by the Academy of Finland, grant 139635, and by the Finnish Foundation for Cardiovascular Disease. Sequencing and genotyping of British individuals was supported by Wellcome Trust grants WT090367, WT090532 and WT098381 and by NIH/NIDDK grant U01-DK085545. Funding for the Jackson Heart Study (JHS) was provided by the National Heart, Lung, and Blood Institute (NHLBI) and by the National Institute on Minority Health and Health Disparities (N01 HC-95170, N01 HC-95171 and N01 HC-95172). A. P. M. acknowledges support from Wellcome Trust grants WT098017, WT090532 and WT064890. F.V.-S. and H. S. were supported by the European Union Seventh Framework Programme, DIAPREPP (Diabetes Type 1 Prediction, Early Pathogenesis and Prevention, grant agreement 202013), and by the Swedish Child Diabetes Foundation (Barndiabetesfonden). NR 28 TC 128 Z9 129 U1 7 U2 43 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 2014 VL 46 IS 4 BP 357 EP + DI 10.1038/ng.2915 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AF1YP UT WOS:000334510100011 PM 24584071 ER PT J AU Knoechel, B Roderick, JE Williamson, KE Zhu, J Lohr, JG Cotton, MJ Gillespie, SM Fernandez, D Ku, M Wang, H Piccioni, F Silver, SJ Jain, M Pearson, D Kluk, MJ Ott, CJ Shultz, LD Brehm, MA Greiner, DL Gutierrez, A Stegmaier, K Kung, AL Root, DE Bradner, JE Aster, JC Kelliher, MA Bernstein, BE AF Knoechel, Birgit Roderick, Justine E. Williamson, Kaylyn E. Zhu, Jiang Lohr, Jens G. Cotton, Matthew J. Gillespie, Shawn M. Fernandez, Daniel Ku, Manching Wang, Hongfang Piccioni, Federica Silver, Serena J. Jain, Mohit Pearson, Daniel Kluk, Michael J. Ott, Christopher J. Shultz, Leonard D. Brehm, Michael A. Greiner, Dale L. Gutierrez, Alejandro Stegmaier, Kimberly Kung, Andrew L. Root, David E. Bradner, James E. Aster, Jon C. Kelliher, Michelle A. Bernstein, Bradley E. TI An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia SO NATURE GENETICS LA English DT Article ID LENTIVIRAL RNAI LIBRARY; ACUTE MYELOID-LEUKEMIA; C-MYC; NOTCH1; CANCER; INHIBITION; CHROMATIN; GENOME; GENES; PATHWAY AB The identification of activating NOTCH1 mutations in T cell acute lymphoblastic leukemia (T-ALL) led to clinical testing of g-secretase inhibitors (GSIs) that prevent NOTCH1 activation1-4. However, responses to these inhibitors have been transient5, suggesting that resistance limits their clinical efficacy. Here we modeled T-ALL resistance, identifying GSI-tolerant ` persister' cells that expand in the absence of NOTCH1 signaling. Rare persisters are already present in naive T-ALL populations, and the reversibility of their phenotype suggests an epigenetic mechanism. Relative to GSI-sensitive cells, persister cells activate distinct signaling and transcriptional programs and exhibit chromatin compaction. A knockdown screen identified chromatin regulators essential for persister viability, including BRD4. BRD4 binds enhancers near critical T-ALL genes, including MYC and BCL2. The BRD4 inhibitor JQ1 downregulates expression of these targets and induces growth arrest and apoptosis in persister cells, at doses well tolerated by GSI-sensitive cells. Consistently, the GSI-JQ1 combination was found to be effective against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia resistance that may be addressed by incorporating epigenetic modulators in combination therapy. C1 [Knoechel, Birgit; Williamson, Kaylyn E.; Zhu, Jiang; Cotton, Matthew J.; Gillespie, Shawn M.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Knoechel, Birgit; Williamson, Kaylyn E.; Zhu, Jiang; Lohr, Jens G.; Cotton, Matthew J.; Gillespie, Shawn M.; Fernandez, Daniel; Ku, Manching; Piccioni, Federica; Silver, Serena J.; Jain, Mohit; Root, David E.; Bradner, James E.; Bernstein, Bradley E.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Knoechel, Birgit; Williamson, Kaylyn E.; Zhu, Jiang; Lohr, Jens G.; Cotton, Matthew J.; Gillespie, Shawn M.; Fernandez, Daniel; Ku, Manching; Piccioni, Federica; Silver, Serena J.; Jain, Mohit; Root, David E.; Bradner, James E.; Bernstein, Bradley E.] Harvard, Cambridge, MA USA. [Knoechel, Birgit; Gutierrez, Alejandro; Stegmaier, Kimberly; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Knoechel, Birgit; Pearson, Daniel; Gutierrez, Alejandro; Stegmaier, Kimberly; Kung, Andrew L.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Knoechel, Birgit; Williamson, Kaylyn E.; Zhu, Jiang; Cotton, Matthew J.; Gillespie, Shawn M.; Ku, Manching; Wang, Hongfang; Pearson, Daniel; Kluk, Michael J.; Gutierrez, Alejandro; Stegmaier, Kimberly; Kung, Andrew L.; Aster, Jon C.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Roderick, Justine E.; Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Williamson, Kaylyn E.; Zhu, Jiang; Cotton, Matthew J.; Gillespie, Shawn M.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Williamson, Kaylyn E.; Zhu, Jiang; Cotton, Matthew J.; Gillespie, Shawn M.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Lohr, Jens G.; Ott, Christopher J.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fernandez, Daniel] Harvard Univ, Biostat Grad Program, Cambridge, MA 02138 USA. [Wang, Hongfang; Kluk, Michael J.; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jain, Mohit] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jain, Mohit] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Pearson, Daniel] Harvard Univ, Sch Med, Biol & Biomed Sci Grad Program, Boston, MA USA. [Shultz, Leonard D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Brehm, Michael A.; Greiner, Dale L.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM michelle.kelliher@umassmed.edu; bernstein.bradley@mgh.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU US National Institutes of Health (NIH) Training [5-T32-GM007748-33]; Doris Duke Charitable Foundation [2006087]; Fulbright Diabetes UK Fellowship [BDA 11/0004348]; Broad Institute; NIH/NIDDK [5U01DK085526]; DK088389; National Human Genome Research Institute (NHGRI) [U54HG003067]; NIH [U01 DK085501, U01 DK085524, U01 DK085545, U01 DK085584]; Swedish Research Council [Dnr 521-2010-3490, Dnr 349-2006-237]; European Research Council (ERC) [GENETARGET T2D, GA269045]; ENGAGE [2007-201413]; CEED3 [2008-223211]; Sigrid Juselius Foundation and the Folkh lsan Research Foundation; ERC [AdG 293574]; Research Council of Norway [197064/V50]; KG Jebsen Foundation; University of Bergen; Western Norway Health Authority; Lundbeck Foundation; Wellcome Trust [WT098017, WT064890, WT090532]; Uppsala University; Uppsala University Hospital; Swedish Research Council; Swedish Heart- Lung Foundation; Academy of Finland [124243]; Finnish Heart Foundation; Finnish Diabetes Foundation, Tekes [1510/31/06]; Commission of the European Community; Commission of the European Community [HEALTH-F2-2007-201681]; Ministry of Education and Culture of Finland; European Commission Framework Programme 6 Integrated Project (EXGENESIS) [LSHM-CT-2004-005272]; City of Kuopio and Social Insurance Institution of Finland; The Academy of Finland [139635]; Finnish Foundation for Cardiovascular Disease; Wellcome Trust grants [WT098017, WT064890, WT090532, WT090367, WT098381]; National Heart, Lung, and Blood Institute; National Institute on Minority Health and Health Disparities [N01 HC-95170N01, HC-95171N01, HC-95172]; European Union Seventh Framework Programme, DIAPREPP; Swedish Child Diabetes Foundation; US National Institutes of Health (NIH) [HL007574- 30]; St. Baldrick's fellowship; US NIH T32 training [CA130807, HL007627]; American Cancer Society [125087-PF-13247-01-LIB]; National Human Genome Research Institute [ENCODE U54 HG004570]; NIH Common Fund for Epigenomics [U01 ES017155]; NIH/NCI [CA096899, 5P01 CA109901-10]; Howard Hughes Medical Institute; Starr Cancer Consortium; The Leukemia & Lymphoma Society Specialized Center of Research Program; [R01DK062370]; [R01DK072193]; [Z01HG000024]; [102318]; [123885]; [U01-DK085545] FX We are grateful to T. Look, M. Harris, L. Silverman and S. Sallan for providing the pediatric T- ALL samples. We thank the Flow Cytometry Core of the Harvard Stem Cell Institute and the Center for Regenerative Medicine and Technology for excellent flow sorting. We thank E. Rheinbay, M. Suva, R. Ryan, N. Riggi, A. Goren, O. Ram, J. Wu, L. Pan, W. Pear and M. Rivera for helpful discussions; V. Mootha for critical comments on the manuscript; S. Muller- Knapp and the Structural Genomics Consortium (Oxford, UK) for their assistance with inhibitor experiments; L. Hamm and the Broad RNAi Platform for help with the shRNA screen; R. Issner, X. Zhang, C. Epstein, N. Shoresh, T. Durham and the Broad Genome Sequencing Platform for technical assistance; A. Christie for help with mouse experiments; L. Gaffney for help with illustrations; and O. Weigert for providing the BCL2 ORF. B. K. was supported by a US National Institutes of Health (NIH) T32 training grant (HL007574- 30) and by a St. Baldrick's fellowship. J. E. R. was supported by a US NIH T32 training grant (CA130807) and by a postdoctoral fellowship from the American Cancer Society (125087-PF-13247-01-LIB). H. W. is supported by a US NIH T32 training grant (HL007627). This work was supported by the National Human Genome Research Institute (ENCODE U54 HG004570 to B. E. B.), the NIH Common Fund for Epigenomics (U01 ES017155 to B. E. B.), the NIH/NCI (CA096899 to M. A. K. and 5P01 CA109901- 10 to J. E. B.), the Howard Hughes Medical Institute (B. E. B.) and the Starr Cancer Consortium (B. E. B.). The Leukemia & Lymphoma Society Specialized Center of Research Program supports B. E. B., J. C. A., J. E. B., K. S. and A. L. K. NR 43 TC 77 Z9 80 U1 0 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 2014 VL 46 IS 4 BP 364 EP + DI 10.1038/ng.2913 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AF1YP UT WOS:000334510100012 PM 24584072 ER PT J AU Goodman, A Nour, N AF Goodman, Annekathryn Nour, Nawal TI Cervical Cancer Screening: The Complex Interplay of Medical Infrastructure, Society, and Culture SO ONCOLOGIST LA English DT Editorial Material ID LOW-RESOURCE SETTINGS; PREVENTION; DISPARITIES; KNOWLEDGE; PROGRAM; BRAZIL; WOMEN; PERU C1 [Goodman, Annekathryn] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Goodman, Annekathryn] Massachusetts Gen Hosp, Div Womens Global Hlth, Boston, MA 02114 USA. [Nour, Nawal] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Global Hlth, Boston, MA 02115 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Yawkey Bldg Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM agoodman@mgh.harvard.edu NR 25 TC 3 Z9 3 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2014 VL 19 IS 4 BP 315 EP 317 DI 10.1634/theoncologist.2014-0083 PG 3 WC Oncology SC Oncology GA AF0JY UT WOS:000334401300002 PM 24682462 ER PT J AU Moy, B Neven, P Lebrun, F Bellet, M Xu, BH Sarosiek, T Chow, L Goss, P Zacharchuk, C Leip, E Turnbull, K Bardy-Bouxin, N Duvillie, L Lang, I AF Moy, Beverly Neven, Patrick Lebrun, Fabienne Bellet, Meritxell Xu, Binghe Sarosiek, Tomasz Chow, Louis Goss, Paul Zacharchuk, Charles Leip, Eric Turnbull, Kathleen Bardy-Bouxin, Nathalie Duvillie, Ladan Lang, Istvan TI Bosutinib in Combination With the Aromatase Inhibitor Exemestane: A Phase II Trial in Postmenopausal Women With Previously Treated Locally Advanced or Metastatic Hormone Receptor-Positive/HER2-Negative Breast Cancer SO ONCOLOGIST LA English DT Editorial Material AB Background. Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as second-line therapy in previously treated hormone receptor-positive (HR+) locally advanced or metastatic BC. Methods. This was a phase II study with patients enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and initial efficacy was assessed. After the lead-in and dose-determination phase, randomized evaluation of combination therapy versus exemestane was planned. Results. Thirty-nine of 42 patients (93%) experienced treatment related AEs including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on treatment discontinuation. One patient (300 mg/day) achieved confirmed partial response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease for >24 weeks; a best response of progressive disease occurred in 15 of 42 patients (36%). Median progression-free survival was 12.3 weeks (80% confidence interval: 11.0-15.6). Conclusion. The risk-benefit profile of bosutinib at 300mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC. C1 [Moy, Beverly; Goss, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neven, Patrick; Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen] UZ Leuven, Leuven, Belgium. [Lebrun, Fabienne] Inst Jules Bordet, Brussels, Belgium. [Bellet, Meritxell] Vall dHebron Univ Hosp, Barcelona, Spain. [Xu, Binghe] Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. [Sarosiek, Tomasz] Ctr Med Ostrobramska NZOZ MAGODENT, Warsaw, Poland. [Chow, Louis] Comprehens Ctr Breast Dis, Unimed Med Inst, Hong Kong, Hong Kong, Peoples R China. [Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen] Pfizer Inc, Cambridge, MA USA. [Bardy-Bouxin, Nathalie; Duvillie, Ladan] Pfizer Global Res & Dev, Paris, France. [Lang, Istvan] Orszagos Onkol Intezet, Budapest, Hungary. RP Moy, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 9A, Boston, MA 02114 USA. EM bmoy@partners.org NR 0 TC 2 Z9 2 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2014 VL 19 IS 4 BP 346 EP 347 DI 10.1634/theoncologist.2014-0022 PG 2 WC Oncology SC Oncology GA AF0JY UT WOS:000334401300007 PM 24674873 ER PT J AU Moy, B Neven, P Lebrun, F Bellet, M Xu, BH Sarosiek, T Chow, L Goss, P Zacharchuk, C Leip, E Turnbull, K Bardy-Bouxin, N Duvillie, L Lang, I AF Moy, Beverly Neven, Patrick Lebrun, Fabienne Bellet, Meritxell Xu, Binghe Sarosiek, Tomasz Chow, Louis Goss, Paul Zacharchuk, Charles Leip, Eric Turnbull, Kathleen Bardy-Bouxin, Nathalie Duvillie, Ladan Lang, Istvan TI Bosutinib in Combination With the Aromatase Inhibitor Letrozole: A Phase II Trial in Postmenopausal Women Evaluating First-Line Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive/HER2-Negative Breast Cancer SO ONCOLOGIST LA English DT Editorial Material AB Background. Endocrine therapy resistance in hormone receptor-positive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. Methods. Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5mg/day; adverse events (AEs) anddose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Results. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. Conclusion. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole. C1 [Moy, Beverly; Goss, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neven, Patrick] UZ Leuven, Louvain, Belgium. [Lebrun, Fabienne] Inst Jules Bordet, Brussels, Belgium. [Bellet, Meritxell] Vall dHebron Univ Hosp, Barcelona, Spain. [Xu, Binghe] Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. [Sarosiek, Tomasz] Ctr Med Ostrobramska NZOZ MAGODENT, Warsaw, Poland. [Chow, Louis] Comprehens Ctr Breast Dis, Unimed Med Inst, Hong Kong, Hong Kong, Peoples R China. [Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen] Pfizer Inc, Cambridge, MA USA. [Bardy-Bouxin, Nathalie] Pfizer Global Res & Dev, Paris, France. [Lang, Istvan] Orszagos Onkol Intezet, Budapest, Hungary. RP Moy, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 9A, Boston, MA 02114 USA. EM bmoy@partners.org NR 0 TC 5 Z9 5 U1 2 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2014 VL 19 IS 4 BP 348 EP 349 PG 2 WC Oncology SC Oncology GA AF0JY UT WOS:000334401300008 PM 24674874 ER PT J AU Forst, DA Nahed, BV Loeffler, JS Batchelor, TT AF Forst, Deborah A. Nahed, Brian V. Loeffler, Jay S. Batchelor, Tracy T. TI Low-Grade Gliomas SO ONCOLOGIST LA English DT Article DE Glioma; Astrocytoma; Oligodendroglioma; Surgery; Radiation ID MAGNETIC-RESONANCE-SPECTROSCOPY; QUALITY-OF-LIFE; RADIATION-THERAPY; RANDOMIZED-TRIAL; PILOCYTIC ASTROCYTOMA; SURGICAL RESECTION; RESPONSE CRITERIA; MALIGNANT GLIOMA; IDH2 MUTATIONS; DOSE-RESPONSE AB Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated. C1 [Forst, Deborah A.; Batchelor, Tracy T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Nahed, Brian V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Loeffler, Jay S.; Batchelor, Tracy T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [K24 CA125440] NR 59 TC 13 Z9 14 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2014 VL 19 IS 4 BP 403 EP 413 DI 10.1634/theoncologist.2013-0345 PG 11 WC Oncology SC Oncology GA AF0JY UT WOS:000334401300018 PM 24664484 ER PT J AU Chandrasekhar, SS AF Chandrasekhar, Sujana S. TI Vertiginous Headache and Its Management SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Headache; Migraine; Dizziness; Vertigo; Meniere syndrome; Ocular movement disorder ID MIGRAINOUS VERTIGO; VESTIBULAR MIGRAINE; DIZZINESS; REHABILITATION; SYMPTOMS; PATIENT AB Vertiginous headache encompasses patients with dizziness or vertigo as well as headache, even though the symptoms may not occur in an obvious temporal relationship. The type of dizziness experienced by patients is different from the heavy-headedness experienced during rhinogenic headache. Patients may have a personal or family history of typical or atypical migraine. They should be evaluated for possible Meniere syndrome, migraine headaches, and/or eye movement disorders. Management is directed to treatment of the underlying abnormality. Long-term follow-up of these patients is necessary, because further otologic abnormalities may present later. C1 [Chandrasekhar, Sujana S.] New York Otol, New York, NY 10028 USA. [Chandrasekhar, Sujana S.] James J Peters Vet Adm Med Ctr, Bronx, NY USA. [Chandrasekhar, Sujana S.] Northshore LIJ Med Ctr, New York Head & Neck Inst, New York, NY USA. [Chandrasekhar, Sujana S.] Mt Sinai Sch Med, New York, NY USA. RP Chandrasekhar, SS (reprint author), New York Otol, 1421 Third Ave,4th Floor, New York, NY 10028 USA. EM ssc@nyotology.com NR 29 TC 0 Z9 0 U1 0 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 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2014 VL 47 IS 2 BP 333 EP + DI 10.1016/j.otc.2013.11.001 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA AF7KR UT WOS:000334894500012 PM 24680497 ER PT J AU Blashill, AJ AF Blashill, Aaron J. TI A Dual Pathway Model of Steroid Use Among Adolescent Boys: Results From a Nationally Representative Sample SO PSYCHOLOGY OF MEN & MASCULINITY LA English DT Article DE anabolic-androgenic steroids; adolescent boys; depression; victimization; underweight ID ANABOLIC-ANDROGENIC STEROIDS; BODY-MASS INDEX; WEIGHT PERCEPTION; PERCEIVED WEIGHT; RISK; BEHAVIOR; YOUTH; ASSOCIATION; MUSCULARITY; MEDIATION AB Anabolic-androgenic steroid (AAS) use is associated with medical and psychiatric complications; however, despite the identification of psychosocial correlates of AAS use, comprehensive models have rarely been assessed. Thus, AAS use as a function of self-perceived weight status, victimization, and depressive symptoms was examined via simultaneous multiple mediation with nonparametric bootstrapping. Data from the 2009 National Youth Risk Behavior Survey (YRBS) was utilized. The target population consisted of all public, Catholic, and other private school students in Grades 9 through 12 in the United States. The sample comprised 8,065 adolescent high school males. The global and individual indirect effects of self-perceived underweight status to AAS use through depressive symptoms and victimization were significant. However, the victimization pathway was revealed to be stronger in magnitude than the depressive pathway. Depressive symptoms and victimization are two pathways in which self-perceived underweight status predicts AAS use among adolescent boys. C1 [Blashill, Aaron J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blashill, Aaron J.] Harvard Univ, Med School, Dept Psychiat, Cambridge, MA 02138 USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIMH NIH HHS [K23 MH096647] NR 34 TC 4 Z9 4 U1 1 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1524-9220 EI 1939-151X J9 PSYCHOL MEN MASCULIN JI Psychol. Men Masculinity PD APR PY 2014 VL 15 IS 2 BP 229 EP 233 DI 10.1037/a0032914 PG 5 WC Psychology, Social SC Psychology GA AF6ZR UT WOS:000334863600012 PM 25419187 ER PT J AU Mehra, S Tuttle, RM Bergman, D Bernet, V Brett, E Cobin, R Doherty, G Klopper, J Lee, S Machac, J Milas, M Mechanick, JI Orloff, L Randolph, G Ross, DS Smallridge, R Terris, D Tufano, R Alon, E Clain, J Dos Reis, L Scherl, S Urken, ML AF Mehra, Saral Tuttle, R. Michael Bergman, Donald Bernet, Victor Brett, Elise Cobin, Rhoda Doherty, Gerard Klopper, Joshua Lee, Stephanie Machac, Josef Milas, Mira Mechanick, Jeffrey I. Orloff, Lisa Randolph, Gregory Ross, Douglas S. Smallridge, Robert Terris, David Tufano, Ralph Alon, Eran Clain, Jason Dos Reis, Laura Scherl, Sophie Urken, Mark L. TI Improving the Quality of Thyroid Cancer Care: How Does the Thyroid Cancer Care Collaborative Cross the Institute of Medicine's Quality Chasm? SO THYROID LA English DT Review ID INFORMED-CONSENT; INCREASING INCIDENCE; UNITED-STATES; VOLUME; OUTCOMES; SURGERY; ASSOCIATION; DEFINITION; CARCINOMA; PAPILLARY AB Background: The current systems of healthcare delivery in the United States suffer from problems that often leave patients with inadequate quality of care. In their report entitled "Crossing the Quality Chasm," the Institute of Medicine (IOM) identified reasons for poor and/or inconsistent quality of healthcare delivery and provided recommendations to improve it. The purpose of this review is to describe features of an innovative web-based program called the Thyroid Cancer Care Collaborative (TCCC) and see how it addresses IOM recommendations to improve the quality of healthcare delivery. Summary: The TCCC addresses the three actionable IOM recommendations directed at healthcare organizations and clinicians to redesign the care process. It does so by exploiting information technology (IT) in ways suggested by the IOM, and it fits within a set of 10 rules provided by the IOM. Some features of the TCCC include: (i) automated disease staging based on three validated scoring systems; (ii) highly illustrated educational videos on all aspects of thyroid cancer care; (iii) personalized clinical decision-making modules for clinicians and physicians; (iv) portability of data to share among treating physicians; (v) virtual tumor boards, "ask the expert," and frequently asked questions modules; (vi) physician workflow integration; and (vii) data for comprehensive analysis to answer difficult questions in thyroid cancer management. Conclusion: The TCCC has the potential to improve thyroid cancer care delivery and offers several benefits to patients, clinicians, and researchers. The TCCC is a valuable example of how IOM initiatives can improve the healthcare system. C1 [Mehra, Saral] Yale Univ, Dept Surg Otolaryngol, New Haven, CT 06520 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Bergman, Donald; Brett, Elise; Cobin, Rhoda; Machac, Josef; Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Bernet, Victor; Smallridge, Robert] Mayo Clin, Dept Endocrinol, Jacksonville, FL 32224 USA. [Doherty, Gerard] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Klopper, Joshua] Univ Colorado Denver, Dept Endocrinol, Aurora, CO USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Machac, Josef] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY USA. [Milas, Mira] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [Orloff, Lisa] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Dept Med, Harvard Univ, Sch Med, Boston, MA 02114 USA. [Terris, David] Med Coll Georgia, Dept Otolaryngol, Augusta, GA 30912 USA. [Tufano, Ralph] Johns Hopkins Sch Med, Dept Otolaryngol, Baltimore, MD USA. [Alon, Eran] Tel Aviv Univ, Sackler Sch Med, Dept Otolaryngol, Tel Hashomer, Israel. [Clain, Jason; Dos Reis, Laura; Scherl, Sophie; Urken, Mark L.] THANC Fdn, New York, NY USA. [Urken, Mark L.] Mt Sinai Beth Israel, Inst Head & Neck & Thyroid Canc, New York, NY USA. RP Mehra, S (reprint author), Yale Univ, Sch Med, 333 Cedar St,Box 208041, New Haven, CT 06520 USA. EM saral.mehra@yale.edu NR 23 TC 4 Z9 4 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR 1 PY 2014 VL 24 IS 4 BP 615 EP 624 DI 10.1089/thy.2013.0441 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE6NN UT WOS:000334110700001 PM 24512449 ER PT J AU Vanden Borre, P McFadden, DG Gunda, V Sadow, PM Varmeh, S Bernasconi, M Jacks, T Parangi, S AF Vanden Borre, Pierre McFadden, David G. Gunda, Viswanath Sadow, Peter M. Varmeh, Shohreh Bernasconi, Maria Jacks, Tyler Parangi, Sareh TI The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAF(V600E)-Positive Papillary and Anaplastic Thyroid Carcinoma SO THYROID LA English DT Article ID MICE; B-RAF(V600E); PROGRESSION; IPILIMUMAB; SURVIVAL; ANTIBODY AB Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous Braf(V600E/WT) and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system. C1 [Vanden Borre, Pierre; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [McFadden, David G.] Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Boston, MA 02114 USA. [Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Dept Biol, Cambridge, MA USA. RP Parangi, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org FU National Institutes of Health, the American College of Surgeons; American Thyroid Association; National Institutes of Health and National Cancer Institute [Parent F32, K08] FX P.V.B. is a recipient of the Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellows (Parent F32) from the National Institutes of Health and National Cancer Institute. S. P. is funded through the National Institutes of Health, the American College of Surgeons, and the American Thyroid Association. The murine thyroid cancer cell lines were derived from mice generated by D. G. M., recipient of a K08 award from the National Institutes of Health and National Cancer Institute, in the laboratory of T.J. We also thank Derrick Jeon at the Center for Systems Biology at Massachusetts General Hospital for assistance with live imaging and Patricia Della Pelle in the Department of Pathology at Massachusetts General Hospital for histological and immunohistochemical investigations. NR 33 TC 1 Z9 1 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR 1 PY 2014 VL 24 IS 4 BP 705 EP 714 DI 10.1089/thy.2013.0483 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE6NN UT WOS:000334110700012 PM 24295207 ER PT J AU Yu, HH Vu, THK Cho, KS Guo, CY Chen, DF AF Yu, Honghua Thi Hong Khanh Vu Cho, Kin-Sang Guo, Chenying Chen, Dong Feng TI Mobilizing endogenous stem cells for retinal repair SO TRANSLATIONAL RESEARCH LA English DT Review ID PIGMENT EPITHELIAL-CELLS; NEURAL PROGENITOR CELLS; EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; GANGLION-LIKE CELLS; ADULT MAMMALIAN RETINA; CILIARY MARGINAL ZONE; MULLER GLIA; IN-VITRO; BONE-MARROW AB Irreversible vision loss is most often caused by the loss of function and subsequent death of retinal neurons, such as photoreceptor cells the cells that initiate vision by capturing and transducing signals of light. One reason why retinal degenerative diseases are devastating is that, once retinal neurons are lost, they don't grow back. Stem cell-based cell replacement strategy for retinal degenerative diseases are leading the way in clinical trials of transplantation therapy, and the exciting findings in both human and animal models point to the possibility of restoring vision through a cell replacement regenerative approach. A less invasive method of retinal regeneration by mobilizing endogenous stem cells is, thus, highly desirable and promising for restoring vision. Although many obstacles remain to be overcome, the field of endogenous retinal repair is progressing at a rapid pace, with encouraging results in recent years. C1 Liuhuaqiao Hosp, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China. [Chen, Dong Feng] Harvard Univ, Sch Med, Massachusetts Eye & Ear, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands. VA Boston Healthcare Syst, Boston, MA USA. RP Chen, DF (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. EM Dongfeng_Chen@meei.harvard.edu FU NEI NIH HHS [R01 EY017641]; NIDA NIH HHS [R21 DA024803] NR 141 TC 6 Z9 8 U1 0 U2 11 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 APR PY 2014 VL 163 IS 4 BP 387 EP 398 DI 10.1016/j.trsl.2013.11.011 PG 12 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA AF3YL UT WOS:000334648500012 PM 24333552 ER PT J AU Kowalczyk, KJ Gu, XM Nguyen, PL Lipsitz, SR Trinh, QD Lynch, JH Collins, SP Hu, JC AF Kowalczyk, Keith J. Gu, Xiangmei Nguyen, Paul L. Lipsitz, Stuart R. Quoc-Dien Trinh Lynch, John H. Collins, Sean P. Hu, Jim C. TI Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Radical prostatectomy; Radiation therapy; SEER; Outcomes ID ANDROGEN DEPRIVATION THERAPY; QUALITY-OF-LIFE; RANDOMIZED CLINICAL-TRIAL; RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; BIOCHEMICAL RECURRENCE; MEN; MANAGEMENT; REGISTRY; DISEASE AB Objectives: Although post radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART. Materials and methods: From the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3NO disease receiving early (<4 mo after RP, n = 419) vs. delayed (4-12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3NO disease. Results: When compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042). Conclusion: Initiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kowalczyk, Keith J.; Lynch, John H.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Gu, Xiangmei; Lipsitz, Stuart R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Quoc-Dien Trinh] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Collins, Sean P.] Georgetown Univ Hosp, Dept Radiat Oncol, Washington, DC 20007 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Inst Urol Oncol, Los Angeles, CA 90095 USA. RP Kowalczyk, KJ (reprint author), Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. EM keith.kowalczyk@gunet.georgetown.edu FU Department of Defense Prostate Cancer Physician Training Award [W81XWH-08-1-0283] FX Funding: This work was supported by a lDepartment of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) presented to Dr. Hu. NR 30 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD APR PY 2014 VL 32 IS 3 BP 303 EP 308 DI 10.1016/j.urolonc.2013.09.004 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AF3XX UT WOS:000334647100012 PM 24321259 ER PT J AU Lin, XS Hu, L Kirley, S Correll, M Quackenbush, J Wu, CL McDougal, WS AF Lin, Xuanhui Sharron Hu, Lan Kirley, Sandy Correll, Mick Quackenbush, John Wu, Chin-Lee McDougal, William Scott TI Differentiating progressive from nonprogressive T1 bladder cancer by gene expression profiling: Applying RNA-sequencing analysis on archived specimens SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE T1 bladder cancer; RNA-Seq; Tumor progression; Molecular signature ID SEQ; CLASSIFICATION; CARCINOMA; PREDICTION AB Objectives: To identify gene signatures in transitional cell carcinoma that can differentiate high-grade T1 nonprogressive (T1NP) bladder cancer (BCa) from those T1 progressive (T1P) tumors that progress to muscularis propria invasive T2 tumors. Materials and methods: We performed a high-throughput RNA sequencing (RNA-Seq) on forrnalin-fixed and paraffin-embedded BCa specimens with clinical pathologic characteristics best representing the general clinical development of the disease. For the T1NP group, only patients with long-term follow-up (6-17 y) and periodic examinations (average of 4 resections and 9 cytology tests) were selected. For the T1P group, only patients in whom a complete resection was performed after a minimum of 8 months after the initial T1 diagnosis were selected, therefore eliminating the possibility of underdiagnosis. Only samples in which muscularis propria was present and uninvolved were included, further assuring a correct diagnosis. The RNA-Seq reads were mapped to the human genome build NCBI 36 (hg18) using TopHat with no mismatch. After alignment to the transcriptome and expression quantification, a linear statistical model was built using Limma between T1NP and T1P samples to identify differentially expressed genes. Results: Overall, 5,561 genes were mapped to all samples and used for RNA-Seq analysis to identify a gene signature that was significantly and differentially expressed between patients with T1NP BCa and patients with T1P BCa. Signature-based stratification indicated the gene signature correlated notably with the time of T1 development to T2 tumor, suggesting that the molecular signature might be used as an independent predictor for the pace of high-grade T1 BCa progression. Conclusions: This is the first demonstration that RNA-Seq can be applied as a powerful tool to study BCa using formalin-fixed and paraffin-embedded specimens. We identified a gene signature that can distinguish patients diagnosed with high-grade T1 BCas that remain as non muscle invasive tumors from those patients with cancers progressing to muscle-invasive tumors. Our findings will make future large-scale clinical cohort studies and clinical trial based studies possible and help the development of prognostic tools for accurate prediction of T1 BCa progression that may considerably influence the clinical decision making process, treatment regimen, and patient survival. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lin, Xuanhui Sharron; Kirley, Sandy; Wu, Chin-Lee; McDougal, William Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Lin, Xuanhui Sharron; Kirley, Sandy; Wu, Chin-Lee; McDougal, William Scott] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Lan; Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hu, Lan; Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM cwu2@partners.org; wmcdougal@partners.org FU MGH Department of Urology Morrison Bladder Cancer Endowment Fund FX Funded by the MGH Department of Urology Morrison Bladder Cancer Endowment Fund. NR 28 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD APR PY 2014 VL 32 IS 3 BP 327 EP 336 DI 10.1016/j.urolonc.2013.06.014 PG 10 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AF3XX UT WOS:000334647100015 ER PT J AU Xu, RN Horick, N McGovern, FJ Dahl, DM Feldman, AS Blute, ML Olumi, AF Michaelson, MD AF Xu, Rena Horick, Nora McGovern, Francis J. Dahl, Douglas M. Feldman, Adam S. Blute, Michael L. Olumi, Aria F. Michaelson, M. Dror TI Prognostic significance of indeterminate lung nodules in renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Renal cell carcinoma; Prognosis; Indeterminate lung nodule ID PULMONARY NODULES; COLORECTAL-CANCER; CT SCANS; MANAGEMENT AB Objectives: Many patients with renal cell carcinoma (RCC) are found to have lung nodules at the time of diagnosis. The significance of these nodules is unclear. This study sought to determine whether the presence of indeterminate lung nodules affects survival for patients with early-stage RCC. Methods and materials: A retrospective review was performed of patients with stages I to III RCC at an academic hospital who underwent nephrectomy between 2001 and 2006 and had baseline imaging available for review. Presence of lung nodule(s) was determined, along with patient and disease characteristics. The time from diagnosis to last known follow-up, metastasis, and death were determined. The study follow-up period extended to July 2012. Univariate and multivariate Cox proportional hazards models assessed disease-free and overall survival. Results: Of 548 patients, 240 met the inclusion criteria. Lung nodules were absent in 148 and present in 92 cases. Disease-free survival was associated with the presence of nodules (hazard ratio [HR] = 1.90; 95% CI: 1.04-3.46; P = 0.0362), tumor stage (stage II-HR = 5.61; 95% CI: 2.69-11.72; P < 0.001 and stage 111 HR = 2.49; 95% CI: 1.21-5.10; P = 0.0129) and tumor grade (HR = 2.43 for grades 3 or 4; 95% CI: 1.31-4.53; P = 0.005). The number and size of nodules were not associated with survival. Overall survival was associated with Charlson comorbidity score (HR = 1.30; 95% CI: 1.15-1.47; P < 0.0001) and primary tumor size (HR = 1.29; 95% CI: 1.14-1.46; P < 0.0001) but not the presence of lung nodules (HR = 1.73; 95% CI: 0.83-3.60; P = 0.1454). Conclusions: The presence of indeterminate lung nodules had a negative effect on disease-free survival. Stage and grade were also significant. These findings underscore the importance of baseline imaging and vigilant surveillance of patients in whom nodules are identified. (C) 2014 Elsevier Inc. All rights reserved. C1 [McGovern, Francis J.; Dahl, Douglas M.; Feldman, Adam S.; Blute, Michael L.; Olumi, Aria F.; Michaelson, M. Dror] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Horick, Nora; Dahl, Douglas M.; Feldman, Adam S.; Blute, Michael L.; Olumi, Aria F.; Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Xu, Rena; McGovern, Francis J.; Dahl, Douglas M.; Feldman, Adam S.; Blute, Michael L.; Olumi, Aria F.; Michaelson, M. Dror] Harvard Univ, Sch Med, Boston, MA USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM dmichaelson1@mgh.harvard.edu OI Michaelson, Dror/0000-0001-9249-6338 FU John Estrella Foundation for Cancer Research; Dana Farber/Harvard Kidney Cancer Center FX This study was supported by the John Estrella Foundation for Cancer Research and by the Dana Farber/Harvard Kidney Cancer Center. NR 12 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD APR PY 2014 VL 32 IS 3 BP 355 EP 361 DI 10.1016/j.urolonc.2013.09.001 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AF3XX UT WOS:000334647100018 PM 24397994 ER PT J AU Lewiss, RE Tayal, VS Hoffmann, B Kendall, J Liteplo, AS Moak, JH Panebianco, N Noble, VE AF Lewiss, Resa E. Tayal, Vivek S. Hoffmann, Beatrice Kendall, John Liteplo, Andrew S. Moak, James H. Panebianco, Nova Noble, Vicki E. TI The Core Content of Clinical Ultrasonography Fellowship TrainingEl Contenido Basico de la Formacion del Programa Posresidencia en Ecografia Clinica SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-MEDICINE; ULTRASOUND AB Abstract The purpose of developing a core content for subspecialty training in clinical ultrasonography (US) is to standardize the education and qualifications required to provide oversight of US training, clinical use, and administration to improve patient care. This core content would be mastered by a fellow as a separate and unique postgraduate training, beyond that obtained during an emergency medicine (EM) residency or during medical school. The core content defines the training parameters, resources, and knowledge of clinical US necessary to direct clinical US divisions within medical specialties. Additionally, it is intended to inform fellowship directors and candidates for certification of the full range of content that might appear in future examinations. This article describes the development of the core content and presents the core content in its entirety. C1 [Lewiss, Resa E.] St Lukes Roosevelt Mt Sinai Hosp, Dept Emergency Med, New York, NY 10025 USA. [Tayal, Vivek S.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Hoffmann, Beatrice] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Kendall, John] Univ Colorado, Sch Med, Dept Emergency Med, Denver Hlth Med Ctr, Denver, CO USA. [Liteplo, Andrew S.; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Moak, James H.] Univ Virginia, Dept Emergency Med, Charlottesville, VA USA. [Panebianco, Nova] Hosp Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Lewiss, RE (reprint author), St Lukes Roosevelt Mt Sinai Hosp, Dept Emergency Med, New York, NY 10025 USA. EM resaelewiss@gmail.com FU American Association of Nurse Practitioners FX Dr. Hoffmann has been an education consultant for ACEP and has received royalties from UpToDate Inc.; Dr. Kendall has received royalties from Lippincott; Dr. Moak has received payment for development of educational presentations from the American Association of Nurse Practitioners on point of care ultrasound at a national meeting, June 20-22, 2013; Dr. Noble has received royalties from Cambridge University Press. NR 8 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2014 VL 21 IS 4 BP 456 EP 461 DI 10.1111/acem.12349 PG 6 WC Emergency Medicine SC Emergency Medicine GA AE8YE UT WOS:000334288100013 PM 24730409 ER PT J AU Moellman, JJ Bernstein, JA Lindsell, C Banerji, A Busse, PJ Camargo, CA Collins, SP Craig, TJ Lumry, WR Nowak, R Pines, JM Raja, AS Riedl, M Ward, MJ Zuraw, BL Diercks, D Hiestand, B Campbell, RL Schneider, S Sinert, R AF Moellman, Joseph J. Bernstein, Jonathan A. Lindsell, Christopher Banerji, Aleena Busse, Paula J. Camargo, Carlos A., Jr. Collins, Sean P. Craig, Timothy J. Lumry, William R. Nowak, Richard Pines, Jesse M. Raja, Ali S. Riedl, Marc Ward, Michael J. Zuraw, Bruce L. Diercks, Deborah Hiestand, Brian Campbell, Ronna L. Schneider, Sandra Sinert, Richard TI A Consensus Parameter for the Evaluation and Management of Angioedema in the Emergency DepartmentUn Parametro de Consenso para la Evaluacion y Tratamiento del Angioedema en el Servicio de Urgencias SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CONVERTING ENZYME-INHIBITORS; UPPER AIRWAY-OBSTRUCTION; HEREDITARY ANGIOEDEMA; UNITED-STATES; ACQUIRED ANGIOEDEMA; ALLERGIC REACTIONS; DIAGNOSIS; BRADYKININ; HOSPITALIZATIONS; C1-INHIBITOR AB Abstract Despite its relatively common occurrence and life-threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic-mediated angioedema from bradykinin-mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin-mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM). C1 [Moellman, Joseph J.; Lindsell, Christopher] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH 45221 USA. [Bernstein, Jonathan A.] Univ Cincinnati, Coll Med, Dept Internal Med, Div Allergy & Immunol, Cincinnati, OH USA. [Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Div Allergy & Immunol, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Busse, Paula J.] Mt Sinai Hosp, Dept Med & Clin Immunol, New York, NY 10029 USA. [Collins, Sean P.; Ward, Michael J.] Vanderbilt Univ, Dept Emergency Med, Nashville, TN 37235 USA. [Craig, Timothy J.] Penn State Hershey Med Ctr, Dept Internal Med & Pediat, Hershey, PA USA. [Lumry, William R.] Allergy & Asthma Specialists, Dallas, TX USA. [Nowak, Richard] Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA. [Pines, Jesse M.] George Washington Univ, Dept Emergency Med, Washington, DC USA. [Raja, Ali S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Riedl, Marc] David Geffen Sch Med UCLA, Dept Med, Sect Allergy & Immunol, Los Angeles, CA USA. [Zuraw, Bruce L.] UC San Diego Sch Med, Dept Med, Immunol Sect, San Diego, CA USA. RP Moellman, JJ (reprint author), Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH 45221 USA. EM moellmjj@uc.edu FU CSL Behring; Dyax; Santarus; Shire FX Supported by an unrestricted educational grant from CSL Behring, Dyax, Santarus, and Shire. No pharmaceutical company was involved in the planning or execution of the consensus process, and none had input to the development or approval of the consensus parameter. CSL Behring manufactures Berinert-P, Dyax manufactures Ecallantide, and Shire manufactures Icatibant. Each of these medications is approved only for the treatment of hereditary angioedema in the United States. Santarus is partnering with Pharming to distribute conestant-alpha, licensed as Rhucin in the United States, should it be approved by the Food and Drug Administration for the treatment of hereditary angioedema. NR 66 TC 16 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2014 VL 21 IS 4 BP 469 EP 484 DI 10.1111/acem.12341 PG 16 WC Emergency Medicine SC Emergency Medicine GA AE8YE UT WOS:000334288100017 PM 24730413 ER PT J AU Matteau, A Yeh, RW Kereiakes, D Orav, EJ Massaro, J Steg, PG Normand, SL Cutlip, DE Mauri, L AF Matteau, Alexis Yeh, Robert W. Kereiakes, Dean Orav, E. John Massaro, Joseph Steg, P. Gabriel Normand, Sharon-Lise Cutlip, Donald E. Mauri, Laura TI Frequency of the Use of Low- Versus High-Dose Aspirin in Dual Antiplatelet Therapy After Percutaneous Coronary Intervention (from the Dual Antiplatelet Therapy Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DRUG-ELUTING STENT; ASSOCIATION TASK-FORCE; LOGISTIC-REGRESSION; PRACTICE GUIDELINES; TREATMENT PATTERNS; CLINICAL-OUTCOMES; TRIAL; CLOPIDOGREL; IMPACT; PCI AB In randomized trials, low-dose (LD) and high-dose (HD) aspirin (ASA) are equally effective in reducing ischemic complications, but HD ASA is associated with an increased risk of bleeding in the setting of dual antiplatelet therapy after percutaneous coronary intervention (PCI). ASA dose after PCI varies across countries, but little is known about variation within the United States (US) and whether this variation can be explained by clinical characteristics of patients. We used enrollment data from the Dual Antiplatelet Therapy Study, a randomized trial designed to compare 12 versus 30 months of dual antiplatelet therapy after PCI, to quantify the variation in ASA dosing after PCI in the US subjects and assess the extent to which dose variability was attributable to patient characteristics. Of the 23,336 patients enrolled in the US, 28.0% were prescribed LD ASA at discharge after PCI. Patient characteristics explained 1.6% of total variance in ASA dose, whereas the study site accounted for 45.9% of the unexplained variability. The median odds ratio comparing sites was 5.05 (95% confidence interval 4.29 to 5.85), which was greater than any individual predictor of ASA dose. In conclusion, LD ASA after PCI in the US was used in a minority of patients, and heterogeneity in its selection was mainly influenced by the site of enrollment rather than patient characteristics. As HD ASA may be associated with adverse events in the setting of dual antiplatelet therapy, reducing local practice variation in the dose of ASA may be a target for quality improvement. (C) 2014 Elsevier Inc. All rights reserved. C1 [Matteau, Alexis; Orav, E. John; Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yeh, Robert W.; Massaro, Joseph; Cutlip, Donald E.; Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA. [Yeh, Robert W.; Normand, Sharon-Lise; Cutlip, Donald E.; Mauri, Laura] Harvard Univ, Sch Med, Boston, MA USA. [Kereiakes, Dean] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Kereiakes, Dean] Lindner Ctr Res & Educ, Cincinnati, OH USA. [Massaro, Joseph] Boston Univ, Boston, MA 02215 USA. [Steg, P. Gabriel] Hop Bichat Claude Bernard, F-75877 Paris, France. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Normand, Sharon-Lise] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org FU Harvard Clinical Research Institute is contracted FX No funds were received specifically for this analysis. Harvard Clinical Research Institute is contracted and funded to perform the primary data collection and analysis for the DAPT Study by Abbott, Santa Clara, California, Boston Scientific, Marlborough, Massachusetts, Cordis, Bridge-water, New Jersey, Medtronic, Santa Rosa, California, Bristol-Myers Squibb, Princeton. New Jersey. Sanofi-Aventis, Bridge-water, New Jersey, Eli Lilly, Indianapolis. Indiana, and Daiichi Sankyo, Edison, New Jersey. NR 27 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2014 VL 113 IS 7 BP 1146 EP 1152 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE3HW UT WOS:000333868600011 PM 24332248 ER PT J AU Hoff, E Eagle, T Pyeritz, RE Ehrlich, M Voehringer, M Bossone, E Hutchison, S Peterson, MD Suzuki, T Greason, K Forteza, A Montgomery, DG Isseelbacher, EM Nienaber, CA Eagle, KA AF Hoff, Emily Eagle, Taylor Pyeritz, Reed E. Ehrlich, Marek Voehringer, Matthias Bossone, Eduardo Hutchison, Stuart Peterson, Mark D. Suzuki, Toru Greason, Kevin Forteza, Alberto Montgomery, Daniel G. Isseelbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. TI Pulse Pressure and Type A Acute Aortic Dissection In-Hospital Outcomes (from the International Registry of Acute Aortic Dissection) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-PRESSURE; CARDIOVASCULAR MORTALITY; RISK; DISEASE; HYPERTENSION; PREDICTOR; STIFFNESS AB Little is known about the relation between type A acute aortic dissection (TAAAD) and pulse pressure (PP), defined as the difference between systolic and diastolic blood pressure. In this study, we explored the association between PP and presentation, complications, and outcomes of patients with TAAAD. PP at hospital presentation was used to divide 1,960 patients with noniatrogenic TAAAD into quartiles: narrowed (<= 39 mm Hg, n = 430), normal (40 to 56 mm Hg, n = 554), mildly elevated (57 to 75 mm Hg, n = 490), and markedly elevated (>= 76 mm Hg, n = 486). Variables relating to index presentation and in-hospital outcomes were analyzed. Patients with TAAAD in the narrowed PP quartiles were frequently older and Caucasian, whereas patients with markedly elevated PPs tended to be male and have a history of hypertension. Patients who demonstrated abdominal vessel involvement more commonly demonstrated elevated PPs, whereas patients with narrowed PPs were more likely to have periaortic hematoma and/or pericardial effusion. Narrowed PPs were also correlated with greater incidences of hypotension, cardiac tamponade, and mortality. Patients with TAAAD who were managed with endovascular and hybrid procedures and those with renal failure tended to have markedly elevated PPs. No difference in aortic regurgitation at presentation was noted among groups. In conclusion, patients with TAAAD in the third PP quartile had better in-hospital outcomes than patients in the lowest quartile. Patients with narrowed PPs experienced more cardiac complications, particularly cardiac tamponade, whereas those with markedly elevated PPs were more likely to have abdominal aortic involvement. Presenting PP offers a clue to different manifestations of acute aortic dissection that may facilitate initial triage and care. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hoff, Emily; Eagle, Taylor; Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Pyeritz, Reed E.] Univ Penn, Div Med Genet, Philadelphia, PA 19104 USA. [Ehrlich, Marek] Univ Vienna, Dept Cardiothorac Surg, Vienna, Austria. [Voehringer, Matthias] Robert Bosch Krankenhaus, Dept Cardiol & Pulmonol, Stuttgart, Germany. [Bossone, Eduardo] Univ Salerno, Div Cardiol, I-84100 Salerno, Italy. [Hutchison, Stuart] Univ Calgary, Dept Cardiac Sci, Calgary, AB, Canada. [Hutchison, Stuart] Univ Calgary, Dept Med, Calgary, AB, Canada. [Hutchison, Stuart] Univ Calgary, Dept Radiol, Calgary, AB, Canada. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Suzuki, Toru] Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan. [Greason, Kevin] Mayo Clin, Div Cardiovasc Surg, Rochester, MN USA. [Forteza, Alberto] Hosp Univ 12 Octubre, Dept Cardiac Surg, Madrid, Spain. [Isseelbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. RP Eagle, KA (reprint author), Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. EM elisew@umich.edu FU W.L. Gore & Associates, Inc. (Flagstaff, Arizona); Medtronic (Minneapolis, Minnesota); Varbedian Aortic Research Fund (Ann Arbor, Michigan); Hewlett Foundation (Menlo Park, California); Mardigian Foundation (Ann Arbor, Michigan); University of Michigan Faculty Group Practice (Ann Arbor, Michigan); Terumo (Tokyo. Japan) FX The International Registry of Acute Aortic Dissection (IRAD) is funded by grants from W.L. Gore & Associates, Inc. (Flagstaff, Arizona), Medtronic (Minneapolis, Minnesota), the Varbedian Aortic Research Fund (Ann Arbor, Michigan), the Hewlett Foundation (Menlo Park, California), the Mardigian Foundation (Ann Arbor, Michigan), University of Michigan Faculty Group Practice (Ann Arbor, Michigan), and Terumo (Tokyo. Japan). NR 16 TC 1 Z9 2 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2014 VL 113 IS 7 BP 1255 EP 1259 DI 10.1016/j.amjcard.2013.12.037 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE3HW UT WOS:000333868600030 PM 24521716 ER PT J AU Moyers, BS Secemsky, EA Vittinghoff, E Wong, JK Havlir, DV Hsue, PY Tseng, ZH AF Moyers, Brian S. Secemsky, Eric A. Vittinghoff, Eric Wong, Joseph K. Havlir, Diane V. Hsue, Priscilla Y. Tseng, Zian H. TI Effect of Left Ventricular Dysfunction and Viral Load on Risk of Sudden Cardiac Death in Patients With Human Immunodeficiency Virus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; ANTIRETROVIRAL THERAPY; DIASTOLIC FUNCTION; EJECTION FRACTION; HIV; INFECTION; ECHOCARDIOGRAPHY; RECOMMENDATIONS AB Human immunodeficiency virus (HIV) infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF <30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p = 0.01 and FIR 38.5, 95% CI 7.6 to 195.0, p <0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p <0.001) but not AIDS death, even after adjusting for EF. The association between EF <40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p = 0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p = 0.41; p = 0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population. (C) 2014 Elsevier Inc. All rights reserved. C1 [Moyers, Brian S.; Tseng, Zian H.] Univ Calif San Francisco, Dept Med, Div Cardiol, Sect Cardiac Electrophysiol, San Francisco, CA 94143 USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Havlir, Diane V.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA USA. [Secemsky, Eric A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Wong, Joseph K.] Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA USA. RP Tseng, ZH (reprint author), Univ Calif San Francisco, Dept Med, Div Cardiol, Sect Cardiac Electrophysiol, San Francisco, CA 94143 USA. EM zhtseng@medicine.ucsf.edu FU National Institutes of Health/National Heart, Lung, and Blood Institute [5R01 HL102090, 5R01 HL095130, 5R01 HL091526]; Veterans Affairs Merit Review Program [R01 NS501132]; National Institutes of Health [K24 AI5 1982] FX This work was supported by grants 5R01 HL102090 (ZHT), 5R01 HL095130 (PYH), and 5R01 HL091526 (PYH) from the National Institutes of Health/National Heart, Lung, and Blood Institute. grant R01 NS501132 (JKW) from the Veterans Affairs Merit Review Program, and grant K24 AI5 1982 (DVH) from the National Institutes of Health. NR 30 TC 6 Z9 6 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2014 VL 113 IS 7 BP 1260 EP 1265 DI 10.1016/j.amjcard.2013.12.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE3HW UT WOS:000333868600031 PM 24521717 ER PT J AU Jain, M Ngoy, S Sheth, SA Swanson, RA Rhee, EP Liao, R Clish, CB Mootha, VK Nilsson, R AF Jain, Mohit Ngoy, Soeun Sheth, Sunil A. Swanson, Raymond A. Rhee, Eugene P. Liao, Ronglih Clish, Clary B. Mootha, Vamsi K. Nilsson, Roland TI A systematic survey of lipids across mouse tissues SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE tissue physiology and metabolism; lipidomics; lipid metabolism; biomarkers; stroke ID POLYUNSATURATED FATTY-ACIDS; STEAROYL-COA DESATURASE-1; MASS-SPECTROMETRY; BROWN ADIPOCYTES; MEMBRANE-LIPIDS; ADIPOSE-TISSUE; METABOLISM; LIPIDOMICS; EXPRESSION; DISEASE AB Lipids are a diverse collection of macromolecules essential for normal physiology, but the tissue distribution and function for many individual lipid species remain unclear. Here, we report a mass spectrometry survey of lipid abundance across 18 mouse tissues, detecting similar to 1,000 mass spectrometry features, of which we identify 179 lipids from the glycerolipids, glycerophospholipids, lysophospholipids, acylcarnitines, sphingolipids, and cholesteryl ester classes. Our data reveal tissue-specific organization of lipids and can be used to generate testable hypotheses. For example, our data indicate that circulating triglycerides positively and negatively associated with future diabetes in humans are enriched in mouse adipose tissue and liver, respectively, raising hypotheses regarding the tissue origins of these diabetes-associated lipids. We also integrate our tissue lipid data with gene expression profiles to predict a number of substrates of lipid-metabolizing enzymes, highlighting choline phosphotransferases and sterol O-acyltransferases. Finally, we identify several tissue-specific lipids not present in plasma under normal conditions that may be of interest as biomarkers of tissue injury, and we show that two of these lipids are released into blood following ischemic brain injury in mice. This resource complements existing compendia of tissue gene expression and may be useful for integrative physiology and lipid biology. C1 [Jain, Mohit; Rhee, Eugene P.; Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Jain, Mohit; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Jain, Mohit; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Jain, Mohit; Ngoy, Soeun; Liao, Ronglih] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Sheth, Sunil A.; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Sheth, Sunil A.; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA USA. [Nilsson, Roland] Karolinska Inst, Unit Computat Med, S-17176 Stockholm, Sweden. [Nilsson, Roland] Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. RP Nilsson, R (reprint author), Karolinska Inst, Dept Med, L8 01 Karolinska Univ Hosp, S-17176 Stockholm, Sweden. EM roland.nilsson@ki.se OI Swanson, Raymond/0000-0002-3664-5359 FU NIH [K08 HL-107451]; Swedish Research Council [K2012-99X-22007-01-3]; Foundation for Strategic Research [ICA10-0023]; Knut & Alice Wallenberg Foundation; Nestle Research Center FX M. Jain was supported by NIH GRANT K08 HL-107451. R. N. was supported by grants from the Swedish Research Council (K2012-99X-22007-01-3), the Foundation for Strategic Research (ICA10-0023), and the Knut & Alice Wallenberg Foundation. This work was supported by a gift from the Nestle Research Center to the Broad Institute (V. K. M.). NR 58 TC 11 Z9 11 U1 3 U2 28 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2014 VL 306 IS 8 BP E854 EP E868 DI 10.1152/ajpendo.00371.2013 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA AF3FR UT WOS:000334597400002 PM 24518676 ER PT J AU Jones, DR Wu, ZP Chauhan, D Anderson, KC Peng, JM AF Jones, Drew R. Wu, Zhiping Chauhan, Dharminder Anderson, Kenneth C. Peng, Junmin TI A Nano Ultra-Performance Liquid Chromatography-High Resolution Mass Spectrometry Approach for Global Metabolomic Profiling and Case Study on Drug-Resistant Multiple Myeloma SO ANALYTICAL CHEMISTRY LA English DT Article ID LC-MS; MOBILITY SPECTROMETRY; PROTEOMICS; METABOLITES; CELLS; IDENTIFICATION; ALIGNMENT; DATABASE; GLUCOSE; RAT AB Global metabolomics relies on highly reproducible and sensitive detection of a wide range of metabolites in biological samples. Here we report the optimization of metabolome analysis by nanoflow ultraperformance liquid chromatography coupled to high-resolution orbitrap mass spectrometry. Reliable peak features were extracted from the LC-MS runs based on mandatory detection in duplicates and additional noise filtering according to blank injections. The run-to-run variation in peak area showed a median of 14%, and the false discovery rate during a mock comparison was evaluated. To maximize the number of peak features identified, we systematically characterized the effect of sample loading amount, gradient length, and MS resolution. The number of features initially rose and later reached a plateau as a function of sample amount, fitting a hyperbolic curve. Longer gradients improved unique feature detection in part by time-resolving isobaric species. Increasing the MS resolution up to 120000 also aided in the differentiation of near isobaric metabolites, but higher MS resolution reduced the data acquisition rate and conferred no benefits, as predicted from a theoretical simulation of possible metabolites. Moreover, a biphasic LC gradient allowed even distribution of peak features across the elution, yielding markedly more peak features than the linear gradient. Using this robust nUPLC-HRMS platform, we were able to consistently analyze similar to 6500 metabolite features in a single 60 min gradient from 2 mg of yeast, equivalent to, similar to 50 million cells. We applied this optimized method in a case study of drug (bortezomib) resistant and drug-sensitive multiple myeloma cells. Overall, 18% of metabolite features were matched to KEGG identifiers, enabling pathway enrichment analysis. Principal component analysis and heat map data correctly clustered isogenic phenotypes, highlighting the potential for hundreds of small molecule biomarkers of cancer drug resistance. C1 [Jones, Drew R.; Wu, Zhiping; Peng, Junmin] St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA. [Jones, Drew R.; Wu, Zhiping; Peng, Junmin] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Peng, Junmin] St Jude Childrens Res Hosp, St Jude Prote Facil, Memphis, TN 38105 USA. [Chauhan, Dharminder; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peng, JM (reprint author), St Jude Childrens Res Hosp, Dept Struct Biol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM junmin.peng@stjude.org OI Jones, Drew/0000-0001-8732-9818 FU American Cancer Society [RSG-09-181]; ALSAC (American Lebanese Syrian Associated Charities) FX This work was partially supported by the American Cancer Society Grant (RSG-09-181) and ALSAC (American Lebanese Syrian Associated Charities). NR 41 TC 12 Z9 12 U1 4 U2 64 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 2014 VL 86 IS 7 BP 3667 EP 3675 DI 10.1021/ac500476a PG 9 WC Chemistry, Analytical SC Chemistry GA AE2AV UT WOS:000333776600057 PM 24611431 ER PT J AU Kesler, CT Kuo, AH Wong, HK Masuck, DJ Shah, JL Kozak, KR Held, KD Padera, TP AF Kesler, Cristina T. Kuo, Angera H. Wong, Hon-Kit Masuck, David J. Shah, Jennifer L. Kozak, Kevin R. Held, Kathryn D. Padera, Timothy P. TI Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells SO ANGIOGENESIS LA English DT Article DE Lymphedema; Lymphangiogenesis; Radiotherapy; Lymphatic endothelium; VEGF-C ID IN-VITRO; RADIATION; LYMPHANGIOGENESIS; LYMPHEDEMA; VESSELS; BLOCKADE; SURVIVAL; VEGFR-3; SKIN AB Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the radiosensitivity of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC radiosensitivity was also examined. Vascular endothelial growth factor (VEGF)-C enhanced radiosensitivity when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and G2/M phases. These LECs showed higher levels of gamma H2A.X-an indicator of DNA damage-after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence. C1 [Kesler, Cristina T.; Kuo, Angera H.; Wong, Hon-Kit; Masuck, David J.; Shah, Jennifer L.; Kozak, Kevin R.; Held, Kathryn D.; Padera, Timothy P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Padera, TP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM tpadera@steele.mgh.harvard.edu RI Wong, Hon-Kit/G-3944-2014; OI Wong, Hon-Kit/0000-0003-0049-8454; Padera, Timothy/0000-0002-3453-9384 FU NIH [R00CA137167, DP2OD008780]; NCI Federal Share/MGH Proton Beam Income [C06 CA059267] FX This work was funded by NIH R00CA137167, NIH DP2OD008780 and NCI Federal Share/MGH Proton Beam Income on C06 CA059267. We would like to thank Dr. Rakesh Jain, Dr. Brian Seed, Dr. Dai Fukumura, Dr. Jay Loeffler, Nicole Magpayo and members of the Edwin L. Steele Laboratories for helpful discussions. We would also like to thank Dr. David Schoenfeld and Harvard Catalyst Biostatistical Consulting. NR 26 TC 8 Z9 10 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 EI 1573-7209 J9 ANGIOGENESIS JI Angiogenesis PD APR PY 2014 VL 17 IS 2 SI SI BP 419 EP 427 DI 10.1007/s10456-013-9400-7 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AF0MC UT WOS:000334407600010 PM 24201897 ER PT J AU Wexelman, B Martinson, H Tang, R Hughes, K Coopey, S Gadd, M Specht, M Smith, BL AF Wexelman, Barbara Martinson, Holly Tang, Rong Hughes, Kevin Coopey, Suzanne Gadd, Michele Specht, Michelle Smith, Barbara L. TI Cost Analysis of Nipple-Sparing Mastectomy: Must New Always Be More Expensive? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 30-MAY 04, 2014 CL Las Vegas, NV SP Amer Soc Breast Surg C1 [Wexelman, Barbara; Martinson, Holly; Tang, Rong; Hughes, Kevin; Coopey, Suzanne; Gadd, Michele; Specht, Michelle; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2014 VL 21 SU 2 BP 123 EP 124 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA AE7XC UT WOS:000334211800151 ER PT J AU Wexelman, B Shannon, K Patel, D Coopey, S Hughes, K Specht, M Smith, BL Gadd, M AF Wexelman, Barbara Shannon, Kristen Patel, Devanshi Coopey, Suzanne Hughes, Kevin Specht, Michelle Smith, Barbara L. Gadd, Michele TI Do Racial Disparities Exist in Prophylactic Surgery for BRCA Mutation Carriers? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 30-MAY 04, 2014 CL Las Vegas, NV SP Amer Soc Breast Surg C1 [Wexelman, Barbara; Shannon, Kristen; Patel, Devanshi; Coopey, Suzanne; Hughes, Kevin; Specht, Michelle; Smith, Barbara L.; Gadd, Michele] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2014 VL 21 SU 2 BP 124 EP 125 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA AE7XC UT WOS:000334211800152 ER PT J AU Balch, CM Thompson, JF Gershenwald, JE Soong, SJ Ding, S McMasters, KM Coit, DG Eggermont, AMM Gimotty, PA Johnson, TM Kirkwood, JM Leong, SP Ross, MI Byrd, DR Cochran, AJ Mihm, MC Morton, DL Atkins, MB Flaherty, KT Sondak, VK AF Balch, Charles M. Thompson, John F. Gershenwald, Jeffrey E. Soong, Seng-jaw Ding, Shouluan McMasters, Kelly M. Coit, Daniel G. Eggermont, Alexander M. M. Gimotty, Phyllis A. Johnson, Timothy M. Kirkwood, John M. Leong, Stanley P. Ross, Merrick I. Byrd, David R. Cochran, Alistair J. Mihm, Martin C., Jr. Morton, Donald L. Atkins, Michael B. Flaherty, Keith T. Sondak, Vernon K. TI Age as a Predictor of Sentinel Node Metastasis among Patients with Localized Melanoma: An Inverse Correlation of Melanoma Mortality and Incidence of Sentinel Node Metastasis Among Young and Old Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID ACRAL LENTIGINOUS MELANOMA; NECK DESMOPLASTIC MELANOMA; UNIQUE PROGNOSTIC-FACTORS; AMERICAN JOINT COMMITTEE; STAGE-III MELANOMA; CUTANEOUS MELANOMA; LYMPH-NODES; MULTIFACTORIAL ANALYSIS; MELANOCYTIC NEOPLASMS; SINGLE-CENTER AB Purpose. We have previously reported that older patients with clinical stage I and II primary cutaneous. Melanoma had lower survival rates compared to younger patients. We postulated that the incidence of nodal metastasis would therefore be higher among older melanoma patients. Methods. The expanded American Joint Committee on Cancer melanoma staging database contains a cohort of 7,756 melanoma patients who presented without clinical evidence of regional lymph node or distant metastasis and who underwent a sentinel node biopsy procedure as a component of their staging assessment. Results. Although older patients had primary melanoma features associated with more aggressive biology, we paradoxically observed a significant decrease in the incidence of sentinel node metastasis as patient age increased. Overall, the highest incidence of sentinel node metastasis was 25.8 % in patients under 20 years of age, compared to 15.5 % in patients 80 years and older (p < 0.001). In contrast, 5-year mortality rates for clinical stage II patients ranged from a low of 20 % for those 20-40 years of age up to 38 % for those over 70 years of age. Patient age was an independent predictor of sentinel node metastasis in a multifactorial analysis (p < 0.001). Conclusions. Patients with clinical stage I and II melanoma under 20 years of age had a higher incidence of sentinel lymph node metastasis but, paradoxically, a more favorable survival outcome compared to all other age groups. In contrast, patients > 70 years had the most aggressive primary melanoma features and a higher mortality rate compared to all other age groups but a lower incidence of sentinel lymph node metastasis. C1 [Balch, Charles M.] Univ Texas SW Med Ctr Dallas, Dept Surg, Div Surg Oncol, Dallas, TX 75390 USA. [Thompson, John F.] Melanoma Inst Australia, Sydney, NSW, Australia. [Gershenwald, Jeffrey E.; Ross, Merrick I.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Soong, Seng-jaw; Ding, Shouluan] Univ Alabama Birmingham, Birmingham, AL USA. [McMasters, Kelly M.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA. [Coit, Daniel G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Eggermont, Alexander M. M.] Canc Inst Gustave Roussy, Villejuif, France. [Gimotty, Phyllis A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Johnson, Timothy M.] Univ Michigan, Ctr Comprehens Canc, Dept Dermatol, Ann Arbor, MI 48109 USA. [Johnson, Timothy M.] Univ Pittsburgh, Sch Med, Dept Med, Div Oncol, Pittsburgh, PA 15213 USA. [Leong, Stanley P.] Calif Pacific Med Ctr & Res Inst, Dept Surg, San Francisco, CA USA. [Byrd, David R.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Cochran, Alistair J.] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. [Cochran, Alistair J.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. [Mihm, Martin C., Jr.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Morton, Donald L.] John Wayne Canc Inst, Santa Monica, CA USA. [Atkins, Michael B.] Medstar Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Div Cutaneous Oncol, Tampa, FL 33682 USA. RP Balch, CM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Surg, Div Surg Oncol, Dallas, TX 75390 USA. EM balch@asoeditorial.org FU AJCC; National Cancer Institute at the University of Alabama at Birmingham [P30 CA13148]; SPORE Grant in melanoma at The University of Texas M. D. Anderson Cancer Center in Houston, TX, USA [P50 CA93459]; Schering-Plough (Kenilworth, NJ, USA) FX The work of the AJCC/UICC Melanoma Staging Committee was supported by a Grant from the AJCC and by Grants from the National Cancer Institute (P30 CA13148 at the University of Alabama at Birmingham and P50 CA93459 SPORE Grant in melanoma at The University of Texas M. D. Anderson Cancer Center in Houston, TX, USA). Three meetings held by the committee were partially supported by an unrestricted educational Grant from Schering-Plough (Kenilworth, NJ, USA). NR 51 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2014 VL 21 IS 4 BP 1075 EP 1081 DI 10.1245/s10434-013-3464-x PG 7 WC Oncology; Surgery SC Oncology; Surgery GA AE8AX UT WOS:000334222500007 PM 24531700 ER PT J AU Walter, U Kohlert, T Rahbari, NN Weitz, J Welsch, T AF Walter, Ulrike Kohlert, Tobias Rahbari, Nuh N. Weitz, Juergen Welsch, Thilo TI Impact of Preoperative Diabetes on Long-Term Survival After Curative Resection of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Review ID CANCER-PATIENTS; DUCTAL ADENOCARCINOMA; SINGLE-INSTITUTION; RISK-FACTORS; MELLITUS; OUTCOMES; OBESITY; PANCREATICODUODENECTOMY; PREVALENCE; METFORMIN AB Background. Diabetes mellitus (DM) is coupled to the risk and symptomatic onset of pancreatic ductal adenocarcinoma (PDAC). The important question whether DM influences the prognosis of resected PDAC has not been systematically evaluated in the literature. We therefore performed a systematic review and meta-analysis evaluating the impact of preoperative DM on survival after curative surgery. Methods. The databases Medline, Embase, Web of Science, and the Cochrane Library were searched for studies reporting on the impact of preoperative DM on survival after PDAC resection. Hazard ratios and 95 % confidence intervals (CI) were extracted. The meta-analysis was calculated using the random-effects model. Results. The data search identified 4,365 abstracts that were screened for relevant articles. Ten retrospective studies with a cumulative sample size of 4,471 patients were included in the qualitative review. The mean prevalence of preoperative DM was 26.7 % (1,067 patients), and all types of pancreatic resections were considered. The meta-analysis included 8 studies and demonstrated that preoperative DM is associated with a worse overall survival after curative resection of PDAC (hazard ratio 1.32, 95 % CI 1.46-1.60, P = 0.004). Only 2 studies reported separate data for new-onset and long-standing DM. Conclusions. To our knowledge, this is the first metaanalysis evaluating long-term survival after PDAC resection in normoglycemic and diabetic patients, demonstrating a significantly worse outcome in the latter group. The mechanism behind this observation and the question whether different antidiabetic medications or early control of DM can improve survival in PDAC should be evaluated in further studies. C1 [Walter, Ulrike; Kohlert, Tobias; Rahbari, Nuh N.; Weitz, Juergen; Welsch, Thilo] Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany. [Rahbari, Nuh N.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Rahbari, Nuh N.] Harvard Univ, Sch Med, Boston, MA USA. RP Walter, U (reprint author), Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany. EM thilo.welsch@uniklinikum-dresden.de NR 38 TC 11 Z9 13 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2014 VL 21 IS 4 BP 1082 EP 1089 DI 10.1245/s10434-013-3415-6 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA AE8AX UT WOS:000334222500008 PM 24322532 ER PT J AU Shapira, OM Badhwar, V Shahian, D Jacobs, JP Izhar, U Bao, Y Korach, A Lattouf, OM Grover, FL Puskas, JD AF Shapira, Oz M. Badhwar, Vinay Shahian, David Jacobs, Jeffrey P. Izhar, Uzi Bao, Yusheng Korach, Amit Lattouf, Omar M. Grover, Fredrick L. Puskas, John D. TI International Participation in The Society of Thoracic Surgeons National Database SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material AB In 2011 The Society of Thoracic Surgeons (STS) Workforce on National Databases established the International Database Task Force devoted to expanding participation in the STS National Database internationally. The vision for this initiative was to assist in the globalization of outcomes data and share knowledge, facilitating a worldwide quality collaborative in cardiac surgery. The Department of Cardiothoracic Surgery at Hadassah Medical Center, Jerusalem, Israel, was among the first of several international sites to join the collaborative. This report outlines the rationale behind clinical databases outside of North America submitting data to the STS National Database and reviews the unique challenges and practical steps of integration through experiences by Hadassah Medical Center. Our hope is that this procedural learning will serve as a template to assist future international program integration. (C) 2014 by The Society of Thoracic Surgeons C1 Hadassah Med Ctr, Dept Cardiothorac Surg, IL-91120 Jerusalem, Israel. Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA USA. All Childrens Hosp, Johns Hopkins Childrens Heart Surg, Tampa, FL USA. Florida Hosp Children, Tampa, FL USA. Emory Univ, Hosp Midtown, Dept Cardiac Surg, Atlanta, GA 30322 USA. Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. RP Shapira, OM (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Cardiothorac Surg, POB 12000, IL-91120 Jerusalem, Israel. EM ozshapira@hadassah.org.il NR 5 TC 4 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2014 VL 97 IS 4 BP 1127 EP 1130 DI 10.1016/j.athoracsur.2013.12.038 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AE2NQ UT WOS:000333810300011 PM 24694401 ER PT J AU Kim, YI Kim, KW Lee, HK Park, J Chung, JW Youn, H Kim, SJ Kim, DH Tseng, JC Lee, JM AF Kim, Young Il Kim, Kyung Won Lee, Han Kyu Park, Jisuk Chung, Jin Wook Youn, Hyewon Kim, Soo Jin Kim, Dal-Hyun Tseng, Jen-Chieh Lee, Jeong Min TI Enhanced Efficacy of CKD-516 in Combination with Doxorubicin: Pre-clinical Evaluation Using a Hepatocellular Carcinoma Xenograft Model SO ANTICANCER RESEARCH LA English DT Article DE CKD-516; tubulin-binding agents; vascular-disrupting agent; doxorubicin; hepatocellular carcinoma ID TUBULIN POLYMERIZATION INHIBITOR; COMBRETASTATIN A4 PHOSPHATE; TUMOR; AGENT; LIVER; IDENTIFICATION; MURINE; GROWTH AB Aim: To evaluate the anticancer efficacy of CKD-516, a novel vascular-disrupting agent, alone and in combination with doxorubicin in the treatment of hepatocellular carcinoma (HCC). Materials and Methods: In mice bearing luciferized HCC cells, therapeutic efficacy was assessed for seven days after single administration of CKD-516, doxorubicin, or combination of CKD-516 and doxorubicin. Results: Bioluminescence-imaging (BLI) signals in the CKD-516 group abruptly decreased initially, but recovered at seven days after treatment. BLI signals in the doxorubicin group gradually decreased over the 7-day period. In the combination group, BLI signals were abruptly reduced and remained suppressed for the 7-day period. On histopathological examination, CKD-516-treated tumors showed extensive central necrosis, whereas the peripheral layers remained viable. Doxorubicin-treated tumors showed mild and scattered necrosis. Tumors from the combination group showed more extensive central and peripheral necrosis, with smaller viable peripheral layers than the CKD-516 group. Conclusion: Combination therapy can have additive effects for treatment of HCC compared with CKD-516 or doxorubicin monotherapy. C1 [Kim, Young Il; Lee, Han Kyu; Park, Jisuk; Chung, Jin Wook; Lee, Jeong Min] Seoul Natl Univ, Coll Med, SNUMRC, Dept Radiol, Seoul, South Korea. [Kim, Young Il; Lee, Han Kyu; Park, Jisuk; Chung, Jin Wook; Lee, Jeong Min] Seoul Natl Univ, Coll Med, SNUMRC, Inst Radiat Med, Seoul, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst, Seoul 138736, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Youn, Hyewon] Seoul Natl Univ, Canc Res Inst, Lab Mol Imaging & Therapy, Seoul, South Korea. [Kim, Soo Jin; Kim, Dal-Hyun] Chong Kun Dang Pharmaceut, Chong Kun Dang Res Inst, Seoul, South Korea. [Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. RP Kim, KW (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. EM medimash@gmail.com OI Youn, Hyewon/0000-0003-1006-2689; Chung, Jin Wook/0000-0002-1090-6872 FU Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI12C1148]; Chong Kun Dang Pharmaceutical Corporation FX This study was supported in part by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C1148), and a grant from the Chong Kun Dang Pharmaceutical Corporation. NR 24 TC 4 Z9 4 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD APR PY 2014 VL 34 IS 4 SI SI BP 1715 EP 1722 PG 8 WC Oncology SC Oncology GA AE6GS UT WOS:000334089200029 PM 24692701 ER PT J AU Zhang, DX Li, YS Peng, HZ Liu, HJ Cheng, Q Cheng, X Zeng, P Wu, P Chen, HX Huang, YP Ye, DY AF Zhang, Dongxin Li, Yongsheng Peng, Huizhen Liu, Haojing Cheng, Qiong Cheng, Xue Zeng, Pan Wu, Ping Chen, Hongxiang Huang, Yinping Ye, Duyun TI Glucocorticoids Sensitize Rat Placental Inflammatory Responses via Inhibiting Lipoxin A(4) Biosynthesis(1) SO BIOLOGY OF REPRODUCTION LA English DT Article DE arachidonic acid; eicosanoids; glucocorticoids; inflammation; placenta ID POSSIBLE MECHANISMS; CYTOKINE PRODUCTION; LIPID MEDIATORS; KAPPA-B; EXPRESSION; RECEPTORS; PREECLAMPSIA; RESOLUTION; ESTROGEN; PATHWAY AB Inflammation dysregulation in placenta is implicated in the pathogenesis of numerous pregnancy complications. Glucocorticoids (GCs), universally considered anti-inflammatory, can also exert proinflammatory actions under some conditions, whereas whether and how GCs promote placental inflammation have not been intensively investigated. In this paper we report the opposing regulation of rat placental inflammation by synthetic GC dexamethasone (Dex). When Dex was subcutaneously injected 1 h after we administered an intraperitoneal lipopolysaccharide (LPS) challenge, neutrophil infiltration and proinflammatory Il1b, Il6, and Tnfa expression in rat placenta were significantly reduced. In contrast, Dex pretreatment for 24 h potentiated rat placental proinflammatory response to LPS and delayed inflammation resolution, which involved MAPKs and NF-kappaB activation. Mechanically, Dex pretreatment promoted 5-lipoxygenase (ALOX5) activation and increased leukotriene B-4 production, whereas it inhibited the anti-inflammatory and proresolving lipid mediator lipoxin A(4) (LXA(4)) biosynthesis in rat placenta via downregulating ALOX15 and ALOX15B expression. Moreover, LXA(4) supplementation dampened Dex-potentiated placental inflammation and suppressed Dex-mediated ALOX5 activation in vivo and in vitro. Taken together, these findings suggest that GCs exposure could promote placental inflammation initiation and delay resolution via disrupting LXA(4) biosynthesis. C1 [Zhang, Dongxin; Peng, Huizhen; Cheng, Qiong; Cheng, Xue; Zeng, Pan; Wu, Ping; Ye, Duyun] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Wuhan 430030, Peoples R China. [Li, Yongsheng] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. [Li, Yongsheng] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Haojing] Huazhong Univ Sci & Technol, Tongji Med Coll, Puai Hosp, Dept Internal Med, Wuhan 430030, Peoples R China. [Chen, Hongxiang] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Dermatol, Wuhan 430030, Peoples R China. [Chen, Hongxiang] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02115 USA. [Huang, Yinping] Wenzhou Med Coll, Affiliated Hosp 1, Dept Gynecol & Obstet, Wenzhou, Peoples R China. RP Ye, DY (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, 13 Hangkong Rd, Wuhan 430030, Peoples R China. EM yphuangp@126.com; yedy@mails.tjmu.edu.cn FU National Natural Science Foundation of China [81070510, 81171495, 81271765] FX Supported by National Natural Science Foundation of China grants 81070510, 81171495, and 81271765. NR 43 TC 5 Z9 5 U1 0 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2014 VL 90 IS 4 DI 10.1095/biolreprod.113.116384 PG 13 WC Reproductive Biology SC Reproductive Biology GA AE9TF UT WOS:000334352200004 PM 24571985 ER PT J AU Cohen, LE Gordon, JH Popovsky, EY Gunawardene, S Duffey-Lind, E Lehmann, LE Diller, LR AF Cohen, L. E. Gordon, J. H. Popovsky, E. Y. Gunawardene, S. Duffey-Lind, E. Lehmann, L. E. Diller, L. R. TI Late effects in children treated with intensive multimodal therapy for high-risk neuroblastoma: High incidence of endocrine and growth problems SO BONE MARROW TRANSPLANTATION LA English DT Article DE neuroblastoma; late effects; growth hormone; insulin resistance; hypothyroidism; ovary ID BONE-MARROW-TRANSPLANTATION; ADVANCED-STAGE NEUROBLASTOMA; IMPAIRED GLUCOSE-TOLERANCE; STEM-CELL TRANSPLANTATION; CHILDHOOD-CANCER-SURVIVOR; TOTAL-BODY IRRADIATION; LONG-TERM SURVIVORS; DIABETES-MELLITUS; THYROID-DYSFUNCTION; APLASTIC-ANEMIA AB Due to the poor prognosis of high-risk (HR) neuroblastoma (NBL), scant data exist on late effects after treatment. Recently, protocols utilizing intense multimodal treatment have resulted in improved long-term survival. The objective of this study was to determine the prevalence of late effects in survivors of HR NBL. A retrospective review of clinical data for serial patients completing treatment between September 1994 and October 2007 and surviving for at least 1 year was performed. Therapy included aggressive chemotherapy, surgery, radiation and single or tandem SCT. Oncology follow-up was standard; clinical criteria were utilized for referrals to endocrinology and other services. Fifty-one eligible patients were identified. Median follow-up was 6.1 years (range 1.0-15.2). Height was significantly impacted (Delta Z-score -1.91 in those treated with TBI and -0.77 in those without). Pre-diabetes or diabetes, hypothyroidism and ovarian insufficiency were observed in 50, 59 and 75% of at-risk survivors, respectively. Hearing loss and dental issues were common. Nine patients had relapse of NBL; seven died of progressive disease. As there is a high prevalence of late effects in long-term survivors of HR NBL, close monitoring and further studies after treatment are indicated, and in particular after more modern, non-TBI regimens. C1 [Cohen, L. E.; Gordon, J. H.; Popovsky, E. Y.] Boston Childrens Hosp, Boston, MA 02115 USA. [Cohen, L. E.; Gunawardene, S.; Duffey-Lind, E.; Lehmann, L. E.; Diller, L. R.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cohen, LE (reprint author), Boston Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM laurie.cohen@childrens.harvard.edu FU Friends for Life Foundation FX We would like to thank Henry Feldman, PhD for his statistical advice; and Terence Law in the Department of Laboratory Medicine, Boston Children's Hospital for his help with assay methods and correlations. This work was supported in part by the Friends for Life Foundation. NR 36 TC 11 Z9 11 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2014 VL 49 IS 4 BP 502 EP 508 DI 10.1038/bmt.2013.218 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AF1VB UT WOS:000334500900006 PM 24442245 ER PT J AU Lown, RN Marsh, SGE Switzer, GE Latham, KA Madrigal, JA Shaw, BE AF Lown, R. N. Marsh, S. G. E. Switzer, G. E. Latham, K. A. Madrigal, J. A. Shaw, B. E. TI Ethnicity, length of time on the register and sex predict donor availability at the confirmatory typing stage SO BONE MARROW TRANSPLANTATION LA English DT Article DE marrow and SCT; allogeneic transplantation; donor attrition; unrelated donor; ethnicity ID BONE-MARROW DONATION; STEM-CELL DONORS; POTENTIAL DONORS; BLOOD-DONORS; TRANSPLANTATION AB Despite over 20 million unrelated donors being listed worldwide, donor attrition at the confirmatory typing (CT) stage of donor acquisition is a key source of delay. Anthony Nolan undertook a study of CT requests from 2010 to 2011 to identify factors associated with attrition. Of 7541 CT requests, 38.2% were cancelled for donor reasons. Of these, 19.4% were personal, 34.1% medical, 36% no contact, 7.9% emigrated and 2.6% others. African (odds ratio (OR) 2.78, P < 0.001), African-Caribbean (OR 3.07, P < 0.001), Asian (OR 2.65, P < 0.001), Jewish (OR=1.54, P < 0.009) and Mediterranean (OR=2.38, P < 0.001) donors were more likely not to be available compared to Caucasian donors. Female donors were also more likely not to be available (OR=1.32, P < 0.001): primarily due to pregnancy. Older donors were less likely to be available in univariate analysis, but this association was not significant after controlling for other factors. Blood donors and those recruited within the past five years had lower rates of attrition. Accumulation of additional attrition-associated characteristics for a given donor was associated with progressively greater odds of attrition (OR 1.99, 2.52, 3.4 and 5.53, respectively, for 1, 2, 3 and 4 risk factors, P < 0.001). Donor registries must develop evidence-driven strategies to recruit and retain the most reliable donors. C1 [Lown, R. N.; Marsh, S. G. E.; Latham, K. A.; Madrigal, J. A.; Shaw, B. E.] Royal Free Hosp, Anthony Nolan Res Inst, London NW3 2QG, England. [Lown, R. N.; Marsh, S. G. E.; Madrigal, J. A.; Shaw, B. E.] UCL, UCL Canc Inst, London, England. [Switzer, G. E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Shaw, B. E.] Royal Marsden NHS Fdn Trust, London, England. RP Lown, RN (reprint author), Royal Free Hosp, Anthony Nolan Res Inst, Pond St, London NW3 2QG, England. EM robert.lown@anthonynolan.org NR 18 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2014 VL 49 IS 4 BP 525 EP 531 DI 10.1038/bmt.2013.206 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AF1VB UT WOS:000334500900010 PM 24419516 ER PT J AU Kolitz, JE George, SL Benson, DM Maharry, K Marcucci, G Vij, R Powell, BL Allen, SL DeAngelo, DJ Shea, TC Stock, W Bakan, CE Hars, V Hoke, E Bloomfield, CD Caligiuri, MA Larson, RA AF Kolitz, Jonathan E. George, Stephen L. Benson, Don M., Jr. Maharry, Kati Marcucci, Guido Vij, Ravi Powell, Bayard L. Allen, Steven L. DeAngelo, Daniel J. Shea, Thomas C. Stock, Wendy Bakan, Courtney E. Hars, Vera Hoke, Eva Bloomfield, Clara D. Caligiuri, Michael A. Larson, Richard A. CA Alliance Clinical Trials Oncology TI Recombinant Interleukin-2 in Patients Aged Younger Than 60 Years With Acute Myeloid Leukemia in First Complete Remission SO CANCER LA English DT Article DE acute myeloid leukemia; recombinant interleukin-2; phase 3; immunotherapy; adjuvant therapy ID ACUTE MYELOGENOUS LEUKEMIA; NATURAL-KILLER-CELLS; HIGH-DOSE CYTARABINE; GROUP-B; INTENSIFICATION THERAPY; IN-VIVO; CANCER; ADULTS; SURVIVAL; TRANSPLANTATION AB BACKGROUNDRecombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells. METHODSIn the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily rIL-2 were given for the expansion of cytotoxic effector cells, each followed by 3-day high-dose boluses given to trigger cytotoxicity against minimal residual disease. RESULTSOn the protocol-specified intention-to-treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52-1.09; P=.13); the 5-year DFS rate was 42% in the observation arm and 53% in the rIL-2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54-1.23; P=.34); the 5-year OS rate was 58% for the observation arm and 63% for the rIL-2 treatment arm. Twenty-five of the 107 patients randomized to treatment with rIL-2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance. CONCLUSIONSThe efficacy of immunotherapy with rIL-2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol-directed therapy. Neither DFS nor OS was found to be significantly improved. Cancer 2014;120:1010-1017. (c) 2013 American Cancer Society. To the authors' knowledge, the current study is the first phase 3 trial of the subcutaneous administration of recombinant interleukin-2 in patients aged<60 years with acute myeloid leukemia in first complete remission. Although statistical endpoints were not met, important information regarding the use of recombinant interleukin-2 in this setting as well as considerations that may affect the conduct of large phase 3 trials of this nature are presented. C1 [Kolitz, Jonathan E.; Allen, Steven L.] Hofstra North Shore Long Isl Jewish Sch Med, Dept Med, Div Hematol, Don Monti Div Oncol, Lake Success, NY 11042 USA. [George, Stephen L.; Maharry, Kati; Hars, Vera; Hoke, Eva] Mayo Clin, Alliance Clin Trials Oncol, Stat & Data Ctr, Rochester, MN USA. [George, Stephen L.; Hars, Vera; Hoke, Eva] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [George, Stephen L.; Hars, Vera; Hoke, Eva] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Benson, Don M., Jr.; Maharry, Kati; Marcucci, Guido; Bakan, Courtney E.; Bloomfield, Clara D.; Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Vij, Ravi] Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Sect Hematol, Winston Salem, NC 27109 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Sect Oncol, Winston Salem, NC 27109 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Shea, Thomas C.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Stock, Wendy; Larson, Richard A.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Kolitz, JE (reprint author), Hofstra North Shore Long Isl Jewish Sch Med, Monter Canc Ctr, 450 Lakeville Rd, Lake Success, NY 11042 USA. EM kolitz@nshs.edu FU National Cancer Institute [CA31946, CA33601] FX The research for Cancer and Leukemia Group B (CALGB) 19808 (Alliance) was supported in part by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair) and to the Alliance Statistical Center (Daniel J. Sargent, PhD; CA33601). NR 31 TC 12 Z9 12 U1 1 U2 4 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 APR 1 PY 2014 VL 120 IS 7 BP 1010 EP 1017 DI 10.1002/cncr.28516 PG 8 WC Oncology SC Oncology GA AD0IB UT WOS:000332916600022 PM 24382782 ER PT J AU Wang, Y Schrag, D Brooks, GA Dominici, F AF Wang, Yun Schrag, Deborah Brooks, Gabriel A. Dominici, Francesca TI National Trends in Pancreatic Cancer Outcomes and Pattern of Care Among Medicare Beneficiaries, 2000 Through 2010 SO CANCER LA English DT Article DE pancreatic cancer; outcomes; trends; Medicare; mortality; hospitalization ID SINGLE-INSTITUTION EXPERIENCE; UNITED-STATES; 1423 PANCREATICODUODENECTOMIES; HOSPITAL VOLUME; POPULATION; STATISTICS; MORTALITY; RATES; MODEL AB BACKGROUNDPancreatic cancer is a major cause of morbidity and mortality in the Medicare population. Whether the health care burden of pancreatic cancer has changed over the last decade is unknown. METHODSThe authors used Medicare data from 2000 to 2010 to identify beneficiaries aged65 years who were hospitalized for the management of pancreatic cancer. Annual trends were estimated for the age-sex-race-adjusted initial hospitalization rate, the age-sex-race-comorbidity-adjusted 1-year mortality rate after initial hospitalization, age-sex-race-comorbidity-adjusted procedure rates, 1-year all-cause rehospitalizations after initial pancreatic cancer hospitalization, and mean inflation-adjusted Medicare payment for initial hospitalization. RESULTSA total of 130,728 patients had1 hospitalizations for pancreatic cancer and were identified from 56,642,071 beneficiaries during the study period. The age-sex-race-adjusted rate of initial hospitalization for pancreatic cancer was 50 per 100,000 person-years in 2010, representing a 0.5% annual increase since 2000 (95% confidence interval [95% CI], 0.3%-0.7%). In the same period, the age-sex-race-comorbidity-adjusted 1-year mortality rate decreased by 4.4% (95% CI, 3.9%-4.9%), and the age-sex-race-comorbidity-adjusted surgical resection rate increased by 6.9% (95% CI, 6.4%-7.5%). The mean inflation-adjusted Medicare payment for the initial hospitalization decreased, from $14,118 in 2000 to $13,318 in 2010, and the number of 1-year all-cause rehospitalizations after the initial hospitalization increased from 0.75 per patient in 2000 to 0.82 per patient in 2009 (all P<.001). CONCLUSIONSFor Medicare fee-for-service beneficiaries, initial pancreatic cancer hospitalization, surgical resection, and rehospitalization rates increased, but 1-year mortality rates declined over the last decade. Cancer 2014;120:1050-1058. (c) 2013 American Cancer Society. For Medicare fee-for-service beneficiaries, initial pancreatic cancer hospitalization, surgical resection, and rehospitalization rates increased over the last decade, but 1-year mortality rates declined. C1 [Wang, Yun; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schrag, Deborah; Brooks, Gabriel A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Schrag, Deborah; Brooks, Gabriel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Dominici, F (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM fdominic@hsph.harvard.edu OI Brooks, Gabriel/0000-0003-3984-9995 FU National Cancer Institute [P01 CA134294]; Agency for Healthcare Research and Quality [K18 HS021991] FX Drs. Dominici and Wang are partially funded by the National Cancer Institute (P01 CA134294; Principal Investigator: Dr. Lin and co-Principal Investigator: Dr. Dominici) and the Agency for Healthcare Research and Quality (K18 HS021991 to Dr. Dominici). NR 30 TC 2 Z9 2 U1 0 U2 0 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 APR 1 PY 2014 VL 120 IS 7 BP 1050 EP 1058 DI 10.1002/cncr.28537 PG 9 WC Oncology SC Oncology GA AD0IB UT WOS:000332916600027 PM 24382787 ER PT J AU Hettmer, S Archer, NM Somers, GR Novokmet, A Wagers, AJ Diller, L Rodriguez-Galindo, C Teot, LA Malkin, D AF Hettmer, Simone Archer, Natasha M. Somers, Gino R. Novokmet, Ana Wagers, Amy J. Diller, Lisa Rodriguez-Galindo, Carlos Teot, Lisa A. Malkin, David TI Anaplastic Rhabdomyosarcoma in TP53 Germline Mutation Carriers SO CANCER LA English DT Article DE rhabdomyosarcoma; anaplasia; TP53; germline mutations; Li-Fraumeni syndrome ID LI-FRAUMENI-SYNDROME; CHILDRENS ONCOLOGY GROUP; SOFT-TISSUE SARCOMA; MOUSE MODEL; CHILDHOOD RHABDOMYOSARCOMA; P53 GENE; NASOPHARYNGEAL RHABDOMYOSARCOMA; PLEOMORPHIC RHABDOMYOSARCOMA; PEDIATRIC RHABDOMYOSARCOMA; RELATIVE FREQUENCY AB BACKGROUNDRhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies. METHODSThe histology of RMS tumors diagnosed in 8 consecutive children with TP53 germline mutations was reviewed retrospectively. In addition, germline TP53 mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown TP53 status. RESULTSRMS tumors diagnosed in 11 TP53 germline mutation carriers all exhibited nonalveolar, anaplastic histology as evidenced by the presence of enlarged hyperchromatic nuclei with or without atypical mitotic figures. Anaplastic RMS was the first malignant diagnosis for all TP53 germline mutation carriers in this cohort, and median age at diagnosis was 40 months (mean, 40 months15 months; range, 19-67 months). The overall frequency of TP53 germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of TP53 germline mutations in children with anRMS was 100% (5 of 5 children) for those with a family cancer history consistent with Li-Fraumeni syndrome (LFS), and 80% (4 of 5 children) for those without an LFS cancer phenotype. CONCLUSIONSIndividuals harboring germline TP53 mutations are predisposed to develop anRMS at a young age. If future studies in larger anRMS cohorts confirm the findings of this study, the current Chompret criteria for LFS should be extended to include children with anRMS irrespective of family history. Cancer 2014;120:1068-1075. (c) 2013 American Cancer Society. Children with germline TP53 mutations are predisposed to develop anaplastic rhabdomyosarcoma at a young age. Extension of the current Chompret criteria for Li-Fraumeni syndrome to include children with anaplastic rhabdomyosarcoma irrespective of family history should be considered. C1 [Hettmer, Simone; Archer, Natasha M.; Diller, Lisa; Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hettmer, Simone; Archer, Natasha M.; Diller, Lisa; Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Hettmer, Simone; Diller, Lisa; Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hettmer, Simone; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hettmer, Simone; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Somers, Gino R.] Univ Toronto, Hosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. [Somers, Gino R.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Novokmet, Ana; Malkin, David] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Oncol, Toronto, ON M5G 1X8, Canada. [Teot, Lisa A.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Hettmer, S (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM simone.hettmer@childrens.harvard.edu FU Canadian Institutes of Health Research [MOP106639]; SickKids Foundation; SARC-SPORE career development award; Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111] FX The authors declare no competing financial interests. This work was supported in part by a grant from the Canadian Institutes of Health Research (MOP106639) (DM), by the SickKids Foundation (DM), by a SARC-SPORE career development award (SH) and by a Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant, grant number SU2C-AACR-IRG1111 (AJW). AJW is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources. NR 44 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2014 VL 120 IS 7 BP 1068 EP 1075 DI 10.1002/cncr.28507 PG 8 WC Oncology SC Oncology GA AD0IB UT WOS:000332916600029 PM 24382691 ER PT J AU Hoppe, BS Michalski, JM Mendenhall, NP Morris, CG Henderson, RH Nichols, RC Mendenhall, WM Williams, CR Regan, MM Chipman, JJ Crociani, CM Sandler, HM Sanda, MG Hamstra, DA AF Hoppe, Bradford S. Michalski, Jeff M. Mendenhall, Nancy P. Morris, Christopher G. Henderson, Randal H. Nichols, Romaine C. Mendenhall, William M. Williams, Christopher R. Regan, Meredith M. Chipman, Jonathan J. Crociani, Catrina M. Sandler, Howard M. Sanda, Martin G. Hamstra, Daniel A. TI Comparative Effectiveness Study of Patient-Reported Outcomes After Proton Therapy or Intensity-Modulated Radiotherapy for Prostate Cancer SO CANCER LA English DT Article DE proton therapy; intensity-modulated radiotherapy; prostate cancer; outcomes; genitourinary ID QUALITY-OF-LIFE; CONFORMAL RADIATION-THERAPY; LATE RECTAL TOXICITY; SURVIVORS; VALIDATION; MEN AB BACKGROUNDData continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient-reported quality-of-life (QOL) outcomes after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODSA comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank-sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations. RESULTSNo differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P=0.02) and frequent bowel movements (P=0.05) than men who received PT. CONCLUSIONSThere were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up (up to 2-years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT. Cancer 2014;120:1076-1082. (c) 2013 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. No differences in quality-of-life summary scores are observed between an intensity-modulated radiotherapy cohort and a proton therapy cohort during early follow-up (up to 2 years). Responses to individual questions suggest possible differences in specific bowel symptoms between the 2 cohorts. C1 [Hoppe, Bradford S.; Mendenhall, Nancy P.; Morris, Christopher G.; Henderson, Randal H.; Nichols, Romaine C.; Mendenhall, William M.] Univ Florida, Proton Therapy Inst, Jacksonville, FL 32206 USA. [Michalski, Jeff M.] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. [Williams, Christopher R.] Univ Florida, Dept Urol, Jacksonville, FL USA. [Regan, Meredith M.; Chipman, Jonathan J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Crociani, Catrina M.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Urol, Boston, MA 02215 USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Sanda, Martin G.] Emory Univ, Dept Urol, Atlanta, GA 30322 USA. [Hamstra, Daniel A.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Hoppe, BS (reprint author), Univ Florida, Proton Therapy Inst, 2015 North Jefferson St, Jacksonville, FL 32206 USA. EM bhoppe@floridaproton.org RI Sanda, Martin/B-2023-2015; OI Henderson, Randal/0000-0002-1740-738X; Hoppe, Bradford/0000-0002-2312-5418; Mendenhall, Nancy/0000-0003-2893-7703 FU National Institute of Health [RO1 CA95662, 1RC1CA14596]; American College of Radiology-Radiation Therapy Oncology Group FX This work was supported by grants from the National Institute of Health (RO1 CA95662 and 1RC1CA14596) and the American College of Radiology-Radiation Therapy Oncology Group. NR 30 TC 21 Z9 21 U1 1 U2 12 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 APR 1 PY 2014 VL 120 IS 7 BP 1076 EP 1082 DI 10.1002/cncr.28536 PG 7 WC Oncology SC Oncology GA AD0IB UT WOS:000332916600030 PM 24382757 ER PT J AU Kim, J Morley, S Le, M Bedoret, D Umetsu, DT Di Vizio, D Freeman, MR AF Kim, Jayoung Morley, Samantha Minh Le Bedoret, Denis Umetsu, Dale T. Di Vizio, Dolores Freeman, Michael R. TI Enhanced shedding of extracellular vesicles from amoeboid prostate cancer cells Potential effects on the tumor microenvironment SO CANCER BIOLOGY & THERAPY LA English DT Article DE immune cells; extracellular vesicles; miR125a; EMT; microvesicles; amoeboid; AKT1; prostate cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR; DRUG-DELIVERY; PATHWAY ACTIVATION; METASTATIC-DISEASE; T-CELL; MICROVESICLES; INVASION; EXOSOMES; PROGRESSION AB The gene encoding the cytoskeletal regulator DIAPH3 is lost at high frequency in metastatic prostate cancer, and DIAPH3 silencing evokes a transition to an amoeboid tumor phenotype in multiple cell backgrounds. This amoeboid transformation is accompanied by increased tumor cell migration, invasion, and metastasis. DIAPH3 silencing also promotes the formation of atypically large (>1 mu m) membrane blebs that can be shed as extracellular vesicles (EV) containing bioactive cargo. Whether loss of DIAPH3 also stimulates the release of nano-sized EV (e.g., exosomes) is not established. Here we examined the mechanism of release and potential biological functions of EV shed from DIAPH3-silenced and other prostate cancer cells. We observed that stimulation of LNCaP cells with the prostate stroma-derived growth factor heparin-binding EGF-like growth factor (HB-EGF), combined with p38MAPK inhibition caused EV shedding, a process mediated by ERK1/2 hyperactivation. DIAPH3 silencing in DU145 cells also increased rates of EV production. EV isolated from DIAPH3-silenced cells activated AKT1 and androgen signaling, increased proliferation of recipient tumor cells, and suppressed proliferation of human macrophages and peripheral blood mononuclear cells. DU145 EV contained miR-125a, which suppressed AKT1 expression and proliferation in recipient human peripheral blood mononuclear cells and macrophages. Our findings suggest that EV produced as a result of DIAPH3 loss or growth factor stimulation may condition the tumor microenvironment through multiple mechanisms, including the proliferation of cancer cells and suppression of tumor-infiltrating immune cells. C1 [Kim, Jayoung; Di Vizio, Dolores; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Surg, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. [Kim, Jayoung; Di Vizio, Dolores; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Kim, Jayoung; Di Vizio, Dolores; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Kim, Jayoung; Morley, Samantha; Di Vizio, Dolores; Freeman, Michael R.] Boston Childrens Hosp, Urol Dis Res Ctr, Boston, MA USA. [Kim, Jayoung; Morley, Samantha; Di Vizio, Dolores; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Minh Le] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Bedoret, Denis; Umetsu, Dale T.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA. RP Freeman, MR (reprint author), Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Surg, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. EM Michael.Freeman@cshs.org OI LE, Thi Nguyet Minh/0000-0002-6077-1566 FU NIH [1R01CA143777, 1R01CA112303, 5R00CA131472]; US Department of Defense [PC093459]; Ladies Auxiliary VFW Cancer Research Postdoctoral Fellowship; Fishbein Family IC Research Foundation/Interstitial Cystitis Association (ICA); Pilot Research Program/ICA; New York Academy of Medicine; Boston Children's Hospital Faculty Development; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI [UL1TR000124] FX The authors thank Dr Anthony Hill of the Boston Children's Hospital IDDRC Imaging Core for technical assistance with confocal imaging. This study was supported by NIH 1R01CA143777, 1R01CA112303, and US Department of Defense PC093459 (to M. R. F), NIH 5R00CA131472 (to D. D. V.), a Ladies Auxiliary VFW Cancer Research Postdoctoral Fellowship (to S. M.) and the Fishbein Family IC Research Foundation/Interstitial Cystitis Association (ICA), Pilot Research Program/ICA, New York Academy of Medicine, and Boston Children's Hospital Faculty Development (to J.K.). The research described was also supported by NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124. J.K. is an American Urological Association Foundation Research Scholar and a Harvard Medical School Eleanor and Miles Shore Scholar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 13 Z9 14 U1 1 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD APR 1 PY 2014 VL 15 IS 4 BP 409 EP 418 DI 10.4161/cbt.27627 PG 10 WC Oncology SC Oncology GA AD9AX UT WOS:000333558000009 PM 24423651 ER PT J AU Pusztaszeri, MP Sadow, PM Ushiku, A Bordignon, P McKee, TA Faquin, WC AF Pusztaszeri, Marc P. Sadow, Peter M. Ushiku, Aya Bordignon, Patrizia McKee, Thomas A. Faquin, William C. TI MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic carcinoma from pleomorphic adenoma in fine-needle aspiration biopsy specimens SO CANCER CYTOPATHOLOGY LA English DT Article DE immunochemistry; pleomorphic adenoma; fine-needle aspiration; MYB; adenoid cystic carcinoma; biopsy ID LOW-GRADE ADENOCARCINOMA; SALIVARY-GLAND LESIONS; KIT CD117; EXPRESSION; NFIB; CYTOLOGY; REARRANGEMENTS; NEOPLASMS; PROTEIN; FUSION AB BACKGROUND The distinction between adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) on fine-needle aspiration biopsy (FNAB) can be challenging. Recently, a specific translocation t(6;9) involving the v-myb avian myeloblastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) genes was identified in ACCs, in which it contributes to MYB overexpression. The authors investigated the use of MYB immunocytochemistry in FNAB specimens as an ancillary test for the cytologic diagnosis of ACC. METHODS The expression of MYB was assessed in alcohol-fixed cytologic smears of histologically confirmed ACCs (n = 20) and PAs (n = 20) using immunocytochemistry. The corresponding ACCs and PAs from formalin-fixed, paraffin embedded surgical resection specimens also were stained immunohistochemically for MYB. The nuclear expression of MYB was assessed semiquantitatively using a scoring system (from 0 to 6) that combined the proportion and the intensity of staining. A score >= 4 was considered positive, and a score <= 3 was considered negative. RESULTS On FNAB material, 80% of ACCs (N = 16 of 20) were immunocytochemically positive for MYB. In contrast, all PAs (N = 20 of 20) were negative for MYB (P < .0001). The sensitivity of MYB on FNAB was 80%, and the specificity was 100% relative to PA. Results on corresponding histology were similar to the cytology results; however, there was often a zonal staining pattern with central areas of tumor (range, 20%-90%) that lacked immunoreactivity, thus suggesting that the immunoreactivity was maintained better in alcohol-fixed FNAB material. CONCLUSIONS In contrast to PAs, a majority of ACCs are immunocytochemically positive for MYB. The test is more effective using alcohol-fixed FNAB material and is potentially useful for the cytologic distinction of ACC and PA. Cancer (Cancer Cytopathol) 2014;122:257-265. (c) 2013 American Cancer Society. C1 [Pusztaszeri, Marc P.; Bordignon, Patrizia; McKee, Thomas A.] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Sadow, Peter M.; Ushiku, Aya; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadow, Peter M.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Pusztaszeri, MP (reprint author), Hop Cantonal Univ Geneva, Serv Pathol Clin, 1 Rue Michel Servet, CH-1211 Geneva 14, Switzerland. EM marc.pusztaszeri@hcuge.ch FU Adenoid Cystic Carcinoma Research Foundation FX This study was supported by the Adenoid Cystic Carcinoma Research Foundation. NR 32 TC 14 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR PY 2014 VL 122 IS 4 BP 257 EP 265 DI 10.1002/cncy.21381 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA AE6VH UT WOS:000334135600005 PM 24302647 ER PT J AU Schajnovitz, A Scadden, DT AF Schajnovitz, Amir Scadden, David T. TI Bone's dark side: mutated osteoblasts implicated in leukemia SO CELL RESEARCH LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; MARROW NICHE; MICROENVIRONMENT C1 [Schajnovitz, Amir; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Schajnovitz, Amir; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Schajnovitz, Amir; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM david_scadden@harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 7 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD APR PY 2014 VL 24 IS 4 BP 383 EP 384 DI 10.1038/cr.2014.26 PG 2 WC Cell Biology SC Cell Biology GA AF0JR UT WOS:000334400600001 PM 24589711 ER PT J AU Iyer, AS Wells, JM Vishin, S Bhatt, SP Wille, KM Dransfield, MT AF Iyer, Anand S. Wells, J. Michael Vishin, Sonia Bhatt, Surya P. Wille, Keith M. Dransfield, Mark T. TI CT Scan-Measured Pulmonary Artery to Aorta Ratio and Echocardiography for Detecting Pulmonary Hypertension in Severe COPD SO CHEST LA English DT Article ID RIGHT-VENTRICULAR-FUNCTION; COMPUTED-TOMOGRAPHY; LUNG-DISEASE; SEVERE EMPHYSEMA; DIAMETER; PATHOPHYSIOLOGY; EXACERBATION; MANAGEMENT; PRESSURES; SERIES AB Background: COPD is associated with significant morbidity primarily driven by acute exacerbations. Relative pulmonary artery (PA) enlargement, defined as a PA to ascending aorta (A) diameter ratio greater than one (PA:A>1) identifies patients at increased risk for exacerbations. However, little is known about the correlation between PA:A, echocardiography, and invasive hemodynamics in COPD. Methods: A retrospective observational study of patients with severe COPD being evaluated for lung transplantation at a single center between 2007 and 2011 was conducted. Clinical characteristics, CT scans, echocardiograms, and right-sided heart catheterizations were reviewed. The PA diameter at the bifurcation and A diameter from the same CT image were measured. Linear and logistic regression were used to examine the relationships between PA:A ratio by CT scan and PA systolic pressure (PASP) by echocardiogram with invasive hemodynamics. Receiver operating characteristic analysis assessed the usefulness of the PA:A ratio and PASP in predicting resting pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP]>25 mm Hg). Results: Sixty patients with a mean predicted FEV1 of 27% +/- 12% were evaluated. CT scan-measured PA:A correlated linearly with mPAP after adjustment for multiple covariates (r = 0.30, P = .03), a finding not observed with PASP. In a multivariate logistic model, mPAP was independently associated with PA:A>1 (OR, 1.44; 95% CI, 1.02-2.04; P =.04). PA:A>1 was 73% sensitive and 84% specific for identifying patients with resting PH (area under the curve, 0.83; 95% CI, 0.72-0.93; P<.001), whereas PASP was not useful. Conclusions: A PA:A ratio > 1 on CT scan outperforms echocardiography for diagnosing resting PH in patients with severe COPD. C1 [Iyer, Anand S.; Wells, J. Michael; Vishin, Sonia; Wille, Keith M.; Dransfield, Mark T.] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA. [Wells, J. Michael; Vishin, Sonia; Bhatt, Surya P.; Wille, Keith M.; Dransfield, Mark T.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care, Dept Med, Birmingham, AL USA. Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL USA. [Wells, J. Michael; Dransfield, Mark T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Wells, JM (reprint author), 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM jmwells@uab.edu FU National Institutes of Health; Aeris Therapeutics; AstraZeneca; Boehringer Ingelheim GmbH; Boston Scientific; Janssen Biotech, Inc; Forest Laboratories, Inc; GlaxoSmithKline; Ikaria, Inc; Medimmune, LLC; Olmsted Medical Center; Otsuka America Pharmaceutical, Inc; Pfizer, Inc; Pulmonx FX Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Dransfield has served as a consultant to Boehringer Ingelheim GmbH, GlaxoSmithKline, and Ikaria, Inc, and his institution has received research support from the National Institutes of Health; Aeris Therapeutics; AstraZeneca; Boehringer Ingelheim GmbH; Boston Scientific; Janssen Biotech, Inc; Forest Laboratories, Inc; GlaxoSmithKline; Ikaria, Inc; Medimmune, LLC; Olmsted Medical Center; Otsuka America Pharmaceutical, Inc; Pfizer, Inc; and Pulmonx. Drs Iyer, Wells, Vishin, Bhatt, and Wille have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article NR 42 TC 31 Z9 34 U1 1 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2014 VL 145 IS 4 BP 824 EP 832 DI 10.1378/chest.13-1422 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AE6JO UT WOS:000334097700027 PM 24114440 ER PT J AU Gould, MK Wagner, TH Schultz, EM Xu, XY Ghaus, SJ Provenzale, D Au, DH AF Gould, Michael K. Wagner, Todd H. Schultz, Ellen M. Xu, Xiangyan Ghaus, Sharfun J. Provenzale, Dawn Au, David H. CA Canc Care Outcomes Res TI Facility-Level Analysis of PET Scanning for Staging Among US Veterans With Non-small Cell Lung Cancer SO CHEST LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MEDICARE BENEFICIARIES; COMPUTED-TOMOGRAPHY; RANDOMIZED-TRIAL; COMORBIDITY; CARE AB Background: PET scanning has been shown in randomized trials to reduce the frequency of surgery without cure among patients with potentially resectable non-small cell lung cancer (NSCLC). We examined whether more frequent use of PET scanning at the facility level improves survival among patients with NSCLC in real-world practice. Methods: In this prospective cohort study of 622 US veterans with newly diagnosed NSCLC, we compared groups defined by the frequency of PET scan use measured at the facility level and categorized as low (<25%), medium (25%-60%), or high (>60%). Results: The median age of the sample was 69 years. Ninety-eight percent were men, 36% were Hispanic or nonwhite, and 54% had moderate or severe comorbidities. At low-, medium-, and high-use facilities, PET scan was performed in 13%, 40%, and 72% of patients, respectively (P<.0001). Baseline characteristics were similar across groups, including clinical stage based on CT scanning. More frequent use of PET scanning was associated with more frequent invasive staging (P<.001) and nonsignificant improvements in downstaging (P = .13) and surgery without cure (P = .12). After a median of 352 days of follow-up, 22% of the sample was still alive, including 22% at low- and medium- use facilities and 20% at high-use facilities. After adjustment and compared with patients at low- use facilities, the hazard of death was greater for patients at high-use facilities (adjusted hazard ratio [HR], 1.35; 95% CI, 1.05-1.74) but not different for patients at medium-use facilities (adjusted HR, 1.14; 95% CI, 0.88-1.46). Conclusions: In this study of veterans with NSCLC, markedly greater use of PET scanning at the facility level was associated with more frequent use of invasive staging and possible improvements in downstaging and surgery without cure, but greater use of PET scanning was not associated with better survival. C1 [Gould, Michael K.] Dept Vet Affairs, Palo Alto, CA USA. [Wagner, Todd H.; Ghaus, Sharfun J.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Wagner, Todd H.] VA Hlth Econ Res Ctr, Menlo Pk, CA USA. [Schultz, Ellen M.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Xu, Xiangyan] Palo Alto Inst Res & Educ, Palo Alto, CA USA. [Provenzale, Dawn] Durham VA Med Ctr, Durham Epidemiol Res & Informat Ctr, Durham, NC USA. [Provenzale, Dawn] Duke Univ, Durham, NC USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. [Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. RP Gould, MK (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Los Robles, Pasadena, CA 91101 USA. EM michael.k.gould@kp.org FU NCI NIH HHS [U01 CA093344, U01 CA093324, U01 CA093326, U01 CA093329, U01 CA093332, U01 CA093339, U01 CA093348, U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01 CA93344, U01 CA93348] NR 21 TC 0 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2014 VL 145 IS 4 BP 839 EP 847 DI 10.1378/chest.13-1073 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AE6JO UT WOS:000334097700029 PM 24306819 ER PT J AU Sukul, D Bonaca, MP Ruff, CT Kosowsky, J Conrad, M Murphy, SA Sabatine, MS Jarolim, P Morrow, DA AF Sukul, Devraj Bonaca, Marc P. Ruff, Christian T. Kosowsky, Joshua Conrad, Michael Murphy, Sabina A. Sabatine, Marc S. Jarolim, Petr Morrow, David A. TI Diagnostic Performance of Copeptin in Patients With Acute Nontraumatic Chest Pain: BWH- TIMI ED Chest Pain Study SO CLINICAL CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN; RISK STRATIFICATION; SENSITIVITY; VASOPRESSIN; PEPTIDE; ASSAYS; PRECURSOR; RULE AB BackgroundArginine-vasopressin (AVP) is an acute marker of physiologic stress. Copeptin is the C-terminal fragment of vasopressin precursor hormone that is more easily measured than AVP. Studies assessing the utility of copeptin in the diagnosis of myocardial infarction (MI) have demonstrated mixed results. HypothesisThe aim of this study was to test the hypothesis that copeptin improves diagnostic performance when added to troponin for detecting MI in patients presenting to the emergency department with nontraumatic chest pain. MethodsWe measured copeptin, local cardiac troponin I (local cTnI), and a contemporary sensitive cardiac troponin I (sensitive cTnI) at presentation and serially in patients who presented with acute chest pain. A copeptin cutoff of 14 pmol/L was utilized. ResultsMI was diagnosed in 25.7% of patients. Noncoronary acute cardiopulmonary causes of chest pain occurred in 12.8%. Patients with MI had significantly higher copeptin levels than patients with noncardiac chest pain (P < 0.001). The area under the receiver operating characteristic curve (AUC) for copeptin was 0.60 (95% confidence interval: 0.54-0.66), significantly less than the AUC for local cTnI (0.92) or sensitive cTnI (0.96). The combination of copeptin with either the local or sensitive troponin assay (c-statistics 0.92 and 0.95, respectively) did not significantly improve the AUC as compared to either troponin assay alone. This finding persisted in the subgroup of early presenters (6 hours from symptom onset). ConclusionsCopeptin did not improve the diagnostic performance for detecting MI when used alone or in combination with a contemporary sensitive cTnI assay, though our cohort had relatively few early presenters. C1 [Sukul, Devraj; Bonaca, Marc P.; Ruff, Christian T.; Murphy, Sabina A.; Sabatine, Marc S.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Kosowsky, Joshua] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Conrad, Michael; Jarolim, Petr] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bonaca, MP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM mbonaca@partners.org FU BRAHMS-Thermofisher, Inc.; Abbott; Amgen; AstraZeneca; Beckman Coulter; BG Medicine; BRAHMS; Bristol-Myers Squibb; Buhlmann; Critical Diagnostics; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Merck and Co.; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical Diagnostics; Pfizer; Randox; Roche Diagnostics; Sanofi-Aventis; Siemens; Singulex; TIMI Study Group; Daiichi Sankyo; Research Career Development Award from the NHLBI [K12 HL083786] FX Testing of copeptin in this study was supported by BRAHMS-Thermofisher, Inc.; The TIMI Study Group has received research grant support from Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Buhlmann, Critical Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Merck and Co., Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche Diagnostics, Sanofi-Aventis, Siemens, and Singulex. Dr. Sukul: nothing to report. Dr. Bonaca is an investigator and receives salary support from the TIMI Study Group. He has received remuneration for consulting from Roche. Dr. Ruff is an investigator and receives salary support from the TIMI Study Group. He has received remuneration for consulting from Alere, Beckman Coulter, Daiichi Sankyo, Boerhinger-Ingelheim. Dr. Kosowsky: nothing to report. Mr. Conrad: nothing to report. Mrs. Murphy: nothing to report. Dr. Sabatine is an investigator and receives salary from the TIMI Study Group. Dr. Jarolim received research support from Daiichi Sankyo, Roche Diagnostics, AstraZeneca, Siemens, Abbott, and Merck. He has received remuneration for consulting from T2 Biosystems and Quanterix. Dr. Morrow is an investigator and receives salary from the TIMI Study Group. He has received remuneration for consulting from Beckman-Coulter, Boehringher Ingelheim, Critical Diagnostics, Genentech, Gilead, Instrumentation Laboratory, Johnson & Johnson, Merck, Roche Diagnostics, and Servier.; Dr. Bonaca was supported in part by a Research Career Development Award (K12 HL083786) from the NHLBI. NR 27 TC 4 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2014 VL 37 IS 4 BP 227 EP 232 DI 10.1002/clc.22244 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE9MJ UT WOS:000334331600005 PM 24452775 ER PT J AU Garner, O Mochon, A Branda, J Burnham, CA Bythrow, M Ferraro, M Ginocchio, C Jennemann, R Manji, R Procop, GW Richter, S Rychert, J Sercia, L Westblade, L Lewinski, M AF Garner, O. Mochon, A. Branda, J. Burnham, C. -A. Bythrow, M. Ferraro, M. Ginocchio, C. Jennemann, R. Manji, R. Procop, G. W. Richter, S. Rychert, J. Sercia, L. Westblade, L. Lewinski, M. TI Multi-centre evaluation of mass spectrometric identification of anaerobic bacteria using the VITEK (R) MS system SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Anaerobe; bacterial identification; clinical microbiology; matrix-assisted laser desorption ionization time-of-flight mass spectrometry; VITEK-MS ID DESORPTION IONIZATION-TIME; LASER-DESORPTION/IONIZATION-TIME; MALDI-TOF; SPECIES IDENTIFICATION; ROUTINE IDENTIFICATION; LABORATORIES AB Accurate and timely identification of anaerobic bacteria is critical to successful treatment. Classic phenotypic methods for identification require long turnaround times and can exhibit poor species level identification. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an identification method that can provide rapid identification of anaerobes. We present a multi-centre study assessing the clinical performance of the VITEK (R) MS in the identification of anaerobic bacteria. Five different test sites analysed a collection of 651 unique anaerobic isolates comprising 11 different genera. Multiple species were included for several of the genera. Briefly, anaerobic isolates were applied directly to a well of a target plate. Matrix solution (-cyano-4-hydroxycinnamic acid) was added and allowed to dry. Mass spectra results were generated with the VITEK (R) MS, and the comparative spectral analysis and organism identification were determined using the VITEK (R) MS database 2.0. Results were confirmed by 16S rRNA gene sequencing. Of the 651 isolates analysed, 91.2% (594/651) exhibited the correct species identification. An additional eight isolates were correctly identified to genus level, raising the rate of identification to 92.5%. Genus-level identification consisted of Actinomyces, Bacteroides and Prevotella species. Fusobacterium nucleatum, Actinomyces neuii and Bacteroides uniformis were notable for an increased percentage of no-identification results compared with the other anaerobes tested. VITEK (R) MS identification of clinically relevant anaerobes is highly accurate and represents a dramatic improvement over other phenotypic methods in accuracy and turnaround time. C1 [Garner, O.; Mochon, A.; Lewinski, M.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Branda, J.; Ferraro, M.; Rychert, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, J.; Ferraro, M.; Rychert, J.] Harvard Univ, Sch Med, Boston, MA USA. [Burnham, C. -A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Bythrow, M.] North Shore LIJ Hlth Syst Labs, Div Infect Dis Diagnost, Lake Success, NY USA. [Ginocchio, C.; Manji, R.] North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, Lake Success, NY USA. [Jennemann, R.] Barnes Jewish Hosp, Dept Pathol, St Louis, MO 63110 USA. [Procop, G. W.; Richter, S.; Sercia, L.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. [Westblade, L.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. RP Garner, O (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 Conte Ave, Los Angeles, CA 90095 USA. EM ogarner@mednet.ucla.edu FU bioMerieux; Becton; Bruker; Luminex; Nanosphere; Forest Laboratories; Acclerate; Cepheid; T2 Biosystems FX J. Branda, J. Rychert, and M. Ferraro received research funding from bioMerieux and Becton, Dickinson. C. Ginocchio received research funding and consulting fees from bioMerieux and Becton, Dickinson. G. Procop received research funding from bioMerieux, Bruker, and Luminex. S. Richter received research funding from bioMerieux, Nanosphere, and Forest Laboratories. C. Burnham received research funding from bioMerieux, Acclerate, Cepheid, and T2 Biosystems. The other authors have no conflicts to disclose. This study was performed as part of an FDA trial of the Vitek MS v2.0 system funded by the device manufacturer bioMerieux. NR 15 TC 26 Z9 28 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1198-743X EI 1469-0691 J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD APR PY 2014 VL 20 IS 4 BP 335 EP 339 DI 10.1111/1469-0691.12317 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA AC7CR UT WOS:000332685100019 PM 23927597 ER PT J AU Lyon, SM Wunsch, H Asch, DA Carr, BG Kahn, JM Cooke, CR AF Lyon, Sarah M. Wunsch, Hannah Asch, David A. Carr, Brendan G. Kahn, Jeremy M. Cooke, Colin R. TI Use of Intensive Care Services and Associated Hospital Mortality After Massachusetts Healthcare Reform SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; health insurance; health policy; healthcare reform ID CRITICAL ILLNESS; INSURANCE STATUS; UNITED-STATES; OUTCOMES; ACCESS; PERFORMANCE; MEDICINE; COSTS AB Objective: To use the natural experiment of health insurance reform in Massachusetts to study the impact of increased insurance coverage on ICU utilization and mortality. Design: Population-based cohort study. Setting: Massachusetts and four states (New York, Washington, Nebraska, and North Carolina) that did not enact reform. Patients: All nonpregnant nonelderly adults (age 18-64 yr) admitted to nonfederal acute care hospitals in one of the five states of interest were eligible, excluding patients who were not residents of a respective state at the time of admission. Measurements: We used a difference-in-differences approach to compare trends in ICU admissions and outcomes of in-hospital mortality and discharge destination for ICU patients. Main Result: Healthcare reform in Massachusetts was associated with a decrease in ICU patients without insurance from 9.3% to 5.1%. There were no significant changes in adjusted ICU admission rates, mortality, or discharge destination. In a sensitivity analysis excluding a state that enacted Medicaid reform prior to the study period, our difference-in-differences analysis demonstrated a significant increase in mortality of 0.38% per year (95% CI, 0.12-0.64%) in Massachusetts, attributable to a greater per-year decrease in mortality postreform in comparison states (-0.37%; 95% CI, -0.52% to -0.21%) compared with Massachusetts (0.01%; 95% CI, -0.20% to 0.11%). Conclusion: Massachusetts healthcare reform increased the number of ICU patients with insurance but was not associated with significant changes in ICU use or discharge destination among ICU patients. Reform was also not associated with changed in-hospital mortality for ICU patients; however, this association was dependent on the comparison states chosen in the analysis. C1 [Lyon, Sarah M.] Hosp Univ Penn, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Wunsch, Hannah] Columbia Univ, Dept Anesthesiol, New York, NY USA. [Asch, David A.; Carr, Brendan G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Carr, Brendan G.] Hosp Univ Penn, Dept Surg, Div Traumatol Surg Crit Care & Emergency Surg, Philadelphia, PA 19104 USA. [Carr, Brendan G.] Hosp Univ Penn, Dept Emergency Med, Ctr Policy Res, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Dept Crit Care Med, CRISMA Ctr, Pittsburgh, PA USA. [Cooke, Colin R.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Cooke, Colin R.] Univ Michigan, Ctr Healthcare Outcomes & Policy, Ann Arbor, MI 48109 USA. RP Lyon, SM (reprint author), Hosp Univ Penn, Div Pulm Allergy & Crit Care, 3400 Spruce St, Philadelphia, PA 19104 USA. EM arah.lyon@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X; Cooke, Colin/0000-0001-9713-5371 FU National Institutes of Health (NIH) [F32 10762329]; Leonard Davis Institute, University of Pennsylvania; NIH [AHRQ F32]; U.S. Department of Health and Human Services; University of Michigan's Robert Wood Johnson Foundation; Agency for Healthcare Research and Quality [K08]; Robert Wood Johnson Foundation FX Dr. Lyon received support for article research from National Institutes of Health (NIH, F32 10762329) and received grant support from the Leonard Davis Institute, University of Pennsylvania (Pilot Grant). She received support for travel from the American Thoracic Society (ATS Travel Award 2012) and is employed by the Chester County Hospital. Her institution received grant support from the NIH (AHRQ F32). Dr. Wunsch received grant support from NIH. Dr. Carr was supported by Leonard Davis Institute, University of Pennsylvania. He spends a portion of his time as a Senior Policy Analyst in the Office of the Assistant Secretary for Preparedness and Response. Dr. Kahn consulted for the U. S. Department of Veterans Affairs. He received speaking honoraria from the National Association of Long-term Acute Care hospitals and Barlow Respiratory Hospital. His institution received grant support from the U.S. Department of Health and Human Services (research grants). Dr. Cooke was supported by the University of Michigan's Robert Wood Johnson Foundation Clinical Scholars and Health and Society Programs. He and his institution received grant support from the Agency for Healthcare Research and Quality (K08), and his institution received support from Robert Wood Johnson Foundation. The findings and conclusions in this report are those of the author and do not necessarily represent the views of the Department of Health and Human Services or its components. Dr. Asch has disclosed that he does not have any potential conflicts of interest. NR 32 TC 4 Z9 4 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2014 VL 42 IS 4 BP 763 EP 770 DI 10.1097/CCM.0000000000000044 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA AC9FL UT WOS:000332839700017 PM 24275512 ER PT J AU Purtle, SW Moromizato, T McKane, CK Gibbons, FK Christopher, KB AF Purtle, Steven W. Moromizato, Takuhiro McKane, Caitlin K. Gibbons, Fiona K. Christopher, Kenneth B. TI The Association of Red Cell Distribution Width at Hospital Discharge and Out-of-Hospital Mortality Following Critical Illness SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; epidemiology; hospital discharge; intensive care; mortality; red cell distribution width ID LOCALLY WEIGHTED REGRESSION; RENIN-ANGIOTENSIN SYSTEM; CRITICAL-CARE INITIATION; INTENSIVE-CARE; HEART-FAILURE; PROGNOSTIC MARKER; OXIDATIVE STRESS; LIVER-DISEASE; OLDER-ADULTS; ILL PATIENTS AB Objectives: Red cell distribution width is associated with mortality and bloodstream infection risk in the critically ill. In hospitalized patients with critical illness, it is not known if red cell distribution width can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in red cell distribution width at hospital discharge in patients who survived to discharge following critical care would be associated with increased postdischarge mortality. Design: Two-center observational cohort study Setting: All medical and surgical ICUs at the Brigham and Women's Hospital and Massachusetts General Hospital. Patients: We studied 43,212 patients, who were 18 years old or older and received critical care between 1997 and 2007 and survived hospitalization. Interventions: None. Measurements and Main Results: The exposure of interest was red cell distribution width within 24 hours of hospital discharge and categorized a priori in quintiles as less than or equal to 13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, and more than 15.8%. The primary outcome was all-cause mortality in the 30 days following hospital discharge. Secondary outcomes included 90-day and 365-day mortality following hospital discharge. Mortality was determined using the U.S. Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both red cell distribution width and mortality. Adjustment included age, race, gender, Deyo-Charlson Index, patient type (medical vs surgical), sepsis, and number of organs with acute failure. In patients who received critical care and survived hospitalization, the discharge red cell distribution width was a robust predictor of all-cause mortality and remained so following multivariable adjustment. Patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 2.86 (95% CI, 2.25-3.62), 4.57 (95% CI, 3.66-5.72), and 8.80 (95% CI, 7.15-10.83), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Following multivariable adjustment, patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 1.63 (95% CI, 1.27-2.07), 2.36 (95% CI, 1.87-2.97), and 4.18 (95% CI, 3.36-5.20), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 postdischarge. Estimating the receiver-operating characteristic area under the curve shows that discharge red cell distribution width has moderate discriminative power for mortality 30 days following hospital discharge (area under the curve = 0.70; se 0.006; 95% CI, 0.69-0.71; p < 0.0001). Conclusion: In patients treated with critical care who survive hospitalization, an elevated red cell distribution width at the time of discharge is a robust predictor of subsequent all-cause patient mortality. Increased discharge red cell distribution width likely reflects the presence of proinflammatory state, oxidative stress, arterial underfilling, or a combination, thereof which may explain the observed impact on patient survival following discharge. Elevated red cell distribution width at hospital discharge may identify ICU survivors who are at risk for adverse outcomes following hospital discharge. C1 [Purtle, Steven W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [McKane, Caitlin K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org NR 57 TC 28 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2014 VL 42 IS 4 BP 918 EP 929 DI 10.1097/CCM.0000000000000118 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA AC9FL UT WOS:000332839700035 PM 24448196 ER PT J AU Au, DH Wong, ES AF Au, David H. Wong, Edwin S. TI Use of Intensive Care and Healthcare Reform: More Questions Following the Massachusetts Experience SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE health insurance; healthcare costs; healthcare reform; Medicaid; quality of care C1 [Au, David H.] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98108 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2014 VL 42 IS 4 BP 970 EP 971 DI 10.1097/CCM.0000000000000110 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AC9FL UT WOS:000332839700041 PM 24633090 ER PT J AU de Prost, N Melo, MFV AF de Prost, Nicolas Melo, Marcos F. Vidal TI Lung Metabolism During Ventilator-Induced Lung Injury: Stretching the Relevance of the Normally Aerated Lung* SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; fluorodeoxyglucose F18; positron emission tomography; ventilator-induced lung injury ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; INFLATION; INFLAMMATION C1 [de Prost, Nicolas] Hop Henri Mondor, AP HP, Serv Reanimat Med, F-94010 Creteil, France. [de Prost, Nicolas; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP de Prost, N (reprint author), Hop Henri Mondor, AP HP, Serv Reanimat Med, F-94010 Creteil, France. OI de Prost, Nicolas/0000-0002-4833-4320 FU NHLBI NIH HHS [R01 HL086827, R01 HL121228]; PHS HHS [NHLBI 5R01HL086827] NR 24 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2014 VL 42 IS 4 BP 1010 EP 1012 DI 10.1097/CCM.0000000000000251 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AC9FL UT WOS:000332839700064 PM 24633113 ER PT J AU Tse, SM Charland, SL Stanek, E Herrera, V Goldfarb, S Litonjua, AA Weiss, ST Wu, AC AF Tse, Sze Man Charland, Scott L. Stanek, Eric Herrera, Vivian Goldfarb, Seth Litonjua, Augusto A. Weiss, Scott T. Wu, Ann Chen TI Statin use in asthmatics on inhaled corticosteroids is associated with decreased risk of emergency department visits SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Asthma; Exacerbation; Inhaled corticosteroids; Statins ID ALLERGIC-ASTHMA; SIMVASTATIN; ATORVASTATIN; CORONARY; LUNG; HYPERRESPONSIVENESS; INFLAMMATION; THERAPY; TRIAL AB Objective: Statins are hypothesized to have beneficial effects in asthma management through their pleiotropic anti-inflammatory effects. Several studies have examined this relationship, but have yielded conflicting results. This study investigates the effect of statin use on asthma-related hospitalizations and/or emergency department (ED) visits, and whether this relationship varies by concomitant inhaled corticosteroid (ICS) in a large cohort of asthma patients. Methods: Subjects with asthma, a recent history of asthma exacerbation, and who were 18 years or older were selected from the population-based Medco Health Solutions administrative database over a 1 year period. Prescription claims for statins and asthma medications, and asthma-related hospitalizations and/or ED visits were ascertained over a 12 month follow-up period. Subjects were stratified into two groups based on their ICS use. Results: A total of 3747 ICS users and 2905 non-ICS users were included in this study. Statin users represented 21% of ICS users and 11% of non-users. Among ICS users, statin use was significantly associated with decreased odds of asthma-related ED visits (OR = 0.77, 95% Cl 0.64-0.94, p = 0.008), but not with asthma-related hospitalizations (OR = 1.09, 95% CI 0.92-1.30, p = 0.31). No significant associations were found among non-ICS users (for asthma-related ED visits: OR = 0.92, 95% Cl 0.57-1.49, p = 0.73; asthma-related hospitalizations: OR = 1.10, 95% Cl 0.85-1.41, p = 0.48). The statistical interactions between ICS and statin use on asthma-related hospitalizations and/or ED visits were not significant. Conclusion: Statin use is associated with fewer ED visits in asthma patients who are using ICS. C1 [Tse, Sze Man; Litonjua, Augusto A.; Weiss, Scott T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Tse, Sze Man; Litonjua, Augusto A.; Weiss, Scott T.; Wu, Ann Chen] Harvard Univ, Sch Med, Boston, MA USA. [Tse, Sze Man] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Charland, Scott L.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Charland, Scott L.] Sanofi Aventis, Evidence Based Med, Outcomes Liaison, Winter Pk, CO USA. [Charland, Scott L.; Stanek, Eric; Herrera, Vivian; Goldfarb, Seth] Medco Res Inst LLC, Bethesda, MD USA. [Wu, Ann Chen] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, Boston, MA USA. [Wu, Ann Chen] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Tse, SM (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM reszt@channing.harvard.edu FU National Institutes of Health [U01 HL65899, R01 HL92197]; NIH FX This work was funded by National Institutes of Health grants U01 HL65899 and R01 HL92197. This paper is subject to the NIH Public Access Policy (http://publicaccess.nih.gov).; S.T.W. has served as an unpaid consultant for GlaxoSmithKline, Genetech, Novartis, Merck, Genome Network Sciences and Schering Plough. S.L.C. serves as a paid HE/OR advisor to Novo Nordisk, and has previously been employed by Medco Research Institute LLC, a wholly owned subsidiary of Express Scripts Holding Co. Inc. He is currently employed by Sanofi-Aventis. A.C.W. has received grant funding from the NIH. E.S. is an employee of Novartis Pharmaceuticals. S.M.T., V.H., S.G., A.A.L., and A.C.W. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. NR 30 TC 6 Z9 6 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD APR PY 2014 VL 30 IS 4 BP 685 EP 693 DI 10.1185/03007995.2013.865599 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE6ZJ UT WOS:000334146200015 PM 24219830 ER PT J AU Basavappa, M Weinberg, A Huang, Q Mashimo, H AF Basavappa, M. Weinberg, A. Huang, Q. Mashimo, H. TI Markers suggest reduced malignant potential of subsquamous intestinal metaplasia compared with Barrett's esophagus SO DISEASES OF THE ESOPHAGUS LA English DT Article DE Barrett's esophagus; dysplasia; Ki67; Lgr5; subsquamous intestinal metaplasia ID HIGH-GRADE DYSPLASIA; STEM-CELL MARKER; PHOTODYNAMIC THERAPY; RADIOFREQUENCY ABLATION; SQUAMOUS MUCOSA; ADENOCARCINOMA; LGR5; PROLIFERATION AB Esophageal subsquamous intestinal metaplasia (SSIM) is frequently observed in patients with Barrett's esophagus (BE) and can also be found in patients after endoscopic ablative treatments for dysplastic BE. While these buried glands' appear identical to BE glands, features of SSIM and its malignant potency have yet to be fully elucidated. To determine differences in malignant potential between nondysplastic BE and SSIM, the Automated Cellular Imaging System was used to assess and compare changes in DNA content between SSIM and BE. Samples were further immunostained for Ki67 and Lgr5 to gauge general proliferative and possible stem cell features, respectively, in SSIM cells compared with BE glands. No significant differences were found between SSIM and BE with regards to DNA ploidy aberrance. However, significant differences were noted between SSIM and BE upon immunohistochemical analysis. SSIM was found to be negative for both Ki67 and Lgr5 while BE was positive for both markers. SSIM cells appear to be relatively quiescent and behave differently from BE, suggesting a reduced proclivity toward cancer progression. C1 [Basavappa, M.; Weinberg, A.; Huang, Q.; Mashimo, H.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Weinberg, A.; Mashimo, H.] Boston Univ, Med Ctr, Boston, MA USA. [Mashimo, H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mashimo, H.] Harvard Univ, Sch Med, Boston, MA USA. RP Mashimo, H (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy,Bldg 3, Boston, MA 02132 USA. EM hmashimo@hms.harvard.edu FU VA Merit Research Award FX This work was supported by VA Merit Research Award and facility support from the VA Boston Healthcare System. Thanks are also given to Kunal Sangal, Joe Cullaro and Lavanya Rajendran for contributions to the editing of this manuscript. NR 23 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 EI 1442-2050 J9 DIS ESOPHAGUS JI Dis. Esophagus PD APR PY 2014 VL 27 IS 3 BP 262 EP 266 DI 10.1111/dote.12087 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AE1BJ UT WOS:000333700300010 PM 23796148 ER PT J AU Dvoriak, S Karachevsky, A Chhatre, S Booth, R Metzger, D Schumacher, J Chychula, N Pecoraro, A Woody, G AF Dvoriak, Sergii Karachevsky, Andrey Chhatre, Sumedha Booth, Robert Metzger, David Schumacher, Joseph Chychula, Nina Pecoraro, Anna Woody, George TI Methadone maintenance for HIV positive and HIV negative patients in Kyiv: Acceptability and treatment response SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Methadone maintenance; HIV risk; Ukraine; PWID ID INJECTION-DRUG USERS; ADDICTION SEVERITY INDEX; OPIOID DEPENDENCE; ANTIRETROVIRAL THERAPY; UKRAINE; BUPRENORPHINE; TRIAL; INTERVENTIONS; INFECTION; EPIDEMIC AB Background: With up to 40% of opioid injectors infected with HIV, Ukraine has one of the most concentrated HIV epidemics in the world, mainly due to unsterile injection practices and a historical absence of effective prevention services. Harm reduction programs, including syringe exchange and a small buprenorphine treatment program, were introduced in 2004 and methadone maintenance was allowed in 2007. Despite an initial expansion, by 2009, only 3221 injectors were receiving methadone treatment. A growing body of research on methadone maintenance has found high retention rates with reduction in opioid use and HIV risk behaviors. We report on the acceptability and initial outcome of methadone treatment as a function of HIV status, an issue that has not yet been reported for injectors in Ukraine. Methods: Longitudinal observational study of a 12-week course of methadone treatment in 25 HIV+ and 25 HIV opioid addicted individuals recruited from a harm reduction program and the city AIDS Center. Drug use and HIV risk were assessed at baseline and weeks 4, 8, 12 and 20; all patients were offered continued methadone maintenance in the Kyiv city program at the end of 12 weeks. Results: Fifty-four individuals were asked if they were interested in the study and 50, demographically similar to other samples of opioid addicted Ukrainians, agreed to participate. Two died of non-study related causes; the other 48 completed assessments at weeks 4, 8 and 12, and 47 completed followups at week 20. Significant reductions were seen in use of heroin (p < 0.0001), other opiates/analgesics (p < 0.0001), and HIV risk behaviors (drug, sex, total; all p < 0.0001). All 48 patients chose to continue methadone after the 12-weeks of study medication ended. Unlike most opioid treatment studies, sexual risk was somewhat higher than injecting risk at study intake. Conclusions: Methadone maintenance was well accepted by HIV+ and HIV opioid dependent individuals and has the potential for significant public health impact if made more widely available with sustained access and support. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Dvoriak, Sergii] Ukrainian Inst Publ Hlth Policy, UA-01001 Kiev, Ukraine. [Karachevsky, Andrey] OO Bogomolets Natl Med Univ, Dept Psychiat & Drug Abuse, UA-01601 Kiev, Ukraine. [Chhatre, Sumedha; Metzger, David; Pecoraro, Anna; Woody, George] Treatment Res Inst, Philadelphia, PA 19106 USA. [Booth, Robert] Univ Colorado, Dept Psychiat, Denver, CO 80206 USA. [Metzger, David; Pecoraro, Anna; Woody, George] Univ Penn, Perelman Sch Med, Philadelphia, PA 19106 USA. [Schumacher, Joseph] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Chychula, Nina] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Woody, G (reprint author), Univ Penn, Perelman Sch Med, Suite 600,150 South Independence Mall W, Philadelphia, PA 19106 USA. EM woody@tresearch.org RI Metzger, David/D-9499-2012 FU NIDA [5R21DA21073]; INVEST/CTN [U10 DA-13043, KO5 DA-17009, DA024590] FX This research was supported by NIDA grants 5R21DA21073, INVEST/CTN fellowship award to Dr. Dvoryak; U10 DA-13043; KO5 DA-17009 (Woody PI on all); DA024590 (Booth). NR 37 TC 5 Z9 5 U1 5 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2014 VL 137 BP 62 EP 67 DI 10.1016/j.drugalcdep.2014.01.008 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AE6UT UT WOS:000334134200008 PM 24548802 ER PT J AU Kaz, AM Wong, CJ Dzieciatkowski, S Luo, YX Schoen, RE Grady, WM AF Kaz, Andrew M. Wong, Chao-Jen Dzieciatkowski, Slavomir Luo, Yanxin Schoen, Robert E. Grady, William M. TI Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age SO EPIGENETICS LA English DT Article DE DNA methylation; field effect; colorectal cancer; normal colon methylation; methylation microarray ID CPG ISLAND METHYLATION; COLORECTAL-CANCER; ULCERATIVE-COLITIS; RECTAL MUCOSA; FIELD; GENE; HYPOMETHYLATION; CANCERIZATION; ADENOMAS; TUMORS AB Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon's normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays. We found that methylation levels of repetitive elements LINE-1 and SAT-alpha showed minimal variability throughout the colon in contrast to other loci. Promoter methylation of EVL was highest in the rectum and progressively lower in the proximal segments, whereas ESR1 methylation was higher in older individuals. Genome-wide methylation analysis of normal DNA revealed 8388, 82, and 93 differentially methylated loci that distinguished right from left colon, males from females, and older vs. younger individuals, respectively. Although variability in methylation between biopsies and among different colon segments was minimal for repetitive elements, analyses of specific cancer-related genes as well as a genome-wide methylation analysis demonstrated differential methylation based on colon location, individual age, and gender. These studies advance our knowledge regarding the variation of DNA methylation in the normal colon, a prerequisite for future studies aimed at understanding methylation differences indicative of a colon field effect. C1 [Kaz, Andrew M.; Wong, Chao-Jen; Dzieciatkowski, Slavomir; Luo, Yanxin; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Luo, Yanxin] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China. [Luo, Yanxin] Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou 510275, Guangdong, Peoples R China. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. RP Kaz, AM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. EM akaz@fhcrc.org FU NCI NIH HHS [U01 CA152756] NR 39 TC 17 Z9 17 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD APR 1 PY 2014 VL 9 IS 4 BP 492 EP 502 DI 10.4161/epi.27650 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE9DP UT WOS:000334305100003 PM 24413027 ER PT J AU Varraso, R Camargo, CA AF Varraso, Raphaelle Camargo, Carlos A., Jr. TI Processed meat consumption and lung health: more evidence for harm SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; DIETARY PATTERNS; CURED MEATS; RISK; COPD; MORTALITY; NITRATES; NITRITES; DECLINE; WOMEN C1 [Varraso, Raphaelle] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, F-94807 Villejuif, France. [Varraso, Raphaelle] Univ Paris 11, UMRS 1018, Villejuif, France. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Varraso, R (reprint author), INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. EM raphaelle.varraso@inserm.fr RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 NR 32 TC 3 Z9 3 U1 1 U2 5 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD APR PY 2014 VL 43 IS 4 BP 943 EP 946 DI 10.1183/09031936.00228213 PG 4 WC Respiratory System SC Respiratory System GA AE8OT UT WOS:000334261900003 PM 24687660 ER PT J AU Andreoli, MT Yiu, G Hart, L Andreoli, CM AF Andreoli, M. T. Yiu, G. Hart, L. Andreoli, C. M. TI B-scan ultrasonography following open globe repair SO EYE LA English DT Article DE ultrasound; ultrasonography; open globe; ocular trauma ID PENETRATING OCULAR TRAUMA; ULTRASOUND; INJURY AB Purpose To examine the accuracy and predictive ability of B-scan ultrasonography in the post-repair assessment of an open globe injury. Methods In all, 965 open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1 January 2000 and 1 June 2010 were retrospectively reviewed. A total of 427 ultrasound reports on 210 patients were analyzed. Ultrasound reports were examined for the following characteristics: vitreous hemorrhage, vitreous tag, retinal tear, RD (including subcategories total RD, partial RD, closed funnel RD, open funnel RD, and chronic RD), vitreous traction, vitreous debris, serous choroidal detachment, hemorrhagic choroidal detachment, kissing choroidal detachment, dislocated crystalline lens, dislocated intraocular lens (IOL), disrupted crystalline lens, intraocular foreign body (IOFB), intraocular air, irregular posterior globe contour, disorganized posterior intraocular contents, posterior vitreous detachment, choroidal vs retinal detachment, vitreal membranes, and choroidal thickening. The main outcome measure was visual outcome at final follow-up. Results Among 427 B-scan reports, there were a total of 57 retinal detachments, 19 retinal tears, 18 vitreous traction, 59 serous choroidal detachments, 47 hemorrhagic choroidal detachments, and 10 kissing choroidal detachments. Of patients with multiple studies, 26% developed retinal detachments or retinal tears on subsequent scans. Ultrasound had 100% positive predictive value for diagnosing retinal detachment and IOFB. The diagnoses of retinal detachment, disorganized posterior contents, hemorrhagic choroidal detachment, kissing choroidal detachment, and irregular posterior contour were associated with worse visual acuity at final follow-up. Disorganized posterior contents correlated with particularly poor outcomes. Conclusions B-scan ultrasonography is a proven, cost-effective imaging modality in the management of an open globe injury. This tool can offer both diagnostic and prognostic information, useful for both surgical planning and further medical management. Eye (2014) 28, 381-385; doi: 10.1038/eye.2013.289; published online 10 January 2014 C1 [Andreoli, M. T.; Yiu, G.; Hart, L.; Andreoli, C. M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Andreoli, M. T.] Illinois Eye & Ear Infirm, UIC Dept Ophthalmol & Visual, Chicago, IL USA. [Yiu, G.; Hart, L.; Andreoli, C. M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Andreoli, C. M.] Harvard Vanguard Med Associates, Visual Serv, Boston, MA 02215 USA. RP Andreoli, CM (reprint author), Harvard Vanguard Med Associates, 133 Brookline Ave, Boston, MA 02215 USA. EM christopher_andreoli@meei.harvard.edu NR 10 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD APR PY 2014 VL 28 IS 4 BP 381 EP 385 DI 10.1038/eye.2013.289 PG 5 WC Ophthalmology SC Ophthalmology GA AE9VT UT WOS:000334360000002 PM 24406404 ER PT J AU Verma, RU Guex, AA Hancock, KE Durakovic, N McKay, CM Slama, MCC Brown, MC Lee, DJ AF Verma, Rohit U. Guex, Amelie A. Hancock, Kenneth E. Durakovic, Nedim McKay, Colette M. Slama, Michael C. C. Brown, M. Christian Lee, Daniel J. TI Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus SO HEARING RESEARCH LA English DT Article ID BRAIN-STEM IMPLANT; INFERIOR COLLICULUS; OPTICAL STIMULATION; GUINEA-PIGS; NERVE-STIMULATION; PERIPHERAL-NERVE; PROJECTIONS; LASER; WAVELENGTH; CAT AB In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. (C) 2014 Elsevier B.V. All rights reserved. C1 [Verma, Rohit U.] Univ Manchester, Sch Med, Manchester M13 9PL, Lancs, England. [McKay, Colette M.] Univ Manchester, Sch Psychol Sci, Manchester M13 9PL, Lancs, England. [Verma, Rohit U.; Hancock, Kenneth E.; Durakovic, Nedim; Slama, Michael C. C.; Brown, M. Christian; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Guex, Amelie A.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. [McKay, Colette M.] Bion Inst Australia, Melbourne, Vic, Australia. [Verma, Rohit U.; Slama, Michael C. C.; Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Chris_Brown@meei.harvard.edu FU Helene and Grant Wilson Auditory Brainstem Implant Program at the Massachusetts Eye and Ear Infirmary; Med-EL Hearing Solutions Research Grant; Bertarelli Foundation; NIH [DC01089]; Paul and Daisy Soros Fellowship for New Americans; Victorian Government through its Operational Infrastructure Support Program FX Supported by the Helene and Grant Wilson Auditory Brainstem Implant Program at the Massachusetts Eye and Ear Infirmary, a Med-EL Hearing Solutions Research Grant, the Bertarelli Foundation, NIH grant DC01089, and the Paul and Daisy Soros Fellowship for New Americans. The Bionics Institute acknowledges the support it receives from the Victorian Government through its Operational Infrastructure Support Program. We thank Lockheed-Martin for supplying the Aculite laser, and Ishmael Stefanov, Evan Foss, and Haobing Wang for technical assistance. Preliminary versions of this work were presented at the 2012 meeting of the Association for Research in Otolaryngology and are contained in a master's thesis (Guex, 2012). NR 44 TC 15 Z9 15 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD APR PY 2014 VL 310 BP 69 EP 75 DI 10.1016/j.heares.2014.01.008 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AE6FV UT WOS:000334086900008 PM 24508368 ER PT J AU Harte, CB Meston, CM AF Harte, Christopher B. Meston, Cindy M. TI Effects of Smoking Cessation on Heart Rate Variability Among Long-Term Male Smokers SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Smoking; Smoking cessation; Nicotine; Heart rate variability; Cardiac autonomic regulation; Autonomic nervous system ID SUDDEN CARDIAC DEATH; CIGARETTE-SMOKING; SPECTRAL-ANALYSIS; BLOOD-PRESSURE; NICOTINE; EPIDEMIOLOGY; VALIDITY; HEALTH; RISK AB Cigarette smoking has been shown to adversely affect heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. Conversely, smoking cessation is posited to improve cardiac regulation. The aim of the present study was to examine the effects of smoking cessation on HRV among a community sample of chronic smokers. Sixty-two healthy male smokers enrolled in an 8-week smoking cessation program involving a nicotine transdermal patch treatment. Participants were assessed at baseline (while smoking regularly), at mid-treatment (while using a high-dose patch), and at follow-up, 4 weeks after patch discontinuation. Both time-domain (standard deviation of normal-to-normal (NN) intervals (SDNN), square root of the mean squared difference of successive NN intervals (RMSSD), and percent of NN intervals for which successive heartbeat intervals differed by at least 50 ms (pNN50)) and frequency-domain (low frequency (LF), high frequency (HF), LF/HF ratio) parameters of HRV were assessed at each visit. Successful quitters (n = 20), compared to those who relapsed (n = 42), displayed significantly higher SDNN, RMSSD, pNN50, LF, and HF at follow-up, when both nicotine and smoke free. Smoking cessation significantly enhances HRV in chronic male smokers, indicating improved autonomic modulation of the heart. Results suggest that these findings may be primarily attributable to nicotine discontinuation rather than tobacco smoke discontinuation alone. C1 [Harte, Christopher B.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Harte, Christopher B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Meston, Cindy M.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. RP Harte, CB (reprint author), VA Boston Healthcare Syst, Res Serv, 150 S Huntington Ave 116-B4, Boston, MA 02130 USA. EM christopher.harte@va.gov OI Harte, Christopher/0000-0002-8097-7369 FU NICHD NIH HHS [1 R01 HD051676-01 A1]; NIDA NIH HHS [F31DA026276] NR 34 TC 10 Z9 10 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 EI 1532-7558 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD APR PY 2014 VL 21 IS 2 BP 302 EP 309 DI 10.1007/s12529-013-9295-0 PG 8 WC Psychology, Clinical SC Psychology GA AE7JJ UT WOS:000334173500011 PM 23397454 ER PT J AU Naganuma, T Chieffo, A Meliga, E Capodanno, D Park, SJ Onuma, Y Valgimigli, M Jegere, S Makkar, RR Palacios, IF Costopoulos, C Kim, YH Buszman, PP Chakravarty, T Sheiban, I Mehran, R Naber, C Margey, R Agnihotri, A Marra, S Capranzano, P Leon, MB Moses, JW Fajadet, J Lefevre, T Morice, MC Erglis, A Tamburino, C Alfieri, O Serruys, PW Colombo, A AF Naganuma, Toru Chieffo, Alaide Meliga, Emanuele Capodanno, Davide Park, Seung-Jung Onuma, Yoshinobu Valgimigli, Marco Jegere, Sanda Makkar, Raj R. Palacios, Igor F. Costopoulos, Charis Kim, Young-Hak Buszman, Piotr P. Chakravarty, Tarun Sheiban, Imad Mehran, Roxana Naber, Christoph Margey, Ronan Agnihotri, Arvind Marra, Sebastiano Capranzano, Piera Leon, Martin B. Moses, Jeffrey W. Fajadet, Jean Lefevre, Thierry Morice, Marie-Claude Erglis, Andrejs Tamburino, Corrado Alfieri, Ottavio Serruys, Patrick W. Colombo, Antonio TI Long-Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Ostial/Midshaft Lesions in Unprotected Left Main Coronary Artery From the DELTA Registry SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE coronary artery bypass grafting; ostial/midshaft lesion; percutaneous coronary intervention; unprotected left main coronary artery ID DRUG-ELUTING STENT; MULTICENTER REGISTRY; DISEASE; CARDIOLOGY; IMPLANTATION; EFFICACY; SOCIETY; SAFETY AB Objectives The aim of this study was to report the long-term clinical outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for ostial/midshaft lesions in an unprotected left main coronary artery (ULMCA). Background Data regarding outcomes in these patients are limited. Methods Of a total of 2,775 patients enrolled in the DELTA multinational registry, 856 patients with isolated ostial/midshaft lesions in an ULMCA treated by PCI with DES (n = 482) or CABG (n = 374) were analyzed. Results At a median follow-up period of 1,293 days, there were no significant differences in the propensity score-adjusted analyses for the composite endpoint of all-cause death, myocardial infarction (MI), and cerebrovascular accident (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.79 to 1.86; p = 0.372), all-cause death (HR: 1.35, 95% CI: 0.80 to 2.27; p = 0.255), the composite endpoint of all-cause death and MI (HR: 1.33, 95% CI: 0.83 to 2.12; p = 0.235) and major adverse cardiac and cerebrovascular events (HR: 1.34, 95% CI: 0.93 to 1.93; p = 0.113). These results were sustained after propensity-score matching. However, a higher incidence of target vessel revascularization (HR: 1.94, 95% CI: 1.03 to 3.64; p = 0.039) was observed in the PCI compared with the CABG group, with a trend toward higher target lesion revascularization (HR: 2.00, 95% CI: 0.90 to 4.45; p = 0.090). Conclusions This study demonstrates that PCI for ostial/midshaft lesions in an ULMCA is associated with clinical outcomes comparable to those observed with CABG at long-term follow-up, despite the use of older first-generation DES. (JAmColl Cardiol Intv 2014;7:354-61) (C) 2014 by the American College of CardiologyFoundation C1 [Naganuma, Toru; Chieffo, Alaide; Costopoulos, Charis; Alfieri, Ottavio; Colombo, Antonio] Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, I-20132 Milan, Italy. [Meliga, Emanuele] AO Ordine Mauriziano Umberto I, Intervent Cardiol Unit, Turin, Italy. [Capodanno, Davide; Capranzano, Piera; Tamburino, Corrado] Univ Catania, Ferrarotto Hosp, Cardiovasc Dept, Catania, Italy. [Park, Seung-Jung; Kim, Young-Hak] Univ Ulsan, Coll Med, Ctr Med Res & Informat, Dept Cardiol, Seoul, South Korea. [Onuma, Yoshinobu; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Valgimigli, Marco] Univ Ferrara, S Anna Hosp, Cardiovasc Inst, I-44100 Ferrara, Italy. [Jegere, Sanda; Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Latvian Ctr Cardiol, Riga, Latvia. [Jegere, Sanda; Erglis, Andrejs] Latvian State Univ, Inst Cardiol, LV-1063 Riga, Latvia. [Makkar, Raj R.; Chakravarty, Tarun] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Catheterizat Lab, Boston, MA USA. [Buszman, Piotr P.] Ctr Cardiovasc Res & Dev Amer Heart Poland, Katowice, Poland. [Sheiban, Imad; Marra, Sebastiano] Univ Turin, S Giovanni Battista Molinette Hosp, Div Cardiol, Turin, Italy. [Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA. [Leon, Martin B.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA. [Leon, Martin B.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Fajadet, Jean] Clin Pasteur, Toulouse, France. [Lefevre, Thierry; Morice, Marie-Claude] Gen Sante Massy, Inst Hosp Jacques Cartier, Massy, France. RP Colombo, A (reprint author), Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, Via Olgettina 60, I-20132 Milan, Italy. EM colombo.antonio@hsr.it NR 18 TC 9 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD APR PY 2014 VL 7 IS 4 BP 354 EP 361 DI 10.1016/j.jcin.2013.11.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF1YK UT WOS:000334509600005 PM 24630886 ER PT J AU Robertson, JO Ebrahimi, R Lansky, AJ Mehran, R Stone, GW Lincoff, AM AF Robertson, Jason O. Ebrahimi, Ramin Lansky, Alexandra J. Mehran, Roxana Stone, Gregg W. Lincoff, A. Michael TI Impact of Cigarette Smoking on Extent of Coronary Artery Disease and Prognosis of Patients With Non-ST-Segment Elevation Acute Coronary Syndromes SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE ACUITY; non-ST-segment elevation acute coronary syndrome; smoker; smoker's paradox ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; THROMBOLYTIC THERAPY; SMOKERS PARADOX; ACUITY TRIAL; ATHEROSCLEROTIC PLAQUES; CLINICAL-IMPLICATIONS; 30-DAY MORTALITY; OUTCOMES; INSIGHTS AB Objectives This study sought to evaluate the short-and long-term outcomes for smokers with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Background Smoking has been associated with the "paradox"of reduced mortality after acute myocardial infarction (MI). This is thought to be due to favorable baseline characteristics and less diffuse coronary artery disease (CAD) among smokers. Methods In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients (29.1% smokers) with moderate-to high-risk NSTE-ACS underwent angiography and, if indicated, revascularization. Results Smokers were significantly younger and had fewer comorbidities than nonsmokers. Incidence of death and MI were comparable at 30 days, although smokers had significantly reduced risks of 30-day major bleeding (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.67 to 0.96; p = 0.016) and 1-year mortality (HR: 0.797, 95% CI: 0.65 to 0.97; p = 0.027). After correction for baseline and clinical differences, smoking was no longer predictive of major bleeding (odds ratio: 1.06, 95% CI: 0.86 to 1.32; p = 0.56) and was associated with higher 1-year mortality (HR: 1.37, 95% CI: 1.07 to 1.7; p = 0.013). This pattern of reversed risk after multivariable correction held true for those smokers requiring percutaneous coronary intervention. Core laboratory angiographic analysis showed that smokers and nonsmokers were comparable in terms of the extent of CAD, Thrombolysis In Myocardial Infarction flow, myocardial blush, and the presence of thrombi. Conclusions In contrast to the paradox previously described in ST-segment elevation MI, our analysis finds smoking to be an independent predictor of higher 1-year mortality in patients presenting with NSTE-ACS, and our angiographic study demonstrates CAD in smokers that is comparable to that in nonsmokers but evident similar to 1 decade earlier. (C) 2014 by the American College of Cardiology Foundation C1 [Robertson, Jason O.; Lincoff, A. Michael] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Los Angeles, CA USA. [Ebrahimi, Ramin] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [Lansky, Alexandra J.] Yale Univ, Sch Med, New Haven, CT USA. [Mehran, Roxana] Icahn Sch Med Mt Sinai, New York, NY USA. [Mehran, Roxana; Stone, Gregg W.] Cardiovasc Res Fdn, New York, NY USA. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. RP Lincoff, AM (reprint author), Cleveland Clin, Dept Cardiovasc Med F25, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM lincofa@ccf.org NR 37 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD APR PY 2014 VL 7 IS 4 BP 372 EP 379 DI 10.1016/j.jcin.2013.11.017 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF1YK UT WOS:000334509600007 PM 24630881 ER PT J AU Pickerodt, PA Francis, RC Hohne, C Neubert, F Telalbasic, S Boemke, W Swenson, ER AF Pickerodt, Philipp A. Francis, Roland C. Hoehne, Claudia Neubert, Friederike Telalbasic, Stella Boemke, Willehad Swenson, Erik R. TI Pulmonary vasodilation by acetazolamide during hypoxia: impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE hypoxic pulmonary vasoconstriction; acetazolamide; N-methyl-acetazolamide; pulmonary arterial pressure; pulmonary vascular resistance ID CARBONIC-ANHYDRASE INHIBITION; ARTERIAL SMOOTH-MUSCLE; INTRACELLULAR PH; RAT LUNGS; VASOCONSTRICTION; EDEMA; RESPONSES; PRESSURE; CHANNELS; NITRITE AB Acetazolamide (ACZ) prevents hypoxic pulmonary vasoconstriction (HPV) in isolated lungs, animals, and humans, but not by carbonic anhydrase (CA) inhibition. We studied administration routes in, and certain structural aspects of, ACZ critical to HPV inhibition. Analogs of ACZ during acute hypoxia were tested in unanesthetized dogs. Dogs breathed normoxic gas for 1 h (inspired O-2 fraction = 0.21), followed by 10% O-2 for 2 h ( hypoxia) in these protocols: 1) controls; 2) ACZ intravenously (2 mg center dot kg(-1) center dot h(-1)); 3) ACZ orally (5 mg/kg, 12 and 1 h before the experiment); 4) inhaled ACZ (750 mg); 5) methazolamide (MTZ) intravenously (3 mg center dot kg(-1) center dot h(-1)); and 6) N-methyl-acetazolamide (NMA) intravenously (10 mg center dot kg(-1) center dot h(-1)). In controls, mean pulmonary arterial pressure (MPAP) increased 7 mmHg, and pulmonary vascular resistance (PVR) 224 dyn center dot s center dot cm(-5) with hypoxia (P < 0.05). With intravenous and inhaled ACZ, MPAP and PVR did not change during hypoxia. With oral ACZ, HPV was only slightly suppressed; MPAP increased 5 mmHg and PVR by 178 dyn center dot s center dot cm(-5) during hypoxia. With MTZ and NMA, the MPAP rise (4 +/- 2 mmHg) was reduced, and PVR did not increase during hypoxia compared with normoxia (MTZ intravenous: 81 +/- 77 and 68 +/- 82 dyn center dot s center dot cm(-5) with NMA intravenous). Inhaled ACZ prevents HPV, but not without causing systemic CA inhibition. NMA, a compound lacking CA inhibiting effects by methylation at the sulfonamide moiety, and MTZ, a CA-inhibiting analog methylated at the thiadiazole ring, are only slightly less effective than ACZ in reducing HPV. C1 [Pickerodt, Philipp A.; Francis, Roland C.; Neubert, Friederike; Telalbasic, Stella; Boemke, Willehad] Charite, Campus Charite Mitte, Dept Anesthesiol & Intens Care Med, D-13353 Berlin, Germany. [Pickerodt, Philipp A.; Francis, Roland C.; Neubert, Friederike; Telalbasic, Stella; Boemke, Willehad] Charite, Campus Virchow Klinikum, Dept Anesthesiol & Intens Care Med, D-13353 Berlin, Germany. [Hoehne, Claudia] Univ Leipzig, Dept Anesthesiol & Crit Care Med, D-04109 Leipzig, Germany. [Swenson, Erik R.] Univ Washington, Dept Pulm & Crit Care Med, Seattle, WA 98195 USA. [Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Pickerodt, PA (reprint author), Charite, Campus Charite Mitte, Dept Anesthesiol & Intens Care Med, Augustenburger Pl 1, D-13353 Berlin, Germany. EM philipp.pickerodt@charite.de FU Deutsche Forschungsgemeinschaft [Ho 3295/2-1, Pi 795/2-1]; National Heart, Lung, and Blood Institute [HL-24163] FX This study was supported by a grant from the Deutsche Forschungsgemeinschaft to C. Hohne (Ho 3295/2-1), to P. Pickerodt and W. Boemke (Pi 795/2-1), and by a grant from the National Heart, Lung, and Blood Institute to E. R. Swenson (HL-24163). NR 28 TC 7 Z9 7 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 2014 VL 116 IS 7 BP 715 EP 723 DI 10.1152/japplphysiol.01235.2013 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA AE6PK UT WOS:000334115800003 PM 24481964 ER PT J AU Kwon, YM AF Kwon, Young-Min TI Cross-Sectional Imaging in Evaluation of Soft Tissue Reactions Secondary to Metal Debris SO JOURNAL OF ARTHROPLASTY LA English DT Article DE metal on metal hips; taper corrosion; pseudotumours; adverse tissue reactions; ultrasound; MARS MRI ID TOTAL HIP-ARTHROPLASTY; JOHN-CHARNLEY; EARLY FAILURE; MODULAR NECK; CORROSION; PSEUDOTUMORS; PROSTHESES; TAPER; JUNCTION; RESURFACINGS AB An integral component of systematic treatment algorithms to optimize evaluation and management of patients with MoM hip arthroplasty recommend the use of cross-sectional imaging to diagnose the presence of adverse local tissue reactions. Cross-sectional imaging studies such as ultrasound is a useful screening tool to detect the presence of a soft-tissue mass adjacent to a MoM implant. MARS MRI is a useful diagnostic test for assessing MoM hip arthroplasty and modular taper corrosion for adverse tissue reactions. Each cross-sectional imaging modality has unique utility and limitations. As metal artifact reduction technique continues to be refined, the utility of MARS MRI in evaluating patients with MoM hip arthroplasty and modular taper corrosion is likely to have an increased role in the clinical decision making process. However, over-reliance on any single investigative tool in the clinical decision-making process should be avoided. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Kwon, YM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 33 TC 10 Z9 10 U1 1 U2 2 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 APR PY 2014 VL 29 IS 4 BP 653 EP 656 DI 10.1016/j.arth.2014.02.007 PG 4 WC Orthopedics SC Orthopedics GA AE6IN UT WOS:000334094000002 PM 24655608 ER PT J AU Choi, HR Freiberg, AA Malchau, H Rubash, HE Kwon, YM AF Choi, Ho-Rim Freiberg, Andrew A. Malchau, Henrik Rubash, Harry E. Kwon, Young-Min TI The Fate of Unplanned Retention of Prosthetic Articulating Spacers for Infected Total Hip and Total Knee Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE periprosthetic joint infection; two-stage revision; prosthetic articulating spacer; retained spacer; fate ID 2-STAGE REVISION; CEMENT; SYSTEM AB Eighteen patients with periprosthetic joint infection (11 hips and 7 knees) treated by prosthetic articulating spacers retained their spacers and were followed up at an average of 43.8 months(range, 13-78 months). Fifteen patients maintained well-functioning spacers for an average of 42.7 months, of which 4 patients died with the spacers in situ at an average of 48.7 months. The mean Harris Hip Score and Knee Society knee and function scores of survivors were 92, 92, 88, respectively. Spacers were revised in 3 patients because of recurrent infection (n = 1) at 24 months and mechanical loosening (n = 2) at 74 and 50 months. Findings of this study suggest that a proportion of patients with unplanned retention of prosthetic spacers appear to function well up to 6 years without necessarily requiring further surgical intervention. (C) 2014 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Choi, HR (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 21 TC 4 Z9 4 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 APR PY 2014 VL 29 IS 4 BP 690 EP 693 DI 10.1016/j.arth.2013.07.013 PG 4 WC Orthopedics SC Orthopedics GA AE6IN UT WOS:000334094000013 PM 23932758 ER PT J AU Asefzadeh, B Rett, D Pogoda, TK Selvin, G Cavallerano, A AF Asefzadeh, Baharak Rett, Douglas Pogoda, Terri K. Selvin, Gerald Cavallerano, Anthony TI Glaucoma Medication Adherence in Veterans and Influence of Coexisting Chronic Disease SO JOURNAL OF GLAUCOMA LA English DT Article DE adherence; PTSD; glaucoma; hearing loss ID POSTTRAUMATIC-STRESS-DISORDER; MANAGED CARE POPULATION; NORMAL-TENSION GLAUCOMA; PHARMACY CLAIMS DATA; OPEN-ANGLE GLAUCOMA; FOLLOW-UP VISITS; RISK-FACTORS; INTRAOCULAR-PRESSURE; PATIENT PERSISTENCY; THERAPY AB Background: The aim of this study was to characterize veterans' adherence to glaucoma medications and follow-up eye care, and to examine the influence of coexisting chronic conditions such as posttraumatic stress disorder (PTSD)/anxiety. Patients and Methods: A retrospective review of computerized medical records was performed for 161 veterans taking topical glaucoma medications. Medication possession ratio (MPR) was calculated using pharmacy data. Mean follow-up ratio (FUR) was calculated using the number of days between visits. Results: Among the health conditions examined, the most prevalent was hearing loss (0.34), followed by arthritis (0.29), PTSD, or other anxiety disorder (0.27), and dementia or other memory disorder (0.09). The average rates of MPR and FUR were 0.69 +/- 0.20 and 0.84 +/- 0.19, respectively. Group comparisons found that patients with hearing loss had higher MPR compared with patients without hearing loss, and patients who were white had higher FUR than African American patients. When demographic and health characteristics were examined simultaneously in multiple linear regressions, hearing loss emerged as a significant predictor of MPR, and being older was significantly related to FUR. Younger age was also associated with MPR and being white (vs. African American) or having a PTSD/other anxiety disorder was related to FUR, although these findings did not reach statistical significance. Conclusions: FUR was better than MPR in a veteran population being treated for glaucoma. Hearing loss was significantly related to higher MPR, whereas being older was significantly associated with higher FUR. These characteristics should be taken into consideration in future programs to improve adherence to glaucoma care. C1 [Asefzadeh, Baharak; Rett, Douglas; Pogoda, Terri K.; Selvin, Gerald; Cavallerano, Anthony] VA Boston Hlth Care Syst, Eye Clin, Jamaica Plain, MA 02130 USA. RP Asefzadeh, B (reprint author), VA Boston Hlth Care Syst, Eye Clin, Jamaica Plain Campus,8th Floor 112, Jamaica Plain, MA 02130 USA. EM baharak.asefzadeh@va.gov NR 34 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD APR-MAY PY 2014 VL 23 IS 4 BP 240 EP 245 DI 10.1097/IJG.0000000000000044 PG 6 WC Ophthalmology SC Ophthalmology GA AE8JG UT WOS:000334245600009 PM 24522105 ER PT J AU Buijze, GA Goslings, JC Rhemrev, SJ Weening, AA Van Dijkman, B Doornberg, JN Ring, D AF Buijze, G. A. Goslings, J. C. Rhemrev, S. J. Weening, A. A. Van Dijkman, B. Doornberg, J. N. Ring, D. CA CAST Trial Collaboration TI Cast Immobilization With and Without Immobilization of the Thumb for Nondisplaced and Minimally Displaced Scaphoid Wist Fractures: A Multicenter, Randomized, Controlled Trial SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Scaphoid; waist; fracture; treatment; union ID COMPUTED-TOMOGRAPHY; WAIST FRACTURES; SCREW FIXATION; UNION; RADIOGRAPHY; MANAGEMENT AB Purpose The aim of this prospective randomized trial was to test the null hypothesis that there was no difference in the percentage of the fracture line of scaphoid waist fractures that demonstrated bridging bone on computed tomography (CT) 10 weeks after injury between patients treated in a below-elbow cast including or excluding the thumb. Methods A total of 62 patients with a CT or magnetic resonance image confirmed non-displaced or minimally displaced fracture of the scaphoid were enrolled in a prospective, multicenter, randomized trial comparing treatment in a below-elbow cast including or excluding the thumb. There were 55 waist and 7 distal fractures (owing to a miscommunication at 3 of the centers). We adhered to intention-to-treat principles. The primary outcome was the extent of union on CT performed after 10 weeks of cast treatment, expressed as a percentage of the fracture line that had bridging bone, determined by musculoskeletal radiologists blinded to treatment. Secondary study outcomes included wrist motion; grip strength; the Mayo Modified Wrist Score; the Disabilities of the Arm, Shoulder and Hand score; a visual analog scale for pain; and radiographic union at 6 months after injury. Results There was a significant difference in the average extent of union on CT at 10 weeks (85% vs 70%) favoring treatment with a cast excluding the thumb. The overall union rate was 98%. The 1 exception was a patient in the thumb immobilization group who elected operative treatment 1 week after enrollment, used crutches, and failed to heal. There were no significant differences between groups for wrist motion; grip strength; Mayo Modified Wrist Score; Disabilities of the Arm, Shoulder, and Hand score; or pain intensity. Conclusions Immobilization of the thumb appears unnecessary for CT or magnetic resonance image confirmed nondisplaced or minimally displaced fractures of the waist of the scaphoid. (Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved.) C1 Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, NL-1012 WX Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Surg, Trauma Unit, NL-1012 WX Amsterdam, Netherlands. Onze Lieu Vrouwe Gasthuis, Dept Orthoped Surg, Amsterdam, Netherlands. Med Ctr Haaglanden, Dept Gen Surg, The Hague, Netherlands. Flevozieltenhuis, Dept Gen Surg, Almere, Netherlands. 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, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. EM dring@partners.org FU Netherlands Organisation for Scientific Research [021.002.019] FX G.A.B. is appreciative of The Netherlands Organisation for Scientific Research for Supporting his scaphoid fracture research with Unrestricted Research Grant 021.002.019. NR 27 TC 8 Z9 10 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2014 VL 39 IS 4 BP 621 EP 627 DI 10.1016/j.jhsa.2013.12.039 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AE6DV UT WOS:000334081700002 PM 24582846 ER PT J AU Ardehali, A Esmailian, F Deng, M Soltesz, E Hsich, E Naka, Y Mancini, D Camacho, M Baran, D Zucker, M Leprince, P Madsen, J Tsui, S Simon, A Livi, U Guzzi, G Kobashigawa, J AF Ardehali, A. Esmailian, F. Deng, M. Soltesz, E. Hsich, E. Naka, Y. Mancini, D. Camacho, M. Baran, D. Zucker, M. Leprince, P. Madsen, J. Tsui, S. Simon, A. Livi, U. Guzzi, G. Kobashigawa, J. TI The Proceed II International Heart Transplant Trial with the Organ Care System (OCS (TM)) Technology SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Ardehali, A.] Univ Calif Los Angeles, Med Ctr, Div Cardiothorac Surg, Los Angeles, CA 90024 USA. [Esmailian, F.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Deng, M.] Univ Calif Los Angeles, Med Ctr, Heart Transplant Program, Los Angeles, CA 90024 USA. [Soltesz, E.] Cleveland Clin Fdn, Div Cardiothorac Surg, Cleveland, OH 44195 USA. [Hsich, E.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Naka, Y.] Columbia Univ, Dept Cardiac Surg, New York, NY USA. [Mancini, D.] Columbia Univ, Heart Transplant Program, New York, NY USA. [Camacho, M.] Newark Beth Israel Med Ctr, Barnabas Hlth Heart Ctr, Cardiac Transplantat & Mech Device Program, Newark, NJ USA. [Baran, D.; Zucker, M.] Newark Beth Israel Med Ctr, Barnabas Hlth Heart Ctr, Newark, NJ USA. [Leprince, P.] Grp Hosp Pitie Salpetriere, F-75634 Paris, France. [Madsen, J.] Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02114 USA. [Tsui, S.] Papworth Hosp, Div Cardiothorac Surg, Cambridge CB3 8RE, England. [Simon, A.] Harefield Hosp, Harefield UB9 6JH, Middx, England. [Livi, U.; Guzzi, G.] Santa Maria della Misericordia Univ Hosp, Cardiac Surg & Transplantat Unit, Udine, Italy. [Kobashigawa, J.] Cedars Sinai Med Ctr, Heart Transplant Program, Adv Heart Dis Sect, Los Angeles, CA 90048 USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 308 BP S118 EP S118 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700309 ER PT J AU Di Salvo, T Hemnes, A Januzzi, J Maltais, S AF Di Salvo, T. Hemnes, A. Januzzi, J. Maltais, S. TI RNAseq Identifies Novel Potential Right Ventricular Biomarkers in Human Heart Failure SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Di Salvo, T.; Hemnes, A.; Maltais, S.] Vanderbilt, Nashville, TN USA. [Januzzi, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 629 BP S232 EP S233 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700630 ER PT J AU Lowalekar, SK Cao, H Lu, X Treanor, PR Thatte, HS AF Lowalekar, S. K. Cao, H. Lu, X. Treanor, P. R. Thatte, H. S. TI Hearts Preserved in Somah at Sub-normothermia Demonstrate Rapid Functional Restoration and Are Less Likely To Develop Heart Failure Upon Transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Lowalekar, S. K.; Cao, H.; Lu, X.; Thatte, H. S.] Harvard Univ, Sch Med, Boston, MA USA. [Treanor, P. R.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 468 BP S176 EP S176 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700469 ER PT J AU Lowalekar, SK Cao, H Lu, X Treanor, PR Thatte, HS AF Lowalekar, S. K. Cao, H. Lu, X. Treanor, P. R. Thatte, H. S. TI Functional Resuscitation of Hearts Preserved in Somah at Subnormothermia: A Comparative Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Lowalekar, S. K.; Cao, H.; Lu, X.; Thatte, H. S.] Harvard Univ, Sch Med, Boston, MA USA. [Treanor, P. R.] VA Boston Healthcare Syst, Surg, Boston, MA USA. NR 0 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 314 BP S120 EP S120 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700315 ER PT J AU McElderry, T Waxman, A Gomberg-Maitland, M Burke, M Ross, E Bersohn, M Tarver, J Zwicke, D Feldman, J Chakinala, M Frantz, R Torres, F Li, P Morris, M Peterson, L Bourge, R AF McElderry, T. Waxman, A. Gomberg-Maitland, M. Burke, M. Ross, E. Bersohn, M. Tarver, J. Zwicke, D. Feldman, J. Chakinala, M. Frantz, R. Torres, F. Li, P. Morris, M. Peterson, L. Bourge, R. TI Totally Implantable IV Treprostinil Therapy in Pulmonary Arterial Hypertension: Assessment of the Implantation Procedure SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [McElderry, T.; Bourge, R.] Univ Alabama Birmingham, Birmingham, AL USA. [Waxman, A.; Ross, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gomberg-Maitland, M.; Burke, M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Bersohn, M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tarver, J.] Orlando Reg Med Ctr Orlando Hlth, Orlando, FL USA. [Zwicke, D.] Aurora Cardiovasc Serv, Milwaukee, WI USA. [Feldman, J.] Arizona Pulm Specialists Ltd, Cardiol, Phoenix, AZ USA. [Chakinala, M.] Washington Univ, Sch Med, St Louis, MO USA. [Frantz, R.] Mayo Clin, Rochester, MN USA. [Torres, F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Li, P.; Morris, M.] Medtronic, Mounds View, MN USA. [Peterson, L.] United Therapeut Corp, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 624 BP S231 EP S231 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700625 ER PT J AU Niehaus, ED Tabtabai, SR Sarswat, N Stone, JR Gilstrap, L Maurer, M Witteles, R Estep, JD Baran, D Zucker, MJ Feltrin, G Seldin, DC Semigran, MJ AF Niehaus, E. D. Tabtabai, S. R. Sarswat, N. Stone, J. R. Gilstrap, L. Maurer, M. Witteles, R. Estep, J. D. Baran, D. Zucker, M. J. Feltrin, G. Seldin, D. C. Semigran, M. J. TI Need for Renal Replacement Therapy after Cardiac Transplantation in Patients with AL Amyloidosis Is Associated with Poor Survival SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Niehaus, E. D.; Tabtabai, S. R.; Sarswat, N.; Stone, J. R.; Semigran, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilstrap, L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Maurer, M.] Columbia Univ, Med Ctr, New York, NY USA. [Witteles, R.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Estep, J. D.] Houston Methodist Hosp, Houston, TX USA. [Baran, D.; Zucker, M. J.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Feltrin, G.] Univ Padua, Padua, Italy. [Seldin, D. C.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 236 BP S91 EP S92 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700237 ER PT J AU Sarswat, N Niehaus, E Tabtabai, SR Stone, JR Gilstrap, L Mauer, M Witteles, R Estep, JD Baran, D Zucker, MJ Guiseppe, F Seldin, DC Semigran, MJ AF Sarswat, N. Niehaus, E. Tabtabai, S. R. Stone, J. R. Gilstrap, L. Mauer, M. Witteles, R. Estep, J. D. Baran, D. Zucker, M. J. Guiseppe, F. Seldin, D. C. Semigran, M. J. TI Pre-transplant Chemotherapy Does Not Affect Cardiac Transplant Survival in Light-Chain Amyloid Patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Sarswat, N.; Niehaus, E.; Tabtabai, S. R.; Stone, J. R.; Semigran, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilstrap, L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mauer, M.] Columbia Univ, Med Ctr, Nyc, NY USA. [Witteles, R.] Stanford Hosp, Stanford, CA USA. [Estep, J. D.] Houston Methodist Hosp, Houston, TX USA. [Baran, D.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Zucker, M. J.] Newark Beth Israel Med Ctr, Newark, CA USA. [Guiseppe, F.] Univ Padua, Padua, Italy. [Seldin, D. C.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 124 BP S51 EP S52 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700125 ER PT J AU Song, TH Baker, JN Melnitchouk, SI Sundt, TM Garcia, JP AF Song, T. H. Baker, J. N. Melnitchouk, S. I. Sundt, T. M. Garcia, J. P. TI Ambulatory Extracorporeal Membrane Oxygenation with Right Atrium to Pulmonary Artery Cannulation Through Hemisternotomy for Longterm Support SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Song, T. H.; Baker, J. N.; Melnitchouk, S. I.; Sundt, T. M.; Garcia, J. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 674 BP S249 EP S249 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700674 ER PT J AU Tabtabai, S Niehaus, E Sarswat, N Stone, JR Gilstrap, L Maurer, M Witteles, R Estep, JD Baran, D Zucker, MJ Feltrin, G Seldin, D Semigran, MJ AF Tabtabai, S. Niehaus, E. Sarswat, N. Stone, J. R. Gilstrap, L. Maurer, M. Witteles, R. Estep, J. D. Baran, D. Zucker, M. J. Feltrin, G. Seldin, D. Semigran, M. J. TI Reduced Survival in Lambda Predominant Cardiac AL Amyloidosis Patients Awaiting Heart Transplant SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Tabtabai, S.; Niehaus, E.; Sarswat, N.; Stone, J. R.; Semigran, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilstrap, L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Maurer, M.] Columbia Univ, Med Center, New York, NY USA. [Witteles, R.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Estep, J. D.] Houston Methodist Hosp, Houston, TX USA. [Baran, D.; Zucker, M. J.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Feltrin, G.] Univ Padua, Padua, Italy. [Seldin, D.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 125 BP S52 EP S52 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700126 ER PT J AU Van Raemdonck, D Warnecke, G Kukreja, J Smith, M Loor, G Garcia, J Hertz, M Madsen, J Haverich, A Ardehali, A AF Van Raemdonck, D. Warnecke, G. Kukreja, J. Smith, M. Loor, G. Garcia, J. Hertz, M. Madsen, J. Haverich, A. Ardehali, A. TI The EXPAND Lung International Trial to Evaluate the Safety and Effectiveness of the Portable Organ Care System (OCS (TM)) Lung for Recruiting, Preserving and Assessing Expanded Criteria Donor Lungs for Transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Van Raemdonck, D.] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Warnecke, G.; Haverich, A.] Hannover Med Sch, Hannover, Germany. [Kukreja, J.] UCSF Med Ctr, San Francisco, CA USA. [Smith, M.] St Josephs Med Ctr, Phoenix, AZ USA. [Loor, G.; Hertz, M.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Garcia, J.] Masschusetts Gen Hosp, Boston, MA USA. [Madsen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ardehali, A.] UCLA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 26 BP S17 EP S18 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700027 ER PT J AU Warnecke, G Van Raemdonck, D Massard, G Rea, F Smith, M Kukreja, J De Robertis, F Dhital, K Nagendran, J Moradiellos, J Bermudez, C Tsui, S Leseche, G Knosalla, C McCurry, K Thomas, P Loor, G Garcia, J Wang, I Avsar, M Tudorache, I Kuhn, C Wiegmann, B Sommer, W Santelmo, N Falcoz, P Olland, A Schiavon, M Marulli, G Di Gregorio, G Simon, A Hetzer, R Varela, A Madsen, J Hertz, M Haverich, A Ardehali, A AF Warnecke, G. Van Raemdonck, D. Massard, G. Rea, F. Smith, M. Kukreja, J. De Robertis, F. Dhital, K. Nagendran, J. Moradiellos, J. Bermudez, C. Tsui, S. Leseche, G. Knosalla, C. McCurry, K. Thomas, P. Loor, G. Garcia, J. Wang, I. Avsar, M. Tudorache, I. Kuehn, C. Wiegmann, B. Sommer, W. Santelmo, N. Falcoz, P. Olland, A. Schiavon, M. Marulli, G. Di Gregorio, G. Simon, A. Hetzer, R. Varela, A. Madsen, J. Hertz, M. Haverich, A. Ardehali, A. TI The INSPIRE Lung International Trial Evaluating the Impact of Portable Ex-vivo Perfusion Using the Organ Care System (OCS (TM)) Lung Technology on Routine Lung Transplant Outcomes SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 10-13, 2014 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Warnecke, G.; Avsar, M.; Tudorache, I.; Kuehn, C.; Wiegmann, B.; Sommer, W.; Haverich, A.] Hannover Med Sch, Hannover, Germany. [Van Raemdonck, D.] Univ Hosp Leuven, Louvain, Belgium. [Massard, G.; Santelmo, N.; Falcoz, P.; Olland, A.] Strasbourg Univ Hosp, Strasbourg, France. [Rea, F.; Schiavon, M.; Marulli, G.; Di Gregorio, G.] Hosp Univ Padova, Padua, Italy. [Smith, M.] St Josephs Med Ctr, Phoenix, AZ USA. [Kukreja, J.] UCSF Med Ctr, San Francisco, CA USA. [De Robertis, F.; Simon, A.] Harefield Hosp, London, England. [Dhital, K.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Nagendran, J.] Univ Alberta, Med Ctr, Edmonton, AB, Canada. [Moradiellos, J.; Varela, A.] Univ Hosp Puerta de Hierro, Madrid, Spain. [Bermudez, C.] UPMC Med Ctr, Pittsburgh, PA USA. [Tsui, S.] Papworth Hosp, Cambridge CB3 8RE, England. [Leseche, G.] Hop Xavier Bichat, Paris, France. [Knosalla, C.; Hetzer, R.] German Heart Inst, Berlin, Germany. [McCurry, K.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Thomas, P.] Hosp Univ Marseille, Marseille, France. [Loor, G.] Univ Minnesota, Minneapolis, MN USA. [Garcia, J.; Madsen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, I.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Hertz, M.] Univ Minnesota, Minneapolis, MN USA. [Ardehali, A.] UCLA Med Ctr, Los Angeles, CA USA. RI falcoz, pierre-emmanuel/N-1239-2016; Varela de Ugarte, Andres/B-4837-2017 OI Varela de Ugarte, Andres/0000-0001-8827-2454 NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2014 VL 33 IS 4 SU S MA 182 BP S72 EP S72 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AE3HD UT WOS:000333866700183 ER PT J AU Malone, JC Westen, D Levendosky, AA AF Malone, Johanna C. Westen, Drew Levendosky, Alytia A. TI Personality Constellations of Adolescents With Histories of Traumatic Parental Separations SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE personality subtypes; SWAP-II-A; Traumatic parental separation; attachment disruption; adolescent personality pathology ID EARLY MATERNAL SEPARATION; CALLOUS-UNEMOTIONAL TRAITS; ASSESSING AXIS II; BORDERLINE PERSONALITY; ATTACHMENT PATTERNS; CHILDHOOD TRAUMA; CONDUCT PROBLEMS; FAMILY-HISTORY; DISORDER; PSYCHOPATHOLOGY AB Consistent with attachment theory and a developmental psychopathology framework, a growing body of research suggests that traumatic parental separations may lead to unique pathways of personality adaptation and maladaptation. The present study both examined personality characteristics and identified personality subtypes of adolescents with histories of traumatic separations. Randomly selected psychologists and psychiatrists provided data on 236 adolescents with histories of traumatic separations using a personality pathology instrument designed for use by clinically experienced observers, the Shedler-Westen Assessment Procedure. Using a Q factor analysis, five distinct personality subtypes were identified as follows: internalizing/avoidant, psychopathic, resilient, impulsive dysregulated, and immature dysregulated. Initial support for the validity of the subtypes was established on the basis of axis I and axis II pathology, adaptive functioning, developmental history, and family history variables. The personality subtypes demonstrated substantial incremental validity in predicting adaptive functioning, above and beyond demographic variables and histories of other traumatic experiences. C1 [Malone, Johanna C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Malone, Johanna C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Westen, Drew] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Westen, Drew] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Levendosky, Alytia A.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. RP Malone, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 8th Floor,15 Parkman St, Boston, MA 02114 USA. EM Johanna.malone@gmail.com; dwesten@emory.edu FU NIMH [R01-MH62378] FX This research was funded by NIMH grant R01-MH62378 to the second author. NR 68 TC 1 Z9 1 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2014 VL 202 IS 4 BP 333 EP 345 DI 10.1097/NMD.0000000000000127 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE7NU UT WOS:000334185600013 PM 24647212 ER PT J AU Gray, ST Lin, A Curry, WT Barker, FG Busse, P Sanan, A Deschler, DG Lin, DT AF Gray, Stacey T. Lin, Alice Curry, William T. Barker, Fred G. Busse, Paul Sanan, Akshay Deschler, Daniel G. Lin, Derrick T. TI Delayed Complications after Anterior Craniofacial Resection of Malignant Skull Base Tumors SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE complications; anterior craniofacial resection; skull base; anterior skull base malignancy ID PARANASAL SINUSES; MANAGEMENT; SURGERY AB ObjectiveTo report complications occurring at least 6 months after completion of treatment for patients with anterior skull base malignancy undergoing anterior craniofacial resection (CFR). DesignRetrospective review of medical records of all patients undergoing traditional CFR for treatment of anterior skull base malignancy from 2002 through 2011. SettingMassachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center. ParticipantsThirty-one consecutive patients who had at least 18 months of follow-up for analysis were reviewed. All patients underwent traditional CFR. A total of 28 patients received postoperative proton beam radiation therapy. Eleven patients received adjuvant chemotherapy. Main Outcome MeasuresA delayed complication was any complication occurring at least 6 months after the completion of treatment. ResultsSeventeen patients had delayed complications. Orbital complications were the most common type (13 patients) followed by issues with wound healing (6 patients). The most common orbital complication was epiphora (7 patients). The most common wound complication was a nasocutaneous fistula (5 patients). ConclusionsPatients with anterior skull malignancy can develop complications months to years after the completion of treatment. Therefore, it is important to continue to follow and report complications for several years when deciding on the optimal approach for treatment of these patients. C1 [Gray, Stacey T.; Lin, Alice; Sanan, Akshay; Deschler, Daniel G.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Gray, Stacey T.; Lin, Alice; Deschler, Daniel G.; Lin, Derrick T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Curry, William T.; Barker, Fred G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Busse, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu NR 18 TC 4 Z9 4 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD APR PY 2014 VL 75 IS 2 BP 110 EP 116 DI 10.1055/s-0033-1359306 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AE0QT UT WOS:000333671900005 PM 24719797 ER PT J AU Aasted, C Yucel, M Petkov, M Borsook, D Boas, D Becerra, L AF Aasted, C. Yucel, M. Petkov, M. Borsook, D. Boas, D. Becerra, L. TI Detecting brain activity related to pain using near-infrared spectroscopy SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Aasted, C.; Yucel, M.; Petkov, M.; Borsook, D.; Boas, D.; Becerra, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2014 VL 15 IS 4 SU 1 MA 322 BP S56 EP S56 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF3YN UT WOS:000334648700222 ER PT J AU McQuaid, J Peterzell, D Rutledge, T Cone, R Nance, P Velez, D Coeshott, R Ortega, I Van Duyn, M Otilingam, P Atkinson, J AF McQuaid, J. Peterzell, D. Rutledge, T. Cone, R. Nance, P. Velez, D. Coeshott, R. Ortega, I. Van Duyn, M. Otilingam, P. Atkinson, J. TI Integrated Cognitive-Behavioral Therapy (CBT) and Mirror Visual Feedback (MVF) for phantom limb pain: a randomized clinical trial SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [McQuaid, J.; Peterzell, D.; Rutledge, T.; Cone, R.; Nance, P.; Velez, D.; Coeshott, R.; Ortega, I.; Van Duyn, M.; Otilingam, P.; Atkinson, J.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 3 U2 26 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2014 VL 15 IS 4 SU 1 MA 529 BP S108 EP S108 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF3YN UT WOS:000334648700428 ER PT J AU Morasco, B Peters, D Krebs, E Kovas, A Dobscha, S AF Morasco, B. Peters, D. Krebs, E. Kovas, A. Dobscha, S. TI Rates and predictors of urine drug testing in a national sample of VA patients SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Morasco, B.; Peters, D.; Krebs, E.; Kovas, A.; Dobscha, S.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2014 VL 15 IS 4 SU 1 MA 142 BP S11 EP S11 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF3YN UT WOS:000334648700043 ER PT J AU Stevenson, K Blair, T Collins, E Ebert, I Johnson, D Schiffman, J AF Stevenson, K. Blair, T. Collins, E. Ebert, I. Johnson, D. Schiffman, J. TI Establishment of a Controlled Substance Advisory Review consult process for patients on chronic opioid therapy SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Stevenson, K.; Blair, T.; Collins, E.; Ebert, I.; Johnson, D.; Schiffman, J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2014 VL 15 IS 4 SU 1 MA 261 BP S41 EP S41 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF3YN UT WOS:000334648700161 ER PT J AU Voscopoulos, C Galvagno, S Ladd, D Mullen, G George, E AF Voscopoulos, C. Galvagno, S. Ladd, D. Mullen, G. George, E. TI A comparison of non-intubated patients after general anesthesia and spinal anesthesia using a non-invasive respiratory volume monitor to assess respiratory status and response to opioids SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Voscopoulos, C.; Galvagno, S.; Ladd, D.; Mullen, G.; George, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2014 VL 15 IS 4 SU 1 MA 127 BP S7 EP S7 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF3YN UT WOS:000334648700028 ER PT J AU Young, BC Nadel, A Kaimal, A AF Young, B. C. Nadel, A. Kaimal, A. TI Does previa location matter? Surgical morbidity associated with location of a placenta previa SO JOURNAL OF PERINATOLOGY LA English DT Article DE blood transfusion; cesarean delivery; hysterectomy; placenta accreta; placenta previa ID PRIOR CESAREAN-SECTION; MATERNAL OBESITY; RISK-FACTORS; ACCRETA; DELIVERIES; WOMEN; HEMORRHAGE AB OBJECTIVE: To evaluate the effect of placenta previa location (anterior vs posterior) on cesarean morbidity. STUDY DESIGN: Retrospective cohort of women undergoing cesarean for placenta previa. The rate of hysterectomy and blood transfusion in the setting of anterior previa was compared with posterior previa. Planned stratified analysis based on delivery history was performed. Logistic regression was performed to control for potential confounders. RESULT: Two hundred and eighty-five women undergoing cesarean delivery for placenta previa were identified. Women undergoing primary cesareans with an anterior previa had higher rates of blood transfusion (adjusted odds ratio (aOR) 3.13 95% confidence interval (CI) (1.18 to 8.36) and hysterectomy (7.4% vs 0, P = 0.001) compared with those with a posterior previa; similarly, women undergoing repeat cesarean with anterior previa had higher rates of hysterectomy (aOR 4.60 95% CI (1.02 to 20.7). The majority of hysterectomies (93.8%) were due to abnormal placentation. CONCLUSION: An anterior placenta previa increases the risk of hysterectomy for both primary and repeat cesareans due to abnormal placentation. In the absence of accreta, blood transfusion remained a significant cause of maternal morbidity in both anterior and posterior placenta previas. This information may be useful for operative planning. C1 [Young, B. C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol,Div Maternal Fe, Boston, MA 02215 USA. [Nadel, A.; Kaimal, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol,Div Maternal Fetal, Boston, MA 02215 USA. RP Young, BC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol,Div Maternal Fe, Boston 330 Brookline Ave, Boston, MA 02215 USA. EM brettcyoung@gmail.com NR 23 TC 7 Z9 8 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 EI 1476-5543 J9 J PERINATOL JI J. Perinatol. PD APR PY 2014 VL 34 IS 4 BP 264 EP 267 DI 10.1038/jp.2013.185 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA AE2PA UT WOS:000333814200003 PM 24480901 ER PT J AU Delahanty, LM AF Delahanty, Linda M. TI The Look AHEAD Study: Implications for Clinical Practice Go Beyond the Headlines SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Editorial Material DE Lifestyle intervention; Type 2 diabetes; Weight loss; Health outcomes ID LIFE-STYLE INTERVENTION; DIABETES PREVENTION PROGRAM; OBSTRUCTIVE SLEEP-APNEA; DISEASE RISK-FACTORS; WEIGHT-LOSS; AHEAD TRIAL; OBESE-PATIENTS; INDIVIDUALS; ADULTS; HEALTH C1 [Delahanty, Linda M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM ldelahanty@partners.org FU NIDDK NIH HHS [U01 DK057131] NR 27 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD APR PY 2014 VL 114 IS 4 BP 537 EP 542 DI 10.1016/j.jand.2014.01.008 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AE6DT UT WOS:000334081500006 PM 24656503 ER PT J AU Turner, BJ Navuluri, NL Vale, S Finley, E AF Turner, Barbara J. Navuluri, Nee Lima Vale, Shruthi Finley, Erin TI A Qualitative Study of Family Healthy Lifestyle Behaviors of Mexican-American and Mexican Immigrant Fathers and Mothers SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Obesity; Children; Mexican-American; Stages of change; Parenting styles ID PHYSICAL-ACTIVITY; CHILDHOOD OBESITY; PARENTING STYLES; CHILDREN; WEIGHT; US AB This study qualitatively examines contrasting parental decision-making styles about family food choices and physical activities as well as willingness to change behaviors among Mexican-American and Mexican immigrant mothers and fathers of school-aged children. Twelve sex-specific focus groups were held in English or Spanish in 2012. Qualitative analysis informed by grounded theory examined parenting styles (ie, authoritative, authoritarian, or permissive), barriers to healthy lifestyle, and parents' stage of change about healthy lifestyles. One third of the 33 participating couples were born in Mexico. The majority of mothers and fathers described being permissive and allowing unhealthy food choices, and a minority of mothers reported more authoritarian approaches to promoting a healthier diet for their children. Mothers were more permissive than fathers about family physical activities and less engaged in these activities. Most mothers and fathers described only contemplating a healthier diet and more physical activity, while wanting their children to have a healthier lifestyle. These data suggest that clinicians need to assess and address differential parental roles when promoting a healthy lifestyle for children. Clinicians should also adopt culturally competent approaches to overcome barriers to parental engagement in diverse aspects of a healthy family lifestyle. C1 [Turner, Barbara J.] ReACH Ctr, San Antonio, TX 78229 USA. [Turner, Barbara J.] Univ Texas Hlth Sci Ctr San Antonio, Univ Texas Sch Publ Hlth, San Antonio, TX USA. [Navuluri, Nee Lima] South Cent Area Hlth Educ Ctr, San Antonio, TX USA. [Vale, Shruthi] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Finley, Erin] South Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Finley, Erin] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Turner, BJ (reprint author), ReACH Ctr, One Technol Ctr,411 John Smith Rd,Suite 1050, San Antonio, TX 78229 USA. EM turner@uthscsa.e_du OI Finley, Erin/0000-0003-4497-7721 FU National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI) FX E. Finley is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University in St Louis through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI). NR 21 TC 5 Z9 5 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD APR PY 2014 VL 114 IS 4 BP 562 EP 569 DI 10.1016/j.jand.2013.12.010 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AE6DT UT WOS:000334081500009 PM 24529984 ER PT J AU Zeng, X Nunes, MCP Dent, J Gillam, L Mathew, JP Gammie, JS Ascheim, DD Moquete, E Hung, J AF Zeng, Xin Nunes, Maria Carmo P. Dent, John Gillam, Linda Mathew, Joseph P. Gammie, James S. Ascheim, Deborah D. Moquete, Ellen Hung, Judy TI Asymmetric versus Symmetric Tethering Patterns in Ischemic Mitral Regurgitation: Geometric Differences from Three-Dimensional Transesophageal Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Ischemic mitral regurgitation; Mitral valve; Three-dimensional; Transesophageal echocardiography ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; TENTING VOLUME; VALVE; REPAIR; ANNULOPLASTY; RECOMMENDATIONS; CARDIOMYOPATHY; MECHANISMS; DYNAMICS AB Background: Ischemic mitral regurgitation (IMR) results from mitral leaflet tethering from left ventricular remodeling. Heterogeneity in local or global left ventricular remodeling can result in differential tethering patterns and affect mitral valve function and the degree of mitral regurgitation. The aims of this study were to compare mitral valve geometry in asymmetric and symmetric tethering patterns using three-dimensional transesophageal echocardiography and to examine the impact of tethering pattern on IMR severity. Methods: Sixty-two patients with moderate or greater IMR underwent three-dimensional transesophageal echocardiography for the assessment of mitral valve geometry. Symmetric and asymmetric tethering patterns were determined by mitral regurgitation jet direction and coaptation of the mitral leaflets. The ratio of posterior to anterior leaflet tethering angle was a measure of tethering pattern (the higher the ratio, the more asymmetric the pattern). Overall tethering degree was assessed by tenting volume (TV). Results: Compared with the symmetric group, the asymmetric group had less annular dilatation, greater annular heights (10.3 +/- 1.9 vs 8.5 +/- 1.9 mm, P < .01), greater ratios of posterior to anterior leaflet tethering angle (3.19 +/- 0.88 vs 1.95 +/- 0.46, P < .01), and smaller TVs with more posterior displacement of the coaptation line. Vena contracta normalized to TV was greater in the asymmetric group (0.38 +/- 0.24 vs 0.19 +/- 0.13 cm/mL, P < .01). Multivariate analysis showed that both ratio of posterior to anterior leaflet tethering angle (beta = 0.46, P < .001) and TV (beta = 0.41, P = .001) were predictors of IMR severity. Conclusions: Differences in mitral valve geometry are observed between asymmetric and symmetric tethering patterns in IMR. IMR degree is affected by both the pattern of tethering and the total degree of tethering. For the same degree of tethering, an asymmetric pattern is associated with increased MR severity. The pattern of mitral leaflet tethering may be considered in therapeutic decision making. C1 [Zeng, Xin; Nunes, Maria Carmo P.; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Dent, John] Univ Virginia, Div Cardiovasc, Charlottesville, VA USA. [Gillam, Linda] Atlantic Hlth Syst, Morristown, NJ USA. [Mathew, Joseph P.] Duke Univ, Med Ctr, Div Cardiothorac Anesthesiol, Durham, NC USA. [Gammie, James S.] Univ Maryland, Sch Med, Div Cardiac Surg, Baltimore, MD 21201 USA. [Ascheim, Deborah D.; Moquete, Ellen] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Ascheim, Deborah D.] Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 256, Boston, MA 02114 USA. EM jhung@partners.org FU National Heart, Lung, and Blood Institute (Bethesda, MD) [R01 HL092101]; National Heart, Lung, and Blood Institute; Canadian Institute of Health Research (Ottawa, ON, Canada); National Institute of Neurological Diseases and Stroke (Bethesda, MD) [U01-HL088942] FX This work was supported in part by grant R01 HL092101 to Dr Hung from the National Heart, Lung, and Blood Institute (Bethesda, MD). The Cardiothoracic Surgery Network is funded by the National Heart, Lung, and Blood Institute, the Canadian Institute of Health Research (Ottawa, ON, Canada), and grant U01-HL088942 from the National Institute of Neurological Diseases and Stroke (Bethesda, MD). NR 29 TC 10 Z9 10 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2014 VL 27 IS 4 BP 367 EP 375 DI 10.1016/j.echo.2014.01.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE9GZ UT WOS:000334315700002 PM 24513242 ER PT J AU Kuchenbecker, JA Greenwald, SH Neitz, M Neitz, J AF Kuchenbecker, James A. Greenwald, Scott H. Neitz, Maureen Neitz, Jay TI Cone-isolating ON-OFF electroretinogram for studying chromatic pathways in the retina SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID WAVELENGTH-SENSITIVE CONES; SPECTRAL SENSITIVITIES; S-CONE; MACAQUE RETINA; MIDGET PATHWAY; BIPOLAR CELLS; PHOTORECEPTORS; RESPONSES; PIGMENTS; WAVE AB The electroretinogram (ERG) provides information about outer retina function in both clinical and research applications. ERG components elicited by light increments and decrements can be separated using a long-flash paradigm in which periods of light ON and OFF are alternated. Here, the ON-OFF ERG is combined with a silent substitution technique to elicit responses from individual cone photoreceptor classes by modulating the intensities of three color lights between the two periods. The results focus on the short wavelength ( S) cone pathways since they are vulnerable to disease and because there are many unanswered questions about S-cone ON and OFF circuitry. (c) 2014 Optical Society of America C1 [Kuchenbecker, James A.; Neitz, Maureen; Neitz, Jay] Univ Washington, Dept Ophthalmol, Seattle, WA 98109 USA. [Greenwald, Scott H.] Massachusettes Eye & Ear Infirm, Boston, MA 02214 USA. RP Kuchenbecker, JA (reprint author), Univ Washington, Dept Ophthalmol, 750 Republican St, Seattle, WA 98109 USA. EM jkuchen@uw.edu FU NEI [R01EY09303, P30EY01730, T32EY007030]; Research to Prevent Blindess; Bishop Foundation; Ray H. Hill foundation FX This study was supported by NEI grants R01EY09303, P30EY01730, and T32EY007030, and by unrestricted funds from the Research to Prevent Blindess, the Bishop Foundation, and the Ray H. Hill foundation. NR 32 TC 1 Z9 1 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD APR PY 2014 VL 31 IS 4 BP A208 EP A213 DI 10.1364/JOSAA.31.00A208 PG 6 WC Optics SC Optics GA AE4EG UT WOS:000333933600029 PM 24695171 ER PT J AU Kline, JA Nordenholz, KE Courtney, DM Kabrhel, C Jones, AE Rondina, MT Diercks, DB Klinger, JR Hernandez, J AF Kline, J. A. Nordenholz, K. E. Courtney, D. M. Kabrhel, C. Jones, A. E. Rondina, M. T. Diercks, D. B. Klinger, J. R. Hernandez, J. TI Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ventricular function, right; quality of life; thrombolytic therapy; pulmonary embolism; randomized controlled trial ID QUALITY-OF-LIFE; DEEP VENOUS THROMBOSIS; NORMOTENSIVE PATIENTS; THROMBOLYTIC THERAPY; BOLUS TENECTEPLASE; FOLLOW-UP; QUESTIONNAIRE; MANAGEMENT; DYSFUNCTION; VALIDATION AB Background Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance. Objective Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE. Methods Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low-molecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36((R)) Physical Component (PCS) score Results Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P=0.017). Conclusions Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome. C1 [Kline, J. A.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Kline, J. A.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Nordenholz, K. E.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Courtney, D. M.] Northwestern Univ, Dept Emergency Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Kabrhel, C.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, A. E.] Univ Mississippi, Med Ctr, Dept Emergency Med, Jackson, MS 39216 USA. [Rondina, M. T.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Diercks, D. B.] Univ Calif Davis, Dept Emergency Med, Sacramento, CA 95817 USA. [Klinger, J. R.] Brown Univ, Alpert Med Sch, Dept Internal Med, Providence, RI 02912 USA. [Hernandez, J.] Carolinas, Dept Emergency Med, Charlotte, NC USA. RP Kline, JA (reprint author), Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Regenstrief R2200,1050 Wishard Blvd, Indianapolis, IN 46202 USA. EM jefkline@iupui.edu OI Kabrhel, Christopher/0000-0002-8699-7176 FU Agency for Healthcare Reform, National Institutes for Health; Genentech, Inc.; National Institutes of Health; Radiometer; Alere; DOD FX J. A. Kline owns stock in CP Diagnostics LLC, is a consultant for Daiichi Sankyo Inc, Donawa Lifesciences Consulting and Stago Diagnostica, and has received funding from the Agency for Healthcare Reform, National Institutes for Health. This study was funded by an investigator-initiated grant from Genentech, Inc. A. E. Jones has received funding from the National Institutes of Health. D. B. Diercks serves as a consultant for Daiichi Sankyo, Beckmann Coulter, Mylan, and has received research support from Radiometer, Alere, DOD and the National Institutes of Health. C. Kabrhel is a consultant for Stago Diagnostica. NR 35 TC 47 Z9 47 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD APR PY 2014 VL 12 IS 4 BP 459 EP 468 DI 10.1111/jth.12521 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AE7DN UT WOS:000334157000006 PM 24484241 ER PT J AU Geller, BJ Mega, JL Morrow, DA Guo, JP Hoffman, EB Gibson, CM Ruff, CT AF Geller, Bram J. Mega, Jessica L. Morrow, David A. Guo, Jianping Hoffman, Elaine B. Gibson, C. Michael Ruff, Christian T. TI Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the ATLAS ACS-TIMI 46 trial SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE IgM autoantibodies to phosphorylcholine; Acute coronary syndrome; Prognosis ID OXIDATION-SPECIFIC EPITOPES; OXIDIZED LDL; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; NATURAL ANTIBODIES; PHOSPHOLIPASE A(2); DEFICIENT MICE; ATHEROGENESIS; HYPERTENSION; PEROXIDATION AB Atherogenesis is a complex inflammatory process stemming from the accumulation and oxidation of low density lipoproteins (LDL). IgM autoantibodies against phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL), inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC auto-antibodies have been reported to be protective against atherothrombosis. We investigated the relationship of anti-PC concentrations with cardiovascular outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The primary endpoint was death, myocardial infarction (MI), stroke, or severe recurrent ischemia (SRI) requiring revascularization during 6 months. The median baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4, 67.4). There was no significant association between anti-PC levels and the primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87), all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0. 96), or any of the other individual endpoint components (MI: p-trend = 0.87, Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti-PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC concentrations and cardiovascular outcomes (< 17 U/mL: 8.1 % vs. >= 17 U/mL: 5.8 %; p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not reveal a significant association (p = 0.30). In this study of patients early after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers did not exhibit a significant relationship with cardiovascular outcomes. C1 [Geller, Bram J.; Mega, Jessica L.; Morrow, David A.; Guo, Jianping; Hoffman, Elaine B.; Ruff, Christian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA USA. RP Geller, BJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, 350 Longwood Ave,First Floor, Boston, MA 02115 USA. EM bgeller@partners.org; jmega@partners.org; dmorrow@partners.org; jguo4@partners.org; ehoffman3@partners.org; charlesmichaelgibson@gmail.com; cruff@partners.org FU Athera; Abbott; Amgen; AstraZeneca; Bayer Healthcare; Beckman Coulter; BG Medicine; BRAHMS; Bristol-Myers Squibb; Buhlmann; Critical Diagnostics; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Johnson Johnson; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical Diagnostics; Pfizer; Randox; Roche Diagnostics; Sanofi-Aventis; Siemens; Singulex; TIMI Study Group; Beckman-Coulter; Boehringher Ingelheim; Genentech; Gilead; Instrumentation Laboratory; Merck; Servier; Alere; Daiichi Sankyo; Boerhinger-Ingelheim FX In addition to study support provided by Athera, the TIMI Study Group has received research grant support from Abbott, Amgen, AstraZeneca, Bayer Healthcare, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Buhlmann, Critical Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Johnson & Johnson, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche Diagnostics, Sanofi-Aventis, Siemens, and Singulex. Dr. Geller-None to report. Dr. Mega-Is an investigator and receives salary from the TIMI Study Group. She has received honoraria from Merck and Janssen. Dr. Morrow-Is an investigator and receives salary from the TIMI Study Group. He has received remuneration for consulting from Beckman-Coulter, Boehringher Ingelheim, Critical Diagnostics, Genentech, Gilead, Instrumentation Laboratory, Johnson & Johnson, Merck, Roche Diagnostics, and Servier. Jianping Guo-None to report. Dr. Hoffman-None to report. Dr. Gibson-He has received honoraria from Johnson & Johnson. Dr. Ruff-Is an investigator and receives salary support from the TIMI Study Group. He has received remuneration for consulting from Alere, Beckman Coulter, Daiichi Sankyo, Boerhinger-Ingelheim. NR 31 TC 1 Z9 1 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2014 VL 37 IS 3 BP 310 EP 316 DI 10.1007/s11239-013-0968-y PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AE6RO UT WOS:000334122100011 PM 23860881 ER PT J AU Mitchell, KS Dick, AM DiMartino, DM Smith, BN Niles, B Koenen, KC Street, A AF Mitchell, Karen S. Dick, Alexandra M. DiMartino, Dawn M. Smith, Brian N. Niles, Barbara Koenen, Karestan C. Street, Amy TI A Pilot Study of a Randomized Controlled Trial of Yoga as an Intervention for PTSD Symptoms in Women SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY-REPLICATION; BRAIN GABA LEVELS; VALIDATION; DEPRESSION; CLINICIAN; SURVIVORS; EXPOSURE AB Posttraumatic stress disorder (PTSD) is a debilitating condition that affects approximately 10% of women in the United States. Although effective psychotherapeutic treatments for PTSD exist, clients with PTSD report additional benefits of complementary and alternative approaches such as yoga. In particular, yoga may downregulate the stress response and positively impact PTSD and comorbid depression and anxiety symptoms. We conducted a pilot study of a randomized controlled trial comparing a 12-session Kripalu-based yoga intervention with an assessment control group. Participants included 38 women with current full or subthreshold PTSD symptoms. During the intervention, yoga participants showed decreases in reexperiencing and hyperarousal symptoms. The assessment control group, however, showed decreases in reexperiencing and anxiety symptoms as well, which may be a result of the positive effect of self-monitoring on PTSD and associated symptoms. Between-groups effect sizes were small to moderate (0.08-0.31). Although more research is needed, yoga may be an effective adjunctive treatment for PTSD. Participants responded positively to the intervention, suggesting that it was tolerable for this sample. Findings underscore the need for future research investigating mechanisms by which yoga may impact mental health symptoms, gender comparisons, and the long-term effects of yoga practice. C1 [Mitchell, Karen S.; Dick, Alexandra M.; Smith, Brian N.; Niles, Barbara; Street, Amy] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Mitchell, Karen S.; Smith, Brian N.; Niles, Barbara; Street, Amy] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [DiMartino, Dawn M.] Simmons Coll, Sch Social Work, Boston, MA 02115 USA. [Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Mitchell, KS (reprint author), 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM ksmitche@bu.edu RI Koenen, Karestan/K-5402-2014 OI Koenen, Karestan/0000-0003-3293-4281 NR 35 TC 14 Z9 14 U1 5 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2014 VL 27 IS 2 BP 121 EP 128 DI 10.1002/jts.21903 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AF2II UT WOS:000334535400001 PM 24668767 ER PT J AU Shnaider, P Pukay-Martin, ND Fredman, SJ Macdonald, A Monson, CM AF Shnaider, Philippe Pukay-Martin, Nicole D. Fredman, Steffany J. Macdonald, Alexandra Monson, Candice M. TI Effects of Cognitive-Behavioral Conjoint Therapy for PTSD on Partners' Psychological Functioning SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; CAREGIVER BURDEN; INITIAL FINDINGS; COMBAT VETERANS; WAR VETERANS; DISTRESS; ADJUSTMENT; EXPOSURE; COUPLES AB A number of studies have documented that posttraumatic stress disorder (PTSD) symptoms in "one" partner are negatively associated with their intimate partner's psychological functioning. The present study investigated intimate partners' mental health outcomes (i.e., depression, anxiety, and anger) in a sample of 40 partners of individuals with PTSD within a randomized waitlist controlled trial of cognitive-behavioral conjoint therapy for PTSD (Monson & Fredman, ). There were no significant differences between active treatment and waitlist in intimate partners' psychological functioning at posttreatment. Subgroup analyses, however, of partners exhibiting clinical levels of distress at pretreatment on several measures showed reliable and clinically significant improvements in their psychological functioning at posttreatment and no evidence of worsening. Results suggest that cognitive-behavioral conjoint therapy for PTSD may have additional benefits for partners presenting with psychological distress. C1 [Shnaider, Philippe; Pukay-Martin, Nicole D.; Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Fredman, Steffany J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fredman, Steffany J.] Harvard Univ, Sch Med, Boston, MA USA. [Macdonald, Alexandra] US VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Macdonald, Alexandra] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Shnaider, P (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM philippe.shnaider@psych.ryerson.ca FU Canadian Institutes of Health Research; NIMH NIH HHS [R34 MH076813, R34MH076813] NR 33 TC 9 Z9 9 U1 7 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2014 VL 27 IS 2 BP 129 EP 136 DI 10.1002/jts.21893 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AF2II UT WOS:000334535400002 PM 24706354 ER PT J AU Kimerling, R Serpi, T Weathers, F Kilbourne, AM Kang, H Collins, JF Cypel, Y Frayne, SM Furey, J Huang, GD Reinhard, MJ Spiro, A Magruder, K AF Kimerling, Rachel Serpi, Tracey Weathers, Frank Kilbourne, Amy M. Kang, Han Collins, Joseph F. Cypel, Yasmin Frayne, Susan M. Furey, Joan Huang, Grant D. Reinhard, Matthew J. Spiro, Avron Magruder, Kathryn TI Diagnostic Accuracy of the Composite International Diagnostic Interview (CIDI 3.0) PTSD Module Among Female Vietnam-Era Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WORLD-HEALTH-ORGANIZATION; PRIMARY-CARE; COMORBIDITY; PREVALENCE; VERSION; SUBTHRESHOLD; DSM-5; SCALE; FULL AB The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) posttraumatic stress disorder (PTSD) module is widely used in epidemiological studies of PTSD, yet relatively few data attest to the instrument's diagnostic utility. The current study evaluated the diagnostic utility of the CIDI 3.0 PTSD module with U. S. women Vietnam-era veterans. The CIDI and the Clinician-Administered PTSD Scale (CAPS) were independently administered to a stratified sample of 160 women, oversampled for current PTSD. Both lifetime PTSD and recent (past year) PTSD were assessed within a 3-week interval. Forty-five percent of the sample met criteria for a CAPS diagnosis of lifetime PTSD, and 21.9% of the sample met criteria for a CAPS diagnosis of past-year PTSD. Using CAPS as the diagnostic criterion, the CIDI correctly classified 78.8% of cases for lifetime PTSD (kappa = .56) and 82.0% of past year PTSD cases (kappa = .51). Estimates of diagnostic performance for the CIDI were sensitivity of .61 and specificity of .91 for lifetime PTSD and sensitivity of .71 and specificity of .85 for past-year PTSD. Results suggest that the CIDI has good utility for identifying PTSD, though it is a somewhat conservative indicator of lifetime PTSD as compared to the CAPS. C1 [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Kimerling, Rachel; Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. [Serpi, Tracey; Collins, Joseph F.] VA Maryland Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Weathers, Frank] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Kilbourne, Amy M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Kang, Han; Cypel, Yasmin] US Dept Vet Affairs, Post Deployment Strateg Healthcare Grp, Off Publ Hlth, Washington, DC USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. [Furey, Joan] Vietnam Vet, New York, NY USA. [Huang, Grant D.] VA Off Res & Dev, Cooperat Studies Program Cent Off, Washington, DC USA. [Reinhard, Matthew J.] DC VA Med Ctr, War Related Illness & Injury Ctr, Washington, DC USA. [Reinhard, Matthew J.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Spiro, Avron] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, Avron] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Magruder, Kathryn] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Kimerling, R (reprint author), VA Palo Alto Hlth Care Syst, 795 Willow Rd,PTSD 324, Menlo Pk, CA 94025 USA. EM Rachel.Kimerling@va.gov OI Kimerling, Rachel/0000-0003-0996-4212 NR 32 TC 4 Z9 4 U1 5 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2014 VL 27 IS 2 BP 160 EP 167 DI 10.1002/jts.21905 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AF2II UT WOS:000334535400006 PM 24740869 ER PT J AU Wisco, BE Marx, BP Holowka, DW Vasterling, JJ Han, SC Chen, MS Gradus, JL Nock, MK Rosen, RC Keane, TM AF Wisco, Blair E. Marx, Brian P. Holowka, Darren W. Vasterling, Jennifer J. Han, Sohyun C. Chen, May S. Gradus, Jaimie L. Nock, Matthew K. Rosen, Raymond C. Keane, Terence M. TI Traumatic Brain Injury, PTSD, and Current Suicidal Ideation Among Iraq and Afghanistan U.S. Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID MILITARY PERSONNEL; RISK; DEPLOYMENT; INTERVIEW; PROJECT; HISTORY AB Suicide is a prevalent problem among veterans deployed to Iraq and Afghanistan. Traumatic brain injury (TBI) and psychiatric conditions, such as posttraumatic stress disorder (PTSD), are potentially important risk factors for suicide in this population, but the literature is limited by a dearth of research on female veterans and imprecise assessment of TBI and suicidal behavior. This study examined 824 male and 825 female U.S. veterans who were enrolled in the baseline assessment of the Veterans After-Discharge Longitudinal Registry (Project VALOR), an observational registry of veterans with and without PTSD who deployed in support of the wars in Iraq and Afghanistan and were enrolled in the Veterans Affairs healthcare system. Results indicated that current depressive symptoms, PTSD, and history of prior TBI were all significantly associated with current suicidal ideation (Cohen's d = 0.91, Cramers' Vs = .19 and .08, respectively). After adding a number of variables to the model, including psychiatric comorbidity, TBI history was associated with increased risk of current suicidal ideation among male veterans only (RR = 1.55). TBI is an important variable to consider in future research on suicide among veterans of the wars in Iraq and Afghanistan, particularly among male veterans. C1 [Wisco, Blair E.; Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Han, Sohyun C.; Chen, May S.; Gradus, Jaimie L.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wisco, Blair E.; Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Gradus, Jaimie L.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Rosen, Raymond C.] New England Res Inst, Watertown, MA 02172 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave,116B-4, Boston, MA 02130 USA. EM brian.marx@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU NIMH NIH HHS [T32MH019836] NR 14 TC 19 Z9 19 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2014 VL 27 IS 2 BP 244 EP 248 DI 10.1002/jts.21900 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AF2II UT WOS:000334535400017 PM 24639101 ER PT J AU Murphy, TP Cooper, CJ Cutlip, DE Matsumoto, A Jamerson, K Rundback, J Rosenfield, KA Henrich, W Shapiro, J Massaro, J Yen, CH Burtch, H Thum, C Reid, D Dworkin, L AF Murphy, Timothy P. Cooper, Christopher J. Cutlip, Donald E. Matsumoto, Alan Jamerson, Kenneth Rundback, John Rosenfield, Kenneth A. Henrich, William Shapiro, Joseph Massaro, Joseph Yen, Chen-Hsing Burtch, Holly Thum, Claudia Reid, Diane Dworkin, Lance TI Roll-in Experience from the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) Study SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ARTERY STENOSIS; RANDOMIZED-TRIAL; MEDICAL THERAPY; BLOOD-PRESSURE; ANGIOPLASTY; REVASCULARIZATION; HYPERTENSION; PREVENTION AB Purpose: To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study. Materials and Methods: The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y +/- 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months. Results: Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly More endpoints reported by site in subjects with bilateral renal artery stenosis (P = .01) and prior history of stroke (P = .03). Conclusions: In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly. C1 [Murphy, Timothy P.] Rhode Isl Hosp, Vasc Dis Res Ctr, Providence, RI 02903 USA. [Dworkin, Lance] Rhode Isl Hosp, Div Nephrol, Providence, RI 02903 USA. [Cooper, Christopher J.; Burtch, Holly] Univ Toledo, Div Cardiol, Toledo, OH 43606 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. [Cutlip, Donald E.; Massaro, Joseph; Yen, Chen-Hsing; Thum, Claudia] Harvard Clin Res Inst, Boston, MA USA. [Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Massaro, Joseph] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Matsumoto, Alan] Univ Virginia, Dept Radiol, Charlottesville, VA USA. [Jamerson, Kenneth] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Rundback, John] Holy Name Med Ctr, Intervent Inst, Teaneck, NJ USA. [Henrich, William] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shapiro, Joseph] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA. [Reid, Diane] NHLBI, NIH, Bethesda, MD 20892 USA. RP Murphy, TP (reprint author), Rhode Isl Hosp, Vasc Dis Res Ctr, Gerry 337,593 Eddy St, Providence, RI 02903 USA. EM tmurphy@lifespan.org FU National Heart, Lung and Blood Institute of the National Institutes of Health [U01HL071556, U01HL072734, U01HL072735, U01HL072736, U01HL072737]; Cordis/JohnsonJohnson; Pfizer, Inc.; Abbott Vascular; Otsuka America; AstraZeneca; Pfizer; Medtronic; Cook, Inc. FX Research reported in this article was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under Award Numbers U01HL071556, U01HL072734, U01HL072735, U01HL072736, and U01HL072737. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drug for this study was provided by AstraZeneca (Wilmington, Delaware), device support was provided by Cordis/Johnson&Johnson (Bridgewater, New Jersey), and supplemental financial support was granted by both Cordis/Johnson&Johnson and Pfizer, Inc.; T.P.M. receives research support from Abbott Vascular, Cordis/Johnson&Johnson, and Otsuka America. C.J.C. receives research support from Cordis/Johnson&Johnson, AstraZeneca, and Pfizer. D.E.C. is a consultant for St. Jude Medical. A.M. receives research, support from Medtronic and Cook, Inc., and is on the scientific advisory board for Boston Scientific. K.A.R. is on the scientific advisory board for Abbott Vascular and Complete Conference Management, receives honoraria from Covidien and royalty payments from Cordis/Johnson&Johnson, and is on the board of VIVA Physicians. None of the other authors have identified a conflict of interest. NR 12 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2014 VL 25 IS 4 BP 511 EP 520 DI 10.1016/j.jvir.2013.09.018 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AE3HR UT WOS:000333868100002 PM 24325931 ER PT J AU Butros, SR Walker, G Salazar, GM Kalva, SP Oklu, R Wicky, S Ganguli, S AF Butros, Selim R. Walker, Gregory Salazar, Gloria M. Kalva, Sanjeeva P. Oklu, Rahmi Wicky, Stephan Ganguli, Suvranu TI Direct Translumbar Inferior Vena Cava Ports for Long-Term Central Venous Access in Patients with Cancer SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMBAR; COMPLICATIONS; PLACEMENT; IMPLANTATION; CATHETERS; HEMODIALYSIS; CANNULATION; LYMPHEDEMA; INFECTION; SYSTEMS AB Purpose: To evaluate the indications, complications, and long-term results of translumbar port placements to the inferior vena cava for long-term central venous access in a single tertiary center. Materials and Methods: This retrospective study included all patients with cancer who underwent translumbar port placement from January 2000 to July 2012; 31 patients (all women) with an average age of 53.1 years +/- 11.1 (range, 30-77 y) were included in the study. Of these patients, 26 (81%) had breast cancer, 3 had lung cancer, 1 had ovarian cancer, and 1 had rectal cancer. Indications included Central venous occlusion in 9 patients (29%) and bilateral mastectomy and lymph node dissection in 22 patients (71%). Results: All procedures were technically successful. The overall 30-day complication rate was 9.7% (n = 3). Average catheter use was 14.1 months +/- 21 (range, 0.75-108 mo). Thirteen (41.9%) ports were removed because they were no,longer needed; 4 (12.9%) ports required removal for port Malfunction; 12 (38.7%) patients died with their ports still in place; 2 (6.5%) pints remain in use. Three (9.7%) ports requited delayed secondary intervention to remain. functional. One patient had a systemic infection attributed to the port; resulting in an overall infection rate of 0.08 per 1,000 catheter days. Conclusions: Translumbar inferior Arena cava port placement is a technically feasible and safe alternative method for long-term central venous access. C1 [Butros, Selim R.; Walker, Gregory; Salazar, Gloria M.; Kalva, Sanjeeva P.; Oklu, Rahmi; Wicky, Stephan; Ganguli, Suvranu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Sect Intervent Radiol, Boston, MA 02114 USA. RP Ganguli, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Sect Intervent Radiol, 55 Fruit St,GRB 290, Boston, MA 02114 USA. EM sganguli@partners.org NR 29 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2014 VL 25 IS 4 BP 556 EP 560 DI 10.1016/j.jvir.2013.12.016 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AE3HR UT WOS:000333868100007 PM 24507994 ER PT J AU Oklu, R Stone, JR Albadawi, H Watkins, MT AF Oklu, Rahmi Stone, James R. Albadawi, Hassan Watkins, Michael T. TI Extracellular Traps in Lipid-Rich Lesions of Carotid Atherosclerotic Plaques: Implications for Lipoprotein Retention and Lesion Progression SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ATHEROGENIC LIPOPROTEINS; DNA; MATRIX AB Purpose: To investigate the presence and location of extracellular traps (El's) in atherosclerotic plaques and to determine whether they are spatially associated with inflammatory cells and the lipid core. Materials and Methods: Human carotid Atherosclerotic plaques were collected from seven patients after surgical endarterectomy. Sequential tissue sections were stained with hematoxylin-eosin or subjected to immunohistochemistry to detect ETs, neutrophils and macrophages or apolipoprotein B (ApoB). To demonstrate the specificity of the antibody used to detect ETs, the adjacent tissue section was pretreated with deoxyribonuclease-1 (DNase-1) before immunostaining for ETs. Results: All seven carotid plaques demonstrated advanced atherosclerotic lesions. Extensive ET and ApoB immunostaining was detected predominantly within the acellular lipid core. Along the edges of the lipid core, confocal microscopy revealed areas suggestive of active release of ETs from MPO-positive cells. Pretreatment of tissue sections with DNase-1 abolished ET signal in the extracellular matrix, but not the signal within the cells along the margins of the core. Conclusions: The localization of ETs to the lipid core suggests a possible binding site for lipoproteins, which may further promote lesion progression and inflammation. C1 [Oklu, Rahmi] Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Albadawi, Hassan; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg, Boston, MA 02114 USA. [Oklu, Rahmi; Stone, James R.; Albadawi, Hassan; Watkins, Michael T.] Harvard Univ, Sch Med, Boston, MA USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, 290 Gray Bigelow,55 Fruit St, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu OI Albadawi, Hassan/0000-0001-5913-8571 NR 21 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2014 VL 25 IS 4 BP 631 EP 634 DI 10.1016/j.jvir.2013.12.567 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AE3HR UT WOS:000333868100018 PM 24581730 ER PT J AU Duncan, LM AF Duncan, Lyn McDivitt TI Atypical Spitz tumours and sentinel lymph nodes SO LANCET ONCOLOGY LA English DT Editorial Material ID MELANOCYTIC TUMORS; MELANOMA; OUTCOMES; BIOPSY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv,Dermatopathol Unit, Boston, MA 02115 USA. RP Duncan, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv,Dermatopathol Unit, Boston, MA 02115 USA. EM duncan@helix.mgh.harvard.edu NR 11 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2014 VL 15 IS 4 BP 377 EP 378 PG 3 WC Oncology SC Oncology GA AE9CN UT WOS:000334301900033 PM 24694629 ER PT J AU Goss, PE Hershman, DL Cheung, AM Ingle, JN Khosla, S Stearns, V Chalchal, H Rowland, K Muss, HB Linden, HM Scher, J Pritchard, KI Elliott, CR Badovinac-Crnjevic, T St Louis, J Chapman, JAW Shepherd, LE AF Goss, Paul E. Hershman, Dawn L. Cheung, Angela M. Ingle, James N. Khosla, Sundeep Stearns, Vered Chalchal, Haji Rowland, Kendrith Muss, Hyman B. Linden, Hannah M. Scher, Judite Pritchard, Kathleen I. Elliott, Catherine R. Badovinac-Crnjevic, Tanja St Louis, Jessica Chapman, Judith-Anne W. Shepherd, Lois E. TI Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): a companion analysis of a randomised controlled trial SO LANCET ONCOLOGY LA English DT Article ID HEALTHY POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; INTERGROUP EXEMESTANE; VERTEBRAL FRACTURES; TAMOXIFEN; PREVENTION; LETROZOLE; RISK; AROMATIZATION; METAANALYSIS AB Background Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental eff ect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods In MA. 27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA. 27B recruited two groups of women from MA. 27: those with BMD T-scores of -2.0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2 . 0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2 . 0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2 . 0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2 . 0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2 . 0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0 . 92%, 95% CI -2 . 35 to 0 . 50 vs -2 . 39%, 95% CI -3.77 to -1 . 01; p= 0.08). Respective mean loss in the hip was -1 . 93% (95% CI -2 . 93 to -0 . 93) versus -2 . 71% (95% CI -4.32 to -1.11; p= 0.10). Likewise for those who started with T-scores of less than -2 . 0, mean change of spine bone mineral density at 2 years did not diff er signifi cantly between the exemestane and anastrozole treatment groups (2 . 11%, 95% CI -0 . 84 to 5.06 vs 3.72%, 95% CI 1 . 54 to 5 . 89; p= 0 . 26), nor did hip bone mineral density (2 . 09%, 95% CI -1 . 45 to 5 . 63 vs 0 . 0%, 95% CI -3 . 67 to 3 . 66; p= 0 . 28). Patients with baseline T-score of -2 3 0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had fi ve fragility fractures and one other fracture. Interpretation Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2.0. C1 [Goss, Paul E.; Badovinac-Crnjevic, Tanja; St Louis, Jessica] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY USA. [Cheung, Angela M.; Scher, Judite] Univ Toronto, Toronto, ON, Canada. [Ingle, James N.; Khosla, Sundeep] Mayo Clin, Rochester, MN USA. [Stearns, Vered] Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. [Chalchal, Haji] Allan Blair Canc Ctr, Regina, SK, Canada. [Rowland, Kendrith] Carle CCOP, Urbana, IL USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comp Canc Ctr, Chapel Hill, NC USA. [Linden, Hannah M.] Univ Washington, Seattle, WA 98195 USA. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Elliott, Catherine R.; Chapman, Judith-Anne W.; Shepherd, Lois E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. RP Goss, PE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org RI Pritchard, Kathleen/I-2184-2014; OI Pritchard, Kathleen/0000-0003-0758-9666; Khosla, Sundeep/0000-0002-2936-4372 FU Canadian Cancer Society Research Institute; Pfizer; Canadian Institutes of Health Research FX Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research. NR 33 TC 14 Z9 15 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2014 VL 15 IS 4 BP 474 EP 482 DI 10.1016/S1470-2045(14)70035-X PG 9 WC Oncology SC Oncology GA AE9CN UT WOS:000334301900045 PM 24636210 ER PT J AU Chen, RC Hamstra, DA Sandler, HM Zietman, AL AF Chen, Ronald C. Hamstra, Daniel A. Sandler, Howard M. Zietman, Anthony L. TI Complications of prostate cancer treatment SO LANCET ONCOLOGY LA English DT Letter ID RADIOTHERAPY; GUIDELINE C1 [Chen, Ronald C.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Hamstra, Daniel A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chen, RC (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA. EM ronald_chen@med.unc.edu NR 6 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2014 VL 15 IS 4 BP E150 EP E150 PG 1 WC Oncology SC Oncology GA AE9CN UT WOS:000334301900004 PM 24694635 ER PT J AU Li, H Wawrose, JS Gooding, WE Garraway, LA Lui, VWY Peyser, ND Grandis, JR AF Li, Hua Wawrose, John S. Gooding, William E. Garraway, Levi A. Lui, Vivian Wai Yan Peyser, Noah D. Grandis, Jennifer R. TI Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection SO MOLECULAR CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; CANCER-CELLS; PI3K PATHWAY; DRUG-SENSITIVITY; BREAST-CANCER; EXPRESSION; TELOMERASE; RESISTANCE; MUTATIONS; INVASION AB Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The increasing amount of genomic information on human tumors and cell lines provides more biologic data to design preclinical studies. We and others previously reported whole-exome sequencing data of 106 HNSCC primary tumors. In 2012, high-throughput genomic data and pharmacologic profiling of anticancer drugs of hundreds of cancer cell lines were reported. Here, we compared the genomic data of 39 HNSCC cell lines with the genomic findings in 106 HNSCC tumors. Amplification of eight genes (PIK3CA, EGFR, CCND2, KDM5A, ERBB2, PMS1, FGFR1, and WHSCIL1) and deletion of five genes (CDKN2A, SMAD4, NOTCH2, NRAS, and TRIM33) were found in both HNSCC cell lines and tumors. Seventeen genes were only mutated in HNSCC cell lines (>10%), suggesting that these mutations may arise through immortalization in tissue culture. Conversely, 11 genes were only mutated in >10% of human HNSCC tumors. Several mutant genes in the EGF receptor (EGFR) pathway are shared both in cell lines and in tumors. Pharmacologic profiling of eight anticancer agents in six HNSCC cell lines suggested that PIK3CA mutation may serve as a predictive biomarker for the drugs targeting the EGFR/PI3K pathway. These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research. Implications: These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research. (C) 2014 AACR. C1 [Li, Hua; Wawrose, John S.; Lui, Vivian Wai Yan; Peyser, Noah D.; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. [Gooding, William E.] Univ Pittsburgh, Sch Med, Dept Biostat, Pittsburgh, PA 15213 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Ctr Canc Genome Discovery, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu RI LI, HUA/I-9569-2014; Lui, Vivian/I-5458-2016 FU grants NIH [P50CA097190, R01CA77308, R01CA098372]; American Cancer Society FX This study was funded by grants NIH P50CA097190, R01CA77308, and R01CA098372 and the American Cancer Society (to J.R. Grandis). NR 37 TC 24 Z9 24 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2014 VL 12 IS 4 BP 571 EP 582 DI 10.1158/1541-7786.MCR-13-0396 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AF3AN UT WOS:000334583900010 PM 24425785 ER PT J AU Thurber, GM Reiner, T Yang, KS Kohler, RH Weissleder, R AF Thurber, Greg M. Reiner, Thomas Yang, Katherine S. Kohler, Rainer H. Weissleder, Ralph TI Effect of Small-Molecule Modification on Single-Cell Pharmacokinetics of PARP Inhibitors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IN-VIVO; SOLID TUMORS; PENETRATION; PERMEABILITY; TRANSPORT; KINASE; CANCER; HETEROGENEITY; METASTASIS; RESISTANCE AB The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging, given the complex tumor microenvironment including intra- and intertumor heterogeneity. The difficulty in studying this distribution is even more significant for small-molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, wefollowed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small-molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model. Mol Cancer Ther; 13(4); 986-95. (C)2014 AACR. C1 [Thurber, Greg M.; Reiner, Thomas; Yang, Katherine S.; Kohler, Rainer H.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480; Thurber, Greg/0000-0001-7570-2080 FU NIH [P50 CA086355, R01 EB010011, K01 DK093766] FX This work was supported by NIH Grants P50 CA086355 (to R. Weissleder), R01 EB010011 (to R. Weissleder), and K01 DK093766 (to G. M. Thurber). NR 64 TC 8 Z9 8 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2014 VL 13 IS 4 BP 986 EP 995 DI 10.1158/1535-7163.MCT-13-0801 PG 10 WC Oncology SC Oncology GA AE9QE UT WOS:000334342300020 PM 24552776 ER PT J AU Kuruppu, S Chou, SHY Feske, SK Suh, S Hanchapola, I Lo, EH Ning, MM Smith, AI AF Kuruppu, Sanjaya Chou, Sherry H. -Y. Feske, Steven K. Suh, Sarah Hanchapola, Iresha Lo, Eng H. Ning, MingMing Smith, A. Ian TI Soluble and Catalytically Active Endothelin Converting Enzyme-1 is Present in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PROTEIN-KINASE-C; CELLS AB Endothelin converting Enzyme-1 (ECE-1) is essential for the production of Endothelin-1 (ET-1), which is associated with vasospasm following subarachnoid hemorrhage (SAH). We have previously demonstrated the presence of a catalytically active soluble form of ECE-1 in the media of endothelial cells. We aimed to determine if this form of ECE-1 exists in vivo, in cerebrospinal fluid (CSF) of SAH patients. We examined CSF taken from SAH subjects for the presence of soluble ECE-1 using a bradykinin based quenched fluorescent substrate assay. We obtained further confirmation by characterizing the CSF mediated cleavage products of BigET-1 and BigET(18-34) (6 mu g/ml) using mass spectrometry. The specificity of cleavage was confirmed using the ECE-1 inhibitor CGS35066 5nmol/L. SAH CSF samples had mean ECE-1 activity of 0.127 +/- 0.037 mu mols of substrate cleaved/mu l of CSF/24 h. The C-terminal peptides generated upon the cleavage of BigET-1 and BigET(18-34) were detected 48 h after incubation of these substrates with CSF. Cleavage of these substrates was inhibited by CGS35066. Results of Western blots also produced strong evidence for the presence of truncated soluble ECE-1 in CSF. These results strongly suggest the presence of a truncated but catalytically active form of ECE-1 in the CSF of SAH subjects. Further studies are necessary to determine the biological significance of soluble ECE-1 in CSF of SAH subjects, including an association with vasospasm after SAH. C1 [Kuruppu, Sanjaya; Hanchapola, Iresha; Smith, A. Ian] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. [Chou, Sherry H. -Y.; Feske, Steven K.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Suh, Sarah] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, Boston, MA 02114 USA. [Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Kuruppu, S (reprint author), Monash Univ, Dept Biochem & Mol Biol, Bldg 77,Wellington Rd, Clayton, Vic 3800, Australia. EM Sanjaya.Kuruppu@monash.edu RI Chou, Sherry/G-5779-2015; Kuruppu, Sanjaya/I-2258-2014 OI Kuruppu, Sanjaya/0000-0003-1674-3645 FU NINDS NIH HHS [K23 NS073806, P01 NS055104] NR 10 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2014 VL 13 IS 4 BP 1091 EP 1094 DI 10.1074/mcp.M113.027359 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AE4BC UT WOS:000333921700012 PM 23816989 ER PT J AU Burgess, MW Keshishian, H Mani, DR Gillette, MA Carr, SA AF Burgess, Michael W. Keshishian, Hasmik Mani, D. R. Gillette, Michael A. Carr, Steven A. TI Simplified and Efficient Quantification of Low-abundance Proteins at Very High Multiplex via Targeted Mass Spectrometry* SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PEPTIDE IMMUNOAFFINITY ENRICHMENT; LIQUID-CHROMATOGRAPHY; KINETIC PERFORMANCE; PEAK-CAPACITY; PLASMA; BIOMARKERS; VERIFICATION; SEPARATIONS; PIPELINE; ASSAYS AB Liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS) of plasma that has been depleted of abundant proteins and fractionated at the peptide level into six to eight fractions is a proven method for quantifying proteins present at low nanogram-per-milliliter levels. A drawback of fraction-MRM is the increased analysis time due to the generation of multiple fractions per biological sample. We now report that the use of heated, long, fused silica columns (> 30 cm) packed with 1.9 mu m of packing material can reduce or eliminate the need for fractionation prior to LC-MRM-MS without a significant loss of sensitivity or precision relative to fraction-MRM. We empirically determined the optimal column length, temperature, gradient duration, and sample load for such assays and used these conditions to study detection sensitivity and assay precision. In addition to increased peak capacity, longer columns packed with smaller beads tolerated a 4- to 6-fold increase in analyte load without a loss of robustness or reproducibility. The longer columns also provided a 4-fold improvement in median limit-of-quantitation values with increased assay precision relative to the standard 12 cm columns packed with 3 mu m material. Overall, the optimized chromatography provided an approximately 3-fold increase in analysis throughput with excellent robustness and less than a 2-fold reduction in quantitative sensitivity relative to fraction-MRM. The value of the system for increased multiplexing was demonstrated by the ability to configure an 800-plex MRM-MS assay, run in a single analysis, comprising 2400 transitions with retention time scheduling to monitor 400 unlabeled and heavy labeled peptide pairs. C1 [Burgess, Michael W.; Keshishian, Hasmik; Mani, D. R.; Gillette, Michael A.; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Gillette, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM hasmik@broadinstitute.org; scarr@broadinstitute.org FU National Institutes of Health from NCI Clinical Proteomics Tumor Analysis Consortium Initiative [U24CA160034]; NHLBI [HHSN268201000033C, R01HL096738] FX This work was supported in part by grants from National Institutes of Health: Grant U24CA160034 from NCI Clinical Proteomics Tumor Analysis Consortium Initiative (to S. A. C.) and Grants HHSN268201000033C and R01HL096738 from NHLBI (to S.A.C.). NR 23 TC 36 Z9 38 U1 0 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2014 VL 13 IS 4 BP 1137 EP 1149 DI 10.1074/mcp.M113.034660 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AE4BC UT WOS:000333921700017 PM 24522978 ER PT J AU Loeken, MR AF Loeken, Mary R. TI Intersection of complex genetic traits affecting maternal metabolism, fetal metabolism, and neural tube defect risk: Looking for needles in multiple haystacks SO MOLECULAR GENETICS AND METABOLISM LA English DT Editorial Material DE Neural tube defect; Fuel metabolism; Diabetes; Insulin resistance; Glucose transport ID GENOME-WIDE ASSOCIATION; PREGNANCY OUTCOME HAPO; DIABETIC EMBRYOPATHY; BIRTH-DEFECTS; SPINA-BIFIDA; GLUCOSE; HYPERGLYCEMIA; TRANSPORTER; OBESITY; MALFORMATIONS C1 Joslin Diabet Ctr, Sect Islet & Regenerat Cell Biol, Boston, MA 02215 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Islet & Regenerat Cell Biol, One Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NIDDK NIH HHS [R01 DK058300, R01 DK052865, R01DK52865, R01DK58300] NR 37 TC 0 Z9 0 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2014 VL 111 IS 4 BP 415 EP 417 DI 10.1016/j.ymgme.2014.01.010 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AF2SX UT WOS:000334563400001 PM 24503137 ER PT J AU Vakoc, CR Garcia-Manero, G Look, AT AF Vakoc, Christopher R. Garcia-Manero, Guillermo Look, A. Thomas TI Cancer therapy resistance: chasing epigenetics SO NATURE MEDICINE LA English DT Editorial Material C1 [Vakoc, Christopher R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Look, A. Thomas] Harvard Univ, Childrens Hosp Boston, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Vakoc, CR (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD APR PY 2014 VL 20 IS 4 BP 340 EP 341 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AE9WF UT WOS:000334361500012 ER PT J AU Polyak, K AF Polyak, Kornelia TI A case for Darwinian tumor evolution SO NATURE MEDICINE LA English DT Editorial Material ID METASTATIC BREAST-CANCER; ENDOCRINE RESISTANCE; MUTATIONS C1 [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu NR 15 TC 21 Z9 21 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD APR PY 2014 VL 20 IS 4 BP 344 EP 346 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AE9WF UT WOS:000334361500014 PM 24710378 ER PT J AU Greer, DM Rosenthal, ES Wu, O AF Greer, David M. Rosenthal, Eric S. Wu, Ona TI Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era SO NATURE REVIEWS NEUROLOGY LA English DT Review ID NEURON-SPECIFIC ENOLASE; CARDIAC-ARREST PATIENTS; SOMATOSENSORY-EVOKED-POTENTIALS; RESUSCITATION COUNCIL GUIDELINES; DIFFUSION-WEIGHTED MRI; CARDIOPULMONARY-RESUSCITATION; PROGNOSTIC VALUE; MILD HYPOTHERMIA; BISPECTRAL INDEX; OUTCOME PREDICTION AB Neurological prognostication after cardiac arrest has always been challenging, and has become even more so since the advent of therapeutic hypothermia (TH) in the early 2000s. Studies in this field are prone to substantial biases-most importantly, the self-fulfilling prophecy of early withdrawal of life-sustaining therapies-and physicians must be aware of these limitations when evaluating individual patients. TH mandates sedation and prolongs drug metabolism, and delayed neuronal recovery is possible after cardiac arrest with or without hypothermia treatment; thus, the clinician must allow an adequate observation period to assess for delayed recovery. Exciting advances have been made in clinical evaluation, electrophysiology, chemical biomarkers and neuroimaging, providing insights into the underlying pathophysiological mechanisms of injury, as well as prognosis. Some clinical features, such as pupillary reactivity, continue to provide robust information about prognosis, and EEG patterns, such as reactivity and continuity, seem promising as prognostic indicators. Evoked potential information is likely to remain a reliable prognostic tool in TH-treated patients, whereas traditional serum biomarkers, such as neuron-specific enolase, may be less reliable. Advanced neuroimaging techniques, particularly those utilizing MRI, hold great promise for the future. Clinicians should continue to use all the available tools to provide accurate prognostic advice to patients after cardiac arrest. C1 [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Rosenthal, Eric S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wu, Ona] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Greer, DM (reprint author), Yale Univ, Sch Med, Dept Neurol, LLCI 912,15 York St, New Haven, CT 06520 USA. EM david.greer@yale.edu OI Rosenthal, Eric/0000-0003-3900-356X FU Massachusetts General Hospital Institute for Heart, Vascular, and Stroke Care FX The authors would like to thank Dr Jennifer E. Fugate and Dr Alejandro Rabinstein from the Mayo Clinic for sharing their original data from their study. We would also like to thank Dr Mark R. J. R. Bouts of the MGH Athinoula A. Martinos Centre for his assistance in the literature review. We would also like to thank the Massachusetts General Hospital Institute for Heart, Vascular, and Stroke Care for funding support. NR 151 TC 18 Z9 18 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD APR PY 2014 VL 10 IS 4 BP 190 EP 203 DI 10.1038/nrneurol.2014.36 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA AE9UE UT WOS:000334355100005 PM 24614515 ER PT J AU Van Agthoven, JF Xiong, JP Alonso, JL Rui, XL Adair, BD Goodman, SL Arnaout, MA AF Van Agthoven, Johannes F. Xiong, Jian-Ping Alonso, Jose Luis Rui, Xianliang Adair, Brian D. Goodman, Simon L. Arnaout, M. Amin TI Structural basis for pure antagonism of integrin alpha(V)beta(3) by a high-affinity form of fibronectin SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; ALPHA-V-BETA-3 INTEGRIN; EXTRACELLULAR SEGMENT; THERAPEUTIC TARGETS; ENDOTHELIAL-CELLS; HUMAN-MELANOMA; BINDING-SITE; LIGAND; DOMAIN; RECEPTOR AB Integrins are important therapeutic targets. However, current RGD-based anti-integrin drugs are also partial agonists, inducing conformational changes that trigger potentially fatal immune reactions and paradoxical cell adhesion. Here we describe the first crystal structure of alpha(V)beta(3) bound to a physiologic ligand, the tenth type III RGD domain of wild-type fibronectin (wtFN10), or to a high-affinity mutant (hFN10) shown here to act as a pure antagonist. Comparison of these structures revealed a central pi-pi interaction between Trp1496 in the RGD-containing loop of hFN10 and Tyr122 of the beta(3) subunit that blocked conformational changes triggered by wtFN10 and trapped hFN10-bound alpha(V)beta(3) in an inactive conformation. Removing the Trp1496 or Tyr122 side chains or reorienting Trp1496 away from Tyr122 converted hFN10 into a partial agonist. These findings offer new insights into the mechanism of integrin activation and a basis for the design of RGD-based pure antagonists. C1 [Van Agthoven, Johannes F.; Xiong, Jian-Ping; Adair, Brian D.; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Struct Biol Program,Dept Med, Charlestown, MA USA. [Alonso, Jose Luis; Rui, Xianliang; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukocyte Biol & Inflammat Program,Dept Med, Charlestown, MA USA. [Goodman, Simon L.] Merck KGaA, Translat Innovat Platform, Global Res & Early Dev, Oncol, Darmstadt, Germany. RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Struct Biol Program,Dept Med, Charlestown, MA USA. EM aarnaout1@mgh.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health [DK088327, DK48549, DK096334, DK007540] FX We thank H. P. Erickson (Duke University) for providing the FN7-10 plasmid, T.J. Kunicki (The Scripps Research Institute) for access to AP5 antibody, M. Ginsberg (University of California, San Diego) for providing LIBS-1 and LIBS-6 mAbs, G. A. Petsko (Brandeis University) for helpful discussions and Z. Ding and D. Mueller-Pompalla for expert technical assistance. This work was supported by grants DK088327, DK48549, DK096334 and DK007540 (M.A.A.) from the National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health. NR 45 TC 11 Z9 11 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2014 VL 21 IS 4 BP 383 EP U174 DI 10.1038/nsmb.2797 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AE9SH UT WOS:000334349000017 PM 24658351 ER PT J AU Mullur, R Liu, YY Brent, GA AF Mullur, Rashmi Liu, Yan-Yun Brent, Gregory A. TI THYROID HORMONE REGULATION OF METABOLISM SO PHYSIOLOGICAL REVIEWS LA English DT Review ID BROWN ADIPOSE-TISSUE; THYROTROPIN-RELEASING-HORMONE; ACTIVATED PROTEIN-KINASE; TYPE-2 IODOTHYRONINE DEIODINASE; RECEPTOR-ALPHA GENE; CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; RESTING ENERGY-EXPENDITURE; COLD-INDUCED THERMOGENESIS; MESSENGER-RNA EXPRESSION AB Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, alpha and beta, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T-4), to the active form, triiodothyronine (T-3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. C1 [Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU Veterans Affairs Merit Review Funds; National Institute of Diabetes and Digestive and Kidney Diseases Grant [RO1 DK98576] FX This work was supported by Veterans Affairs Merit Review Funds and National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1 DK98576. NR 284 TC 142 Z9 147 U1 20 U2 100 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 EI 1522-1210 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2014 VL 94 IS 2 BP 355 EP 382 DI 10.1152/physrev.00030.2013 PG 28 WC Physiology SC Physiology GA AF2YD UT WOS:000334577500002 PM 24692351 ER PT J AU Goel, S Duda, DG Xu, L Munn, LL Boucher, Y Fukumura, D Jain, RK AF Goel, Shom Duda, Dan G. Xu, Lei Munn, Lance L. Boucher, Yves Fukumura, Dai Jain, Rakesh K. TI Normalization of the Vasculature for Treatment of Cancer and Other Diseases. (vol 91, pg 1071, 2011) SO PHYSIOLOGICAL REVIEWS LA English DT Correction C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Goel, Shom] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Camperdown, NSW, Australia. RP Goel, S (reprint author), Univ Sydney, Centenary Inst Canc Med & Cell Biol, Camperdown, NSW, Australia. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 1 TC 0 Z9 0 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 EI 1522-1210 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2014 VL 94 IS 2 BP 707 EP 707 DI 10.1152/physrev.z9j-2692-corr.2014 PG 1 WC Physiology SC Physiology GA AF2YD UT WOS:000334577500009 ER PT J AU Cattaneo, Z Renzi, C Bona, S Merabet, LB Carbon, CC Vecchi, T AF Cattaneo, Zaira Renzi, Chiara Bona, Silvia Merabet, Lotfi B. Carbon, Claus-Christian Vecchi, Tomaso TI Hemispheric asymmetry in discriminating faces differing for featural or configural (second-order relations) aspects SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Configural; Featural; Face processing; Lateralization; Divided visual field; Jane faces task ID FACIAL IDENTITY; INFORMATION; PERCEPTION; FAMILIAR AB The human capacity to discriminate among different faces relies on distinct parallel subprocesses, based either on the analysis of configural aspects or on the sequential analysis of the single elements of a face. A particular type of configural processing consists of considering whether two faces differ in terms of internal spacing among their features, referred to as second-order relations processing. Findings from electrophysiological, neuroimaging, and lesion studies suggest that, overall, configural processes rely more on the right hemisphere, whereas analysis of single features would involve more the left. However, results are not always consistent, and behavioral evidence for a right-hemisphere specialization in second-order relations processing is lacking. Here, we used divided visual field presentation to investigate the possible different contributions of the two hemispheres to face discrimination based on relational versus featural processing. Our data indicate a right-hemispheric specialization in relational processing of upright (but not inverted) faces. Furthermore, we provide evidence regarding the involvement of both the right and left hemispheres in the processing of faces differing for inner features, suggesting that both analytical and configural modes of processing are at play. C1 [Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, Milan, Italy. [Cattaneo, Zaira; Renzi, Chiara; Vecchi, Tomaso] Natl Neurol Inst C Mondino, Brain Connect Ctr, Pavia, Italy. [Bona, Silvia] Aalto Univ, Sch Sci, Brain Res Unit, OV Lounasmaa Lab, Espoo, Finland. [Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Carbon, Claus-Christian] Otto Friedrich Univ Bamberg, Dept Gen Psychol & Methodol, D-96047 Bamberg, Germany. [Vecchi, Tomaso] Univ Pavia, Dept Brain & Behav Sci, I-27100 Pavia, Italy. RP Cattaneo, Z (reprint author), Natl Neurol Inst C Mondino, Brain Connect Ctr, Pavia, Italy. EM zaira.cattaneo@unimib.it RI Carbon, Claus-Christian/A-7494-2008 OI Carbon, Claus-Christian/0000-0002-3446-9347 NR 25 TC 6 Z9 6 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 EI 1531-5320 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD APR PY 2014 VL 21 IS 2 BP 363 EP 369 DI 10.3758/s13423-013-0484-2 PG 7 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA AE7JU UT WOS:000334174700011 PM 23888423 ER PT J AU Demers, M Wagner, DD AF Demers, Melanie Wagner, Denisa D. TI NETosis: A New Factor in Tumor Progression and Cancer-Associated Thrombosis SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE cancer; NETs; biomarkers; thrombosis ID NEUTROPHIL EXTRACELLULAR TRAPS; CELL-FREE DNA; DEEP-VEIN THROMBOSIS; COLONY-STIMULATING FACTOR; IN-VIVO; MAMMALIAN TARGET; CIRCULATING DNA; GENE-EXPRESSION; INNATE IMMUNITY; BLOOD-STREAM AB Neutrophils have long been known as innate immune cells that phagocytose and kill pathogens and mount inflammatory responses protecting the host from infection. In the past decades, new aspects of neutrophils have emerged unmasking their importance not only in inflammation but also in many pathological conditions including thrombosis and cancer. The 2004 discovery that neutrophils, upon strong activation, release decondensed chromatin to form neutrophil extracellular traps (NETs), has unveiled new avenues of research. Here, we review current knowledge regarding NETs in thrombosis, with a special focus on cancer-associated thrombosis as well as their potential role in cancer growth and metastasis. We discuss the prospective use of NET-specific biomarkers, such as citrullinated histone H3 and NET inhibitors, as tools to anticipate and fight cancer-associated thrombosis. We propose that the rapid developments in the field of NETosis may provide new targets to combat the thrombotic consequences of cancer and perhaps even help to contain the disease itself. C1 [Demers, Melanie; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Demers, Melanie; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Wagner, DD (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med,Div Hematol Oncol, 3 Blackfan Circle,Third Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL102101] FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grant R01 HL102101 (to D.D.W.). We thank Lesley Cowan and Kimberly Martinod for critical review of the article. We thank Bernhard Lammle and Johanna A. Kremer Hovinga for kindly providing the human cancer/TMA plasma samples and Kimberly Martinod for the western blot analysis. We also thank Siu Ling Wong for help with confocal microscopy. NR 77 TC 26 Z9 27 U1 2 U2 18 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 EI 1098-9064 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2014 VL 40 IS 3 BP 277 EP 283 DI 10.1055/s-0034-1370765 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AD7SK UT WOS:000333466100002 PM 24590420 ER PT J AU Jo, JT Schiff, D Perry, JR AF Jo, Jasmin T. Schiff, David Perry, James R. TI Thrombosis in Brain Tumors SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE bevacizumab; tissue factor; thromboembolism; glioma; brain tumors ID MOLECULAR-WEIGHT HEPARIN; TISSUE FACTOR EXPRESSION; HIGH-GRADE GLIOMA; GROWTH-FACTOR RECEPTOR; VENOUS THROMBOEMBOLISM; MALIGNANT GLIOMA; INTRACRANIAL HEMORRHAGE; BEVACIZUMAB THERAPY; MELANOMA PATIENTS; CANCER AB Venous thromboembolism (VTE) is common in patients with brain tumors, occurring in up to 30% of patients with high-grade glioma and up to 20% of those with brain metastasis and primary central nervous system (CNS) lymphoma. The risk is correlated with higher grade malignancies and is directly associated with the production of the potent procoagulant, tissue factor (TF). Upregulation of TF influences both the coagulation pathway and oncogenic signaling mechanisms important for cancer progression. The risk of intracranial hemorrhage with the use of anticoagulants complicates the management of VTE in patients with brain tumor. We discuss the recommended anticoagulants used for initial and long-term treatment of established VTE, including unfractionated heparin, low-molecular-weight heparin (LMWH), and warfarin. Therapeutic anticoagulation, particularly LMWH followed by secondary prophylaxis, is generally safe and effective in the treatment of VTE, including patients on antiangiogenic agents. Anticoagulation also reduces the risk of VTE during the perioperative period. However, despite the high risk of VTE throughout the course of disease, present data do not support routine thromboprophylaxis in brain tumor patients. Further investigation regarding the mechanisms underlying the hypercoagulable state of patients with brain tumors and the potential role of the factors and products of thrombogenesis as biomarkers for risk stratification will be useful in identification and management of patients at risk of developing VTE. Novel oral anticoagulants that directly inhibit thrombin such as dabigatran or factor Xa, including rivaroxaban and apixaban have several potential advantages; however, due to limited data in the cancer population, the use of these newer oral anticoagulants is not currently recommended for patients with malignancy and VTE. Recent studies have explored the role of anticoagulants as anticancer agents, which may contribute to cancer treatment in the future. C1 [Jo, Jasmin T.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Div Neurooncol, Boston, MA 02114 USA. [Schiff, David] Univ Virginia, Div Neurooncol, Charlottesville, VA USA. [Perry, James R.] Univ Toronto, Sunnybrook Hlth Sci & Odette Canc Ctr, Div Neurol, Toronto, ON, Canada. RP Perry, JR (reprint author), Sunnybrook Hlth Sci Ctr, Div Neurol, A402,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM james.perry@sunnybrook.ca NR 63 TC 13 Z9 14 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 EI 1098-9064 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2014 VL 40 IS 3 BP 325 EP 331 DI 10.1055/s-0034-1370791 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AD7SK UT WOS:000333466100008 PM 24599439 ER PT J AU Amore, M Innamorati, M Di Vittorio, C Weinberg, I Turecki, G Sher, L Paris, J Girardi, P Pompili, M AF Amore, Mario Innamorati, Marco Di Vittorio, Cristina Weinberg, Igor Turecki, Gustavo Sher, Leo Paris, Joel Girardi, Paolo Pompili, Maurizio TI Suicide Attempts in Major Depressed Patients with Personality Disorder SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID NEUROPSYCHIATRIC INTERVIEW MINI; II COMPARISON SUBJECTS; IOWA RECORD-LINKAGE; DSM-IV PERSONALITY; TOWER-OF-BABEL; BORDERLINE PERSONALITY; FOLLOW-UP; MENTAL-DISORDERS; FUNCTIONAL IMPAIRMENT; RISK-FACTORS AB Suicide attempters who met criteria for borderline personality disorder (BPD) comorbid with major depressive disorder (MDD) were compared to both suicide attempters suffering from MDD alone and to attempters with comorbid MDD and other personality disorders (PD). Participants were 239 (158 patients with comorbid PD and 81 patients with MDD without comorbidity) inpatients consecutively admitted after a suicide attempt made in the last 24hours. Suicide attempters with comorbid MDD and BPD had more frequent previous suicide attempts and were more likely to have a history of aggressive behaviors and alcohol and drug use disorders compared with patients suffering from MDD without Axis II comorbidity. C1 [Amore, Mario] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Sect Psychiat, Genoa, Italy. [Innamorati, Marco; Di Vittorio, Cristina] Univ Parma, Div Psychiat, Dept Neurosci, I-43100 Parma, Italy. [Weinberg, Igor] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. [Turecki, Gustavo; Paris, Joel] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Sher, Leo] James J Peters VA Med Ctr, New York, NY USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Girardi, Paolo; Pompili, Maurizio] Univ Roma La Sapienza, St Andrea Hosp, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, I-00185 Rome, Italy. RP Pompili, M (reprint author), St Andrea Hosp, Dept Psychiat, Via Grottarossa,Rome 1035, Rome, Italy. EM maurizio.pompili@uniroma1.it OI Pompili, Maurizio/0000-0003-1886-4977 NR 68 TC 4 Z9 4 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD APR PY 2014 VL 44 IS 2 BP 155 EP 166 DI 10.1111/sltb.12059 PG 12 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE9RO UT WOS:000334346700004 PM 24138208 ER PT J AU Basu, PP Aloysius, MM Shah, NJ Brown, RS AF Basu, P. P. Aloysius, M. M. Shah, N. J. Brown, R. S., Jr. TI Review article: the endocannabinoid system in liver disease, a potential therapeutic target SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID HEPATIC ISCHEMIA/REPERFUSION INJURY; CANNABINOID CB2 RECEPTORS; ALCOHOLIC FATTY LIVER; AMP-ACTIVATED KINASE; MOLECULAR CHARACTERIZATION; ENDOGENOUS CANNABINOIDS; METABOLIC SYNDROME; NONALCOHOLIC STEATOHEPATITIS; AUTOIMMUNE HEPATITIS; STELLATE CELLS AB Background Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. Aims To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Methods Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. Results The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. Conclusions The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. C1 [Basu, P. P.] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA. [Basu, P. P.] Columbia Univ, Med Ctr, Ctr Liver Dis & Transplantat, New York, NY 10027 USA. [Aloysius, M. M.; Brown, R. S., Jr.] Kings Cty Hosp, Med Ctr, Brooklyn, NY 11203 USA. [Shah, N. J.] James J Peters VA Med Ctr, Mt Sinai Sch Med, New York, NY USA. RP Aloysius, MM (reprint author), Kings Cty Hosp, Med Ctr, 451 Clarkson Ave, Brooklyn, NY 11203 USA. EM mark.aloysius5@gmail.com NR 90 TC 9 Z9 10 U1 0 U2 14 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 APR PY 2014 VL 39 IS 8 BP 790 EP 801 DI 10.1111/apt.12673 PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AC8PO UT WOS:000332796200005 PM 24612021 ER PT J AU Bartel, AP Beaulieu, ND Phibbs, CS Stone, PW AF Bartel, Ann P. Beaulieu, Nancy D. Phibbs, Ciaran S. Stone, Patricia W. TI Human Capital and Productivity in a Team Environment: Evidence from the Healthcare Sector SO AMERICAN ECONOMIC JOURNAL-APPLIED ECONOMICS LA English DT Article ID PATIENT OUTCOMES; HOSPITALS; QUALITY; PERFORMANCE; IMPACT; WORK AB Using panel data from a large hospital system, this paper presents estimates of the productivity effects of human capital in a team production environment. Proxying nurses' general human capital by education and their unit-specific human capital by experience on the nursing unit, we find that greater amounts of both types of human capital significantly improve patient outcomes. Disruptions to team functioning attributable to the departure of experienced nurses, the absorption of new hires, and the inclusion of temporary contract nurses are associated with significant decreases in productivity beyond those attributable to changes in nurses' skill and experience. C1 [Bartel, Ann P.] Columbia Business Sch, New York, NY 10027 USA. [Bartel, Ann P.] NBER, New York, NY 10027 USA. [Beaulieu, Nancy D.; Phibbs, Ciaran S.] US Dept Vet Affairs, Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Beaulieu, Nancy D.; Phibbs, Ciaran S.] Stanford Univ, Sch Med, Hlth Econ Resource Ctr, Vet Affairs Med Ctr, Menlo Pk, CA 94025 USA. [Stone, Patricia W.] Columbia Univ, Sch Nursing, New York, NY 10032 USA. RP Bartel, AP (reprint author), Columbia Business Sch, 623 Uris Hall,3022 Broadway, New York, NY 10027 USA. EM apb2@columbia.edu; ndbeaulieu@gmail.com; cphibbs@stanford.edu; ps2024@columbia.edu NR 28 TC 12 Z9 12 U1 4 U2 19 PU AMER ECONOMIC ASSOC PI NASHVILLE PA 2014 BROADWAY, STE 305, NASHVILLE, TN 37203 USA SN 1945-7782 EI 1945-7790 J9 AM ECON J-APPL ECON JI Am. Econ. J.-Appl. Econ. PD APR PY 2014 VL 6 IS 2 BP 231 EP 259 DI 10.1257/app.6.2.231 PG 29 WC Economics SC Business & Economics GA AE4UL UT WOS:000333980000010 ER PT J AU Farris, AB Chan, S Climenhaga, J Adam, B Bellamy, COC Seron, D Colvin, RB Reeve, J Mengel, M AF Farris, A. B. Chan, S. Climenhaga, J. Adam, B. Bellamy, C. O. C. Seron, D. Colvin, R. B. Reeve, J. Mengel, M. TI Banff Fibrosis Study: Multicenter Visual Assessment and Computerized Analysis of Interstitial Fibrosis in Kidney Biopsies SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft monitoring; Banff schema; chronic graft deterioration; collagen; end points; fibrosis; graft function; image analysis; kidney; pathologist; pathology of renal transplantation ID RENAL-ALLOGRAFT BIOPSIES; IMAGE-ANALYSIS; INTERNATIONAL VARIATION; WORKING CLASSIFICATION; CYCLOSPORINE THERAPY; EXTRACELLULAR-MATRIX; PROTOCOL BIOPSIES; TUBULAR ATROPHY; GRAFT-SURVIVAL; QUANTIFICATION AB Increasing interstitial fibrosis (IF) in native and kidney transplant biopsies is associated with functional decline and serves as a clinical trial end point. A Banff 2009 Conference survey revealed a range in IF assessment practices. Observers from multiple centers were asked to assess 30 renal biopsies with a range of IF and quantitate IF using two approaches on trichrome, Periodic acid-Schiff (PAS) and computer-assisted quantification of collagen III immunohistochemistry (C-IHC) slides, as well as assessing percent of cortical tubular atrophy% (TA%) and Banff total cortical inflammation score (ti-score). C-IHC using whole slide scans was performed. C-IHC assessment showed a higher correlation with organ function (r=-0.48) than did visual assessments (r=-0.32--0.42); computerized and visual C-IHC assessment also correlated (r=0.64-0.66). Visual assessment of trichrome and C-IHC showed better correlations with organ function and C-IHC, than PAS, TA% and ti-score. However, visual assessment of IF, independent of approach, was variable among observers, and differences in correlations with organ function were not statistically significant among C-IHC image analysis and visual assessment methods. C-IHC image analysis correlated among three centers (r>0.90, p<0.0001, between all centers). Given the difficulty of visual IF assessment standardization, C-IHC image could potentially accomplish standardized IF assessment in multicenter settings. Renal fibrosis assessment on histopathology varies between observers, as demonstrated by multicenter Banff Working Group studies, which also show that computerized image analysis could provide standardized measurements that correlate with organ function. C1 [Farris, A. B.] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Chan, S.; Climenhaga, J.; Adam, B.; Reeve, J.; Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Bellamy, C. O. C.] Univ Edinburgh, Royal Edinburgh Infirm, Dept Pathol, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland. [Seron, D.] Univ Autonoma Barcelona, Dept Nephrol, Hosp Univ Vall dHebron, E-08193 Barcelona, Spain. [Colvin, R. B.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Reeve, J.] Univ Alberta, Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada. RP Farris, AB (reprint author), Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. EM abfarri@emory.edu FU Astellas Canada, Inc.; Banff Foundation for Allograft Pathology; Roche Organ Transplant Research Foundation (ROTRF) FX Many thanks to those who participated in this study, including pathologists, nephrologists and others with a special interest in fibrosis assessment (Table S2). We greatly appreciate the assistance of Patricia A. Della Pelle, Catherine D. Adams, Nicole Brousaides and A. Bernard Collins with the collagen III immunohistochemistry staining and Aperio whole slide image scanning at Massachusetts General Hospital and Mingqing Song with whole slide image scanning at Emory University. The Banff Working Group trials were supported by a research grant from Astellas Canada, Inc. This publication was supported by the Banff Foundation for Allograft Pathology. We thank the Roche Organ Transplant Research Foundation (ROTRF) for a grant to support the establishment of the Banff Foundation for Allograft Pathology. NR 57 TC 13 Z9 13 U1 0 U2 1 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 APR PY 2014 VL 14 IS 4 BP 897 EP 907 DI 10.1111/ajt.12641 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA AD5UN UT WOS:000333318800020 PM 24712330 ER PT J AU Lee, PW Hanekamp, JS Villani, V Vagefi, PA Cina, RA Kamano, C O'Malley, PE Arn, S Yamada, K Sachs, DH AF Lee, P. W. Hanekamp, J. S. Villani, V. Vagefi, P. A. Cina, R. A. Kamano, C. O'Malley, P. E. Arn, S. Yamada, K. Sachs, D. H. TI Evidence for a Gene Controlling the Induction of Transplantation Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE MGH miniature swine; MHC; thymus; tolerance; suppression; anergy; transplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; MISMATCHED RENAL-ALLOGRAFTS; MINIATURE SWINE; CLASS-I; MODEL; CYCLOSPORINE; SUPPRESSION; LYMPHOCYTES; CELLS AB Class I mismatched kidney transplantation in Massachusetts General Hospital MHC-defined miniature swine has been studied extensively as a model for induction of systemic allograft tolerance. In a large series of juvenile swine, long-term graft acceptance has been observed consistently following a 12-day course of cyclosporine. It was therefore surprising when three of five recipients in one of our studies rejected their grafts. Examination of the origins of the rejecting animals revealed that they were derived from a subline of the SLA(dd) miniature swine herd that was intentionally being inbred toward full homozygosity and had been inbred for eight generations prior to these experiments. A blinded study of additional class I mismatched renal transplants into animals from this subline confirmed the genetic basis of this rejection. We present here preliminary evidence suggesting that a likely explanation for this phenomenon is that the rejectors in this subline are homozygous for a recessive mutant allele of a gene normally involved in the induction of tolerance. Subsequent studies will be directed toward identification and characterization of the gene(s) involved, since existence of a similar genetic locus in humans might have implications for assessing an individual's likelihood of graft rejection versus tolerance induction prior to organ transplantation. The unexpected rejection of kidney transplants across a class I MHC mismatch in a subline of miniature swine with a high coefficient of inbreeding provides evidence for mutation in a gene required for the induction of tolerance. C1 [Lee, P. W.; Hanekamp, J. S.; Villani, V.; Vagefi, P. A.; Cina, R. A.; Kamano, C.; O'Malley, P. E.; Arn, S.; Yamada, K.; Sachs, D. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM david.sachs@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU [NIH5R01AI31036]; [5P01AI45897]; [5R01AI086134]; [5R01AI31046]; [CO6RR020135-01] FX The authors acknowledge project support from NIH5R01AI31036, 5P01AI45897, 5R01AI086134, 5R01AI31046 and CO6RR020135-01 for construction of the facility utilized for production and maintenance of miniature swine. The authors would like to thank Isabel M. Hanekamp, PhD, Christene Huang, PhD, Ashok Muniappan, MD, and Yongguang Yang, PhD, for their critical review of the manuscript and Rebecca Brophy for expert editorial assistance. NR 20 TC 1 Z9 1 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 APR PY 2014 VL 14 IS 4 BP 952 EP 959 DI 10.1111/ajt.12646 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA AD5UN UT WOS:000333318800026 PM 24592880 ER PT J AU Lee, J Jiang, JY Wu, WC Lesage, F Boas, DA AF Lee, Jonghwan Jiang, James Y. Wu, Weicheng Lesage, Frederic Boas, David A. TI Statistical intensity variation analysis for rapid volumetric imaging of capillary network flux SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; BLOOD-FLOW-VELOCITY; IN-VIVO; ANGIOGRAPHY; PERFUSION; MICROVASCULATURE; MICROSCOPY; SPEED AB We present a novel optical coherence tomography (OCT)-based technique for rapid volumetric imaging of red blood cell (RBC) flux in capillary networks. Previously we reported that OCT can capture individual RBC passage within a capillary, where the OCT intensity signal at a voxel fluctuates when an RBC passes the voxel. Based on this finding, we defined a metric of statistical intensity variation (SIV) and validated that the mean SIV is proportional to the RBC flux [RBC/s] through simulations and measurements. From rapidly scanned volume data, we used Hessian matrix analysis to vectorize a segment path of each capillary and estimate its flux from the mean of the SIVs gathered along the path. Repeating this process led to a 3D flux map of the capillary network. The present technique enabled us to trace the RBC flux changes over hundreds of capillaries with a temporal resolution of similar to 1 s during functional activation. (C) 2014 Optical Society of America C1 [Lee, Jonghwan; Wu, Weicheng; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Jiang, James Y.] Thorlabs Inc, Newton, NJ 07860 USA. [Lesage, Frederic] Polytech Montreal, Dept Elect Engn, Montreal, PQ, Canada. RP Lee, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM jonghwan@nmr.mgh.harvard.edu FU NIH [K99-EB014879, R01-EB000790]; AFOSR [MFEL FA9550-07-1-0101] FX This study was supported by the NIH (K99-EB014879, R01-EB000790) and the AFOSR (MFEL FA9550-07-1-0101). NR 26 TC 19 Z9 19 U1 1 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD APR 1 PY 2014 VL 5 IS 4 BP 1160 EP 1172 DI 10.1364/BOE.5.001160 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AE6DB UT WOS:000334078100016 PM 24761298 ER PT J AU Reddy, AK Jogendra, MRD Rosendorff, C AF Reddy, Arun K. Jogendra, Mather R. D. Rosendorff, Clive TI Blood pressure measurement in the geriatric population SO BLOOD PRESSURE MONITORING LA English DT Review DE orthostatic hypotension; ambulatory blood pressure monitoring; geriatric; blood pressure; elderly; home blood pressure monitoring; pseudohypertension; blood pressure variability; blood pressure measurement ID ISOLATED SYSTOLIC HYPERTENSION; AMERICAN-HEART-ASSOCIATION; CROSS-SECTIONAL ANALYSIS; WHITE-COAT HYPERTENSION; ELDERLY-PATIENTS; AMBULATORY HYPERTENSION; ORTHOSTATIC HYPOTENSION; INTERNATIONAL DATABASE; CARDIOVASCULAR EVENTS; MASKED HYPERTENSION AB As the population above 60 years of age is the fastest growing and hypertension is highly prevalent in this group, accurate blood pressure (BP) measurement in the elderly is a very important and widely applicable subject. As with any other population, an accurate measurement of BP is essential to plan therapy and this remains an important consideration in the elderly as well. There are some unique problems of BP measurement in the elderly, including drug-induced orthostatic hypotension, white-coat hypertension, and advanced atherosclerotic disease with stiff arteries. For clinical use, home blood pressure monitoring (HBPM), office measurement, and ambulatory blood pressure monitoring all play a role in patient management. In the office setting, aneroid devices, hybrid devices with electronic transducers, and oscillometric devices are available; all of these require frequent calibration, well-trained operators and technically sound execution. Because the white-coat effect is common in this group, there is a good case for the use of HBPM, which could also be used to detect orthostatic changes at home. Also, HBPM predicts cardiovascular events better than clinical BP, and is also useful in monitoring treatment. Ambulatory blood pressure monitoring provides the most precise assessment of BP over an extended period, but is more complex and expensive. Finally, the utility of noninvasive central arterial pressure through radial artery applanation tonometry, especially in patients with resistant hypertension and likely in the elderly because of advanced atherosclerotic disease and stiff arteries, may prove to be a useful tool to guide or modify drug therapy in the future and requires further study. C1 [Reddy, Arun K.; Jogendra, Mather R. D.; Rosendorff, Clive] Mt Sinai Heart, Icahn Sch Med Mt Sinai, New York, NY USA. [Reddy, Arun K.; Jogendra, Mather R. D.; Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 67 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1359-5237 EI 1473-5725 J9 BLOOD PRESS MONIT JI Blood Press. Monit. PD APR PY 2014 VL 19 IS 2 BP 59 EP 63 DI 10.1097/MBP.0000000000000021 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AD1ZJ UT WOS:000333031900001 PM 24621822 ER PT J AU Sood, S Baheti, AD Shinagare, AB Jagannathan, JP Hornick, JL Ramaiya, NH Tirumani, SH AF Sood, S. Baheti, A. D. Shinagare, A. B. Jagannathan, J. P. Hornick, J. L. Ramaiya, N. H. Tirumani, S. H. TI Imaging features of primary and metastatic alveolar soft part sarcoma: single institute experience in 25 patients SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID LYMPH-NODE METASTASIS; TISSUE SARCOMA; TUMORS; MR; NEOPLASMS; TFE3; GENE AB Objective: To describe imaging features of primary and metastatic alveolar soft part sarcoma (ASPS). Methods: In this institutional review board-approved and Health Insurance Portability and Accountability Act-compliant retrospective study, 25 patients (14 males; mean age, 25 years; range, 18-40 years) with pathologically proven ASPS seen at our institute between 1995 and 2013 were included. Imaging of primary tumours in 5 patients and follow-up imaging in 25 patients were reviewed by 2 radiologists in consensus. Clinical information was obtained from electronic medical records. Results: The most common sites for the primary tumour were extremities (17/25, 68%) and torso (6/25, 24%). Primary tumours (n = 5) were well circumscribed, compared with skeletal muscle, were isodense on CT, hyperintense on T-1 and T-2 weighted images with intense post-contrast enhancement, prominent feeders on CT and flow voids on MRI. Metastases developed in 23/25 (92%) patients, 18 at presentation. The most common sites of metastases were the lungs (100%), lymph nodes (74%), bones (57%) and brain (43%). Visceral and nodal metastases were hypervascular. At the time of reporting the results, 15 patients have died, 6 are alive and 4 were lost to follow-up. Median survival was 74 months for those without brain metastases (n = 8) and 60 months for those with brain metastases (n = 7). Median survival was shorter for patients with metastases at presentation. Conclusion: ASPS most commonly involves the lower extremities of young adults, is hypervascular on imaging, often metastasizes at presentation, frequently to lung, nodes, bones and brain, and has an indolent course despite metastases. Brain metastases and high tumour burden (number of metastatic sites) at presentation decreased survival in our study. Advances in knowledge: ASPS has an unusual pattern of metastases to the brain and nodes in addition to lung and bones. It has an indolent course despite metastases. C1 [Sood, S.; Baheti, A. D.; Shinagare, A. B.; Jagannathan, J. P.; Ramaiya, N. H.; Tirumani, S. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Baheti, A. D.; Shinagare, A. B.; Jagannathan, J. P.; Ramaiya, N. H.; Tirumani, S. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, J. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM sreeharsha_tirumani@dfci.harvard.edu NR 30 TC 8 Z9 8 U1 0 U2 7 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PD APR PY 2014 VL 87 IS 1036 AR 20130719 DI 10.1259/bjr.20130719 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE8ZK UT WOS:000334291900018 PM 24641199 ER PT J AU Winters, ZE Colwell, AS AF Winters, Z. E. Colwell, A. S. TI Role of acellular dermal matrix-assisted implants in breast reconstruction SO BRITISH JOURNAL OF SURGERY LA English DT Editorial Material ID COMPLICATIONS; METAANALYSIS AB Too many unanswered questions to justify widespread adoption C1 [Winters, Z. E.] Univ Bristol, Breast Canc Surg Patient Reported & Clin Outcome, Southmead Hosp, Bristol Breast Care Ctr,Sch Clin Sci, Bristol BS10 5NB, Avon, England. [Colwell, A. S.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Winters, ZE (reprint author), Univ Bristol, Breast Canc Surg Patient Reported & Clin Outcome, Southmead Hosp, Bristol Breast Care Ctr,Sch Clin Sci, Bristol BS10 5NB, Avon, England. EM zoe.winters@bristol.ac.uk NR 8 TC 4 Z9 4 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1323 EI 1365-2168 J9 BRIT J SURG JI Br. J. Surg. PD APR PY 2014 VL 101 IS 5 BP 444 EP 445 DI 10.1002/bjs.9415 PG 2 WC Surgery SC Surgery GA AC7HZ UT WOS:000332700100002 PM 24615338 ER PT J AU Zhu, ZH Todorova, K Lee, KK Wang, J Kwon, E Kehayov, I Kim, HG Kolev, V Dotto, GP Lee, SW Mandinova, A AF Zhu, Zehua Todorova, Kristina Lee, Kevin K. Wang, Jun Kwon, Eunjeong Kehayov, Ivan Kim, Hyung-Gu Kolev, Vihren Dotto, G. Paolo Lee, Sam W. Mandinova, Anna TI Small GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; P53 TARGET GENE; RHO-GTPASES; IN-VIVO; PROSTATE-CANCER; DIFFERENTIATION; IDENTIFICATION; TRAFFICKING; SUPPRESSION; ACTIVATION AB Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise. (C)2014 AACR. C1 [Zhu, Zehua; Todorova, Kristina; Lee, Kevin K.; Wang, Jun; Kwon, Eunjeong; Kim, Hyung-Gu; Kolev, Vihren; Dotto, G. Paolo; Lee, Sam W.; Mandinova, Anna] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Zhu, Zehua; Todorova, Kristina; Lee, Kevin K.; Wang, Jun; Kwon, Eunjeong; Kim, Hyung-Gu; Kolev, Vihren; Dotto, G. Paolo; Lee, Sam W.; Mandinova, Anna] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, Sam W.; Mandinova, Anna] Brord Inst Harvard & MIT, Cambridge Ctr, Cambridge, MA USA. [Kehayov, Ivan] Inst Immunol, Sofia, Bulgaria. [Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Mandinova, A (reprint author), Massachusetts Gen Hosp, 149 13th St,3rd Floor, Charlestown, MA 02129 USA. EM amandinova@partners.org FU NIH [CA140615, CA127247, CA97216, CA80058, AR39190, CA16038, CA73796]; Swiss National Foundation; European Union (Epistem, Sixth Framework Program) [LSHB-CT-2005-019067]; Shiseido Research FX This work was supported by NIH Grants, CA140615, CA127247, CA97216, CA80058, AR39190, CA16038, and CA73796, the Swiss National Foundation, a grant from the European Union (Epistem, Sixth Framework Program, LSHB-CT-2005-019067), and Shiseido Research Core funding. NR 38 TC 10 Z9 10 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2014 VL 74 IS 7 BP 2082 EP 2093 DI 10.1158/0008-5472.CAN-12-0452 PG 12 WC Oncology SC Oncology GA AE3TL UT WOS:000333900500020 PM 24525741 ER PT J AU Jeselsohn, R Yelensky, R Buchwalter, G Frampton, G Meric-Bernstam, F Gonzalez-Angulo, AM Ferrer-Lozano, J Perez-Fidalgo, JA Cristofanilli, M Gomez, H Arteaga, CL Giltnane, J Balko, JM Cronin, MT Jarosz, M Sun, J Hawryluk, M Lipson, D Otto, G Ross, JS Dvir, A Soussan-Gutman, L Wolf, I Rubinek, T Gilmore, L Schnitt, S Come, SE Pusztai, L Stephens, P Brown, M Miller, VA AF Jeselsohn, Rinath Yelensky, Roman Buchwalter, Gilles Frampton, Garrett Meric-Bernstam, Funda Gonzalez-Angulo, Ana Maria Ferrer-Lozano, Jaime Perez-Fidalgo, Jose A. Cristofanilli, Massimo Gomez, Henry Arteaga, Carlos L. Giltnane, Jennifer Balko, Justin M. Cronin, Maureen T. Jarosz, Mirna Sun, James Hawryluk, Matthew Lipson, Doron Otto, Geoff Ross, Jeffrey S. Dvir, Addie Soussan-Gutman, Lior Wolf, Ido Rubinek, Tamar Gilmore, Lauren Schnitt, Stuart Come, Steven E. Pusztai, Lajos Stephens, Philip Brown, Myles Miller, Vincent A. TI Emergence of Constitutively Active Estrogen Receptor-alpha Mutations in Pretreated Advanced Estrogen Receptor-Positive Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID POSTMENOPAUSAL WOMEN; TRIAL AB Purpose: We undertook this study to determine the prevalence of estrogen receptor (ER) alpha ( ESR1) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations. Experimental Design: We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER+/HER2(-)) and, as controls, 115 ER-negative (ER-) tumors. The ER+ samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes. Results: Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER+ metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95%confidence interval (CI), 6%-21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95%CI, 7%-41%). These mutations were not detected in primary or treatment-naive ER+ cancer or in any stage of ER(-)disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments. Conclusions: In this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER+ breast cancer. (C) 2014 AACR. C1 [Jeselsohn, Rinath; Buchwalter, Gilles; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Jeselsohn, Rinath; Buchwalter, Gilles; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Jeselsohn, Rinath; Buchwalter, Gilles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gilmore, Lauren; Schnitt, Stuart] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. [Come, Steven E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Breast Med Oncol Program, Boston, MA USA. [Yelensky, Roman; Frampton, Garrett; Cronin, Maureen T.; Jarosz, Mirna; Sun, James; Hawryluk, Matthew; Lipson, Doron; Otto, Geoff; Ross, Jeffrey S.; Stephens, Philip; Miller, Vincent A.] Fdn Med, Cambridge, MA USA. [Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. [Gonzalez-Angulo, Ana Maria] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol & Breast Med Oncol, Houston, TX 77030 USA. [Ferrer-Lozano, Jaime] Hosp Clin Univ Valencia, Fdn Invest INCLIVA, Inst Hlth Res, Valencia, Spain. [Perez-Fidalgo, Jose A.] Hosp Clin Univ Valencia, Dept Hematol Oncol, Valencia, Spain. [Cristofanilli, Massimo] Thomas Jefferson Univ, Kimmel Canc Ctr, Jefferson Breast Care Ctr, Philadelphia, PA 19107 USA. [Gomez, Henry] INEN, Lima, Peru. [Arteaga, Carlos L.; Giltnane, Jennifer; Balko, Justin M.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Breast Canc Program, Nashville, TN USA. [Dvir, Addie; Soussan-Gutman, Lior] Teva Pharmaceut, Petah Tiqwa, Israel. [Wolf, Ido; Rubinek, Tamar] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Div Oncol, IL-69978 Tel Aviv, Israel. [Pusztai, Lajos] Yale Univ, Sch Med, Sect Breast Med Oncol, New Haven, CT USA. RP Brown, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D730, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu OI Gomez, Henry/0000-0003-2660-1843; Brown, Myles/0000-0002-8213-1658 FU Susan G. Komen for the Cure; NCI [P01 CA080111]; NIDDK [R01 DK074967] FX This study was supported in part by grants from Susan G. Komen for the Cure (to M. Brown), the NCI (P01 CA080111; to M. Brown), and NIDDK (R01 DK074967; to M. Brown). NR 45 TC 120 Z9 121 U1 2 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2014 VL 20 IS 7 BP 1757 EP 1767 DI 10.1158/1078-0432.CCR-13-2332 PG 11 WC Oncology SC Oncology GA AE3TH UT WOS:000333900000010 PM 24398047 ER PT J AU Riester, M Werner, L Bellmunt, J Selvarajah, S Guancial, EA Weir, BA Stack, EC Park, RS O'Brien, R Schutz, FAB Choueiri, TK Signoretti, S Lloreta, J Marchionni, L Gallardo, E Rojo, F Garcia, DI Chekaluk, Y Kwiatkowski, DJ Bochner, BH Hahn, WC Ligon, AH Barletta, JA Loda, M Berman, DM Kantoff, PW Michor, F Rosenberg, JE AF Riester, Markus Werner, Lillian Bellmunt, Joaquim Selvarajah, Shamini Guancial, Elizabeth A. Weir, Barbara A. Stack, Edward C. Park, Rachel S. O'Brien, Robert Schutz, Fabio A. B. Choueiri, Toni K. Signoretti, Sabina Lloreta, Josep Marchionni, Luigi Gallardo, Enrique Rojo, Federico Garcia, Denise I. Chekaluk, Yvonne Kwiatkowski, David J. Bochner, Bernard H. Hahn, William C. Ligon, Azra H. Barletta, Justine A. Loda, Massimo Berman, David M. Kantoff, Philip W. Michor, Franziska Rosenberg, Jonathan E. TI Integrative Analysis of 1q23.3 Copy-Number Gain in Metastatic Urothelial Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; JUNCTIONAL ADHESION MOLECULE; TRANSITIONAL-CELL CARCINOMA; INVASIVE BLADDER-CANCER; DOMAIN-CONTAINING PROTEIN; BREAST-CANCER; GENE-EXPRESSION; PROGNOSTIC-FACTORS; IDENTIFICATION; PROGRESSION AB Purpose: Metastatic urothelial carcinoma of the bladder is associated with multiple somatic copy-number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Experimental Design: We obtained overall survival (OS) and array DNA copy-number data from patients with metastatic urothelial carcinoma in two cohorts. Associations between recurrent SCNAs and OS were determined by a Cox proportional hazard model adjusting for performance status and visceral disease. mRNA expression was evaluated for potential candidate genes by NanoString nCounter to identify transcripts from the region that are associated with copy-number gain. In addition, expression data from an independent cohort were used to identify candidate genes. Results: Multiple areas of recurrent significant gains and losses were identified. Gain of 1q23.3 was independently associated with a shortened OS in both cohorts [adjusted HR, 2.96; 95% confidence interval (CI), 1.35-6.48; P=0.01 and adjusted HR, 5.03; 95% CI, 1.43-17.73; P < 0.001]. The F11R, PFDN2, PPOX, USP21, and DEDD genes, all located on 1q23.3, were closely associated with poor outcome. Conclusions: 1q23.3 copy-number gain displayed association with poor survival in two cohorts of metastatic urothelial carcinoma. The identification of the target of this copy-number gain is ongoing, and exploration of this finding in other disease states may be useful for the early identification of patients with poor-risk urothelial carcinoma. Prospective validation of the survival association is necessary to demonstrate clinical relevance. (C) 2014 AACR. C1 [Riester, Markus; Werner, Lillian; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Guancial, Elizabeth A.; Park, Rachel S.; O'Brien, Robert; Schutz, Fabio A. B.; Choueiri, Toni K.; Hahn, William C.; Kantoff, Philip W.; Rosenberg, Jonathan E.] Harvard Univ, Sch Publ Hlth, Dept Med Oncol, Boston, MA 02115 USA. [Selvarajah, Shamini; Stack, Edward C.; Garcia, Denise I.; Ligon, Azra H.; Loda, Massimo] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Riester, Markus; Signoretti, Sabina; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Selvarajah, Shamini; Stack, Edward C.; Ligon, Azra H.; Barletta, Justine A.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chekaluk, Yvonne; Kwiatkowski, David J.] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA. [Weir, Barbara A.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Marchionni, Luigi] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Berman, David M.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Bochner, Bernard H.] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. [Bellmunt, Joaquim; Lloreta, Josep; Rojo, Federico] Hosp del Mar, Res Inst IMIM, Barcelona, Spain. [Gallardo, Enrique] Hosp Parc Tauli, Sabadell, Spain. RP Michor, F (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mailstop CLS 11007, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu; rosenbj1@mskcc.org RI Lloreta, J/I-2112-2014; Rojo, Federico/S-6551-2016; OI Lloreta, J/0000-0003-1644-9470; Riester, Markus/0000-0002-4759-8332 FU NCI [R21 CA164613-01]; Instituto de Salud Carlos III FEDER [RD09/0076/00101]; DFCI Physical Sciences-Oncology Center [U54CA1437980]; DFCI PART Fellowship FX This work was supported by NCI R21 CA164613-01. Spanish tissue collection supported by biobank grants from Instituto de Salud Carlos III FEDER, RD09/0076/00101. J.E. Rosenberg acknowledges support from the DFCI PART Fellowship, and M. Riester and F. Michor were supported by the DFCI Physical Sciences-Oncology Center (U54CA1437980). NR 48 TC 11 Z9 11 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2014 VL 20 IS 7 BP 1873 EP 1883 DI 10.1158/1078-0432.CCR-13-0759 PG 11 WC Oncology SC Oncology GA AE3TH UT WOS:000333900000021 PM 24486590 ER PT J AU Borger, DR Goyal, L Yau, T Poon, RT Ancukiewicz, M Deshpande, V Christiani, DC Liebman, HM Yang, H Kim, H Yen, K Faris, JE Iafrate, AJ Kwak, EL Clark, JW Allen, JN Blaszkowsky, LS Murphy, JE Saha, SK Hong, TS Wo, JY Ferrone, CR Tanabe, KK Bardeesy, N Straley, KS Agresta, S Schenkein, DP Ellisen, LW Ryan, DP Zhu, AX AF Borger, Darrell R. Goyal, Lipika Yau, Thomas Poon, Ronnie T. Ancukiewicz, Marek Deshpande, Vikram Christiani, David C. Liebman, Hannah M. Yang, Hua Kim, Hyeryun Yen, Katharine Faris, Jason E. Iafrate, A. John Kwak, Eunice L. Clark, Jeffrey W. Allen, Jill N. Blaszkowsky, Lawrence S. Murphy, Janet E. Saha, Supriya K. Hong, Theodore S. Wo, Jennifer Y. Ferrone, Cristina R. Tanabe, Kenneth K. Bardeesy, Nabeel Straley, Kimberly S. Agresta, Sam Schenkein, David P. Ellisen, Leif W. Ryan, David P. Zhu, Andrew X. TI Circulating Oncometabolite 2-Hydroxyglutarate Is a Potential Surrogate Biomarker in Patients with Isocitrate Dehydrogenase-Mutant Intrahepatic Cholangiocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; 2 MUTATIONS; DIFFERENTIATION; CANCER; IDH1; SUFFICIENT; INHIBITOR; THERAPIES; PHENOTYPE; CELLS AB Purpose: Mutations in the IDH1 and IDH2 (IDH1/2) genes occur in approximately 20% of intrahepatic cholangiocarcinoma and lead to accumulation of 2-hydroxyglutarate (2HG) in the tumor tissue. However, it remains unknown whether IDH1/2 mutations can lead to high levels of 2HG circulating in the blood and whether serum 2HG can be used as a biomarker for IDH1/2 mutational status and tumor burden in intrahepatic cholangiocarcinoma. Experimental Design: Weinitially measured serum 2HG concentration in blood samples collected from 31 patients with intrahepatic cholangiocarcinoma in a screening cohort. Findings were validated across 38 resected patients with intrahepatic cholangiocarcinoma from a second cohort with tumor volume measures. Circulating levels of 2HG were evaluated relative to IDH1/2 mutational status, tumor burden, and a number of clinical variables. Results: Circulating levels of 2HG in the screening cohort were significantly elevated in patients with IDH1/2-mutant (median, 478 ng/mL) versus IDH1/2-wild-type (median, 118 ng/mL) tumors (P<0.001). This significance was maintained in the validation cohort (343 ng/mL vs. 55 ng/mL, P<0.0001) and levels of 2HG directly correlated with tumor burden in IDH1/2-mutant cases (P<0.05). Serum 2HG levels >= 170 ng/mL could predict the presence of an IDH1/2 mutation with a sensitivity of 83% and a specificity of 90%. No differences were noted between the allelic variants IDH1 or IDH2 in regard to the levels of circulating 2HG. Conclusions: This study indicates that circulating 2HG may be a surrogate biomarker of IDH1 or IDH2 mutation status in intrahepatic cholangiocarcinoma and that circulating 2HG levels may correlate directly with tumor burden. (C) 2014 AACR. C1 [Borger, Darrell R.; Goyal, Lipika; Ancukiewicz, Marek; Deshpande, Vikram; Christiani, David C.; Liebman, Hannah M.; Faris, Jason E.; Iafrate, A. John; Kwak, Eunice L.; Clark, Jeffrey W.; Allen, Jill N.; Blaszkowsky, Lawrence S.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Bardeesy, Nabeel; Ellisen, Leif W.; Ryan, David P.; Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Yang, Hua; Kim, Hyeryun; Yen, Katharine; Straley, Kimberly S.; Agresta, Sam; Schenkein, David P.] Agios Pharmaceut, Cambridge, MA USA. [Yau, Thomas; Poon, Ronnie T.] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org FU MGH Cancer Center; Federal Share of program income earned by Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX This work was supported by internal MGH Cancer Center funds and the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center NR 29 TC 23 Z9 23 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2014 VL 20 IS 7 BP 1884 EP 1890 DI 10.1158/1078-0432.CCR-13-2649 PG 7 WC Oncology SC Oncology GA AE3TH UT WOS:000333900000022 PM 24478380 ER PT J AU Brugeaud, A Tong, MJ Luo, L Edge, ASB AF Brugeaud, Aurore Tong, Mingjie Luo, Li Edge, Albert S. B. TI Inhibition of repulsive guidance molecule, RGMa, increases afferent synapse formation with auditory hair cells SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE RGMa; cochlear regeneration; cochlear synaptogenesis; spiral ganglion neuron ID SPINAL-CORD-INJURY; CENTRAL-NERVOUS-SYSTEM; SPIRAL GANGLION NEURONS; PROMOTES AXONAL GROWTH; SENSORY NEURONS; DEVELOPMENTAL GUIDANCE; MULTIPLE ROLES; HEARING-LOSS; STEM-CELLS; REGENERATION AB The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 457-466, 2014 C1 [Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S. B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Edge, Albert S. B.] Harvard & MIT, Program Speech & Hearing Biosci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM albert_edge@meei.harvard.edu FU National Institute on Deafness and other Communicative Disorders (NIDCD) [RO1 DC007174, P30 DC005209] FX Contract grant sponsor: National Institute on Deafness and other Communicative Disorders (NIDCD); contract grant numbers: RO1 DC007174 and P30 DC005209. NR 53 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8451 EI 1932-846X J9 DEV NEUROBIOL JI Dev. Neurobiol. PD APR PY 2014 VL 74 IS 4 BP 457 EP 466 DI 10.1002/dneu.22136 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AC0LJ UT WOS:000332185800004 PM 24123853 ER PT J AU Rogus-Pulia, NM Pierce, MC Mittal, BB Zecker, SG Logemann, JA AF Rogus-Pulia, Nicole M. Pierce, Margaret C. Mittal, Bharat B. Zecker, Steven G. Logemann, Jeri A. TI Changes in Swallowing Physiology and Patient Perception of Swallowing Function Following Chemoradiation for Head and Neck Cancer SO DYSPHAGIA LA English DT Article DE Deglutition; Deglutition disorders; Dysphagia; Chemoradiation; Head and neck cancer; Perception; Swallow efficiency ID QUALITY-OF-LIFE; RADIATION-THERAPY; SJOGRENS-SYNDROME; DYSPHAGIA; PERFORMANCE; XEROSTOMIA; VIDEOFLUOROSCOPY; RADIOTHERAPY; ASPIRATION; AWARENESS AB Patients treated with chemoradiation for head and neck cancer often report difficulty with swallowing and are frequently diagnosed with dysphagia. The extent to which patient awareness of dysphagia corresponds to observed physiologic changes in swallowing is unclear. The purpose of this study was to determine how both patient awareness of swallowing function and swallowing physiology individually change following chemoradiation and then to clarify the relationship between them. Twenty-one patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with twenty-one control subjects. The modified barium swallow test was utilized to examine swallowing physiology. Each subject was also given a series of items regarding awareness of specific dysphagia symptoms. Results showed decreased swallow efficiencies, higher percentages of residue, and more occurrences of penetration and aspiration following chemoradiation. Patients also had significantly higher ratings for 4 of the 12 items ("dry mouth," "food sticking in my mouth," "need water to help food go down," and "change in sense of taste"). Only one strong and significant correlation was found between ratings for "I have difficulty swallowing" and swallow efficiency values. Based on these findings, it appears that patients sense a general difficulty with swallowing but have less awareness of specific symptoms of dysphagia. C1 [Rogus-Pulia, Nicole M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Rogus-Pulia, Nicole M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Speech Swallowing & Dining Enhancement Program, Madison, WI USA. [Pierce, Margaret C.] NW Mem Hosp, Chicago, IL 60611 USA. [Mittal, Bharat B.] Northwestern Univ, Dept Radiat Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Zecker, Steven G.; Logemann, Jeri A.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. RP Rogus-Pulia, NM (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Madison GRECC 11G,Room, Madison, WI 53705 USA. EM Nicole.Pulia@va.gov NR 43 TC 11 Z9 11 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X EI 1432-0460 J9 DYSPHAGIA JI Dysphagia PD APR PY 2014 VL 29 IS 2 BP 223 EP 233 DI 10.1007/s00455-013-9500-y PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA AE6SS UT WOS:000334125800005 PM 24402239 ER PT J AU Cipriani, NA Letovanec, I Hornicek, FJ Mullen, JT Duan, ZF Borger, DR Nielsen, GP AF Cipriani, Nicole A. Letovanec, Igor Hornicek, Francis J. Mullen, John T. Duan, Zhenfeng Borger, Darrell R. Nielsen, Gunnlaugur Petur TI BRAF mutation in 'sarcomas': a possible method to detect de-differentiated melanomas SO HISTOPATHOLOGY LA English DT Article DE undifferentiated pleomorphic sarcoma; de-differentiated melanoma; BRAF; malignant fibrous histiocytoma; NRAS; melanoma ID DESMOPLASTIC MELANOMA; SEQUENCING ANALYSIS; SPINDLE-CELL; HUMAN CANCER; TUMORS; NRAS AB Aims BRAF is mutated in 50-60% of melanomas, but BRAF mutation in sarcomas has not been systematically evaluated. Some melanomas are spindled and may show no immunohistochemical evidence of melanocytic differentiation. Similarly, many sarcomas are undifferentiated, i.e. undifferentiated pleomorphic sarcomas (UPS). Diagnosing melanoma versus sarcoma in an undifferentiated spindle cell malignancy can be challenging. Our aim was to evaluate the prevalence of BRAF mutation in sarcomas and the use of BRAF mutational status in the diagnosis of spindle cell malignancies. Methods and results BRAF mutational analysis was performed on tissue from 104 patients: 90 with sarcoma only (50 UPS) and 14 with sarcoma and melanoma (seven UPS). In the sarcoma-only group, BRAF mutation was absent. In the sarcoma-melanoma group, three sarcomas showed BRAF mutation; all were UPS, occurred after the melanomas and did not stain for melanocytic markers. One melanoma-sarcoma pair showed identical BRAF V600E mutations. Conclusions The presence of BRAF mutation in these tumours raises the possibility that poorly differentiated spindle cell malignancies with BRAF mutation may represent melanomas, and BRAF mutational analysis should be considered in a patient with a spindle cell malignancy and a history of melanoma, as a positive result may indicate de-differentiated melanoma. C1 [Cipriani, Nicole A.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Letovanec, Igor] CHU Vaudois, Inst Univ Pathol, CH-1011 Lausanne, Switzerland. [Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA USA. [Mullen, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol,Dept Surg, Boston, MA USA. [Borger, Darrell R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. [Borger, Darrell R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Nielsen, Gunnlaugur Petur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Cipriani, NA (reprint author), Univ Chicago Med, 5841 S Maryland Ave,MC 6101, Chicago, IL 60637 USA. EM ncipriani@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD APR PY 2014 VL 64 IS 5 BP 639 EP 646 DI 10.1111/his.12305 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AC8MY UT WOS:000332788400005 PM 24117833 ER PT J AU Labarere, J Bertrand, R Fine, MJ AF Labarere, Jose Bertrand, Renaud Fine, Michael J. TI How to derive and validate clinical prediction models for use in intensive care medicine SO INTENSIVE CARE MEDICINE LA English DT Article DE Clinical prediction models; Clinical decision rule; Prognosis; Severity of illness index; Intensive care ID COMMUNITY-ACQUIRED PNEUMONIA; LOGISTIC-REGRESSION ANALYSIS; CLUSTER RANDOMIZED-TRIALS; MISSING OUTCOME DATA; EXTERNAL VALIDATION; PROGNOSTIC MODELS; METHODOLOGICAL STANDARDS; INTERNAL VALIDATION; EARLY ADMISSION; CRITICALLY-ILL AB Clinical prediction models are formal combinations of historical, physical examination and laboratory or radiographic test data elements designed to accurately estimate the probability that a specific illness is present (diagnostic model), will respond to a form of treatment (therapeutic model) or will have a well-defined outcome (prognostic model) in an individual patient. They are derived and validated using empirical data and used to assist physicians in their clinical decision-making that requires a quantitative assessment of diagnostic, therapeutic or prognostic probabilities at the bedside. To provide intensivists with a comprehensive overview of the empirical development and testing phases that a clinical prediction model must satisfy before its implementation into clinical practice. The development of a clinical prediction model encompasses three consecutive phases, namely derivation, (external) validation and impact analysis. The derivation phase consists of building a multivariable model, estimating its apparent predictive performance in terms of both calibration and discrimination, and assessing the potential for statistical over-fitting using internal validation techniques (i.e. split-sampling, cross-validation or bootstrapping). External validation consists of testing the predictive performance of a model by assessing its calibration and discrimination in different but plausibly related patients. Impact analysis involves comparative research [i.e. (cluster) randomized trials] to determine whether clinical use of a prediction model affects physician practices, patient outcomes or the cost of healthcare delivery. This narrative review introduces a checklist of 19 items designed to help intensivists develop and transparently report valid clinical prediction models. C1 [Labarere, Jose] Univ Hosp, Qual Care Unit, F-38043 Grenoble, France. [Labarere, Jose] Univ Grenoble 1, TIMC UMR CNRS 5525, Grenoble, France. [Bertrand, Renaud] Cochin Hosp, Emergency Dept, AP HP, Paris, France. [Bertrand, Renaud] Hop Hotel Dieu, Emergency Dept, AP HP, F-75181 Paris, France. [Bertrand, Renaud] Fac Med Paris Descartes, Paris, France. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equ & Res Promot, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh Med Ctr, Div Gen Internal Med, Pittsburgh, PA USA. [Labarere, Jose] UQEM, F-38043 Grenoble 9, France. RP Labarere, J (reprint author), UQEM, Pavillon Taillefer,CHU BP217, F-38043 Grenoble 9, France. EM JLabarere@chu-grenoble.fr RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 NR 64 TC 28 Z9 28 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2014 VL 40 IS 4 BP 513 EP 527 DI 10.1007/s00134-014-3227-6 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA AE6BW UT WOS:000334074400005 PM 24570265 ER PT J AU Berkowitz, AL Mittal, MK McLane, HC Shen, GC Muralidharan, R Lyons, JL Shinohara, RT Shuaib, A Mateen, FJ AF Berkowitz, Aaron L. Mittal, Manoj K. McLane, Hannah C. Shen, Gordon C. Muralidharan, RajaNandini Lyons, Jennifer L. Shinohara, Russell T. Shuaib, Ashfaq Mateen, Farrah J. TI Worldwide reported use of IV tissue plasminogen activator for acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE epidemiology; global health; stroke; thrombolysis ID DEVELOPING-COUNTRIES; SYSTEMATIC ANALYSIS; INCOME COUNTRIES; MIDDLE-INCOME; GLOBAL BURDEN; THROMBOLYSIS; POPULATION; COMMUNITY; BARRIERS; THERAPY AB Background and PurposeIntravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. Summary of ReviewA systematic review was performed searching each country name AND stroke' OR tissue plasminogen activator' OR thrombolysis' using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996-Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P<0001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 33 per 1000 international dollar increase, 95% confidence interval 14-99, P=002) and reported mortality rate from cerebrovascular disease (odds ratio 102, 95% confidence interval 099-106, P=002) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not (P>005). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. ConclusionsBy reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported. C1 [Berkowitz, Aaron L.; Lyons, Jennifer L.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Mittal, Manoj K.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. [McLane, Hannah C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Shen, Gordon C.] Univ Calif Berkeley, Sch Publ Hlth, Hlth Policy & Management Div, Berkeley, CA 94720 USA. [Muralidharan, RajaNandini] Univ Penn, Dept Neurol, Div Neurocrit Care, Philadelphia, PA 19104 USA. [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shuaib, Ashfaq] Univ Alberta, Div Neurol, Dept Internal Med, Edmonton, AB, Canada. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, AC-720,55 Fruit St, Boston, MA 02114 USA. EM fmateen@partners.org NR 37 TC 4 Z9 5 U1 3 U2 9 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 APR PY 2014 VL 9 IS 3 BP 349 EP 355 DI 10.1111/ijs.12205 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC9II UT WOS:000332847400023 PM 24207029 ER PT J AU Dotto, GP AF Dotto, G. Paolo TI Multifocal epithelial tumors and field cancerization: stroma as a primary determinant SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID UPPER AERODIGESTIVE TRACT; MULTIPLE PRIMARY CANCERS; CARCINOMA IN-SITU; EPIGENETIC FIELD; PROSTATE-CANCER; BREAST-CANCER; CLINICAL-IMPLICATIONS; COLORECTAL-CANCER; GASTRIC-CANCER; COLON-CANCER AB It is increasingly evident that cancer results from altered organ homeostasis rather than from deregulated control of single cells or groups of cells. This applies especially to epithelial cancer, the most common form of human solid tumors and a major cause of cancer lethality. In the vast majority of cases, in situ epithelial cancer lesions do not progress into malignancy, even if they harbor many of the genetic changes found in invasive and metastatic tumors. While changes in tumor stroma are frequently viewed as secondary to changes in the epithelium, recent evidence indicates that they can play a primary role in both cancer progression and initiation. These processes may explain the phenomenon of field cancerization, i.e., the occurrence of multifocal and recurrent epithelial tumors that are preceded by and associated with widespread changes of surrounding tissue or organ "fields." C1 [Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, 1066 Epalinges, Lausanne, Switzerland. EM paolo.dotto@unil.ch FU Swiss National Foundation [CRSI33-130576/1, 310030B_138653/1]; Oncosuisse [OCS-2922-02-2012]; NIH [AR39190] FX I thank Patrice Jichlinski, Gunther Hofbauer, Maryse Fiche, and Fabio Levi for helpful feedback and discussions. This work was supported by grants from the Swiss National Foundation (grants CRSI33-130576/1; 310030B_138653/1), Oncosuisse (grant OCS-2922-02-2012), and the NIH (grant AR39190). Given the broad and complex topic, in many cases only representative papers were referenced, and I apologize to the many colleagues whose work was not included. NR 159 TC 27 Z9 27 U1 0 U2 14 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2014 VL 124 IS 4 BP 1446 EP 1453 DI 10.1172/JCI72589 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1IQ UT WOS:000333723400006 PM 24691479 ER PT J AU Imielinski, M Greulich, H Kaplan, B Araujo, L Amann, J Horn, L Schiller, J Villalona-Calero, MA Meyerson, M Carbone, DP AF Imielinski, Marcin Greulich, Heidi Kaplan, Bethany Araujo, Luiz Amann, Joseph Horn, Leora Schiller, Joan Villalona-Calero, Miguel A. Meyerson, Matthew Carbone, David P. TI Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TYROSINE KINASE; PHASE-II; CANCER; INHIBITOR; GENOME; STAGE AB Targeted cancer therapies often induce "outlier" responses in molecularly defined patient subsets. One patient with advanced-stage lung adenocarcinoma, who was treated with oral sorafenib, demonstrated a near-complete clinical and radiographic remission for 5 years. Whole-genome sequencing and RNA sequencing of primary tumor and normal samples from this patient identified a somatic mutation, ARAF S214C, present in the cancer genome and expressed at high levels. Additional mutations affecting this residue of ARAF and a nearby residue in the related kinase RAF1 were demonstrated across 1% of an independent cohort of lung adenocarcinoma cases. The ARAF mutations were shown to transform immortalized human airway epithelial cells in a sorafenib-sensitive manner. These results suggest that mutant ARAF is an oncogenic driver in lung adenocarcinoma and an indicator of sorafenib response. C1 [Imielinski, Marcin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Imielinski, Marcin; Greulich, Heidi; Kaplan, Bethany; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Imielinski, Marcin; Greulich, Heidi; Kaplan, Bethany; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Greulich, Heidi] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Araujo, Luiz; Amann, Joseph; Villalona-Calero, Miguel A.; Carbone, David P.] Ohio State Univ, Wexner Med Ctr, James Thorac Ctr, Columbus, OH 43210 USA. [Horn, Leora] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Schiller, Joan] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [Meyerson, Matthew] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carbone, DP (reprint author), Ohio State Univ, Med Ctr, Dept Med, James Thorac Ctr, 410 W 10th Ave, Columbus, OH 43210 USA. EM matthew_meyerson@dfci.harvard.edu; david.carbone@osumc.edu FU NCI [T32 CA9216-31, U01CA114771]; Conquer Cancer Foundation of ASCO Long-Term International Fellowship; Uniting Against Lung Cancer; Lung Cancer Research Foundation; Novartis; Department of Defense Congressionally Directed Medical Research Programs Lung Cancer Research Program [W81XWH-12-1-0269]; American Lung Association FX M. Imielinski is supported by NCI training grant T32 CA9216-31. L. Araujo is supported by a Conquer Cancer Foundation of ASCO Long-Term International Fellowship. This work was supported by NCI U01CA114771 (to D.P. Carbone), Uniting Against Lung Cancer (to M. Meyerson and H. Greulich), the Lung Cancer Research Foundation (to M. Meyerson), Novartis (to M. Meyerson), Department of Defense Congressionally Directed Medical Research Programs Lung Cancer Research Program W81XWH-12-1-0269 (to M. Meyerson), and the American Lung Association (to M. Meyerson). We thank Mark Bray and members of the Broad Institute Imaging Platform for development of the CellProfiler pipeline, used to quantify the soft agar photographs. NR 21 TC 36 Z9 37 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2014 VL 124 IS 4 BP 1582 EP 1586 DI 10.1172/JCI72763 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1IQ UT WOS:000333723400020 PM 24569458 ER PT J AU Watanabe, H Ma, QP Peng, SY Adelmant, G Swain, D Song, WY Fox, C Francis, JM Pedamallu, CS DeLuca, DS Brooks, AN Wang, S Que, JW Rustgi, AK Wong, KK Ligon, KL Liu, XS Marto, JA Meyerson, M Bass, AJ AF Watanabe, Hideo Ma, Qiuping Peng, Shouyong Adelmant, Guillaume Swain, Danielle Song, Wenyu Fox, Cameron Francis, Joshua M. Pedamallu, Chandra Sekhar DeLuca, David S. Brooks, Angela N. Wang, Su Que, Jianwen Rustgi, Anil K. Wong, Kwok-kin Ligon, Keith L. Liu, X. Shirley Marto, Jarrod A. Meyerson, Matthew Bass, Adam J. TI SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EMBRYONIC STEM-CELLS; PROTEIN-INTERACTION NETWORK; TRANSCRIPTION FACTORS; LUNG-CANCER; PROGENITOR CELLS; MOUSE TRACHEA; EXPRESSION; ONCOGENE; PROLIFERATION; AMPLIFICATION AB The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology. C1 [Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M.; Pedamallu, Chandra Sekhar; Brooks, Angela N.; Wong, Kwok-kin; Ligon, Keith L.; Liu, X. Shirley; Meyerson, Matthew; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Watanabe, Hideo; Peng, Shouyong; Francis, Joshua M.; Pedamallu, Chandra Sekhar; DeLuca, David S.; Brooks, Angela N.; Meyerson, Matthew; Bass, Adam J.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Watanabe, Hideo; Francis, Joshua M.; Meyerson, Matthew; Bass, Adam J.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Wang, Su; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wang, Su; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Que, Jianwen] Univ Rochester, Dept Biomed Genet, Rochester, NY USA. [Que, Jianwen] Univ Rochester, Stem Cell & Regenerat Med Inst, Rochester, NY USA. [Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Abramson Canc Ctr,Perelman Sch Med, Philadelphia, PA 19104 USA. [Wong, Kwok-kin; Bass, Adam J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ligon, Keith L.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Adam_Bass@dfci.harvard.edu OI wong, kwok kin/0000-0001-6323-235X FU National Cancer Institute [K08 CA134931]; Dana-Farber/Harvard Cancer Center Lung Cancer SPORE Developmental Project Award [NIH P50 CA090578]; Lung Cancer Research Foundation; Clinical Scientist Development Award from the Doris Duke Charitable Foundation; [R00 DX082650]; [P01 CA098101]; [R01 DK060694]; [R01 DK056645]; [P30 DK050306]; [R01 CA109038]; [P01 CA154303]; [P20 CA90578]; [U24 CA126546] FX We thank Ramesh Shivdasani, Myles Brown, and Orit Rozenblatt-Rosen for helpful discussions; Thorsten Schlaeger for providing H9 ES cells; and Fujiko Duke for technical assistance. This work was supported by the National Cancer Institute (K08 CA134931 to A.J. Bass), a Dana-Farber/Harvard Cancer Center Lung Cancer SPORE Developmental Project Award (NIH P50 CA090578 to A.J. Bass and K. Wong), the Lung Cancer Research Foundation (to AJ. Bass), and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (to AJ. Bass). J. Que is supported by grant R00 DX082650; A.K. Rustgi is supported by grants P01 CA098101, R01 DK060694, R01 DK056645, and P30 DK050306; and M. Meyerson is supported by grants R01 CA109038, P01 CA154303, P20 CA90578, and U24 CA126546. NR 57 TC 29 Z9 29 U1 1 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2014 VL 124 IS 4 BP 1636 EP 1645 DI 10.1172/JCI71545 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1IQ UT WOS:000333723400025 PM 24590290 ER PT J AU Gritsman, K Yuzugullu, H Von, T Yan, H Clayton, L Fritsch, C Maira, SM Hollingworth, G Choi, C Khandan, T Paktinat, M Okabe, RO Roberts, TM Zhao, JJ AF Gritsman, Kira Yuzugullu, Haluk Thanh Von Yan, Howard Clayton, Linda Fritsch, Christine Maira, Sauveur-Michel Hollingworth, Gregory Choi, Christine Khandan, Tulasi Paktinat, Mahnaz Okabe, Rachel O. Roberts, Thomas M. Zhao, Jean J. TI Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110 alpha SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STEM-CELLS; MYELOPROLIFERATIVE DISEASE; PHOSPHOINOSITIDE 3-KINASE; EMBRYONIC LETHALITY; LINEAGE CHOICE; ONCOGENIC KRAS; MICE; INHIBITORS; CANCER; ERYTHROPOIETIN AB The genes encoding RAS family members are frequently mutated in juvenile myelomonocytic leukemia (JMML) and acute myeloid leukemia (AML). RAS proteins are difficult to target pharmacologically; therefore, targeting the downstream PI3K and RAF/MEK/ERK pathways represents a promising approach to treat RAS-addicted tumors. The p110 alpha isoforrn of PI3K (encoded by Pik3ca) is an essential effector of oncogenic KRAS in murine lung tumors, but it is unknown whether p110 alpha contributes to leukemia. To specifically examine the role of p110 alpha in murine hematopoiesis and in leukemia, we conditionally deleted p110 alpha in HSCs using the Cre-loxP system. Postnatal deletion of p110 alpha resulted in mild anemia without affecting HSC self-renewal; however, deletion of p110 alpha in mice with KRAS(G12D)-associated JMML markedly delayed their death. Furthermore, the p110 alpha-selective inhibitor BYL719 inhibited growth factor-independent KRAS(G12D) BM colony formation and sensitized cells to a low dose of the MEK inhibitor MEK162. Furthermore, combined inhibition of p110 alpha and MEK effectively reduced proliferation of RAS-mutated AML cell lines and disease in an AML murine xenograft model. Together, our data indicate that RAS-mutated myeloid leukemias are dependent on the PI3K isoform p110 alpha, and combined pharmacologic inhibition of p110 alpha and MEK could be an effective therapeutic strategy for JMML and AML. C1 [Gritsman, Kira; Yuzugullu, Haluk; Thanh Von; Yan, Howard; Clayton, Linda; Choi, Christine; Roberts, Thomas M.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gritsman, Kira; Khandan, Tulasi; Paktinat, Mahnaz; Okabe, Rachel O.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Gritsman, Kira; Roberts, Thomas M.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Fritsch, Christine; Maira, Sauveur-Michel] Novartis Inst Biomed Res, Basel, Switzerland. [Hollingworth, Gregory] Novartis Horsham Res Ctr, Novartis Inst Biomed Res, Horsham, W Sussex, England. RP Gritsman, K (reprint author), 450 Brookline Ave,Smith 970C, Boston, MA 02215 USA. EM kgritsman@partners.org; Jean_Zhao@dfci.harvard.edu FU American Society of Hematology Fellow Scholar Award; Friends of Dana-Farber Fund; NCI grant [K08 CA149208]; NIH grant [R01 CA172461]; Dana-Farber Fund grant [8508054] FX We thank James Griffin for critical review of the manuscript; David Tuveson and Tyler Jacks for KrasLSL-G12D mice; Gary Gilliland for Mx1-Cre mice, cell lines, and valuable advice; Benjamin Ebert for use of the BD FACSCalibur and BD FACSCanto II in the Brigham and Women's Hospital Hematology Division; and Michael Kharas, Steven Lane, Demetrios Kalaitzidis, Lukas Baitsch, and all members of the Roberts and Zhao labs for helpful discussions. This work was supported by an American Society of Hematology Fellow Scholar Award (to K. Gritsman), by the Friends of Dana-Farber Fund (to K. Gritsman), by NCI grant K08 CA149208 (to K. Gritsman), by NIH grant R01 CA172461 (to J.J. Zhao), and by Dana-Farber Fund grant 8508054 (to J.J. Zhao). NR 53 TC 17 Z9 18 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2014 VL 124 IS 4 BP 1794 EP 1809 DI 10.1172/JCI69927 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1IQ UT WOS:000333723400038 PM 24569456 ER PT J AU Chuang, ML Gona, P Hautvast, GLTF Salton, CJ Breeuwer, M O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Hautvast, Gilion L. T. F. Salton, Carol J. Breeuwer, Marcel O'Donnell, Christopher J. Manning, Warren J. TI CMR Reference Values for Left Ventricular Volumes, Mass, and Ejection Fraction Using Computer-Aided Analysis: The Framingham Heart Study SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE left ventricle; reference values; automated border detection; magnetic resonance imaging; epidemiology; aging ID CARDIOVASCULAR MAGNETIC-RESONANCE; CINE-MR-IMAGES; STUDY OFFSPRING COHORT; AUTOMATIC SEGMENTATION; VALIDATION; PARAMETERS; QUANTIFICATION; ATRIAL; AGE AB PurposeTo determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. Materials and MethodsWe examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups. ResultsThe reference group comprised 685 adults (423F; 61 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 +/- 6 versus 71 +/- 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. ConclusionWe present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. J. Magn. Reson. Imaging 2014;39:895-900. (c) 2013 Wiley Periodicals, Inc. C1 [Chuang, Michael L.; Gona, Philimon; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Chuang, Michael L.; Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA. [Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Heathcare, Imaging Syst, Best, Netherlands. [Breeuwer, Marcel] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Chuang, ML (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM mlc48104@gmail.com FU National Institutes of Health [RO1 AG17509, N01-HC-38038]; Philips Healthcare, The Netherlands FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: RO1 AG17509, N01-HC-38038; Contract grant sponsor: Philips Healthcare, The Netherlands. NR 24 TC 14 Z9 14 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2014 VL 39 IS 4 BP 895 EP 900 DI 10.1002/jmri.24239 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD2BQ UT WOS:000333038300017 PM 24123369 ER PT J AU Boehme, AK Kapoor, N Albright, KC Lyerly, MJ Rawal, PV Shahripour, RB Alvi, M Houston, JT Sisson, A Beasley, TM Alexandrov, AW Alexandrov, AV Miller, DW AF Boehme, Amelia K. Kapoor, Niren Albright, Karen C. Lyerly, Michael J. Rawal, Pawan V. Shahripour, Reza Bavarsad Alvi, Muhammad Houston, J. Thomas Sisson, April Beasley, T. Mark Alexandrov, Anne W. Alexandrov, Andrei V. Miller, David W. TI Predictors of Systemic Inflammatory Response Syndrome in Ischemic Stroke Undergoing Systemic Thrombolysis with Intravenous Tissue Plasminogen Activator SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Thrombolysis; systemic inflammatory response syndrome; stroke outcome; inflammation ID MEDICINE CONSENSUS CONFERENCE; CHEST-PHYSICIANS SOCIETY; AMERICAN-COLLEGE; LDL RECEPTOR; SEVERITY; DEFINITIONS; OUTCOMES; SEPSIS; RISK AB Background: Systemic inflammatory response syndrome (SIRS) is an inflammatory process associated with poor outcomes in acute ischemic stroke (AIS) patients. However, no study to date has investigated predictors of SIRS in AIS patients treated with intravenous (IV) tissue plasminogen activator (tPA). Methods: Consecutive patients were retrospectively reviewed for evidence of SIRS during their acute hospitalization. SIRS was defined as the presence of 2 or more of the following: (1) body temperature less than 36 degrees C or greater than 38 degrees C, (2) heart rate greater than 90, (3) respiratory rate greater than 20, or (4) white blood cell count less than 4000/mm or greater than 12,000/mm or more than 10% bands for more than 24 hours. Those diagnosed with an infection were excluded. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cutoff of >= 65% or area under the curve of .6 or more. Results: Of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be black (61% versus 54%; P - .011), have lower median total cholesterol at baseline (143 versus 167 mg/dL; P = .0207), and have history of previous stroke (51% versus 35%; P = .0810). Ranging from 0 to 6, the SIRS prediction score consists of African American (2 points), history of hypertension (1 point), history of previous stroke (1 point), and admission total cholesterol less than 200 (2 points). Patients with an SIRS score of 4 or more were 3 times as likely to develop SIRS when compared with patients with a score of <= 3 (odds ratio = 2.815, 95% confidence interval 1.43-5.56, P = .0029). Conclusions: In our sample of IV tPA-treated AIS patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA. C1 [Boehme, Amelia K.; Albright, Karen C.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Kapoor, Niren; Lyerly, Michael J.; Rawal, Pawan V.; Shahripour, Reza Bavarsad; Alvi, Muhammad; Houston, J. Thomas; Sisson, April; Alexandrov, Anne W.; Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Stroke Ctr, Birmingham, AL 35294 USA. [Albright, Karen C.] Hlth Serv & Outcomes Res Ctr Outcome & Effectiven, Birmingham, AL USA. [Albright, Karen C.] Ctr Excellence Comparat Effectiveness Res Elimina, Minor Hlth & Hlth Dispar Res Ctr, Birmingham, AL USA. [Lyerly, Michael J.] Birmingham VA Med Ctr, Stroke Ctr, Birmingham, AL USA. [Beasley, T. Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Alexandrov, Anne W.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. [Miller, David W.] Univ Alabama Birmingham, Sch Med, Dept Anesthesiol, Birmingham, AL 35294 USA. RP Miller, DW (reprint author), Univ Alabama Birmingham, Sch Med, Dept Anesthesiol, Jefferson Tower 922, Birmingham, AL 35294 USA. EM dwmiller@uab.edu OI Alexandrov, Andrei V/0000-0001-8871-1023; Lyerly, Michael/0000-0003-4236-1018 FU Agency for Healthcare Research and Quality [5 T32 HS013852-10]; National Institute on Minority Health and Health Disparities, National Institutes of Health [3 P60 MD000502-08S1]; American Heart Association [13PRE13830003] FX The project described was supported by award numbers 5 T32 HS013852-10 from the Agency for Healthcare Research and Quality, 3 P60 MD000502-08S1 from the National Institute on Minority Health and Health Disparities, National Institutes of Health and 13PRE13830003 from the American Heart Association. NR 21 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD APR PY 2014 VL 23 IS 4 BP E271 EP E276 DI 10.1016/j.jstrokecerebrovasdis.2013.11.022 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AE2OV UT WOS:000333813700005 PM 24424334 ER PT J AU Tasaki, M Shimizu, A Hanekamp, I Torabi, R Villani, V Yamada, K AF Tasaki, Masayuki Shimizu, Akira Hanekamp, Isabel Torabi, Radbeh Villani, Vincenzo Yamada, Kazuhiko TI Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; IDIOPATHIC MEMBRANOUS NEPHROPATHY; UROKINASE RECEPTOR; NUCLEAR TRANSFER; XENOGRAFTS; GENERATION; EXCRETION; SURVIVAL; THERAPY; DISEASE AB We previously reported life-supporting 1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Sch Med, Surg Res & Head Organ Transplantat Tolerance & Xe, MGH East, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU NIAID NIH HHS [P01 AI045897] NR 25 TC 9 Z9 10 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2014 VL 25 IS 4 BP 737 EP 744 DI 10.1681/ASN.2013040363 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AE1OM UT WOS:000333738800014 PM 24459229 ER PT J AU von Mehren, M Randall, RL Benjamin, RS Boles, S Bui, MM Casper, ES Conrad, EU DeLaney, TF Ganjoo, KN George, S Gonzalez, RJ Heslin, MJ Kane, JM Mayerson, J McGarry, SV Meyer, C O'Donnell, RJ Pappo, AS Paz, IB Pfeifer, JD Riedel, RF Schuetze, S Schupak, KD Schwartz, HS Van Tine, BA Wayne, JD Bergman, MA Sundar, H AF von Mehren, Margaret Randall, R. Lor Benjamin, Robert S. Boles, Sarah Bui, Marilyn M. Casper, Ephraim S. Conrad, Ernest U., III DeLaney, Thomas F. Ganjoo, Kristen N. George, Suzanne Gonzalez, Ricardo J. Heslin, Martin J. Kane, John M., III Mayerson, Joel McGarry, Sean V. Meyer, Christian O'Donnell, Richard J. Pappo, Alberto S. Paz, I. Benjamin Pfeifer, John D. Riedel, Richard F. Schuetze, Scott Schupak, Karen D. Schwartz, Herbert S. Van Tine, Brian A. Wayne, Jeffrey D. Bergman, Mary Anne Sundar, Hema TI Soft Tissue Sarcoma, Version 2.2014 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; ELECTRON-BEAM RADIOTHERAPY; LINE P53 MUTATIONS; RETROPERITONEAL SARCOMA; RADIATION-THERAPY; DESMOID TUMORS; GERMLINE MUTATIONS; CARNEY-STRATAKIS; MANAGEMENT; CANCER AB These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS. C1 [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Boles, Sarah] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Bui, Marilyn M.; Gonzalez, Ricardo J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Casper, Ephraim S.; Schupak, Karen D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Conrad, Ernest U., III] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ganjoo, Kristen N.] Stanford Canc Inst, Stanford, CA USA. [Heslin, Martin J.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kane, John M., III] Roswell Pk Canc Inst, Buffalo, NY USA. [Mayerson, Joel] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Mayerson, Joel] Solove Res Inst, Columbus, OH USA. [McGarry, Sean V.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Meyer, Christian] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [O'Donnell, Richard J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Pappo, Alberto S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Paz, I. Benjamin] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Pfeifer, John D.; Van Tine, Brian A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Pfeifer, John D.; Van Tine, Brian A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Riedel, Richard F.] Duke Canc Inst, Durham, NC USA. [Schuetze, Scott] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Schwartz, Herbert S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wayne, Jeffrey D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP von Mehren, M (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 42 TC 33 Z9 33 U1 0 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2014 VL 12 IS 4 BP 473 EP 483 PG 11 WC Oncology SC Oncology GA AE5GD UT WOS:000334014900006 PM 24717567 ER PT J AU Denlinger, CS Ligibel, JA Are, M Baker, KS Demark-Wahnefried, W Friedman, DL Goldman, M Jones, L King, A Ku, GH Kvale, E Langbaum, TS Leonardi-Warren, K McCabe, MS Melisko, M Montoya, JG Mooney, K Morgan, MA Moslehi, JJ O'Connor, T Overholser, L Paskett, ED Raza, M Syrjala, KL Urba, SG Wakabayashi, MT Zee, P McMillian, N Freedman-Cass, D AF Denlinger, Crystal S. Ligibel, Jennifer A. Are, Madhuri Baker, K. Scott Demark-Wahnefried, Wendy Friedman, Debra L. Goldman, Mindy Jones, Lee King, Allison Ku, Grace H. Kvale, Elizabeth Langbaum, Terry S. Leonardi-Warren, Kristin McCabe, Mary S. Melisko, Michelle Montoya, Jose G. Mooney, Kathi Morgan, Mary Ann Moslehi, Javid J. O'Connor, Tracey Overholser, Linda Paskett, Electra D. Raza, Muhammad Syrjala, Karen L. Urba, Susan G. Wakabayashi, Mark T. Zee, Phyllis McMillian, Nicole Freedman-Cass, Deborah CA NCCN TI Survivorship: Pain Version 1.2014 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LIDOCAINE PATCH 5-PERCENT; BREAST-CANCER SURVIVORS; OF-THE-LITERATURE; NEUROPATHIC PAIN; TOPICAL AMITRIPTYLINE; POSTHERPETIC NEURALGIA; PERIPHERAL NEUROPATHY; OPIOID ASSESSMENT; PHYSICAL-THERAPY AB Many posttreatment cancer survivors experience chronic pain, often leading to psychological distress; decreased activity, motivation, and personal interactions; and an overall poor quality of life. This section of the NCCN Guidelines for Survivorship provides screening and management recommendations for pain in survivors. A multidisciplinary approach is recommended, with a combination of pharmacologic treatments, psychosocial and behavioral interventions, physical therapy and exercise, and interventional procedures. C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Ligibel, Jennifer A.; Moslehi, Javid J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Are, Madhuri] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Baker, K. Scott; Syrjala, Karen L.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Demark-Wahnefried, Wendy; Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Goldman, Mindy; Melisko, Michelle] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Jones, Lee; McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [King, Allison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Ku, Grace H.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Langbaum, Terry S.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Leonardi-Warren, Kristin; Overholser, Linda] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Morgan, Mary Ann] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Paskett, Electra D.] Solove Res Inst, Columbus, OH USA. [Raza, Muhammad] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wakabayashi, Mark T.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Zee, Phyllis] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Denlinger, CS (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI King, Allison/0000-0002-1951-6176 FU NCI NIH HHS [UM1 CA173642] NR 67 TC 3 Z9 3 U1 1 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2014 VL 12 IS 4 BP 488 EP 500 PG 13 WC Oncology SC Oncology GA AE5GD UT WOS:000334014900007 PM 24717568 ER PT J AU Raje, NS Yee, AJ Roodman, GD AF Raje, Noopur S. Yee, Andrew J. Roodman, G. David TI Advances in Supportive Care for Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INDUCED PERIPHERAL NEUROPATHY; LONG-TERM EFFICACY; LENALIDOMIDE PLUS DEXAMETHASONE; HIGH-DOSE DEXAMETHASONE; DEEP-VEIN THROMBOSIS; PHASE-III APEX; ZOLEDRONIC ACID; BONE-DISEASE; DOUBLE-BLIND AB As patients with multiple myeloma live longer, helping them live better through improvements in supportive care is equally as vital. Intrinsic to the disease are bone-related complications at presentation and over the course of illness. Bisphosphonates have been an important therapy for ameliorating the risk of skeletal-related events, and work is ongoing to determine their optimal schedule. Patients with multiple myeloma also encounter several challenges related to their treatment, including peripheral neuropathy, thrombotic complications, and infections. These challenges are being addressed through a better understanding of the risk factors for developing these complications and by mitigating these risks through better dosing schemas and prophylaxis. C1 [Raje, Noopur S.; Yee, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Ctr Multiple Myeloma, Boston, MA USA. [Roodman, G. David] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Roodman, G. David] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. RP Raje, NS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Profess Off Bldg 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU Eli Lilly FX Dr. Raje has disclosed that she is on the advisory board of Amgen Inc. Dr. Yee has disclosed that he has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Roodman has disclosed that he is a consultant for Amgen Inc. and receives research funds from Eli Lilly. NR 100 TC 2 Z9 2 U1 4 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2014 VL 12 IS 4 BP 502 EP 511 PG 10 WC Oncology SC Oncology GA AE5GD UT WOS:000334014900008 PM 24717569 ER PT J AU Gradishar, WJ Anderson, BO Blair, SL Burstein, HJ Cyr, A Elias, AD Farrar, WB Forero, A Giordano, SH Goldstein, LJ Hayes, DF Hudis, CA Isakoff, SJ Ljung, BME Marcom, PK Mayer, IA McCormick, B Miller, RS Pegram, M Pierce, LJ Reed, EC Salerno, KE Schwartzberg, LS Smith, ML Soliman, H Somlo, G Ward, JH Wolff, AC Zellars, R Shead, DA Kumar, R AF Gradishar, William J. Anderson, Benjamin O. Blair, Sarah L. Burstein, Harold J. Cyr, Amy Elias, Anthony D. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goldstein, Lori J. Hayes, Daniel F. Hudis, Clifford A. Isakoff, Steven J. Ljung, Britt-Marie E. Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Miller, Robert S. Pegram, Mark Pierce, Lori J. Reed, Elizabeth C. Salerno, Kilian E. Schwartzberg, Lee S. Smith, Mary Lou Soliman, Hatem Somlo, George Ward, John H. Wolff, Antonio C. Zellars, Richard Shead, Dorothy A. Kumar, Rashmi CA NCCN TI Breast Cancer Version 3.2014 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID GROWTH-FACTOR RECEPTOR; SKIN-SPARING MASTECTOMY; RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; SENTINEL-NODE BIOPSY; PLACEBO-CONTROLLED TRIAL; IN-SITU HYBRIDIZATION; QUALITY-OF-LIFE; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE AB Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. C1 [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Anderson, Benjamin O.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Blair, Sarah L.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Burstein, Harold J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cyr, Amy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Cyr, Amy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Elias, Anthony D.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Solove Res Inst, Columbus, OH USA. [Forero, Andres] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Goldstein, Lori J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hayes, Daniel F.; Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ljung, Britt-Marie E.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Miller, Robert S.; Wolff, Antonio C.; Zellars, Richard] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Pegram, Mark] Stanford Canc Inst, Stanford, CA USA. [Reed, Elizabeth C.] Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, Omaha, NE USA. [Salerno, Kilian E.] Roswell Pk Canc Inst, Buffalo, NY USA. [Schwartzberg, Lee S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Soliman, Hatem] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. NR 307 TC 75 Z9 78 U1 1 U2 15 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2014 VL 12 IS 4 BP 542 EP 590 PG 49 WC Oncology SC Oncology GA AE5GD UT WOS:000334014900011 PM 24717572 ER PT J AU DeAngelo, DJ Neuberg, D Amrein, PC Berchuck, J Wadleigh, M Sirulnik, LA Galinsky, I Golub, T Stegmaier, K Stone, RM AF DeAngelo, Daniel J. Neuberg, Donna Amrein, Philip C. Berchuck, Jacob Wadleigh, Martha Sirulnik, L. Andres Galinsky, Ilene Golub, Todd Stegmaier, Kimberly Stone, Richard M. TI A phase II study of the EGFR inhibitor gefitinib in patients with acute myeloid leukemia SO LEUKEMIA RESEARCH LA English DT Article DE EGFR; Leukemia; Chemotherapy; Gefitinib ID CELL LUNG-CANCER; ACUTE MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; SRC FAMILY KINASES; MYELODYSPLASTIC SYNDROME; ERLOTINIB; AML; DIFFERENTIATION; ACTIVATION; GROWTH AB Novel therapies for the treatment of acute myeloid leukemia are required to overcome disease resistance and to provide potentially less toxic therapies for older adults. Prior clinical trials involving patients with non-small cell lung cancer have demonstrated the safety and biologic activity of the administration of EGFR inhibitors in carefully selected patients. The potential efficacy of this approach in patients with acute myeloid leukemia is unknown. The effects of gefitinib on differentiation induction and cell viability in AML cell lines and primary patient AML cells were previously reported and cell viability was inhibited in a clinically achievable range. To determine if EGFR inhibitors would be therapeutically efficacious in advanced AML, we performed a phase II trial in which 18 patients with a median age of 72 (range, 57-84 years) were treated with gefitinib (750 mg orally daily). While there were no unexpected toxicities, no patients experienced an objective response, though one had stable disease lasting 16 months. We conclude that in spite of pre-clinical activity and anecdotal cases of response to EGFR inhibitors, routine use of the EGFR inhibitor gefitinib as a single agent for advanced AML is not appropriate. (c) 2013 Elsevier Ltd. All rights reserved. C1 [DeAngelo, Daniel J.; Wadleigh, Martha; Sirulnik, L. Andres; Galinsky, Ilene; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Amrein, Philip C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berchuck, Jacob; Golub, Todd; Stegmaier, Kimberly] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Berchuck, Jacob; Golub, Todd; Stegmaier, Kimberly] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Golub, Todd; Stegmaier, Kimberly] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1B30, Boston, MA 02215 USA. EM daniel_deangelo@dfci.harvard.edu FU AstraZeneca; [NCIRO1 CA140292] FX This work was supported in part by AstraZeneca. K.S. is supported by the NCIRO1 CA140292 grant. NR 45 TC 7 Z9 8 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2014 VL 38 IS 4 BP 430 EP 434 DI 10.1016/j.leukres.2013.10.026 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AE2MJ UT WOS:000333806900005 PM 24522247 ER PT J AU Poser, BA Anderson, RJ Guerin, B Setsompop, K Deng, WR Mareyam, A Serano, P Wald, LL Stenger, VA AF Poser, Benedikt A. Anderson, Robert James Guerin, Bastien Setsompop, Kawin Deng, Weiran Mareyam, Azma Serano, Peter Wald, Lawrence L. Stenger, V. Andrew TI Simultaneous Multislice Excitation by Parallel Transmission SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel RF transmission; simultaneous multislice excitation; GRAPPA; SMS-pTX ID 7 T; SUSCEPTIBILITY ARTIFACTS; SLICES PINS; WHOLE-BRAIN; RF PULSES; MRI; INHOMOGENEITY; ARRAY; FIELD; FMRI AB PurposeA technique is described for simultaneous multislice (SMS) excitation using radiofrequency (RF) parallel transmission (pTX). MethodsSpatially distinct slices are simultaneously excited by applying different RF frequencies on groups of elements of a multichannel transmit array. The localized transmit sensitivities of the coil geometry are thereby exploited to reduce RF power. The method is capable of achieving SMS-excitation using single-slice RF pulses, or multiband pulses. SMS-pTX is demonstrated using eight-channel parallel RF transmission on a dual-ring pTX coil at 3 T. The effect on B-1(+) homogeneity and specific absorption rate (SAR) is evaluated experimentally and by simulations. Slice-GRAPPA reconstruction was used for separation of the collapsed slice signals. ResultsPhantom and in vivo brain data acquired with fast low-angle shot (FLASH) and blipped-controlled aliasing results in higher acceleration (CAIPIRINHA) echo-planar imaging are presented at SMS excitation factors of two, four, and six. We also show that with our pTX coil design, slice placement, and binary division of transmitters, SMS-pTX excitations can achieve the same mean flip angles excitations at approximate to 30% lower RF power than a conventional SMS approach with multiband RF pulses. ConclusionThe proposed SMS-pTX allows SMS excitations at reduced RF power by exploiting the local B-1(+) sensitivities of suitable multielement pTX arrays. Magn Reson Med 71:1416-1427, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Poser, Benedikt A.; Anderson, Robert James; Deng, Weiran; Stenger, V. Andrew] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. [Guerin, Bastien; Setsompop, Kawin; Mareyam, Azma; Serano, Peter; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Guerin, Bastien; Setsompop, Kawin; Mareyam, Azma; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Maastricht Univ, Maastricht Brain Imaging Ctr, NL-6200 MD Maastricht, Netherlands. RP Poser, BA (reprint author), Maastricht Univ, Maastricht Brain Imaging Ctr, POB 616, NL-6200 MD Maastricht, Netherlands. EM benedikt.poser@maastrichtuniversity.nl RI Guerin, Bastien/P-1412-2014; Setsompop, Kawin/P-1464-2014; Poser, Benedikt A/F-4992-2010; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; Poser, Benedikt A/0000-0001-8190-4367; FU DFG (German Science Foundation) [Po1576/1-1]; NIH [R01DA019912, R01EB011517, K02DA020569]; NCRR [G12-RR003061, P20-RR011091]; NINDS [U54-NS56883]; NIBIB [R00EB012107]; ONDCP FX Grant sponsor: DFG (German Science Foundation); Grant number: Po1576/1-1. Grant sponsor: NIH; Grant numbers: R01DA019912; R01EB011517; K02DA020569. Grant sponsor: NCRR; Grant numbers: G12-RR003061; P20-RR011091. Grant sponsor: NINDS; Grant number: U54-NS56883. Grant sponsor: NIBIB; Grant number: R00EB012107. Grant sponsor: ONDCP. NR 48 TC 14 Z9 14 U1 0 U2 5 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 APR PY 2014 VL 71 IS 4 BP 1416 EP 1427 DI 10.1002/mrm.24791 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD2CL UT WOS:000333040500008 PM 23716365 ER PT J AU Guerin, B Gebhardt, M Cauley, S Adalsteinsson, E Wald, LL AF Guerin, Bastien Gebhardt, Matthias Cauley, Steven Adalsteinsson, Elfar Wald, Lawrence L. TI Local Specific Absorption Rate (SAR), Global SAR, Transmitter Power, and Excitation Accuracy Trade-Offs in Low Flip-Angle Parallel Transmit Pulse Design SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel transmit; local SAR; global SAR; pulse power; excitation accuracy; spokes ID RF PULSES; 8 CHANNELS; MRI; INHOMOGENEITY; OPTIMIZATION; REDUCTION; COILS; TESLA AB PurposeWe propose a constrained optimization approach for designing parallel transmit (pTx) pulses satisfying all regulatory and hardware limits. We study the trade-offs between excitation accuracy, local and global specific absorption rate (SAR), and maximum and average power for small flip-angle pTx (eight channels) spokes pulses in the torso at 3 T and in the head at 7 T. MethodsWe compare the trade-offs between the above-mentioned quantities using the L-curve method. We use a primal-dual algorithm and a compressed set of local SAR matrices to design radio-frequency (RF) pulses satisfying all regulatory (including local SAR) and hardware constraints. ResultsLocal SAR can be substantially reduced (factor of 2 or more) by explicitly constraining it in the pulse design process compared to constraining global SAR or pulse power alone. This often comes at the price of increased pulse power. ConclusionSimultaneous control of power and SAR is needed for the design of pTx pulses that are safe and can be played on the scanner. Constraining a single quantity can create large increase in the others, which can then rise above safety or hardware limits. Simultaneous constraint of local SAR and power is fast enough to be applicable in a clinical setting. Magn Reson Med 71:1446-1457, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Guerin, Bastien; Cauley, Steven; Wald, Lawrence L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Gebhardt, Matthias] Siemens Healthcare, Erlangen, Germany. [Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Guerin, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM guerin@nmr.mgh.harvard.edu RI Cauley, Stephen/P-1386-2014; Guerin, Bastien/P-1412-2014; Wald, Lawrence/D-4151-2009 FU NIH [R01EB-0068547, R01EB-007942, P41EB-015896]; Siemens-MIT Alliance MKI FX Grant sponsor: NIH; Grant numbers: R01EB-0068547; R01EB-007942; P41EB-015896. Grant sponsor: Siemens-MIT Alliance MKI. NR 23 TC 26 Z9 27 U1 1 U2 8 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 APR PY 2014 VL 71 IS 4 BP 1446 EP 1457 DI 10.1002/mrm.24800 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD2CL UT WOS:000333040500011 PM 23776100 ER PT J AU Hsu, YC Chern, IL Zhao, W Gagoski, B Witzel, T Lin, FH AF Hsu, Yi-Cheng Chern, I-Liang Zhao, Wei Gagoski, Borjan Witzel, Thomas Lin, Fa-Hsuan TI Mitigate B-1(+) Inhomogeneity Using Spatially Selective Radiofrequency Excitation with Generalized Spatial Encoding Magnetic Fields SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE 7T; RF inhomogeneity; nonlinear gradient; SAR; fast imaging ID PARALLEL RF TRANSMISSION; 8 CHANNELS; 7 TESLA; COIL; PULSES; MRI; HOMOGENEITY; GRADIENTS; ARRAY; POWER AB PurposeHigh-field magnetic resonance imaging (MRI) has the challenge of inhomogeneous B-1(+), and consequently inhomogeneous flip angle distribution, which causes spatially dependent contrast and makes clinical diagnosis difficult. MethodWe propose a two-step pulse design procedure in which (1) a combination of linear and nonlinear spatial encoding magnetic fields (SEMs) is used to remap the B-1(+) map in order to reduce the dimensionality of the problem, (2) the locations, amplitudes, and phases of spoke pulses are estimated in one dimension. The advantage of this B-1(+) remapping is that when the isointensity contours of a linear combination of SEMs are similar to the isointensity contours of B-1(+), a simple pulse sequence design using time-varying SEMs can achieve a homogenous flip-angle distribution efficiently. ResultsWe demonstrate that spatially selective radiofrequency (RF) excitation with generalized SEMs (SAGS) using both linear and quadratic SEMs in a multi-spoke k-space trajectory can mitigate the B-1(+) inhomogeneity at 7T efficiently. Numerical simulations based on experimental data suggest that, compared with other methods, SAGS provide a formulation allowing multiple-pulse design, a similar average flip-angle distribution with less RF power, and/or a more homogeneous flip-angle distribution. ConclusionWithout using multiple RF coils for parallel transmission, SAGS can be used to mitigate the B-1(+) inhomogeneity in high-field MRI experiments. Magn Reson Med 71:1458-1469, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Hsu, Yi-Cheng; Chern, I-Liang] Natl Taiwan Univ, Dept Math, Taipei 10764, Taiwan. [Hsu, Yi-Cheng; Lin, Fa-Hsuan] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Zhao, Wei; Witzel, Thomas] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, Charlestown, MA USA. [Gagoski, Borjan] Boston Childrens Hosp, Ctr Fetal Neonatal Neuroimaging & Dev Sci, Boston, MA USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. RP Lin, FH (reprint author), Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. EM fhlin@ntu.edu.tw RI Witzel, Thomas/P-1402-2014; Lin, Fa-Hsuan/G-6988-2012; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Chern, I-Liang/0000-0003-1306-7936 FU National Science Council (NSC), Taiwan [101-2628-B-002-005-MY3, 100-2325-B-002-046]; Ministry of Economic Affairs, Taiwan [100-EC-17-A-19-S1-175]; National Health Research Institute, Taiwan [NHRI-EX102-10247EI]; Finland Distinguished Professor (FiDiPro) programme FX Grant sponsor: National Science Council (NSC), Taiwan; Grant number: 101-2628-B-002-005-MY3, 100-2325-B-002-046. Grant sponsor: Ministry of Economic Affairs, Taiwan; Grant number: 100-EC-17-A-19-S1-175. Grant sponsor: National Health Research Institute, Taiwan; Grant number: NHRI-EX102-10247EI. Grant sponsor: Finland Distinguished Professor (FiDiPro) programme. NR 39 TC 1 Z9 2 U1 0 U2 4 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 APR PY 2014 VL 71 IS 4 BP 1458 EP 1469 DI 10.1002/mrm.24801 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD2CL UT WOS:000333040500012 PM 23794127 ER PT J AU Duong, TQ AF Duong, Timothy Q. TI Magnetic Resonance Imaging of the Retina: From Mice to Men SO MAGNETIC RESONANCE IN MEDICINE LA English DT Review DE BOLD; choroid; blood flow; blood volume; contrast-enhanced MRI; manganese-enhanced MRI; diabetic retinopathy; glaucoma; retinal degeneration; age-related macular degeneration; ocular imaging; optical imaging; eye motion; BOLD fMRI; visual stimulation ID MANGANESE-ENHANCED MRI; BLOOD-FLOW MRI; EXPERIMENTAL DIABETIC-RETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY; DBA/2J MOUSE MODEL; IN-VIVO; OXYGENATION RESPONSE; FUNCTIONAL MRI; RAT RETINA; VASCULAR LAYERS AB This mini-review provides an overview of magnetic resonance imaging (MRI) applications to study rodent, cat, non-human primate, and human retinas. These techniques include T-1- and T-2-weighted anatomical, diffusion, blood flow, blood volume, blood-oxygenation level dependent, manganese-enhanced, physiological, and functional MRI. Applications to study the retinas in diabetic retinopathy, glaucoma, and retinal degeneration are also reviewed. MRI offers some unique advantages compared with existing imaging techniques and has the potential to further our understanding of physiology and function in healthy and diseased retinas. Magn Reson Med 71:1526-1530, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, South Texas Vet Hlth Care Syst, Dept Ophthalmol, San Antonio, TX 78229 USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu FU NIH/NEI [EY014211, EY018855]; CA MERIT FX Grant sponsor: NIH/NEI; Grant numbers: EY014211, EY018855; Grant sponsor: CA MERIT. NR 56 TC 6 Z9 6 U1 0 U2 17 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 APR PY 2014 VL 71 IS 4 BP 1526 EP 1530 DI 10.1002/mrm.24797 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD2CL UT WOS:000333040500019 PM 23716429 ER PT J AU Guilinger, JP Pattanayak, V Reyon, D Tsai, SQ Sander, JD Joung, JK Liu, DR AF Guilinger, John P. Pattanayak, Vikram Reyon, Deepak Tsai, Shengdar Q. Sander, Jeffry D. Joung, J. Keith Liu, David R. TI Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity SO NATURE METHODS LA English DT Article ID ZINC-FINGER NUCLEASES; EFFECTOR NUCLEASES; GENOME; KNOCKOUT; REVEALS; DISEASE; SYSTEM; ZFNS AB Although transcription activator-like effector nucleases (TALENs) can be designed to cleave chosen DNA sequences, TALENs have activity against related off-target sequences. To better understand TALEN specificity, we profiled 30 unique TALENs with different target sites, array length and domain sequences for their abilities to cleave any of 10(12) potential off-target DNA sequences using in vitro selection and high-throughput sequencing. Computational analysis of the selection results predicted 76 off-target substrates in the human genome, 16 of which were accessible and modified by TALENs in human cells. The results suggest that (i) TALE repeats bind DNA relatively independently; (ii) longer TALENs are more tolerant of mismatches yet are more specific in a genomic context; and (iii) excessive DNA-binding energy can lead to reduced TALEN specificity in cells. Based on these findings, we engineered a TALEN variant that exhibits equal on-target cleavage activity but tenfold lower average off-target activity in human cells. C1 [Guilinger, John P.; Pattanayak, Vikram; Liu, David R.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Guilinger, John P.; Pattanayak, Vikram; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. [Reyon, Deepak; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Reyon, Deepak; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu FU Defense Advanced Research Projects Agency [HR0011-11-2-0003, N66001-12-C-4207]; US National Institutes of Health (NIH) [NIGMS R01 GM095501]; Howard Hughes Medical Institute (HHMI); US National Institute of General Medical Sciences [T32GM007753]; NIH [DP1 GM105378]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award FX J.P.G., V.P. and D.R.L. were supported by Defense Advanced Research Projects Agency HR0011-11-2-0003 and N66001-12-C-4207, US National Institutes of Health (NIH) NIGMS R01 GM095501 (D.R.L.), and the Howard Hughes Medical Institute (HHMI). D.R.L. was supported as a HHMI Investigator. V.P. was supported by award T32GM007753 from US National Institute of General Medical Sciences. D.R., S.Q.T., J.D.S. and J.K.J. were supported by a NIH Director Pioneer Award (DP1 GM105378). J.K.J. was supported by the Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. We thank M. L. Maeder for preforming transfections and isolating genomic DNA, and C. Khayter and M. Goodwin for technical assistance. NR 36 TC 78 Z9 80 U1 1 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD APR PY 2014 VL 11 IS 4 BP 429 EP + DI 10.1038/nmeth.2845 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AE1SL UT WOS:000333749900026 PM 24531420 ER PT J AU Driver, TH Loh, AR Joseph, D Keenan, JD Naseri, A AF Driver, Todd H. Loh, Allison R. Joseph, Damien Keenan, Jeremy D. Naseri, Ayman TI Predictors of Matching in Ophthalmology Residency for International Medical Graduates SO OPHTHALMOLOGY LA English DT Editorial Material C1 [Driver, Todd H.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Loh, Allison R.; Keenan, Jeremy D.; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Joseph, Damien] San Francisco Match Program, San Francisco, CA USA. [Keenan, Jeremy D.; Naseri, Ayman] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Naseri, Ayman] San Francisco Vet Adm Med Ctr, Dept Ophthalmol, San Francisco, CA USA. RP Driver, TH (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. NR 5 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 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2014 VL 121 IS 4 BP 974 EP + PG 7 WC Ophthalmology SC Ophthalmology GA AE2MV UT WOS:000333808100033 PM 24433973 ER PT J AU Villiger, M Bouma, BE AF Villiger, Martin Bouma, Brett E. TI Practical decomposition for physically admissible differential Mueller matrices SO OPTICS LETTERS LA English DT Article ID POLARIZATION OPTICS; DEPOLARIZING MEDIA; ANISOTROPIC MEDIA; UNIFORM MEDIA AB The differential Mueller matrix expresses the local action of an optical medium on the evolution of a propagating electromagnetic field, including partially coherent and partially polarized waves. Here, we present a derivation of the differential Mueller matrix from the canonical form of Type I Mueller matrices without making use of the exponential generators of uniform media. We demonstrate how to practically obtain this parameterization numerically using an eigenvalue decomposition and find validity criteria to ensure that the matrix satisfies the constraints of a physical system. This provides a convenient tool-set to investigate depolarization effects and extends previous treatments of the differential Mueller matrix formalism. (C) 2014 Optical Society of America C1 [Villiger, Martin; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Villiger, Martin; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bouma, Brett E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Villiger, M (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM mvilliger@partners.org FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [P41 EB015903]; Terumo Corporation; Swiss National Science Foundation FX Research in this publication was supported in part by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health, award P41 EB015903, and by Terumo Corporation. MV was supported by a fellowship from the Swiss National Science Foundation. NR 11 TC 11 Z9 11 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD APR 1 PY 2014 VL 39 IS 7 BP 1779 EP 1782 DI 10.1364/OL.39.001779 PG 4 WC Optics SC Optics GA AE3PG UT WOS:000333887800019 PM 24686603 ER PT J AU Quinones, AR Richardson, J Freeman, M Fu, R O'Neil, ME Motu'apuaka, M Kansagara, D AF Quinones, Ana R. Richardson, Jeannette Freeman, Michele Fu, Rochelle O'Neil, Maya E. Motu'apuaka, Makalapua Kansagara, Devan TI Educational group visits for the management of chronic health conditions: A systematic review SO PATIENT EDUCATION AND COUNSELING LA English DT Review DE Group visits; Chronic disease; Health education; Chronic disease self-management ID RANDOMIZED-CONTROLLED-TRIAL; DIABETES SELF-MANAGEMENT; OBSTRUCTIVE PULMONARY-DISEASE; COGNITIVE-BEHAVIORAL THERAPY; CENTERED MEDICAL HOME; RHEUMATOID-ARTHRITIS; MEXICAN-AMERICANS; OLDER-ADULTS; PRIMARY-CARE; PATIENT EDUCATION AB Objective: Review the effectiveness of group visits (appointments of multiple patients) on quality of life, function, self-efficacy, utilization, and biophysical outcomes in randomized controlled trials of patients with chronic conditions. Methods: We searched MEDLINE (R), Cochrane, CINAHL, and PsycINFO to January 2013 for English-language trials of educational group visits led by non-prescribing facilitators (e.g., peer educators). Results: We report on 80 arthritis/falls (n = 22), asthma/COPD (n = 10), CHF/hypertension (n = 12), diabetes (n = 29), multiple conditions (n = 4), and pain (n = 4) studies. We found moderate evidence of improved short-term self-efficacy in patients with arthritis (10 studies) and diabetes (10 studies). We found no consistent evidence of improved quality of life; however a moderately strong body of evidence suggests peer-led community-based programs might improve quality of life and utilization in patients with multiple chronic conditions. Meta-analyses found short- (14 studies; mean change HbA1c = -0.27, CI = -0.44, 0.11) and long-term (10 studies; mean change HbA1c = -0.23, Cl = -0.44, -0.02) glycemic improvement. Conclusions: Group visits may improve self-efficacy and glycemic control. There was little consistent evidence of improved quality of life, functional status, or utilization. Practice implications: Group visits represent a reasonable alternative for educating patients with chronic illness, though varied participation/retention suggests they should not be the sole alternative. Published by Elsevier Ireland Ltd. C1 [Quinones, Ana R.; Richardson, Jeannette; Freeman, Michele; Fu, Rochelle; O'Neil, Maya E.; Motu'apuaka, Makalapua; Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA. [Quinones, Ana R.; Fu, Rochelle; O'Neil, Maya E.; Kansagara, Devan] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Quinones, AR (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,CB669, Portland, OR 97239 USA. EM quinones@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Evidence-based Synthesis Program (ESP) [05-225]; American Diabetes Association [7-13-CD-08] FX Funders: The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Evidence-based Synthesis Program (ESP) project #05-225. Dr. Quinones is a Health Science Specialist at the Portland VA Medical Center. Dr. Quinones is also supported by American Diabetes Association Grant 7-13-CD-08. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs nor the American Diabetes Association. NR 107 TC 6 Z9 6 U1 6 U2 24 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 APR PY 2014 VL 95 IS 1 BP 3 EP 29 DI 10.1016/j.pec.2013.12.021 PG 27 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AE6GJ UT WOS:000334088300002 PM 24468199 ER PT J AU An, CR Shi, YJ Li, PY Hu, XM Gan, Y Stetler, RA Leak, RK Gao, YQ Sun, BL Zheng, P Chen, J AF An, Chengrui Shi, Yeije Li, Peiying Hu, Xiaoming Gan, Yu Stetler, Ruth A. Leak, Rehana K. Gao, Yanqin Sun, Bao-Liang Zheng, Ping Chen, Jun TI Molecular dialogs between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Cerebral ischemic injury; Innate immunity; Inflammation; Brain repair ID FOCAL CEREBRAL-ISCHEMIA; REGULATORY T-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERCELLULAR-ADHESION MOLECULE-1; MYELIN BASIC-PROTEIN; NEURAL STEM-CELLS; CHOLINERGIC ANTIINFLAMMATORY PATHWAY AB Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd. C1 [An, Chengrui; Shi, Yeije; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, State Key Laboratoty Med Neurobiol, Shanghai 200032, Peoples R China. [An, Chengrui; Shi, Yeije; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Sun, Bao-Liang] Taishan Med Univ, Affiliated Hosp, Dept Neurol, Key Lab Cerebral Microcirculat Univ Shandong, Tai An 271000, Shandong, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Shi, Yeije; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Shi, Yeije; Hu, Xiaoming; Stetler, Ruth A.; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Chen, J (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15260 USA. EM blsun88@163.com; pzheng@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU NIH [NS036736, NS045048, NS056118]; AHA grant [13SDG14570025]; Chinese Natural Science Foundation [81271275, 81070947, 30770759, 81020108021, 81171149, 81228008]; Natural Science Foundation of Shandong [ZR2012HZ006]; Department of Veterans Affairs; RK Mellon Endowed Chair for Cerebrovascular Disease Research from the University of Pittsburgh Medical Center FX This work was supported by NIH grants NS036736, NS045048, and NS056118 (to J.C.), AHA grant 13SDG14570025 (to X.H.), Chinese Natural Science Foundation grants (81271275, 81070947 and 30770759 to B-L Sun; 81020108021 and 81171149 to Y.G.; and 81228008 to J.C. and P.Z.), Natural Science Foundation of Shandong grant ZR2012HZ006 (to B-L Sun). J.C. is a recipient of the Research Career Scientist Award from Department of Veterans Affairs and the RK Mellon Endowed Chair for Cerebrovascular Disease Research from the University of Pittsburgh Medical Center. We thank Dr. Beth Fischer for editorial assistance. NR 262 TC 48 Z9 50 U1 7 U2 43 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2014 VL 115 SI SI BP 6 EP 24 DI 10.1016/j.pneurobio.2013.12.002 PG 19 WC Neurosciences SC Neurosciences & Neurology GA AE6ET UT WOS:000334084100002 PM 24374228 ER PT J AU Leng, TD Shi, YJ Xiong, ZG Sun, DD AF Leng, Tiandong Shi, Yejie Xiong, Zhi-Gang Sun, Dandan TI Proton-sensitive cation channels and ion exchangers in ischemic brain injury: New therapeutic targets for stroke? SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Acidosis; ASIC; Calcium; NHE1; TRPM7; Zinc ID FOCAL CEREBRAL-ISCHEMIA; POTENTIAL MELASTATIN 7; SODIUM-HYDROGEN EXCHANGE; MOUSE CORTICAL-NEURONS; CENTRAL-NERVOUS-SYSTEM; ACID-EVOKED CURRENTS; UNCONDITIONED FEAR RESPONSES; ARTERY OCCLUSION MODEL; EXCITATORY AMINO-ACIDS; CANCER CELL-MIGRATION AB Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. Disruption of ionic homeostasis plays an important role in cell death following cerebral ischemia. Glutamate receptor-mediated ionic imbalance and neurotoxicity have been well established in cerebral ischemia after stroke. However, non-NMDA receptor-dependent mechanisms, involving acid-sensing ion channel 1 a (ASIC1a), transient receptor potential melastatin 7 (TRPM7), and Na+/H+ exchanger isoform 1 (NHE1), have recently emerged as important players in the dysregulation of ionic homeostasis in the CNS under ischemic conditions. These H+-sensitive channels and/or exchangers are expressed in the majority of cell types of the neurovascular unit. Sustained activation of these proteins causes excessive influx of cations, such as Ca2+, Na+, and Zn2+, and leads to ischemic reperfusion brain injury. In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Leng, Tiandong; Xiong, Zhi-Gang] Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA. [Shi, Yejie; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. RP Sun, DD (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, S-598 South Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15213 USA. EM zxiong@msm.edu; sund@upmc.edu OI Shi, Yejie/0000-0001-7502-9201 FU NIH [R01-NS48216, R01-NS38118, R01-NS66027]; NIMHD [S21-MD000101, U54NS083932]; ALZ [IIRG-10-173350] FX This work was supported by the NIH grants R01-NS48216 and R01-NS38118 (D. Sun), NIH R01-NS66027, NIMHD S21-MD000101, U54NS083932, and ALZ IIRG-10-173350 (Z. Xiong). NR 357 TC 25 Z9 26 U1 3 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2014 VL 115 SI SI BP 189 EP 209 DI 10.1016/j.pneurobio.2013.12.008 PG 21 WC Neurosciences SC Neurosciences & Neurology GA AE6ET UT WOS:000334084100010 PM 24467911 ER PT J AU Gendron, M Roberson, D van der Vyver, JM Barrett, LF AF Gendron, Maria Roberson, Debi van der Vyver, Jacoba Marieta Barrett, Lisa Feldman TI Cultural Relativity in Perceiving Emotion From Vocalizations SO PSYCHOLOGICAL SCIENCE LA English DT Article DE affect; vocalizations; cross-cultural differences; emotions ID FACIAL EXPRESSIONS; ACTION IDENTIFICATION; VOCAL EXPRESSION; BASIC EMOTIONS; RECOGNITION; PERCEPTION; UNIVERSAL; BEHAVIOR; ACCENTS AB A central question in the study of human behavior is whether certain emotions, such as anger, fear, and sadness, are recognized in nonverbal cues across cultures. We predicted and found that in a concept-free experimental task, participants from an isolated cultural context (the Himba ethnic group from northwestern Namibia) did not freely label Western vocalizations with expected emotion terms. Responses indicate that Himba participants perceived more basic affective properties of valence (positivity or negativity) and to some extent arousal (high or low activation). In a second, concept-embedded task, we manipulated whether the target and foil on a given trial matched in both valence and arousal, neither valence nor arousal, valence only, or arousal only. Himba participants achieved above-chance accuracy only when foils differed from targets in valence only. Our results indicate that the voice can reliably convey affective meaning across cultures, but that perceptions of emotion from the voice are culturally variable. C1 [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Affect Sci Inst, Boston, MA 02115 USA. [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Roberson, Debi] Univ Essex, Dept Psychol, Colchester CO4 3SQ, Essex, England. [van der Vyver, Jacoba Marieta] Univ Namibia, Sch Nursing & Publ Hlth, Windhoek, Namibia. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 253 Nightingale Hall, Boston, MA 02115 USA. EM l.barrett@neu.edu RI Roberson, Debi/C-1612-2009 OI Roberson, Debi/0000-0002-6778-8547 FU NIH HHS [DP1 OD003312, DP1OD003312] NR 39 TC 14 Z9 15 U1 4 U2 27 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD APR PY 2014 VL 25 IS 4 BP 911 EP 920 DI 10.1177/0956797613517239 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AE5HE UT WOS:000334017600007 PM 24501109 ER PT J AU Ikeda, A Schwartz, J Peters, JL Baccarelli, AA Hoxha, M Dioni, L Spiro, A Sparrow, D Vokonas, P Kubzansky, LD AF Ikeda, Ai Schwartz, Joel Peters, Junenette L. Baccarelli, Andrea A. Hoxha, Mirjam Dioni, Laura Spiro, Avron Sparrow, David Vokonas, Pantel Kubzansky, Laura D. TI Pessimistic orientation in relation to telomere length in older men: The VA Normative Aging Study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Optimism; Pessimism; Telomere length ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; LONGITUDINAL FINDINGS; OPTIMISM-PESSIMISM; OXIDATIVE STRESS; HEART-DISEASE; RISK-FACTOR; LIFE; HEALTH; INFLAMMATION AB Background: Recent research suggests pessimistic orientation is associated with shorter leukocyte telomere length (LTL). However, this is the first study to look not only at effects of pessimistic orientation on average LTL at multiple time points, but also at effects on the rate of change in LTL over time. Methods: Participants were older men from the VA Normative Aging Study (n = 490). The life orientation test (LOT) was used to measure optimistic and pessimistic orientations at study baseline, and relative LTL by telomere to single copy gene ratio (T:5 ratio) was obtained repeatedly over the course of the study (1999-2008). A total of 1010 observations were included in the analysis. Linear mixed effect models with a random subject intercept were used to estimate associations. Results: Higher pessimistic orientation scores were associated with shorter average LTL (percent difference by 1-SD increase in pessimistic orientation (95% CI): -3.08 (-5.62, -0.46)), and the finding was maintained after adjusting for the higher likelihood that healthier individuals return for follow-up visits (-3.44 (-5.95, 0.86)). However, pessimistic orientation scores were not associated with rate of change in LTL over time. No associations were found between overall optimism and optimistic orientation subscale scores and LTL. Conclusion: Higher pessimistic orientation scores were associated with shorter LTL in older men. While there was no evidence that pessimistic orientation was associated with rate of change in LTL over time, higher levels of pessimistic orientation were associated with shorter LTL at baseline and this association persisted over time. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ikeda, Ai; Kubzansky, Laura D.] Harvard Univ, Dept Social & Behav Sci, Sch Publ Hlth, Boston, MA 02115 USA. [Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02115 USA. [Peters, Junenette L.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Hoxha, Mirjam; Dioni, Laura] Maggiore Hosp, Ctr Mol & Genet Epidemiol, IRCCS, Milan, Italy. [Hoxha, Mirjam; Dioni, Laura] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. [Spiro, Avron] Boston Univ, Sch Publ Hlth, Dept Epidemiol, VA Normat Aging Study,VA Boston Healthcare Syst, Boston, MA USA. [Spiro, Avron] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Sparrow, David; Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, VA Normat Aging Study,VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Kubzansky, LD (reprint author), Harvard Univ, Dept Social & Behav Sci, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM lkubzans@hsph.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640 FU Robert Wood Johnson Foundation's Pioneer Portfolio [NIEHS 2RO1-ES015172, NIH AG018436]; Cooperative Studies Program/ERIC; US Department of Veterans Affairs; Research Career Scientist awards for VA Clinical Science RD Service FX This study was supported by the Robert Wood Johnson Foundation's Pioneer Portfolio,through a grant, "Exploring Concepts of Positive Health", NIEHS 2RO1-ES015172, and NIH AG018436. The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). This study was also supported by a Research Career Scientist awards for VA Clinical Science R&D Service to Avron Spiro, III and to David Sparrow. NR 44 TC 5 Z9 5 U1 1 U2 4 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 APR PY 2014 VL 42 BP 68 EP 76 DI 10.1016/j.psyneuen.2014.01.001 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AE5AM UT WOS:000334000200008 PM 24636503 ER PT J AU Opherk, C Gonik, M Duering, M Malik, R Jouvent, E Herve, D Adib-Samii, P Bevan, S Pianese, L Silvestri, S Dotti, MT De Stefano, N Liem, M Boon, EMJ Pescini, F Pachai, C Bracoud, L Muller-Myhsok, B Meitinger, T Rost, N Pantoni, L Oberstein, SL Federico, A Ragno, M Markus, HS Tournier-Lasserve, E Rosand, J Chabriat, H Dichgans, M AF Opherk, Christian Gonik, Mariya Duering, Marco Malik, Rainer Jouvent, Eric Herve, Dominique Adib-Samii, Poneh Bevan, Steve Pianese, Luigi Silvestri, Serena Dotti, Maria Teresa De Stefano, Nicola Liem, Michael Boon, Elles M. J. Pescini, Francesca Pachai, Chahin Bracoud, Luc Mueller-Myhsok, Bertram Meitinger, Thomas Rost, Natalia Pantoni, Leonardo Oberstein, Saskia Lesnik Federico, Antonio Ragno, Michele Markus, Hugh S. Tournier-Lasserve, Elisabeth Rosand, Jonathan Chabriat, Hugues Dichgans, Martin TI Genome-Wide Genotyping Demonstrates a Polygenic Risk Score Associated With White Matter Hyperintensity Volume in CADASIL SO STROKE LA English DT Article DE CADASIL; cerebral small vessel diseases; genetics; genome-wide association study; leukoaraiosis ID SMALL VESSEL DISEASE; HERITABILITY; LESIONS; STROKE; SCAN AB Background and Purpose White matter hyperintensities (WMH) on MRI are a quantitative marker for sporadic cerebral small vessel disease and are highly heritable. To date, large-scale genetic studies have identified only a single locus influencing WMH burden. This might in part relate to biological heterogeneity of sporadic WMH. The current study searched for genetic modifiers of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease. Methods We performed a genome-wide association study to identify quantitative trait loci for WMH volume by combining data from 517 CADASIL patients collected through 7 centers across Europe. WMH volumes were centrally analyzed and quantified on fluid attenuated inversion recovery images. Genotyping was performed using the Affymetrix 6.0 platform. Individuals were assigned to 2 distinct genetic clusters (cluster 1 and cluster 2) based on their genetic background. Results Four hundred sixty-six patients entered the final genome-wide association study analysis. The phenotypic variance of WMH burden in CADASIL explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21), suggesting a substantial genetic contribution. Using cluster 1 as derivation and cluster 2 as a validation sample, a polygenic score was significantly associated with WMH burden (P=0.001) after correction for age, sex, and vascular risk factors. No single nucleotide polymorphism reached genome-wide significance. Conclusions We found a polygenic score to be associated with WMH volume in CADASIL subjects. Our findings suggest that multiple variants with small effects influence WMH burden in CADASIL. The identification of these variants and the biological pathways involved will provide insights into the pathophysiology of white matter disease in CADASIL and possibly small vessel disease in general. C1 [Opherk, Christian; Gonik, Mariya; Duering, Marco; Malik, Rainer; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, D-83177 Munich, Germany. [Opherk, Christian] Univ Munich, Dept Neurol, Klinikum Univ Munchen, D-83177 Munich, Germany. [Jouvent, Eric; Chabriat, Hugues] Hop Lariboisiere, AP HP, Dept Neurol, DHU NeuroVasc, F-75475 Paris, France. [Herve, Dominique; Tournier-Lasserve, Elisabeth] Univ Paris Diderot, Sorbonne Paris Cite, INSERM UMR S740, Paris, France. [Adib-Samii, Poneh; Bevan, Steve] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Pianese, Luigi; Silvestri, Serena; Ragno, Michele] Mazzoni Hosp, Div Neurol, Ascoli Piceno, Italy. [Pianese, Luigi; Silvestri, Serena; Ragno, Michele] Mazzoni Hosp, Mol Med Sect, Ascoli Piceno, Italy. [Dotti, Maria Teresa; De Stefano, Nicola; Federico, Antonio] Univ Siena, Dept Med Surg & Neurosci, I-53100 Siena, Italy. [Liem, Michael] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Boon, Elles M. J.; Oberstein, Saskia Lesnik] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Pianese, Luigi; Pescini, Francesca] Azienda Ospedaliero Univ Careggi, Stroke Unit, Florence, Italy. [Pachai, Chahin; Bracoud, Luc] BioClin Inc, Lyon, France. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Meitinger, Thomas] Helmholtz Ctr, Inst Human Genet, Munich, Germany. [Rost, Natalia; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rost, Natalia; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Dichgans, M (reprint author), Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Marchioninistr 15, D-83177 Munich, Germany. EM martin.dichgans@med.uni-muenchen.de RI Meitinger, Thomas/O-1318-2015; Lesnik Oberstein, Saskia/C-3643-2016; Chabriat, Hugues/G-5699-2010; OI Chabriat, Hugues/0000-0001-8436-6074; Jouvent, Eric/0000-0001-7797-2236; federico, antonio/0000-0002-5246-1621; Bevan, Steve/0000-0003-0490-6830; Pescini, Francesca/0000-0003-4565-5601 FU Corona Foundation; Vascular Dementia Research Foundation; Deutsche Forschungsgemeinschaft [OP 212/1-1]; Dr Werner Jackstadt Foundation; Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain); American Heart Association-Bugher Foundation; Massachusetts General Hospital Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; National Institute of Neurological Disorders and Stroke [5P50NS051343, R01NS059727]; National Institute for Health Research Senior Investigator award; MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca) programmi di ricerca cofinanziati (MIUR) [2006065719, 20095JPSNA]; Regione Toscana, programma per la Ricerca Regionale in Materia di Salute [AOO GRT 190899/Q.20.70.20] FX This study was supported by the Corona Foundation, the Vascular Dementia Research Foundation, the Deutsche Forschungsgemeinschaft (OP 212/1-1), the Dr Werner Jackstadt Foundation, Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain), the American Heart Association-Bugher Foundation, the Massachusetts General Hospital Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and the National Institute of Neurological Disorders and Stroke (5P50NS051343; R01NS059727). Dr Markus is supported by a National Institute for Health Research Senior Investigator award. Drs Pianese and Pescini were supported by MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca) programmi di ricerca cofinanziati-2006 (MIUR 2006-prot. 2006065719) and programmi di ricerca cofinanziati-2009 (MIUR 2009-prot. 20095JPSNA) and Regione Toscana, programma per la Ricerca Regionale in Materia di Salute, 2009 (Evaluation of NOTCH3 mutations and correlation with clinical phenotypes; prot. reg. AOO GRT 190899/Q.20.70.20). NR 22 TC 9 Z9 9 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2014 VL 45 IS 4 BP 968 EP 972 DI 10.1161/STROKEAHA.113.004461 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AD5OS UT WOS:000333303400017 PM 24578207 ER PT J AU Jha, R Battey, TWK Pham, L Lorenzano, S Furie, KL Sheth, KN Kimberly, WT AF Jha, Ruchira Battey, Thomas W. K. Pham, Ly Lorenzano, Svetlana Furie, Karen L. Sheth, Kevin N. Kimberly, W. Taylor TI Fluid-Attenuated Inversion Recovery Hyperintensity Correlates With Matrix Metalloproteinase-9 Level and Hemorrhagic Transformation in Acute Ischemic Stroke SO STROKE LA English DT Article DE brain edema; brain ischemia; hemorrhage; magnetic resonance imaging; matrix metalloproteinases; stroke ID SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; THROMBOLYTIC THERAPY; MATRIX METALLOPROTEINASES; INJURY; MRI; INHIBITION; MECHANISMS; PREDICT AB Background and Purpose Matrix metalloproteinase-9 (MMP-9) is elevated in patients with acute stroke who later develop hemorrhagic transformation (HT). It is controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity on brain MRI predicts hemorrhagic transformation (HT). We assessed whether FLAIR hyperintensity was associated with MMP-9 and HT. Methods We analyzed a prospectively collected cohort of acute stroke subjects with acute brain MRI images and MMP-9 values within the first 12 hours after stroke onset. FLAIR hyperintensity was measured using a signal intensity ratio between the stroke lesion and corresponding normal contralateral hemisphere. MMP-9 was measured using enzyme-linked immunosorbent assay. The relationships between FLAIR ratio (FR), MMP-9, and HT were evaluated. Results A total of 180 subjects were available for analysis. Patients were imaged with brain MRI at 5.64.3 hours from last seen well time. MMP-9 blood samples were drawn within 7.7 +/- 4.0 hours from last seen well time. The time to MRI (r=0.17, P=0.027) and MMP-9 level (r=0.29, P<0.001) were each associated with FR. The association between MMP-9 and FR remained significant after multivariable adjustment (P<0.001). FR was also associated with HT and symptomatic hemorrhage (P=0.012). Conclusions FR correlates with both MMP-9 level and risk of hemorrhage. FLAIR changes in the acute phase of stroke may predict hemorrhagic transformation, possibly as a reflection of altered blood-brain barrier integrity. C1 [Jha, Ruchira; Battey, Thomas W. K.; Pham, Ly; Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lorenzano, Svetlana] Univ Roma La Sapienza, Policlin Umberto Hosp 1, Dept Neurol & Psychiat, I-00185 Rome, Italy. [Furie, Karen L.] Brown Univ, Warren Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Sheth, Kevin N.] Yale New Haven Med Ctr, Dept Neurol, New Haven, CT 06504 USA. RP Kimberly, WT (reprint author), Lunder 644,55 Fruit St, Boston, MA 02114 USA. EM wtkimberly@partners.org FU National Institutes of Health (NIH) [1K23NS076597]; NIH [5P50NS051343-07] FX This study was supported in part by the National Institutes of Health (NIH) 1K23NS076597 (to W. T. K.). The original enrollment of the subjects and collection of the samples was supported by NIH 5P50NS051343-07 (to K.L.F.). NR 33 TC 13 Z9 15 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2014 VL 45 IS 4 BP 1040 EP 1045 DI 10.1161/STROKEAHA.113.004627 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AD5OS UT WOS:000333303400029 PM 24619394 ER PT J AU Favre, I Zeffiro, TA Detante, O Krainik, A Hommel, M Jaillard, A AF Favre, Isabelle Zeffiro, Thomas A. Detante, Olivier Krainik, Alexandre Hommel, Marc Jaillard, Assia TI Upper Limb Recovery After Stroke Is Associated With Ipsilesional Primary Motor Cortical Activity A Meta-Analysis SO STROKE LA English DT Article DE biomarkers; functional neuroimaging; magnetic resonance imaging; motor cortex; positron-emission tomography ID SENSORIMOTOR CORTEX ACTIVATION; SUBCORTICAL STROKE; FUNCTIONAL MRI; REORGANIZATION; FMRI; INFARCTION; BRAIN; CONNECTIVITY; PLASTICITY; HEMISPHERE AB Background and Purpose Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. Methods Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke. Results When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems. Conclusions Activity in ipsilesional primary motor and medial-premotor cortices in chronic stroke signals good motor recovery, whereas cerebellar vermis activity signals poor recovery. Functional MRI may be useful in identifying recovery biomarkers. C1 [Favre, Isabelle; Detante, Olivier] CHU Grenoble, Unite Neurovasc, F-38043 Grenoble, France. [Krainik, Alexandre] CHU Grenoble, Unite IRM, F-38043 Grenoble, France. [Krainik, Alexandre; Jaillard, Assia] CHU Grenoble, Unite IRM Rech IRMaGe Inserm CNRS UMS 3T US17 355, F-38043 Grenoble, France. [Hommel, Marc; Jaillard, Assia] CHU Grenoble, F-38043 Grenoble, France. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. RP Jaillard, A (reprint author), Unite IRM 3T Rech CHU Grenoble CS 10217, F-38043 Grenoble 9, France. EM Assia.Jaillard@ujf-grenoble.fr RI KRAINIK, Alexandre/L-5874-2014; Detante, Olivier/M-1737-2014; krainik, alexandre/I-2431-2015 FU PHRC 2010 Hermes FX National grant: PHRC 2010 Hermes (HEuristic multiparameter MRI study to assess autologous MEsenchymatous stem cells therapy in subacute stroke). NR 41 TC 16 Z9 17 U1 1 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2014 VL 45 IS 4 BP 1077 EP 1083 DI 10.1161/STROKEAHA.113.003168 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AD5OS UT WOS:000333303400035 PM 24525953 ER PT J AU Boulouis, G Dumas, A Betensky, RA Brouwers, HB Fotiadis, P Vashkevich, A Ayres, A Schwab, K Romero, JM Smith, EE Viswanathan, A Goldstein, JN Rosand, J Gurol, ME Greenberg, SM AF Boulouis, Gregoire Dumas, Andrew Betensky, Rebecca A. Brouwers, H. Bart Fotiadis, Panagiotis Vashkevich, Anastasia Ayres, Alison Schwab, Kristin Romero, Javier M. Smith, Eric E. Viswanathan, Anand Goldstein, Joshua N. Rosand, Jonathan Gurol, M. Edip Greenberg, Steven M. TI Anatomic Pattern of Intracerebral Hemorrhage Expansion Relation to CT Angiography Spot Sign and Hematoma Center SO STROKE LA English DT Article DE cerebral hemorrhage AB Background and Purpose We sought to identify baseline determinants of the anatomic pattern of hematoma expansion in patients with intracerebral hemorrhage and spot sign. Methods We coregistered baseline and follow-up CT scans from 15 intracerebral hemorrhage patients and measured growth at each surface node from baseline to follow-up hematoma. We analyzed the effects of proximity to the spot sign or hematoma center on distance of expansion, controlling for covariates. Results There was substantial node-to-node variation in the extent of expansion around each hematoma surface (mean coefficient of variation for expansion distance, 0.43; 95% confidence interval, 0.39-0.48), indicating nonuniform expansion. Closer proximity to the hematoma center was independently associated with increased expansion (0.185 mm greater expansion for each 1 mm closer to the center; P<0.0001). Closer proximity to the spot sign was not independently associated with increased expansion in models including both terms. Conclusions Hemorrhages expand nonuniformly around their surface with a tendency for greater expansion closer to their center. These findings provide a novel framework for analyzing mechanisms underlying hemorrhage growth and response to treatment. C1 [Boulouis, Gregoire; Dumas, Andrew; Brouwers, H. Bart; Fotiadis, Panagiotis; Vashkevich, Anastasia; Ayres, Alison; Schwab, Kristin; Viswanathan, Anand; Gurol, M. Edip; Greenberg, Steven M.] Harvard Univ, Sch Med, Dept Neurol, Hemorrhag Stroke Res Program,Massachusetts Gen Ho, Boston, MA 02115 USA. [Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Div Neuroradiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. RP Greenberg, SM (reprint author), MGH Stroke Res Ctr, 175 Cambridge St, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Goldstein, Joshua/H-8953-2016; Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Smith, Eric/0000-0003-3956-1668; Boulouis, Gregoire/0000-0001-8422-9205 FU National Institutes of Health [R01 AG26484, R01 NS073344, P50 NS051343] FX This work was supported by National Institutes of Health grants R01 AG26484, R01 NS073344, and P50 NS051343. NR 10 TC 6 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2014 VL 45 IS 4 BP 1154 EP 1156 DI 10.1161/STROKEAHA.114.004844 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AD5OS UT WOS:000333303400047 PM 24603066 ER PT J AU Wijdicks, EFM Sheth, KN Carter, BS Greer, DM Kasner, SE Kimberly, WT Schwab, S Smith, EE Tamargo, RJ Wintermark, M AF Wijdicks, Eelco F. M. Sheth, Kevin N. Carter, Bob S. Greer, David M. Kasner, Scott E. Kimberly, W. Taylor Schwab, Stefan Smith, Eric E. Tamargo, Rafael J. Wintermark, Max CA Amer Heart Assoc Stroke Council TI Recommendations for the Management of Cerebral and Cerebellar Infarction With Swelling A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association SO STROKE LA English DT Review DE AHA Scientific Statements; brain edema; decompressive craniectomy; infarction; patient care management; prognosis; stroke ID ACUTE ISCHEMIC-STROKE; ARTERY TERRITORY INFARCTION; INCREASED INTRACRANIAL-PRESSURE; EARLY DECOMPRESSIVE CRANIECTOMY; BRAIN-BARRIER PERMEABILITY; QUALITY-OF-LIFE; COMPUTED-TOMOGRAPHY; SURGICAL-TREATMENT; MALIGNANT COURSE; HEMISPHERIC STROKE AB Background and Purpose There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere. Methods The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review. Results Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients 60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients. Conclusions Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent. C1 [Wijdicks, Eelco F. M.] Mayo Clin, Rochester, MN 55905 USA. [Sheth, Kevin N.; Greer, David M.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Carter, Bob S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Kasner, Scott E.] Univ Penn, Philadelphia, PA 19104 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schwab, Stefan] Univ Hosp Erlangen, Erlangen, Germany. [Smith, Eric E.] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Tamargo, Rafael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Wintermark, Max] Univ Virginia, Charlottesville, VA 22903 USA. RP Wijdicks, EFM (reprint author), Mayo Clin, Rochester, MN 55905 USA. RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Wintermark, Max/0000-0002-6726-3951 NR 159 TC 66 Z9 75 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2014 VL 45 IS 4 BP 1222 EP 1238 DI 10.1161/01.str.0000441965.15164.d6 PG 17 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AD5OS UT WOS:000333303400062 PM 24481970 ER PT J AU Merlin, JS Walcott, MM Herbey, I Chamot, E Ritchie, C Saag, MS Kertesz, S AF Merlin, Jessica S. Walcott, Melonie M. Herbey, Ivan Chamot, Eric Ritchie, Christine Saag, Michael S. Kertesz, Stefan TI Qualitative Investigation of a Brief Chronic Pain Screening Tool in HIV-Infected Patients SO AIDS PATIENT CARE AND STDS LA English DT Article ID ANTIRETROVIRAL THERAPY; GENERAL-POPULATION; REPORTED OUTCOMES; SYMPTOMS; CARE; PREVALENCE; QUESTIONNAIRE; VALIDATION; ADHERENCE; TAXONOMY AB Chronic pain in HIV-infected patients is prevalent but understudied. A limitation of HIV/chronic pain research to date is the lack of a widely used chronic pain screening tool. A Brief Chronic Pain Screening tool (BCPS) has been described, but has not yet been tested in a clinical population. This study sought to evaluate how the BCPS is experienced by HIV-infected individuals, and adapt its questions if necessary. We conducted cognitive interviews using cognitive inquiry in participants from the UAB 1917 HIV Clinic Cohort. Data were analyzed using a process of inductive, iterative coding by three investigators. Results: Of 30 participants, most were male, African American, and less than 50 years old. Participants reported that the questions were understandable; however, feedback suggested concerns regarding lack of specificity in regard to the intensity and consistency of pain. An introductory statement aimed at improving clarity resulted in more divergent responses. This research team concluded that the version of the BCPS used in the first 30 interviews was optimum. Its inclusive language allows the respondent to decide what pain merits reporting. This study is the first investigation of the BCPS in a clinical population, and should lead to further quantitative validation studies of this tool. C1 [Merlin, Jessica S.; Walcott, Melonie M.; Herbey, Ivan; Saag, Michael S.] Univ Alabama Birmingham, Sch Publ Hlth, Div Infect Dis, Birmingham, AL 35294 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Sch Publ Hlth, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Kertesz, Stefan] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Kertesz, Stefan] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Chamot, Eric] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Ritchie, Christine] Univ Calif San Francisco, Dept Med, Div Geriatr, Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. RP Merlin, JS (reprint author), BBRB 222 1530 3rd Ave South, Birmingham, AL 35294 USA. EM jmerlin@uab.edu FU University of Alabama at Birmingham (UAB) Center for AIDS Research CFAR; NIH [P30 A1027767]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; FIC; OAR; AHRQ [1K12HS02169401]; NIA [7K07AG031779]; Mary Fisher CARE Fund at UAB FX This research was supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research CFAR, an NIH funded program (P30 A1027767) that was made possible by the following institutes: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. JSM is supported by 1K12HS02169401 (AHRQ). CSR is supported by 7K07AG031779 (NIA). Funding was also provided by the Mary Fisher CARE Fund at UAB. NR 34 TC 5 Z9 5 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD APR 1 PY 2014 VL 28 IS 4 BP 176 EP 182 DI 10.1089/apc.2014.0006 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AE1WY UT WOS:000333764700003 PM 24621145 ER PT J AU Videtic, GMM Chang, JY Chetty, IJ Ginsburg, ME Kestin, LL Kong, FM Lally, BE Loo, BW Movsas, B Stinchcombe, TE Willers, H Rosenzweig, KE AF Videtic, Gregory M. M. Chang, Joe Yujiao Chetty, Indrin J. Ginsburg, Mark E. Kestin, Larry L. Kong, Feng-Ming (Spring) Lally, Brian E. Loo, Billy W., Jr. Movsas, Benjamin Stinchcombe, Thomas E. Willers, Henning Rosenzweig, Kenneth E. CA Expert Panel Radiation Oncology Lu TI ACR Appropriateness Criteria((R)) Early-Stage Non-Small-Cell Lung Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE medical operability; adjuvant; surgery; early-stage non-small-cell lung cancer; radiotherapy ID STEREOTACTIC BODY RADIATION; HIGH-RISK PATIENTS; MAJOR PULMONARY RESECTIONS; TRIALIST ASSOCIATION ANITA; VINORELBINE PLUS CISPLATIN; THORACIC-SURGERY LOBECTOMY; FORTHCOMING 7TH EDITION; GUIDELINES 2ND EDITION; ACOSOG Z0030 TRIAL; RADIOFREQUENCY ABLATION AB Early-stage non-small-cell lung cancer (NSCLC) is diagnosed in about 15% to 20% of lung cancer patients at presentation. In order to provide clinicians with guidance in decision making for early-stage NSCLC patients, the American College of Radiology Appropriateness Criteria Lung Cancer Panel was recently charged with a review of the current published literature to generate up-to-date management recommendations for this clinical scenario. For patients with localized, mediastinal lymph node-negative NSCLC, optimal management should be determined by an expert multidisciplinary team. For medically operable patients, surgical resection is the standard of care, with generally no role for adjuvant therapies thereafter. For patients with medical comorbidities making them at high risk for surgery, there is emerging evidence demonstrating the availability of low toxicity curative therapies, such as stereotactic body radiotherapy, for their care. As a general statement, the American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Videtic, Gregory M. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Chang, Joe Yujiao] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chetty, Indrin J.; Movsas, Benjamin] Henry Ford Hlth Syst, Detroit, MI USA. [Ginsburg, Mark E.] Columbia Univ, Dept Surg, New York, NY USA. [Ginsburg, Mark E.] Soc Thorac Surg, New York, NY USA. [Kestin, Larry L.] 21st Century Oncol Michigan Healthcare Profess, Farmington Hills, MI USA. [Kong, Feng-Ming (Spring)] Univ Michigan, Ann Arbor, MI 48109 USA. [Kong, Feng-Ming (Spring)] Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. [Lally, Brian E.] Univ Miami, Dept Radiat Oncol, Miami, FL USA. [Loo, Billy W., Jr.] Stanford Univ, Stanford, CA 94305 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Stinchcombe, Thomas E.] Univ North Carolina Hlth Care Syst, Chapel Hill, NC USA. [Stinchcombe, Thomas E.] Amer Soc Clin Oncol, Chapel Hill, NC USA. [Willers, Henning] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenzweig, Kenneth E.] Mt Sinai Sch Med, New York, NY USA. RP Videtic, GMM (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM videtig@ccf.org FU Varian Inc.; Philips Inc.; Resonant Inc. FX B.M.: Research support to Henry Ford Health System Radiation Oncology Department from Varian Inc., Philips Inc., and Resonant Inc. The other authors declare no conflicts of interest. NR 78 TC 5 Z9 5 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2014 VL 37 IS 2 BP 201 EP 207 DI 10.1097/COC.0000000000000013 PG 7 WC Oncology SC Oncology GA AE1FF UT WOS:000333713100019 PM 25180631 ER PT J AU Grubbs, V Lin, F Vittinghoff, E Shlipak, MG Peralta, CA Bansal, N Jacobs, DR Siscovick, DS Lewis, CE Bibbins-Domingo, K AF Grubbs, Vanessa Lin, Feng Vittinghoff, Eric Shlipak, Michael G. Peralta, Carmen A. Bansal, Nisha Jacobs, David R. Siscovick, David S. Lewis, Cora E. Bibbins-Domingo, Kirsten TI Body Mass Index and Early Kidney Function Decline in Young Adults: A Longitudinal Analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney function decline; obesity; risk factor ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; RENAL-FUNCTION; ALBUMIN EXCRETION; BARIATRIC SURGERY; OBESE-PATIENTS; OLDER-ADULTS; WEIGHT-LOSS; CREATININE; DISEASE AB Background: Identifying potentially modifiable risk factors is critically important for reducing the burden of chronic kidney disease. We sought to examine the association of body mass index (BMI) with kidney function decline in a cohort of young adults with preserved glomerular filtration at baseline. Study Design: Longitudinal cohort. Setting & Participants: 2,839 black and white young adults with cystatin C-based estimated glomerular filtration rate (eGFR(cys)). > 90 mL/min/1.73 m(2) taking part in the year-10 examination (in 1995-1996) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Predictor: BMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and 40.0 kg/m(2). Outcomes: Trajectory of kidney function decline, rapid decline (>3% per year), and incident eGFR(cys) < 60 mL/min/1.73 m(2) over 10 years of follow-up. Measurements: GFR(cys) estimated from the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years 10, 15, and 20. Results: At year 10, participants had a mean age of 35.1 years, median eGFRcys of 114 mL/min/1.73 m(2), and 24.5% had BMI 30.0 kg/m(2). After age 30 years, average eGFR(cys) was progressively lower with each increment in BMI after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and physical activity. Higher BMI category was associated with successively higher odds of rapid decline (for 25.0-29.9, 30.0-39.9, and $ 40.0 kg/m(2), adjusted ORs were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67-3.94], respectively). 18 participants (0.6%) had incident eGFR(cys) < 60 mL/min/1.73 m(2). In unadjusted analysis, higher BMI category was associated with incident eGFR(cys) < 60 mL/min/1.73 m (2) (for 25.0-29.9, 30.0-39.9, and 40.0 kg/m(2), ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and 5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer significant. Limitations: Inability to describe kidney function before differences by BMI category were already evident. Absence of data for measured GFR or GFR estimated from serum creatinine level. Conclusions: Higher BMI categories are associated with greater declines in kidney function in a cohort of young adults with preserved GFR at baseline. Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline. (C) 2014 by the National Kidney Foundation, Inc. C1 [Grubbs, Vanessa; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen A.; Bansal, Nisha; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94110 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Jacobs, David R.] Univ Minnesota, Minneapolis, MN USA. [Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. RP Grubbs, V (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Nephrol, Renal Ctr, Box 1341,1001 Potrero Ave,Bldg 100,Rm 342, San Francisco, CA 94110 USA. EM grubbsv@medsfgh.ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1K23DK093710-01A1]; Robert Wood Johnson Foundation; NIDDK [R01DK078124, P30-DK092924]; National Heart, Lung and Blood Institute (NHLBI) [N01HC48050]; Center for Health and Risk in Minority Youth and Adults (CHARM); National Institute on Minority Health and Health Disparities, Comprehensive Centers of Excellence [1P60MD006902]; National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI [KL2 TR000143]; NHLBI [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN26820-1300028C, HHSN268201300029C, HHSN268200900041C]; Intramural Research Program of the National Institute on Aging FX Dr Grubbs was supported by grant 1K23DK093710-01A1 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation. Dr Bibbins-Domingo was supported in part by grant R01DK078124 from the NIDDK, grant N01HC48050 from the National Heart, Lung and Blood Institute (NHLBI), and from the Center for Health and Risk in Minority Youth and Adults (CHARM) grant 1P60MD006902 from the National Institute on Minority Health and Health Disparities, Comprehensive Centers of Excellence, and from grant P30-DK092924 from the NIDDK. This project was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI grant KL2 TR000143. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The CARDIA Study is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN26820-1300028C, HHSN268201300029C, and HHSN268200900041C from the NHLBI and the Intramural Research Program of the National Institute on Aging. The manuscript was reviewed by CARDIA for scientific content prior to submission. NR 37 TC 18 Z9 18 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2014 VL 63 IS 4 BP 590 EP 597 DI 10.1053/j.ajkd.2013.10.055 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AD7GB UT WOS:000333429500013 PM 24295611 ER PT J AU Tan, WH Bird, LM Thibert, RL Williams, CA AF Tan, Wen-Hann Bird, Lynne M. Thibert, Ronald L. Williams, Charles A. TI If Not Angelman, What Is It? A Review of Angelman- like Syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Angelman syndrome; differential diagnoses; Phelan-McDermid syndrome; MBD5 deficiency; KANSL1 deficiency; Pitt-Hopkins syndrome; Christianson syndrome; Mowat-Wilson syndrome; Kleefstra syndrome; HERC2 deficiency; Adenylosuccinase lyase deficiency; ADSL deficiency; Rett syndrome; CDKL5 syndrome; FOXG1 syndrome; MECP2 duplication; MEF2C syndrome; ATRX ID PITT-HOPKINS-SYNDROME; ADENYLOSUCCINATE LYASE DEFICIENCY; SEVERE MENTAL-RETARDATION; MOWAT-WILSON-SYNDROME; 17Q21.31 MICRODELETION SYNDROME; MECP2 DUPLICATION SYNDROME; AUTISM SPECTRUM DISORDER; 22Q13 DELETION SYNDROME; OF-THE-LITERATURE; BEHAVIORAL-PHENOTYPE AB Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan-McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt-Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat-Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes. (c) 2014 Wiley Periodicals, Inc. C1 [Williams, Charles A.] Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, 1600 SW Archer Rd,M-351,POB 100296, Gainesville, FL 32610 USA. [Tan, Wen-Hann; Bird, Lynne M.] NIH, Rare Dis Clin Res Network, Angelman Rett & Prader Willi Syndromes Consortium, Birmingham, AL USA. [Tan, Wen-Hann] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Tan, Wen-Hann; Thibert, Ronald L.] Harvard Univ, Sch Med, Boston, MA USA. [Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Bird, Lynne M.] Rady Childrens Hosp San Diego, Div Genet Dysmorphol, San Diego, CA USA. [Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Williams, CA (reprint author), Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, 1600 SW Archer Rd,M-351,POB 100296, Gainesville, FL 32610 USA. EM willicx@peds.ufl.edu FU National Center for Research Resources (NCRR) [NIH U54 RR019478]; National Institute of Child Health and Human Development [NIH U54 HD061222]; NIH Office of Rare Diseases Research (ORDR); Angelman Syndrome Foundation - Western Area Chapter; Food and Drug Administration (FDA) Office of Orphan Products Development [R01 FD003523-01A2] FX Grant sponsor: National Center for Research Resources (NCRR); Grant number: NIH U54 RR019478; Grant sponsor: National Institute of Child Health and Human Development; Grant number: NIH U54 HD061222; Grant sponsor: NIH Office of Rare Diseases Research (ORDR); Grant sponsor: Angelman Syndrome Foundation - Western Area Chapter; Grant sponsor: Food and Drug Administration (FDA) Office of Orphan Products Development; Grant number: R01 FD003523-01A2. NR 90 TC 17 Z9 19 U1 2 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2014 VL 164 IS 4 BP 975 EP 992 DI 10.1002/ajmg.a.36416 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA AD4CL UT WOS:000333193800040 PM 24779060 ER PT J AU Jones, HE Deppen, K Hudak, ML Leffert, L McClelland, C Sahin, L Starer, J Terplan, M Thorp, JM Walsh, J Creanga, AA AF Jones, Hendree E. Deppen, Krisanna Hudak, Mark L. Leffert, Lisa McClelland, Carol Sahin, Leyla Starer, Jacquelyn Terplan, Mishka Thorp, John M., Jr. Walsh, James Creanga, Andreea A. TI Clinical care for opioid-using pregnant and postpartum women: the role of obstetric providers SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE opioid-agonist; opioid use; substance use ID NEONATAL ABSTINENCE SYNDROME; OPIATE WITHDRAWAL; ALCOHOL-USE; METHADONE; BUPRENORPHINE; OUTCOMES; EMPATHY; ISSUES AB We review clinical care issues that are related to illicit and therapeutic opioid use among pregnant women and women in the postpartum period and outline the major responsibilities of obstetrics providers who care for these patients during the antepartum, intrapartum, and postpartum periods. Selected patient treatment issues are highlighted, and case examples are provided. Securing a strong rapport and trust with these patients is crucial for success in delivering high-quality obstetric care and in coordinating services with other specialists as needed. Obstetrics providers have an ethical obligation to screen, assess, and provide brief interventions and referral to specialized treatment for patients with drug use disorders. Opioid-dependent pregnant women often can be treated effectively with methadone or buprenorphine. These medications are classified as pregnancy category C medications by the Food and Drug Administration, and their use in the treatment of opioid-dependent pregnant patients should not be considered "off-label." Except in rare special circumstances, medication-assisted withdrawal during pregnancy should be discouraged because of a high relapse rate. Acute pain management in this population deserves special consideration because patients who use opioids can be hypersensitive to pain and because the use of mixed opioid-agonist/antagonists can precipitate opioid withdrawal. In the absence of other indications, pregnant women who use opioids do not require more intense medical care than other pregnant patients to ensure adequate treatment and the best possible outcomes. Together with specialists in pain and addiction medicine, obstetricians can coordinate comprehensive care for pregnant women who use opioids and women who use opioids in the postpartum period. C1 [Jones, Hendree E.; McClelland, Carol; Thorp, John M., Jr.] Univ North Carolina Chapel Hill, UNC Sch Med, Dept Obstet & Gynecol, UNC Horizons Program, Carrboro, NC USA. [Deppen, Krisanna] Grant Med Ctr, Dept Family Med, Columbus, OH USA. [Hudak, Mark L.] Univ Florida, Coll Med Jacksonville, Dept Pediat, Gainesville, FL 32611 USA. [Leffert, Lisa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sahin, Leyla] US FDA, Maternal Hlth Team, Off New Drugs, Silver Spring, MD USA. [Starer, Jacquelyn] Brigham & Womens Faulkner Hosp, Addict Recovery Program, Boston, MA USA. [Terplan, Mishka] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA. [Walsh, James] Swedish Med Ctr, Addict Recovery Serv, Seattle, WA USA. [Creanga, Andreea A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. RP Jones, HE (reprint author), UNC Horizons, 400 Roberson St, Carrboro, NC 27510 USA. EM hendree_jones@med.unc.edu NR 46 TC 17 Z9 17 U1 0 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2014 VL 210 IS 4 BP 302 EP 310 DI 10.1016/j.ajog.2013.10.010 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AD6WM UT WOS:000333401900003 PM 24120973 ER PT J AU Stewart, T Liu, CQ Ginghina, C Cain, KC Auinger, P Cholerton, B Shi, M Zhang, J AF Stewart, Tessandra Liu, Changqin Ginghina, Carmen Cain, Kevin C. Auinger, Peggy Cholerton, Brenna Shi, Min Zhang, Jing CA Parkinson Study Grp DATATOP Invest TI Cerebrospinal Fluid alpha-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CORTICAL LEWY BODIES; ALZHEIMERS-DISEASE; DEMENTIA; CSF; IMPAIRMENT; LEVODOPA; MODEL; TRANSPORTERS; ASSOCIATION; DEFICITS AB Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although alpha-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and alpha-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess alpha-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing cc-synuclein (phase 1 to phase 2 change of -0.05 +/- 0.21 log-transformed values, P < 0.001), no correlations were observed between alpha-synuclein and motor symptoms. Longitudinally, lower alpha-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall alpha-synuclein x time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, alpha-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. C1 [Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Cholerton, Brenna] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Dept Endocrinol & Metab, Xiamen, Peoples R China. [Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Xiamen Diabet Inst, Xiamen, Peoples R China. [Cain, Kevin C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98104 USA. [Auinger, Peggy] Univ Rochester, Sch Med & Dent, Dept Neurol, Ctr Human Expt Therapeut, Rochester, NY 14642 USA. [Cholerton, Brenna] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Harborview Med Ctr Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU Michael J. Fox Foundation; Parkinson Study Group; NTH grants [NIEHS T32ES015459, AG033398, ES004696-5897, ES007033-6364, ES016873, ES019277, NS057567, NS060252, NS062684-6221, NS082137] FX This work was supported by the Michael J. Fox Foundation, the Parkinson Study Group, and NTH grants NIEHS T32ES015459 (T.S.) and AG033398, ES004696-5897, ES007033-6364, ES016873, ES019277, NS057567, NS060252, NS062684-6221, and NS082137 (J.Z.). NR 41 TC 37 Z9 38 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2014 VL 184 IS 4 BP 966 EP 975 DI 10.1016/j.ajpath.2013.12.007 PG 10 WC Pathology SC Pathology GA AD8XI UT WOS:000333548600009 PM 24625392 ER PT J AU Wang, HZ Melton, DW Porter, L Sarwar, ZU McManus, LM Shireman, PK AF Wang, Hanzhou Melton, David W. Porter, Laurel Sarwar, Zaheer U. McManus, Linda M. Shireman, Paula K. TI Altered Macrophage Phenotype Transition Impairs Skeletal Muscle Regeneration SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IN-VIVO; FIBRO/ADIPOGENIC PROGENITORS; MONONUCLEAR PHAGOCYTES; INFLAMMATORY MONOCYTES; CELLS CONTRIBUTE; EPITHELIAL-CELLS; DIPHTHERIA-TOXIN; GENE-EXPRESSION; DENDRITIC CELLS; TISSUE-REPAIR AB Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b(+)(CD90/B220/CD49b/NK1.1/Ly6G)(-)(F4/80/I-Ab/CD11c)(-)Ly6C(+/-)] accumulation occurred; interestingly, Ly6C(+) and Ly6C(-) monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C(+) macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b(+)F4/80(+) cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b(+)F4/80(+)Ly6C(-)CD301(-) macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C(-) macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration. C1 [Wang, Hanzhou; Melton, David W.; Porter, Laurel; Sarwar, Zaheer U.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Melton, David W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Melton, David W.; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, 7703 Floyd Curl Dr,MC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU NIH NHLBI grants [R01 HL074236, F30 HL110743]; NIH NCATS grant [UL1TR001120]; NIH NCI grant [P30 CA054174]; Veterans Administration Merit Review grant [1I01BX001186] FX Supported by NIH NHLBI grants R01 HL074236 and F30 HL110743, NIH NCATS grant UL1TR001120, NIH NCI grant P30 CA054174 [to the Core Flow Cytometry Facility (Cancer Therapy & Research Center) of the University of Texas Health Science Center, San Antonio] and Veterans Administration Merit Review grant 1I01BX001186. NR 93 TC 31 Z9 32 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2014 VL 184 IS 4 BP 1167 EP 1184 DI 10.1016/j.ajpath.2013.12.020 PG 18 WC Pathology SC Pathology GA AD8XI UT WOS:000333548600027 PM 24525152 ER PT J AU Kasaie, P Andrews, JR Kelton, WD Dowdy, DW AF Kasaie, Parastu Andrews, Jason R. Kelton, W. David Dowdy, David W. TI Timing of Tuberculosis Transmission and the Impact of Household Contact Tracing An Agent-based Simulation Model SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tuberculosis; contact tracing; models, theoretical; epidemiology ID COMMUNITY-RANDOMIZED-TRIAL; REINFECTION; STRATEGIES; INFECTION; DISEASE; HIV; METAANALYSIS; DIAGNOSIS; DYNAMICS; BENEFITS AB Rationale: Household contact tracing has recently been endorsed for global tuberculosis (TB) control, but its potential population-level impact remains uncertain. Objectives: To project the maximum impact of household contact tracing for TB in a moderate-burden setting. Methods: We developed a stochastic, agent-based simulation model of a simplified TB epidemic, calibrated to a setting of moderate TB incidence. We used data from the literature to generate "community-driven" and "household-driven" scenarios in which 22 and 50% of TB transmission occurred within the household, respectively. In each scenario, we simulated an intervention in which the household members are screened and treated for TB at the time of an index patient's active TB diagnosis. Measurements and Main Results: By the time of TB diagnosis, 75 to 95% of initial household infections had already occurred, but only 1.5 to 3.0% of contacts had sufficient time to progress to active TB. With 100% sensitive tracing of all contacts for 5 consecutive years, TB incidence declined by 10 to 15%, with a mean year-over- year decline of 2% per year. Effects were sustained for many years after stopping the intervention. Providing preventive therapy with contact tracing nearly doubled this impact (17-27% decline in incidence). Impact was proportional to sensitivity and coverage; thus, if 50% of contacts were screened with a 50% sensitive test, TB incidence declined by only 0.5% per year. Conclusions: Household contact tracing is unlikely to transform TB epidemiology in isolation but has the potential, especially with provision of preventive therapy, to augment a comprehensive package of interventions that could substantially reduce the population-level burden of TB. C1 [Kasaie, Parastu; Kelton, W. David] Univ Cincinnati, Coll Business, Dept Operat Business Analyt & Informat Syst, Cincinnati, OH USA. [Andrews, Jason R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Dowdy, David W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Dowdy, DW (reprint author), 615 N Wolfe St,E6531, Baltimore, MD 21205 USA. EM ddowdy@jhsph.edu OI Andrews, Jason/0000-0002-5967-251X FU B. Frank and Kathleen Polk Assistant Professorship in Epidemiology, Johns Hopkins Bloomberg School of Public Health; Graduate School Dean's Fellowship, University of Cincinnati FX This work was supported by a B. Frank and Kathleen Polk Assistant Professorship in Epidemiology, Johns Hopkins Bloomberg School of Public Health (D.W.D.) and by a Graduate School Dean's Fellowship, University of Cincinnati 2013-2014 (P.K.). NR 38 TC 14 Z9 14 U1 0 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2014 VL 189 IS 7 BP 845 EP 852 DI 10.1164/rccm.201310-1846OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AD9DS UT WOS:000333565600014 PM 24559425 ER PT J AU Johnson, C Khalilzadeh, O Novelline, RA Choy, G AF Johnson, Connor Khalilzadeh, Omid Novelline, Robert A. Choy, Garry TI Coronary Artery Calcification Is Often Not Reported in Pulmonary CT Angiography in Patients With Suspected Pulmonary Embolism: An Opportunity to Improve Diagnosis of Acute Coronary Syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE acute coronary syndrome; coronary calcification; coronary heart disease; pulmonary CT angiography; pulmonary thromboemboli ID CARDIOVASCULAR EVENTS; HEART-DISEASE AB OBJECTIVE. In patients with suspected pulmonary thromboembolism (PTE), coronary artery calcification (CAC) can be an incidental finding on pulmonary CT angiography. We evaluated the frequency of CAC not being reported and its association with a diagnosis of acute coronary syndrome (ACS). MATERIALS AND METHODS. Data of 469 consecutive patients who were referred to the emergency radiology department for pulmonary CT angiography of suspected PTE were reviewed. Radiology reports were rechecked and positive CAC findings were recorded. All pulmonary CT angiograms were reevaluated by one radiologist and CAC findings were recorded. The rates of ACS and PTE as final diagnoses for that hospital admission were calculated. The association between CAC and ACS diagnosis was assessed in different subgroups of patients. RESULTS. Approximately 11.1% of patients had PTE and 43.8% had CAC. The incidence of CAC was significantly higher in patients with an ACS diagnosis than in those without ACS (56.2% vs 40.4%, respectively; odds ratio [OR] = 1.9). There was a strong positive association (OR = 3.5) between CAC and ACS in younger patients (men <= 45 years and women <= 55 years), patients without PTE (OR = 2.2), and those without cardiometabolic risk factors (OR = 3.8). CAC was not reported in 45% of patients (n = 98) with positive CAC findings on imaging. ACS was the final diagnosis in 31.6% of patients with unreported CAC. There was a significant association between CAC and ACS in patients with unreported CAC (OR = 2.2). This association was more prominent in the subgroups described. CONCLUSION. CAC is often not reported in pulmonary CT angiography studies. CAC is a significant predictor of ACS particularly in younger patients, patients without PTE, and those without cardiometabolic risk factors. Especially in these subgroups, radiologists should assess CAC findings. C1 [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Choy, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 55 Fruit St,FND216, Boston, MA 02114 USA. EM gchoy@partners.org NR 14 TC 2 Z9 2 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP 725 EP 729 DI 10.2214/AJR.13.11326 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300023 PM 24660698 ER PT J AU Tirumani, SH Shinagare, AB Jagannathan, JP Krajewski, KM Munshi, NC Ramaiya, NH AF Tirumani, Sree Harsha Shinagare, Atul B. Jagannathan, Jyothi P. Krajewski, Katherine M. Munshi, Nikhil C. Ramaiya, Nikhil H. TI MRI Features of Extramedullary Myeloma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE extramedullary myeloma; MRI; multiple myeloma ID MULTIPLE-MYELOMA; EXTRAOSSEOUS MYELOMA; ABDOMINAL MANIFESTATIONS; DISEASE; CT; PLASMACYTOMAS; SURVIVAL; SPECTRUM; PET/CT AB OBJECTIVE. The purpose of this study was to describe the MRI features of extramedullary myeloma and to evaluate the role of MRI in extramedullary myeloma. MATERIALS AND METHODS. The cases of 28 patients (15 men, 13 women; mean age, 57.53 years; range, 34-83 years) with extramedullary myeloma who underwent MRI at one institution from January 2004 through December 2012 were retrospectively identified through an electronic search of an institutional radiology database. Two radiologists reviewed images from 44 MRI examinations in consensus to document the morphologic, signal-intensity, and enhancement characteristics of extramedullary myeloma. Electronic medical records were reviewed to document the indication for MRI and subsequent management of extramedullary myeloma. RESULTS. A total of 72 sites of extramedullary myeloma were noted, most commonly the paraspinal-epidural location (28/72, 39%). Two radiologic patterns were identified: lesions contiguous with bone (n = 44) and lesions noncontiguous with bone (n = 28). Lesions contiguous with bone were larger (p = 0.001; Student t test). Of 28 paraspinal-epidural lesions, 13 compressed the cord. Compared with skeletal muscle, most of the lesions were hypointense to isointense on T1-weighted images (67/72, 93.1%) and isointense to hyperintense on T2-weighted images (62/72, 86.1%). Lesions noncontiguous with bone were more often hypointense on T2-weighted images (8/28 vs 2/44; p = 0.006; Fisher exact test). Neurologic symptoms prompted MRI in most cases (n = 32/44). MRI was helpful in management by radiotherapy and surgery (19/28). CONCLUSION. Extramedullary myeloma can be contiguous or noncontiguous with bone. Lesions contiguous with bone are larger, often occur in a paraspinal or epidural location, and can cause cord compression. Lesions noncontiguous with bone can be T2 hypointense. MRI helps in treatment planning. C1 [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 23 TC 6 Z9 6 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP 803 EP 810 DI 10.2214/AJR.13.10856 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300035 PM 24660710 ER PT J AU Callahan, MJ Servaes, S Lee, EY Towbin, AJ Westra, SJ Frush, DP AF Callahan, Michael J. Servaes, Sabah Lee, Edward Y. Towbin, Alexander J. Westra, Sjirk J. Frush, Donald P. TI Practice Patterns for the Use of Iodinated IV Contrast Media for Pediatric CT Studies: A Survey of the Society for Pediatric Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE children; CT; IV contrast media ID CENTRAL VENOUS CATHETERS; ADVERSE-REACTIONS; POWER INJECTORS; CHILDREN; SAFETY; EVENTS; AGENTS AB OBJECTIVE. There are limited data available on the use of IV contrast media for CT studies in the pediatric population. The purpose of this study is to determine the practice patterns of IV contrast media usage for pediatric CT by members of the Society for Pediatric Radiology (SPR). MATERIALS AND METHODS. SPR members were surveyed regarding the use of IV contrast media for pediatric CT studies. Questions pertained to information required before administering IV contrast media, types of central catheters for injecting IV contrast media, injection rates based on angiocatheter size and study type, and management of IV contrast media extravasation. RESULTS. The response rate of 6% (88/1545) represented practice patterns of 26% (401/1545) of the SPR membership. Most respondents thought the following clinical information was mandatory before IV contrast media administration: allergy to IV contrast media (97%), renal insufficiency (97%), current metformin use (72%), significant allergies (61%), diabetes (54%), and asthma (52%). Most administered IV contrast media through nonimplanted central venous catheters (78%), implanted venous ports (78%), and peripherally inserted central catheters (72%). The most common maximum IV contrast media injection rates were 5.0 mL/s or greater for a 16-gauge angiocatheter, 4.0 mL/s for an 18-gauge angiocatheter, 3.0 mL/s for a 20-gauge angiocatheter, and 2.0 mL/s for a 22-gauge angiocatheter. For soft-tissue extravasation of IV contrast media, 95% elevate the affected extremity, 76% use ice, and 45% use heat. CONCLUSION. The results of this survey illustrate the collective opinion of a subset of SPR members relating to the use of IV contrast media in pediatric CT, providing guidelines for clinical histories needed before IV contrast media, maximum IV contrast injection rates for standard angiocatheters, contrast media injection rates for specific CT studies, and management of IV contrast media soft-tissue extravasation. C1 [Callahan, Michael J.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Servaes, Sabah] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Lee, Edward Y.] Boston Childrens Hosp, Div Pulm, Dept Med Radiol, Boston, MA USA. [Towbin, Alexander J.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Frush, Donald P.] Duke Univ, Med Ctr, McGovern Davison Childrens Hlth Ctr, Div Pediat Radiol, Durham, NC USA. RP Callahan, MJ (reprint author), Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM michael.callahan@childrens.harvard.edu RI Frush, Donald/M-6457-2015; OI Frush, Donald/0000-0002-6928-4465; Towbin, Alexander/0000-0003-1729-5071 NR 23 TC 1 Z9 1 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP 872 EP 879 DI 10.2214/AJR.13.11106 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300044 PM 24660719 ER PT J AU Aran, S Besheli, LD Karcaaltincaba, M Gupta, R Flores, EJ Abujudeh, HH AF Aran, Shima Besheli, Laleh Daftari Karcaaltincaba, Musturay Gupta, Rajiv Flores, Efren J. Abujudeh, Hani H. TI Applications of Dual-Energy CT in Emergency Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE clinical applications; dual-energy CT; emergency radiology ID ACUTE PULMONARY-EMBOLISM; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ABDOMINAL AORTIC-ANEURYSM; LOW KILOVOLTAGE SETTINGS; RENAL STONE COMPOSITION; MULTIDETECTOR CT; URINARY CALCULI; IMAGE QUALITY; INTRAARTERIAL THROMBOLYSIS; MYOCARDIAL-INFARCTION AB OBJECTIVE. Recent technologic advances in MDCT have led to the introduction of dual- energy CT (DECT). The basic principle of DECT is to acquire images at two different energy levels simultaneously and to use the attenuation differences at these different energy levels for deriving additional information, such as virtual monochromatic images, artifact suppression, and material composition of various tissues. CONCLUSION. A variety of image reconstruction and postprocessing techniques are available for better demonstration and characterization of pathologic abnormalities. DECT can provide both anatomic and functional information of different organ systems. This article focuses on the main applications of DECT in emergency radiology. C1 [Aran, Shima; Besheli, Laleh Daftari; Gupta, Rajiv; Flores, Efren J.; Abujudeh, Hani H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Karcaaltincaba, Musturay] Hacettepe Univ, Fac Med, Dept Radiol, TR-06100 Ankara, Turkey. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders Bldg,Rm 210, Boston, MA 02114 USA. EM Abujudeh.Hani@mgh.harvard.edu RI Karcaaltincaba, Musturay/A-3866-2016 OI Karcaaltincaba, Musturay/0000-0002-3384-0909 FU Turkish Academy of Sciences [EA-TUBA-GEBIP/2011] FX M. Karcaaltincaba has received support from the Turkish Academy of Sciences (Young Scientist Award Program EA-TUBA-GEBIP/2011). NR 99 TC 8 Z9 8 U1 1 U2 9 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP W314 EP W324 DI 10.2214/AJR.13.11682 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300002 PM 24660729 ER PT J AU Carter, BW Lichtenberger, JP Wu, CC AF Carter, Brett W. Lichtenberger, John P., III Wu, Carol C. TI Congenital Abnormalities of the Pulmonary Arteries in Adults SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE congenital; CT; MDCT; pulmonary arteries ID IDIOPATHIC DILATATION; PROXIMAL INTERRUPTION; AGENESIS; STENOSIS; DISEASE C1 [Carter, Brett W.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Lichtenberger, John P., III] Travis AFB, David Grant Med Ctr, Dept Radiol, Fairfield, CA USA. [Wu, Carol C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Carter, BW (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Diagnost Radiol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM bcarter2@mdanderson.org NR 22 TC 1 Z9 1 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP W308 EP W313 DI 10.2214/AJR.13.11759 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300001 PM 24660728 ER PT J AU Psoter, KJ Roudsari, BS Dighe, MK Richardson, ML Katz, DS Bhargava, P AF Psoter, Kevin J. Roudsari, Bahman S. Dighe, Manjiri K. Richardson, Michael L. Katz, Douglas S. Bhargava, Puneet TI Biostatistics Primer for the Radiologist SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE data analysis; medical statistics; regression analysis; statistical education; statistical tests ID CLINICAL-RESEARCH; STATISTICAL-ANALYSIS; CT; CONTRAST; FUNDAMENTALS; MAMMOGRAPHY; PERFORMANCE; AGREEMENT; CANCER; TRAUMA AB OBJECTIVE. The purpose of this article is to review the most common data analysis methods encountered in radiology-based studies. Initially, description of variable types and their corresponding summary measures are provided; subsequent discussion focuses on comparison of these summary measures between groups, with a particular emphasis on regression analysis. CONCLUSION. Knowledge of statistical applications is critical for radiologists to accurately evaluate the current literature and to conduct scientifically rigorous studies. Misapplication of statistical methods can lead to inappropriate conclusions and clinical recommendations. C1 [Psoter, Kevin J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Roudsari, Bahman S.; Dighe, Manjiri K.; Richardson, Michael L.; Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Roudsari, Bahman S.] Univ Washington, Comparat Effectiveness Cost & Outcomes Res Ctr, Seattle, WA 98195 USA. [Richardson, Michael L.] Roosevelt Radiol, Seattle, WA USA. [Katz, Douglas S.] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Roudsari, BS (reprint author), Univ Washington, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM roudsari@u.washington.edu OI Bhargava, Puneet/0000-0002-3849-9666 FU National Institutes of Health [R01-AA017497] FX Supported by grant R01-AA017497 from the National Institutes of Health. NR 56 TC 1 Z9 1 U1 0 U2 9 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP W365 EP W375 DI 10.2214/AJR.13.11657 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300007 PM 24660735 ER PT J AU McCormick, F Nwachukwu, BU Solomon, D Dewing, C Golijanin, P Gross, DJ Provencher, MT AF McCormick, Frank Nwachukwu, Benedict U. Solomon, Dan Dewing, Christopher Golijanin, Petar Gross, Daniel J. Provencher, Matthew T. TI The Efficacy of Biceps Tenodesis in the Treatment of Failed Superior Labral Anterior Posterior Repairs SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE revision; shoulder; SLAP; biceps tenodesis; outcome analysis ID ARTHROSCOPIC SLAP REPAIR; LESIONS; OUTCOMES; SHOULDER; SURGERY; AGE; FIXATION AB Background: The incidence and arthroscopic treatment of superior labral anterior posterior (SLAP) tears have increased over the past decade. Recent evidence has identified factors associated with poor outcomes, including age, overhead activity, and concomitant rotator cuff tears. Biceps tenodesis has also been suggested as an alternative treatment to repair. Moreover, there are no studies demonstrating effective treatment strategies for failed type II SLAP repairs. Purpose: To prospectively evaluate the surgical outcomes of biceps tenodesis for patients who undergo elected revision surgery after an arthroscopically repaired type II SLAP tear. Study Design: Case series; Level of evidence, 4. Methods: After institutional review board approval, 46 patients who met failure criteria for an arthroscopically repaired type II SLAP tear elected to undergo open subpectoral tenodesis by 2 fellowship-trained surgeons from 2006 to 2010 at a tertiary care military treatment facility. Objective outcomes were preoperative and postoperative assessments with the American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and Western Ontario Shoulder Instability Index (WOSI) scores and an independent physical examination. Statistical analysis was performed via analysis of variance. Results: Of the 46 patients, 42 completed the study (91% follow-up rate). The mean age of the patients was 39.2 years, 85% were male, and the mean follow-up period was 3.5 years (range, 2.0-6.0 years). The rate of return to active duty and sports was 81%. There was a clinically and statistically significant improvement across all outcome assessments after revision surgery (preoperative mean scores: ASES = 68, SANE = 64, WOSI = 65; postoperative mean scores: ASES = 89, SANE = 84, WOSI = 81) (P < .0001) and shoulder range of motion (preoperative mean values: forward flexion = 135 degrees, abduction = 125 degrees; postoperative mean values: forward flexion = 155 degrees, abduction = 155 degrees) (P < .0001). There was 1 case of transient musculocutaneous nerve neurapraxia. Conclusion: Biceps tenodesis is a predictable, safe, and effective treatment for failed arthroscopic SLAP tears at a minimum 2-year follow-up. The majority of patients obtained good to excellent outcomes using validated measures with a significant improvement in range of motion. C1 [McCormick, Frank; Nwachukwu, Benedict U.; Solomon, Dan; Dewing, Christopher; Golijanin, Petar; Gross, Daniel J.; Provencher, Matthew T.] Naval Med Ctr San Diego, San Diego, CA USA. RP Provencher, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. EM mtprovencher@partners.org NR 29 TC 13 Z9 13 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 EI 1552-3365 J9 AM J SPORT MED JI Am. J. Sports Med. PD APR PY 2014 VL 42 IS 4 BP 820 EP 825 DI 10.1177/0363546513520122 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA AE0WD UT WOS:000333686100011 PM 24519182 ER PT J AU Itani, KMF AF Itani, Kamal M. F. TI Longer length of stay or readmissions: can we achieve a balance? SO AMERICAN JOURNAL OF SURGERY LA English DT Editorial Material DE Surgery; Readmission; Quality; Length of stay; Metrics C1 [Itani, Kamal M. F.] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Itani, KMF (reprint author), Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. EM kitani@va.gov NR 1 TC 1 Z9 1 U1 0 U2 2 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 APR PY 2014 VL 207 IS 4 BP 457 EP 458 DI 10.1016/j.amjsurg.2013.12.014 PG 2 WC Surgery SC Surgery GA AD7BN UT WOS:000333416100002 PM 24674825 ER PT J AU Mull, HJ Borzecki, AM Loveland, S Hickson, K Chen, Q MacDonald, S Shin, MH Cevasco, M Itani, KMF Rosen, AK AF Mull, Hillary J. Borzecki, Ann M. Loveland, Susan Hickson, Kathleen Chen, Qi MacDonald, Sally Shin, Marlena H. Cevasco, Marisa Itani, Kamal M. F. Rosen, Amy K. TI Detecting adverse events in surgery: comparing events detected by the Veterans Health Administration Surgical Quality Improvement Program and the Patient Safety Indicators SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Veterans Health Administration; VA Surgical Quality Improvement Program; Patient Safety Indicators; Adverse surgical events; Administrative data ID AMERICAN-COLLEGE; CARE; RELIABILITY; VA; PERFORMANCE; HOSPITALS; NSQIP AB BACKGROUND: The Patient Safety Indicators (PSIs) use administrative data to screen for select adverse events (AEs). In this study, VA Surgical Quality Improvement Program (VASQIP) chart review data were used as the gold standard to measure the criterion validity of 5 surgical PSIs. Independent chart review was also used to determine reasons for PSI errors. METHODS: The sensitivity, specificity, and positive predictive value of PSI software version 4.1a were calculated among Veterans Health Administration hospitalizations (2003-2007) reviewed by VASQIP (n = 268,771). Nurses re-reviewed a sample of hospitalizations for which PSI and VASQIP AE detection disagreed. RESULTS: Sensitivities ranged from 31% to 68%, specificities from 99.1% to 99.8%, and positive predictive values from 31% to 72%. Reviewers found that coding errors accounted for some PSI-VASQIP disagreement; some disagreement was also the result of differences in AE definitions. CONCLUSIONS: These results suggest that the PSIs have moderate criterion validity; however, some surgical PSIs detect different AEs than VASQIP. Future research should explore using both methods to evaluate surgical quality. Published by Elsevier Inc. C1 [Mull, Hillary J.; Loveland, Susan; Chen, Qi; Shin, Marlena H.; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA. [Mull, Hillary J.; Itani, Kamal M. F.; Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Borzecki, Ann M.; Hickson, Kathleen; MacDonald, Sally] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Hickson, Kathleen; Cevasco, Marisa; Itani, Kamal M. F.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Hickson, Kathleen; Cevasco, Marisa; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM hillary.mull@va.gov FU Intramural VA [VA999999] NR 41 TC 5 Z9 5 U1 1 U2 2 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 APR PY 2014 VL 207 IS 4 BP 584 EP 595 DI 10.1016/j.amjsurg.2013.08.031 PG 12 WC Surgery SC Surgery GA AD7BN UT WOS:000333416100020 PM 24290888 ER PT J AU Sedaghat, AR Sheehan, WJ Bharmanee, A Harrisx, K Phipatanakul, W AF Sedaghat, Ahmad R. Sheehan, William J. Bharmanee, Apinya Harrisx, Kendra Phipatanakul, Wanda TI Characterization of tree allergy prevalence in children younger than 4 years SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID SKIN-TEST REACTIVITY; AEROALLERGEN SENSITIZATION; BIRTH COHORT; ASTHMA; CONJUNCTIVITIS; CHILDHOOD C1 [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sedaghat, Ahmad R.] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Sheehan, William J.; Bharmanee, Apinya; Harrisx, Kendra; Phipatanakul, Wanda] Harvard Univ, Sch Med, Dept Pediat, Div Allergy & Immunol,Boston Childrens Hosp, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu FU NIAID NIH HHS [K24 AI106822] NR 10 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 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2014 VL 112 IS 4 BP 388 EP 389 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AD8OO UT WOS:000333525700023 PM 24518565 ER PT J AU Hartung, DM Zarin, DA Guise, JM McDonagh, M Paynter, R Helfand, M AF Hartung, Daniel M. Zarin, Deborah A. Guise, Jeanne-Marie McDonagh, Marian Paynter, Robin Helfand, Mark TI Reporting Discrepancies Between the ClinicalTrials.gov Results Database and Peer-Reviewed Publications SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; BONE MORPHOGENETIC PROTEIN-2; CLINICAL-TRIALS; OUTCOMES; DISSEMINATION; ISSUES AB Background: ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. Purpose: To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. Data Sources: ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. Study Selection: 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. Data Extraction: One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Data Synthesis: Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Limitation: Small sample that included earliest results posted to the database. Conclusion: Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. Natl Lib Med, Bethesda, MD USA. RP Hartung, DM (reprint author), Oregon Hlth & Sci Univ, Coll Pharm, Oregon State Univ, 3303 SW Bond Ave,CH12C, Portland, OR 97239 USA. EM hartungd@ohsu.edu OI Paynter, Robin/0000-0002-6969-4261 FU National Library of Medicine [HHSN 276-2009-00128P]; Agency for Healthcare Research and Quality [K12HS019456]; Agency for Healthcare Research and Quality career development award [K12 HS019456]; intramural research program of the National Library of Medicine FX By contract HHSN 276-2009-00128P from the National Library of Medicine and grant K12HS019456 from the Agency for Healthcare Research and Quality. Dr. Hartung received support from an Agency for Healthcare Research and Quality career development award (K12 HS019456). Dr. Zarin was funded by the intramural research program of the National Library of Medicine. NR 18 TC 40 Z9 40 U1 0 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 2014 VL 160 IS 7 BP 477 EP + DI 10.7326/M13-0480 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AE6IL UT WOS:000334093800005 PM 24687070 ER PT J AU Li, J Dufrene, SL Okulicz, JF AF Li, Julius Dufrene, Staci L. Okulicz, Jason F. TI Systemic Preexposure Prophylaxis for HIV: Translating Clinical Data to Clinical Practice SO ANNALS OF PHARMACOTHERAPY LA English DT Review DE human immunodeficiency virus; HIV; preexposure prophylaxis; prevention; tenofovir; emtricitabine ID TENOFOVIR DISOPROXIL FUMARATE; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; INTERMITTENT PROPHYLAXIS; POSTEXPOSURE PROPHYLAXIS; SERODISCORDANT COUPLES; COST-EFFECTIVENESS; ORAL PREEXPOSURE; INTERIM GUIDANCE; RISK BEHAVIOR AB Objective: To assess the real-world implications of oral tenofovir emtricitabine (TDF-FTC) for HIV preexposure prophylaxis (PrEP) in clinical practice and highlight important considerations for its implementation. Data Sources: A search of PubMed (January 1996 through June 2013) was conducted using the terms HIV preexposure prophylaxis, HIV prevention, tenofovir, and emtricitabine. Abstracts from 2012-2013 HIV/AIDS conferences were also reviewed. Study Selection and Data Extraction: All pertinent original studies and review articles published in English were evaluated for inclusion. Reference citations from identified articles were examined for additional content. Data Synthesis: Although antiretroviral therapy has been highly successful in reducing AIDS outcomes and death in HIV-infected patients worldwide, transmission of HIV remains a major global health problem. The recent approval of oral TDF-FTC for HIV PrEP represents the latest biomedical intervention to help control this epidemic. Four published randomized studies evaluated the efficacy and safety of this combination to prevent HIV transmission in several at-risk populations, including men who have sex with men, serodiscordant couples, and heterosexuals residing in endemic regions. Overall, these studies demonstrated significant risk reductions in the incidence of new HIV infections with good short-term tolerability. Despite promising results from clinical studies, several limitations may hinder the utility of PrEP in clinical practice. Most importantly, PrEP was studied in the context of a comprehensive prevention program, including intensive counseling on adherence, high-risk behaviors, and traditional preventative measures. If PrEP is implemented without these adjunct measures, concerns about failure and increased resistance may eventually be realized. Conclusion: The greatest impact of PrEP, both clinically and financially, will likely arise from judicious application in select high-risk populations. If used appropriately, PrEP has the potential to augment reductions in the current incidence of new HIV infections, and pharmacists will have an important role in the careful selection and counseling of these targeted populations. C1 [Li, Julius; Dufrene, Staci L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Okulicz, Jason F.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. RP Okulicz, JF (reprint author), San Antonio Mil Med Ctr, Infect Dis Serv, HIV Med Educ Unit, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM jason.f.okulicz.mil@mail.mil NR 78 TC 0 Z9 0 U1 3 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD APR PY 2014 VL 48 IS 4 BP 507 EP 518 DI 10.1177/1060028014520880 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD8IP UT WOS:000333510000010 PM 24473492 ER PT J AU Eschenauer, GA Nguyen, MH Shoham, S Vazquez, JA Morris, AJ Pasculle, WA Kubin, CJ Klinker, KP Carver, PL Hanson, KE Chen, S Lam, SW Potoski, BA Clarke, LG Shields, RK Clancy, CJ AF Eschenauer, Gregory A. Nguyen, M. Hong Shoham, Shmuel Vazquez, Jose A. Morris, Arthur J. Pasculle, William A. Kubin, Christine J. Klinker, Kenneth P. Carver, Peggy L. Hanson, Kimberly E. Chen, Sharon Lam, Simon W. Potoski, Brian A. Clarke, Lloyd G. Shields, Ryan K. Clancy, Cornelius J. TI Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MINIMUM INHIBITORY CONCENTRATIONS; EUCAST TECHNICAL NOTE; INVASIVE CANDIDIASIS; ANTIFUNGAL AGENTS; CASPOFUNGIN MICS; GLABRATA; ANIDULAFUNGIN; BREAKPOINTS; RESISTANCE; CLSI AB Reference broth microdilution methods of Candida echinocandin susceptibility testing are limited by interlaboratory variability in caspofungin MICs. Recently revised Clinical and Laboratory Standards Institute (CLSI) breakpoint MICs for echinocandin nonsusceptibility may not be valid for commercial tests employed in hospital laboratories. Indeed, there are limited echinocandin susceptibility testing data from hospital laboratories. We conducted a multicenter retrospective study of 9 U. S., Australian, and New Zealand hospitals that routinely tested Candida bloodstream isolates for echinocandin susceptibility from 2005 to 2013. Eight hospitals used Sensititre YeastOne assays. The Candida spp. were C. albicans (n = 1,067), C. glabrata (n = 911), C. parapsilosis (n = 476), C. tropicalis (n = 185), C. krusei (n = 104), and others (n = 154). Resistance and intermediate rates were <= 1.4% and <= 3%, respectively, for each echinocandin against C. albicans, C. parapsilosis, and C. tropicalis. Resistance rates among C. glabrata and C. krusei isolates were <= 7.5% and <= 5.6%, respectively. Caspofungin intermediate rates among C. glabrata and C. krusei isolates were 17.8% and 46.5%, respectively, compared to <= 4.3% and <= 4.4% for other echinocandins. Using CLSI breakpoints, 18% and 19% of C. glabrata isolates were anidulafungin susceptible/caspofungin nonsusceptible and micafungin susceptible/caspofungin nonsusceptible, respectively; similar discrepancies were observed for 38% and 39% of C. krusei isolates. If only YeastOne data were considered, interhospital modal MIC variability was low (within 2 doubling dilutions for each agent). In conclusion, YeastOne assays employed in hospitals may reduce the interlaboratory variability in caspofungin MICs against Candida species that are observed between reference laboratories using CLSI broth microdilution methods. The significance of classifying isolates as caspofungin intermediate and anidulafungin/micafungin susceptible will require clarification in future studies. C1 [Eschenauer, Gregory A.; Clarke, Lloyd G.] Univ Pittsburgh, Med Ctr, Dept Pharm, Pittsburgh, PA 15260 USA. [Eschenauer, Gregory A.; Nguyen, M. Hong; Potoski, Brian A.; Clarke, Lloyd G.; Shields, Ryan K.; Clancy, Cornelius J.] Univ Pittsburgh, Med Ctr, Antibiot Management Program, Pittsburgh, PA USA. [Nguyen, M. Hong; Shields, Ryan K.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Shoham, Shmuel] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Vazquez, Jose A.] Henry Ford Hosp, Detroit, MI 48202 USA. [Morris, Arthur J.] Auckland City Hosp, Clin Microbiol Lab, Auckland, New Zealand. [Pasculle, William A.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA. [Kubin, Christine J.] New York Presbyterian Hosp, Dept Pharm, New York, NY USA. [Klinker, Kenneth P.] UF Hlth Shands Hosp, Dept Pharm, Gainesville, FL USA. [Carver, Peggy L.] Univ Michigan, Coll Pharm, Dept Clin Social & Adm Sci, Ann Arbor, MI 48109 USA. [Carver, Peggy L.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Hanson, Kimberly E.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Chen, Sharon] Westmead Hosp, Ctr Infect Dis & Microbiol, Westmead, NSW, Australia. [Lam, Simon W.] Cleveland Clin Fdn, Dept Pharm, Cleveland, OH 44195 USA. [Potoski, Brian A.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Clancy, Cornelius J.] VA Pittsburgh Hlth Syst, Dept Med, Pittsburgh, PA USA. RP Eschenauer, GA (reprint author), Univ Pittsburgh, Med Ctr, Dept Pharm, Pittsburgh, PA 15260 USA. EM geschena@gmail.com FU Pfizer; Merck; CSL Behring; Biotherapies for Life; Astellas; Forest; National Center for Advancing Translational Sciences of the National Institutes of Health [KL2TR000146]; Gilead Sciences; Pfizer (Australia); Astra-Zeneca FX M.H.N. has received investigator-initiated research funding from Pfizer, Merck, CSL Behring, and Biotherapies for Life. S. S. has received research funding from Pfizer, Merck, and Astellas. J.A.V. has received grant support from Forest, Pfizer, and Merck and has served on speaker bureaus for Pfizer and Astellas. R. K. S. is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR000146 and has received investigator-initiated funding from Merck and Astellas. P. L. C. has received funding from Astellas (consulting and grant support) and Merck (grant support). S. C. has served on antifungal advisory boards for Merck, Gilead Sciences, and Pfizer (Australia) and has received grant support from Merck, Gilead Sciences, and Pfizer (Australia). C.J.C. has received grant support for investigator-initiated research projects from Pfizer, Merck, and Astra-Zeneca. We have no other disclosures to report. NR 18 TC 27 Z9 28 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2014 VL 58 IS 4 BP 1897 EP 1906 DI 10.1128/AAC.02163-13 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AD9SU UT WOS:000333605600008 PM 24395235 ER PT J AU Fofana, I Jilg, N Chung, RT Baumert, TF AF Fofana, Isabel Jilg, Nikolaus Chung, Raymond T. Baumert, Thomas F. TI Entry inhibitors and future treatment of hepatitis C SO ANTIVIRAL RESEARCH LA English DT Editorial Material DE Entry inhibitors; Direct-acting antivirals; Resistance; Liver transplantation; Difficult-to-treat patients ID TREATMENT-NAIVE PATIENTS; TO-CELL TRANSMISSION; PEGYLATED INTERFERON ALPHA-2A; GENOTYPE 1 INFECTION; B TYPE-I; CHRONIC HCV INFECTION; VIRUS LIFE-CYCLE; DOUBLE-BLIND; NEUTRALIZING ANTIBODIES; LIVER-TRANSPLANTATION AB Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Furthermore, HCVinduced liver disease is the leading indication for liver transplantation. The recent introduction of directacting antivirals (DAAs) has revolutionized HCV treatment by making possible the cure of the majority of patients. However, their efficacy and safety in difficult-to-treat patients such as patients receiving immunosuppression, those with advanced liver disease, co-morbidity and HIV/HCV-co-infection remain to be determined. Furthermore, prevention of livergraft infection remains a pressing issue. HCV entry inhibitors target the very first step of the HCV life cycle and efficiently inhibit cell-cell transmission -a key prerequisite for viral spread. Because of their unique mechanism of action on cell-cell transmission they may provide a promising and simple perspective for prevention of liver graft infection. A high genetic barrier to resistance and complementary mechanism of action compared to DAAs makes entry inhibitors attractive as a new strategy for treatment of multi-resistant or difficult-to-treat patients. Clinical studies are needed to determine the future role of entry inhibitors in the arsenal of antivirals to combat HCV infection. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." (C) 2014 Published by Elsevier B.V. C1 [Fofana, Isabel; Baumert, Thomas F.] INSERM, U1110, Strasbourg, France. [Fofana, Isabel; Baumert, Thomas F.] Univ Strasbourg, F-67000 Strasbourg, France. [Jilg, Nikolaus; Chung, Raymond T.; Baumert, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. RP Baumert, TF (reprint author), Univ Strasbourg, INSERM, U1110, 3 Rue Koeberle, F-67000 Strasbourg, France. EM Thomas.Baumert@unistra.fr NR 114 TC 11 Z9 12 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2014 VL 104 BP 136 EP 142 DI 10.1016/j.antiviral.2014.02.001 PG 7 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA AE1KY UT WOS:000333729400017 PM 24525381 ER PT J AU Yeh, DD AF Yeh, Daniel Dante TI Packed red blood cell transfusions in the intensive care unit: treating the patient or the doctor? SO ANZ JOURNAL OF SURGERY LA English DT Editorial Material ID REQUIREMENTS; SURGERY; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1445-1433 EI 1445-2197 J9 ANZ J SURG JI ANZ J. Surg. PD APR PY 2014 VL 84 IS 4 BP 202 EP 203 DI 10.1111/ans.12529 PG 2 WC Surgery SC Surgery GA AE0JY UT WOS:000333652000004 PM 24812705 ER PT J AU Caplan, L Wolfe, F Michaud, K Quinzanos, I Hirsh, JM AF Caplan, Liron Wolfe, Frederick Michaud, Kaleb Quinzanos, Itziar Hirsh, Joel M. TI Strong Association of Health Literacy With Functional Status Among Rheumatoid Arthritis Patients: A Cross-Sectional Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID NATIONAL-DATA-BANK; QUALITY-OF-LIFE; WORK DISABILITY; IDENTIFY PATIENTS; DISEASE SEVERITY; OUTCOMES; ADHERENCE; SKILLS AB ObjectiveStudies linking health literacy to outcomes in rheumatoid arthritis (RA) have been underpowered and have not adequately accounted for confounders. We examined the association of health literacy with functional status in 6,052 subjects participating in a prospective observational study, controlling for numerous important covariates. MethodsUsing linear regression, we analyzed the cross-sectional association of health literacy, as measured by 2 validated single-item literacy screening questions (SILS1 and SILS2), and functional status, assessed by the Health Assessment Questionnaire (HAQ) disability index. Subjects reported demographics, comorbidities, social support, educational attainment, visual problems, and memory problems, as well as use of prednisone, disease-modifying antirheumatic drugs, and biologic agents. Each SILS measure was forced into the final model. ResultsLow health literacy was present in 7.0% and 4.3% of subjects (per SILS1 and SILS2, respectively). When controlling for all covariates, low health literacy was associated with a 0.376-point greater HAQ score, compared to subjects with adequate health literacy (95% confidence interval 0.306, 0.447; P < 0.001). This relationship persisted, even after modeling educational attainment. Results were similar for the 2 SILS instruments. Low health literacy was also associated with poorer self-reported adherence to RA medications. Visual and memory problems were associated with worse functional status. ConclusionHealth literacy was more strongly associated with functional status than prednisone use, smoking history, and biologic agent use, and independent of educational attainment. Health literacy may play an important role in understanding functional status in RA patients. Single-item questions amenable to use in the clinical setting may identify subjects with low health literacy, who are at risk for poor RA outcomes. C1 [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Caplan, Liron; Quinzanos, Itziar; Hirsh, Joel M.] Univ Colorado, Sch Med, Denver, CO 80045 USA. [Wolfe, Frederick; Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Wolfe, Frederick] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Wichita, KS USA. [Quinzanos, Itziar; Hirsh, Joel M.] Denver Hlth Med Ctr, Denver, CO USA. RP Caplan, L (reprint author), Univ Colorado, Sch Med, POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@ucdenver.edu FU US Department of Veterans Affairs Health Services Research and Development Career Development Award [CDA 07-221, CDP 09-388] FX Dr. Caplan's work was supported by a US Department of Veterans Affairs Health Services Research and Development Career Development Award (CDA 07-221 and CDP 09-388). NR 35 TC 14 Z9 14 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2014 VL 66 IS 4 BP 508 EP 514 DI 10.1002/acr.22165 PG 7 WC Rheumatology SC Rheumatology GA AD6OK UT WOS:000333380400002 PM 24023051 ER PT J AU Geary, K Knaub, LA Schauer, IE Keller, AC Watson, PA Miller, MW Garat, CV Nadeau, KJ Cree-Green, M Pugazhenthi, S Regensteiner, JG Klemm, DJ Reusch, JEB AF Geary, Kate Knaub, Leslie A. Schauer, Irene E. Keller, Amy C. Watson, Peter A. Miller, Matthew W. Garat, Chrystelle V. Nadeau, Kristen J. Cree-Green, Melanie Pugazhenthi, Subbiah Regensteiner, Judith G. Klemm, Dwight J. Reusch, Jane E. B. TI Targeting mitochondria to restore failed adaptation to exercise in diabetes SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE cAMP-response-element-binding protein (CREB); cardiovascular disease; diabetes; exercise; mitochondrion; nitric oxide synthase (NOS) ID ELEMENT-BINDING PROTEIN; SMOOTH-MUSCLE-CELLS; UPTAKE KINETIC RESPONSES; MEDIATED DOWN-REGULATION; NITRIC-OXIDE; TRANSCRIPTION FACTOR; DILATED CARDIOMYOPATHY; PEPTIDE-1 RECEPTOR; METABOLIC SYNDROME; BCL-2 PROMOTER AB Our translational research group focuses on addressing the problem of exercise defects in diabetes with basic research efforts in cell and rodent models and clinical research efforts in subjects with diabetes mellitus. CREB (cAMP-response-element-binding protein) regulates cellular differentiation of neurons, beta-cells, adipocytes and smooth muscle cells; it is also a potent survival factor and an upstream regulator of mitochondrial biogenesis. In diabetes and cardiovascular disease, CREB protein content is decreased in the vascular media, and its regulation in aberrant in beta-cells, neurons and cardiomyocytes. Loss of CREB content and function leads to decreased vascular target tissue resilience when exposed to stressors such as metabolic, oxidative or sheer stress. This basic research programme set the stage for our central hypothesis that diabetes-mediated CREB dysfunction predisposes the diabetes disease progression and cardiovascular complications. Our clinical research programme revealed that diabetes mellitus leads to defects in functional exercise capacity. Our group has determined that the defects in exercise correlate with insulin resistance, endothelial dysfunction, decreased cardiac perfusion and diastolic dysfunction, slowed muscle perfusion kinetics, decreased muscle perfusion and slowed oxidative phosphorylation. Combined basic and clinical research has defined the relationship between exercise and vascular function with particular emphasis on how the signalling to CREB and eNOS [endothelial NOS (nitric oxide synthase)] regulates tissue perfusion, mitochondrial dynamics, vascular function and exercise capacity. The present review summarizes our current working hypothesis that restoration of eNOS/NOS dysfunction will restore cellular homoeostasis and permit an optimal tissue response to an exercise training intervention. C1 [Geary, Kate; Knaub, Leslie A.; Schauer, Irene E.; Keller, Amy C.; Watson, Peter A.; Miller, Matthew W.; Garat, Chrystelle V.; Nadeau, Kristen J.; Cree-Green, Melanie; Pugazhenthi, Subbiah; Regensteiner, Judith G.; Klemm, Dwight J.; Reusch, Jane E. B.] Univ Colorado, Aurora, CO 80045 USA. [Knaub, Leslie A.; Schauer, Irene E.; Keller, Amy C.; Watson, Peter A.; Pugazhenthi, Subbiah; Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Nadeau, Kristen J.; Cree-Green, Melanie] Childrens Hosp, Aurora, CO 80045 USA. RP Reusch, JEB (reprint author), Univ Colorado, Anschutz Med Campus,13001 E 17th Pl, Aurora, CO 80045 USA. EM jane.reusch@ucdenver.edu FU Veterans' Administration Merit Award; Denver Research Institute; National Institutes of Health [RO1-DK064741, T32HL007171, P01HL014985, UL1RR025780]; Bristol-Myers Squibb; University of Colorado Center for Women's Health Research; American Diabetes Association; American Heart Association; Juvenile Diabetes Research Foundation International FX Our work is funded by a Veterans' Administration Merit Award (Basic and Clinical), Denver Research Institute, National Institutes of Health [grant numbers RO1-DK064741, T32HL007171, P01HL014985 and UL1RR025780], Bristol-Myers Squibb, the University of Colorado Center for Women's Health Research, American Diabetes Association, American Heart Association and Juvenile Diabetes Research Foundation International. NR 49 TC 5 Z9 5 U1 1 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 EI 1470-8752 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD APR PY 2014 VL 42 BP 231 EP 238 DI 10.1042/BST20130283 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE0LX UT WOS:000333658900002 PM 24646223 ER PT J AU Guddati, AK Kuter, DJ AF Guddati, Achuta K. Kuter, David J. TI Rituximab therapy for factor II inhibitor in a patient with antiphospholipid antibody syndrome SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE inhibitors; rituximab; hemostasis; factor II ID B-LYMPHOCYTE DEPLETION; FACTOR-V; BOVINE THROMBIN AB Factor II inhibitors have been associated with an increased risk of bleeding. The management of patients with factor II inhibitors has not been adequately described. We describe a patient with an increased bleeding tendency due to factor II inhibitor who was unable to undergo surgery due to her bleeding tendency. The patient was successfully treated with a course of rituximab, which markedly reduced her factor II inhibitor: the factor II level rose from 12 to 61%; prothrombin time decreased from 20 to 14.7 s; and partial thromboplastin time (PTT) decreased from 148 to 38.8 s. She was able to undergo abdominal surgery without any hemorrhagic complications. This case exemplifies the possibility of treating patients with factor II inhibitors with rituximab therapy. C1 [Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. [Kuter, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. RP Guddati, AK (reprint author), Massachusetts Gen Hosp, 50 Fruit St, Boston, MA 02114 USA. EM aguddati@partners.org NR 21 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 EI 1473-5733 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD APR PY 2014 VL 25 IS 3 BP 289 EP 291 DI 10.1097/MBC.0000000000000072 PG 3 WC Hematology SC Hematology GA AE0IX UT WOS:000333648900018 PM 24448153 ER PT J AU van Berge, L Hamilton, EM Linnankivi, T Uziel, G Steenweg, ME Isohanni, P Wolf, NI Krageloh-Mann, I Brautaset, NJ Andrews, PI de Jong, BA al Ghamdi, M van Wieringen, WN Tannous, BA Hulleman, E Wurdinger, T van Berkel, CGM Polder, E Abbink, TEM Struys, EA Scheper, GC van der Knaap, MS AF van Berge, Laura Hamilton, Eline M. Linnankivi, Tarja Uziel, Graziella Steenweg, Marjan E. Isohanni, Pirjo Wolf, Nicole I. Kraegeloh-Mann, Ingeborg Brautaset, Nils J. Andrews, P. Ian de Jong, Brigit A. al Ghamdi, Malak van Wieringen, Wessel N. Tannous, Bakhos A. Hulleman, Esther Wuerdinger, Thomas van Berkel, Carola G. M. Polder, Emiel Abbink, Truus E. M. Struys, Eduard A. Scheper, Gert C. van der Knaap, Marjo S. CA LBSL Res Grp TI Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy SO BRAIN LA English DT Article DE white matter disorder; DARS2; genotype-phenotype correlation; enzyme activity; compound screen ID TRANSFER-RNA SYNTHETASE; CLASSIFICATION-SYSTEM; MESSENGER-RNA; DARS2 GENE; MUTATION; LBSL; DIAGNOSIS; CHILDREN; VALIDITY AB Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a disorder caused by recessive mutations in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. Recent observations indicate that the phenotypic range of the disease is much wider than initially thought. Currently, no treatment is available. The aims of our study were (i) to explore a possible genotype-phenotype correlation; and (ii) to identify potential therapeutic agents that modulate the splice site mutations in intron 2 of DARS2, present in almost all patients. A cross-sectional observational study was performed in 78 patients with two DARS2 mutations in the Amsterdam and Helsinki databases up to December 2012. Clinical information was collected via questionnaires. An inventory was made of the DARS2 mutations in these patients and those previously published. An assay was developed to assess mitochondrial aspartyl-tRNA synthetase enzyme activity in cells. Using a fluorescence reporter system we screened for drugs that modulate DARS2 splicing. Clinical information of 66 patients was obtained. The clinical severity varied from infantile onset, rapidly fatal disease to adult onset, slow and mild disease. The most common phenotype was characterized by childhood onset and slow neurological deterioration. Full wheelchair dependency was rare and usually began in adulthood. In total, 60 different DARS2 mutations were identified, 13 of which have not been reported before. Except for 4 of 42 cases published by others, all patients were compound heterozygous. Ninety-four per cent of the patients had a splice site mutation in intron 2. The groups of patients sharing the same two mutations were too small for formal assessment of genotype-phenotype correlation. However, some combinations of mutations were consistently associated with a mild phenotype. The mitochondrial aspartyl-tRNA synthetase activity was strongly reduced in patient cells. Among the compounds screened, cantharidin was identified as the most potent modulator of DARS2 splicing. In conclusion, the phenotypic spectrum of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is wide, but most often the disease has a relatively slow and mild course. The available evidence suggests that the genotype influences the phenotype, but because of the high number of private mutations, larger numbers of patients are necessary to confirm this. The activity of mitochondrial aspartyl-tRNA synthetase is significantly reduced in patient cells. A compound screen established a 'proof of principle' that the splice site mutation can be influenced. This finding is promising for future therapeutic strategies. C1 [van Berge, Laura; Hamilton, Eline M.; Steenweg, Marjan E.; Wolf, Nicole I.; van Berkel, Carola G. M.; Polder, Emiel; Abbink, Truus E. M.; Scheper, Gert C.; van der Knaap, Marjo S.] Vrije Univ Amsterdam Med Ctr, Dept Child Neurol, NL-1081 HV Amsterdam, Netherlands. [Linnankivi, Tarja; Isohanni, Pirjo] Univ Helsinki, Childrens Hosp, Dept Child Neurol, Helsinki 00029, Finland. [Linnankivi, Tarja; Isohanni, Pirjo] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland. [Uziel, Graziella] Fdn Ist Neurol Besta, Dept Child Neurol, I-20133 Milan, Italy. [Isohanni, Pirjo] Univ Helsinki, Biomedicum Helsinki, Res Program Unit, FIN-00290 Helsinki, Finland. [Kraegeloh-Mann, Ingeborg] Univ Tubingen, Univ Childrens Hosp, Dept Neuropaediat, D-72076 Tubingen, Germany. [Brautaset, Nils J.] Sykehuset Vestfold, Dept Neurol, N-3103 Tonsberg, Norway. [Andrews, P. Ian] Sydney Childrens Hosp, Dept Neurol, Sydney, NSW 2031, Australia. [de Jong, Brigit A.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. [al Ghamdi, Malak] Univ British Columbia, BC Childrens Hosp, Dept Paediat, Vancouver, BC V6H 3V4, Canada. [van Wieringen, Wessel N.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands. [van Wieringen, Wessel N.] Vrije Univ Amsterdam, Dept Math, NL-1081 HV Amsterdam, Netherlands. [Tannous, Bakhos A.; Wuerdinger, Thomas] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Charlestown, MA 02129 USA. [Tannous, Bakhos A.; Wuerdinger, Thomas] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Dept Paediat Oncol Haematol, NL-1081 HV Amsterdam, Netherlands. [Hulleman, Esther; Wuerdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Struys, Eduard A.] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands. [van der Knaap, Marjo S.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. RP van der Knaap, MS (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Child Neurol, Neurosci Campus,Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM ms.vanderknaap@vumc.nl RI Wolf, Nicole/H-3943-2014; temple, isabel/K-2391-2015 OI Wolf, Nicole/0000-0003-1721-0728; FU Prinses Beatrix Fonds [WAR07/31]; Optimix Foundation for Scientific Research FX This study was supported by the Prinses Beatrix Fonds [grant WAR07/31] and the Optimix Foundation for Scientific Research. NR 32 TC 12 Z9 12 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR PY 2014 VL 137 BP 1019 EP 1029 DI 10.1093/brain/awu026 PN 4 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD4ZM UT WOS:000333260900018 PM 24566671 ER PT J AU Kuter, DJ AF Kuter, David J. TI Milestones in understanding platelet production: a historical overview SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE thrombocytopenia; haematopoietic growth factors; thrombocytopenia; thrombopoietin; thrombopoietin receptor agonists ID HUMAN MEGAKARYOCYTE GROWTH; C-MPL LIGAND; RECOMBINANT HUMAN THROMBOPOIETIN; PLACEBO-CONTROLLED TRIAL; EMBRYONIC KIDNEY-CELLS; FACTOR PEG-RHUMGDF; IMMUNE THROMBOCYTOPENIA; MYELODYSPLASTIC SYNDROMES; LONG-TERM; HYPERSPLENIC THROMBOCYTOPENIA AB The discovery of thrombopoietin (TPO, also termed THPO) in 1994 was a major achievement in understanding the regulation of platelet production. In prior decades, physiological studies had demonstrated that platelets were produced from bone marrow megakaryocytes and that the megakaryocytes responded to thrombocytopenia by increasing their number, size and DNA ploidy. In 1958, it was proposed that a 'thrombopoietin' must exist that regulated this interaction between the circulating platelet mass and the bone marrow megakaryocytes. After over three decades of effort, TPO was finally purified by five independent laboratories. TPO stimulated megakaryocyte colony-forming cell growth and increased the number, size and ploidy of megakaryocytes. When the genes for TPO or TPO receptor were eliminated in mice, megakaryocytes grew and platelets were made, but at 15% of their normal number. A first generation of recombinant human (rh) TPO molecules [rhTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rhMGDF)] rapidly entered clinical trials in 1995 and increased platelet counts in humans undergoing non-myeloablative chemotherapy but not in those undergoing stem cell transplantation. Antibodies developed against PEG-rhMGDF and development of these recombinant thrombopoietins ended. A second generation of TPO receptor agonists (romiplostim and eltrombopag) was then developed. Neither of these TPO receptor agonists demonstrated any significant untoward effects and both are now licensed in many countries for the treatment of immune thrombocytopenia. This review describes the significant experiments that have surrounded the discovery of TPO and its clinical development. C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7858,55 Fruit St, Boston, MA 02114 USA. EM dkuter@MGH.harvard.edu NR 111 TC 24 Z9 25 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2014 VL 165 IS 2 BP 248 EP 258 DI 10.1111/bjh.12781 PG 11 WC Hematology SC Hematology GA AD9ET UT WOS:000333568300011 PM 24528208 ER PT J AU Shyn, PB Tatli, S Sahni, VA Sadow, CA Forgione, K Mauri, G Morrison, PR Catalano, PJ Silverman, SG AF Shyn, P. B. Tatli, S. Sahni, V. A. Sadow, C. A. Forgione, K. Mauri, G. Morrison, P. R. Catalano, P. J. Silverman, S. G. TI PET/CT-guided percutaneous liver mass biopsies and ablations: Targeting accuracy of a single 20 s breath-hold PET acquisition SO CLINICAL RADIOLOGY LA English DT Article ID LUNG-CANCER; RADIOFREQUENCY; INTERVENTIONS; PATIENT AB AIM: To determine whether a single 20 s breath-hold positron-emission tomography (PET) acquisition obtained during combined PET/computed tomography (CT)-guided percutaneous liver biopsy or ablation procedures has the potential to target 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG)-avid liver masses as accurately as up to 180 s breath-hold PET acquisitions. MATERIALS AND METHODS: This retrospective study included 10 adult patients with 13 liver masses who underwent FDG PET/CT-guided percutaneous biopsies (n = 5) or ablations (n = 5). PET was acquired as nine sequential 20 s, monitored, same-level breath-hold frames and CT was acquired in one monitored breath-hold. Twenty, 40, 60, and 180 s PET datasets were reconstructed. Two blinded readers marked tumour centres on randomized PET and CT datasets. Three-dimensional spatial localization differences between PET datasets and either 180 s PET or CT were analysed using multiple regression analyses. Statistical tests were two-sided and p < 0.05 was considered significant. RESULTS: Targeting differences between 20 s PET and 180 s PET ranged from 0.7-20.3 mm (mean 5.3 +/- 4.4 mm; median 4.3) and were not statistically different from 40 or 60 s PET (p = 0.74 and 0.91, respectively). Targeting differences between 20 s PET and CT ranged from 1.4-36 mm (mean 9.6 +/- 7.1 mm; median 8.2 mm) and were not statistically different from 40, 60, or 180 s PET (p = 0.84, 0.77, and 0.35, respectively). CONCLUSION: Single 20 s breath-hold PET acquisitions from PET/CT-guided percutaneous liver procedures have the potential to target FOG-avid liver masses with equivalent accuracy to 180 s summed, breath-hold PET acquisitions and may facilitate strategies that improve image registration and shorten procedure times. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Shyn, P. B.; Tatli, S.; Sahni, V. A.; Sadow, C. A.; Forgione, K.; Mauri, G.; Morrison, P. R.; Silverman, S. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Catalano, P. J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Shyn, PB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM pshyn@partners.org NR 16 TC 13 Z9 13 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2014 VL 69 IS 4 BP 410 EP 415 DI 10.1016/j.crad.2013.11.013 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE3CP UT WOS:000333854900013 PM 24411824 ER PT J AU Ferrario, CM Ahmad, S Nagata, S Simington, SW Varagic, J Kon, N Dell'italia, LJ AF Ferrario, Carlos Maria Ahmad, Sarfaraz Nagata, Sayaka Simington, Stephen W. Varagic, Jasmina Kon, Neal Dell'italia, Louis Joseph TI An evolving story of angiotensin-II-forming pathways in rodents and humans SO CLINICAL SCIENCE LA English DT Review DE angiotensin-(1-7); angiotensin-(1-12); angiotensin-converting enzyme (ACE); atrial fibrillation; chymase; pro-angiotensin-12; renin ID HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; CONVERTING ENZYME 2; MAST-CELL CHYMASE; CARDIOVASCULAR ACTIONS; BLOOD-PRESSURE; HUMAN HEART; PROANGIOTENSIN-12 PA12; VASOPRESSIN RELEASE; RECEPTOR BLOCKERS; ALTITUDE TRIAL AB Lessons learned from the characterization of the biological roles of Ang-(1-7) [angiotensin-(1-7)] in opposing the vasoconstrictor, proliferative and prothrombotic actions of Angll (angiotensin II) created an underpinning for a more comprehensive exploration of the multiple pathways by which the RAS (renin angiotensin system) of blood and tissues regulates homoeostasis and its altered state in disease processes. The present review summarizes the progress that has been made in the novel exploration of intermediate shorter forms of angiotensinogen through the characterization of the expression and functions of the dodecapeptide Ang-(1-12) [angiotensin-(1-12)] in the cardiac production of Angll. The studies reveal significant differences in humans compared with rodents regarding the enzymatic pathway by which Ang-(1-12) undergoes metabolism. Highlights of the research include the demonstration of chymase-directed formation of Angll from Ang-(1-12) in human left atrial myocytes and left ventricular tissue, the presence of robust expression of Ang-(1-12) and chymase in the atrial appendage of subjects with resistant atrial fibrillation, and the preliminary observation of significantly higher Ang-(1-12) expression in human left atrial appendages. C1 [Ferrario, Carlos Maria; Ahmad, Sarfaraz; Nagata, Sayaka; Simington, Stephen W.; Varagic, Jasmina; Kon, Neal] Wake Forest Univ, Bowman Gray Sch Med, Dept Gen Surg, Winston Salem, NC 27157 USA. [Ferrario, Carlos Maria; Ahmad, Sarfaraz; Nagata, Sayaka; Simington, Stephen W.; Varagic, Jasmina; Kon, Neal] Wake Forest Univ, Bowman Gray Sch Med, Dept Cardiothorac Surg, Winston Salem, NC 27157 USA. [Varagic, Jasmina] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC 27157 USA. [Dell'italia, Louis Joseph] Univ Alabama Birmingham, Med Ctr, Birmingham Vet Affair Med Ctr, Birmingham, AL 35294 USA. RP Ferrario, CM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Gen Surg, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. EM cferrari@wakehealth.edu FU National Heart, Lung and Blood Institute of the National Institutes of Health [HL-051952] FX The authors were primarily supported by the National Heart, Lung and Blood Institute of the National Institutes of Health [grant number HL-051952]. NR 95 TC 23 Z9 24 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0143-5221 EI 1470-8736 J9 CLIN SCI JI Clin. Sci. PD APR PY 2014 VL 126 IS 7-8 BP 461 EP 469 DI 10.1042/CS20130400 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1KU UT WOS:000333729000001 PM 24329563 ER PT J AU Kirby, NA Stepanek, AM Vernet, A Schmidt, SM Schultz, CL Parry, NMA Niemi, SM Fox, JG Brown, DE AF Kirby, Naomi A. Stepanek, Aaron M. Vernet, Andyna Schmidt, Sarah M. Schultz, Carrie L. Parry, Nicola M. A. Niemi, Steven M. Fox, James G. Brown, Diane E. TI Urinary MCP1 and Microalbumin Increase Prior to Onset of Azotemia in Mice with Polycystic Kidney Disease SO COMPARATIVE MEDICINE LA English DT Article DE ADPKD; autosomal dominant polycystic kidney disease; MCP1; monocyte chemoattractant protein 1; PE diet; protein-restricted experimental diet ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; RENAL INJURY; MODEL; RESTRICTION; PROGRESSION; BIOMARKERS; ANEMIA; LEVEL; MOUSE; RATS AB Urinary biomarkers may offer a more sensitive and less invasive means to monitor kidney disease than traditional blood chemistry biomarkers such as creatinine. CD1(pcylpcy) (pcy) mice have a slowly progressive disease phenotype that resembles human autosomal dominant polycystic kidney disease with renal cyst formation and inflammation. Previous reports suggest that dietary protein restriction may slow disease progression in mice and humans with polycystic kidney disease. Accordingly, we fed pcy mice either a standard chow (22.5% protein) or a protein-restricted (11.5% soy-based protein) diet from weaning until 34 wk of age. Every 6 wk we measured markers of kidney disease, including serum creatinine, BUN, and serum albumin as well as urinary monocyte chemoattractant protein 1 (MCP1), microalbumin, and specific gravity. Progression of kidney disease was equivalent for both diet groups despite dietary protein restriction. Urinary biomarkers proved useful for early detection of disease, in that urinary microalbumin was elevated as early as 22 wk of age and urinary MCP1 was increased by 28 wk of age, whereas increases in serum creatinine and BUN were detected later (at 34 wk of age) in both diet groups. Thus, urinary microalburnin and MCP1 analyses provided earlier, noninvasive indicators for detection of kidney disease and disease progression in pcy mice than did serum creatinine and BUN. C1 [Kirby, Naomi A.; Stepanek, Aaron M.; Vernet, Andyna; Schmidt, Sarah M.; Niemi, Steven M.; Brown, Diane E.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Schultz, Carrie L.] Purina LabDiet, St Louis, MO USA. [Parry, Nicola M. A.; Fox, James G.] MIT, Div Comparat Med, Boston, MA USA. [Niemi, Steven M.; Brown, Diane E.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Brown, DE (reprint author), Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. EM dbrown31@partners.org FU Harvard Catalyst, The Harvard Clinical and Translational Science Center [8UL1TR000170-05]; Massachusetts General Hospital Department of Pathology (DEB); Purina Mills-Land O' Lakes FX This work was conducted with statistical analysis support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH award no. 8UL1TR000170-05 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 health care centers or the NIH. We acknowledge the Massachusetts Institute of Technology Division of Comparative Medicine mouse husbandry staff and the Massachusetts General Hospital Center for Comparative Medicine Veterinary Clinical Pathology Laboratory staff for animal care and blood sample analyses, respectively, and Kyle W Brown for technical image support. These studies were conducted in part with a Vickery Grant from the Massachusetts General Hospital Department of Pathology (DEB) and funding from Purina Mills-Land O' Lakes. NR 28 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2014 VL 64 IS 2 BP 99 EP 105 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA AE1IK UT WOS:000333722800003 PM 24674583 ER PT J AU Storch, EA De Nadai, AS Jacob, ML Lewin, AB Muroff, J Eisen, J Abramowitz, JS Geller, DA Murphy, TK AF Storch, Eric A. De Nadai, Alessandro S. Jacob, Marni L. Lewin, Adam B. Muroff, Jordana Eisen, Jane Abramowitz, Jonathan S. Geller, Daniel A. Murphy, Tanya K. TI Phenomenology and correlates of insight in pediatric obsessive-compulsive disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; SCALE RELIABILITY; POOR INSIGHT; DISRUPTIVE BEHAVIOR; SYMPTOM DIMENSIONS; CLINICAL-FEATURES; BROWN ASSESSMENT; CONTROLLED-TRIAL; BELIEFS SCALE; CHILD VERSION AB Obsessive-compulsive disorder (OCD) is marked by the presence of obsessions and/or compulsions that cause significant interference in an individual's life. Insight regarding symptoms in youth with OCD may affect accurate assessment, acceptance and motivation for treatment, tolerance of negative valence states (i.e., fear) and treatment outcome, so assessment of this construct and associated clinical characteristics is important. Accordingly, the current study sought to expand the literature on symptom insight by examining multi-informant ratings of insight from children, parents, and clinicians simultaneously and its relationship to varied clinical characteristics. One-hundred and ten treatment-seeking youth with a primary diagnosis of OCD, aged 6-17, participated in the study along with a parent/guardian. The nature of symptom conviction, fixity of ideas, and perceptions about the cause of the problems were important indicators in assessing child insight and resulted in a comprehensive, psychometrically-sound measure of insight. Insight was generally not strongly associated with clinical characteristics. Poor insight was moderately associated with less resistance of obsessive compulsive symptoms, increased externalizing symptoms, and ordering symptoms. Overall, this study contributes further information into the nature and correlates of insight in youth with OCD, and provides a psychometrically sound approach for its assessment. (C) 2014 Elsevier Inc. All rights reserved. C1 [Storch, Eric A.; De Nadai, Alessandro S.; Jacob, Marni L.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA. [Storch, Eric A.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat & Behav Neurosci, St Petersburg, FL 33701 USA. [Storch, Eric A.; De Nadai, Alessandro S.] Univ S Florida, Dept Psychol, St Petersburg, FL 33701 USA. [Muroff, Jordana] Boston Univ, Dept Social Work, Boston, MA 02215 USA. [Eisen, Jane] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Abramowitz, Jonathan S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, 880 6th St South 4th Floor, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu RI Murphy, Tanya/J-7079-2013 NR 54 TC 4 Z9 4 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD APR PY 2014 VL 55 IS 3 BP 613 EP 620 DI 10.1016/j.comppsych.2013.09.014 PG 8 WC Psychiatry SC Psychiatry GA AE0NA UT WOS:000333661800029 PM 24238933 ER PT J AU Stasko, K Hansen, H AF Stasko, K. Hansen, H. TI A WEB BASED FORUM FOR EDUCATION & COMMUNICATION IN A CHALLENGING WORKPLACE ENVIRONMENT SO CYTOTHERAPY LA English DT Meeting Abstract C1 [Stasko, K.; Hansen, H.] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD APR PY 2014 VL 16 IS 4 SU S MA 151 BP S47 EP S47 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA AD7IT UT WOS:000333438100145 ER PT J AU Sullivan, SD Jablonski, KA Florez, JC Dabelea, D Franks, PW Dagogo-Jack, S Kim, C Knowler, WC Christophi, CA Ratner, R AF Sullivan, Shannon D. Jablonski, Kathleen A. Florez, Jose C. Dabelea, Dana Franks, Paul W. Dagogo-Jack, Sam Kim, Catherine Knowler, William C. Christophi, Costas A. Ratner, Robert CA Diabet Prevention Program Res Grp TI Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive Lifestyle or Metformin in Prediabetic Women With and Without a History of Gestational Diabetes Mellitus SO DIABETES CARE LA English DT Article ID PREVENTION PROGRAM; COHORT AB OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing beta-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS beta-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to beta-cell dysfunction. C1 [Sullivan, Shannon D.] MedStar Washington Hosp Ctr, Dept Med, Endocrine Div, Washington, DC USA. [Jablonski, Kathleen A.; Christophi, Costas A.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dabelea, Dana] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Dagogo-Jack, Sam] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN USA. [Kim, Catherine] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kim, Catherine] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Ratner, Robert] Amer Diabet Assoc, Alexandria, VA USA. RP Sullivan, SD (reprint author), MedStar Washington Hosp Ctr, Dept Med, Endocrine Div, Washington, DC USA. EM dppmail@bsc.gwu.edu OI Franks, Paul/0000-0002-0520-7604 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health [U01-DK-048489]; NIDDK [R01-DK-072041]; Indian Health Service; Office of Research on Minority Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; Novo Nordisk; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Diabetes Association; AstraZeneca; Bristol-Myers Squibb; Boehringer Ingelheim FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the coordinating center for the design and conduct of the study and the collection, management, analysis, and interpretation of the data (U01-DK-048489). The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. This research was also supported, in part, by the intramural research program of the NIDDK. Genotyping for this project was supported by NIDDK R01-DK-072041 to J.C.F. and K.A.J.; Bristol-Myers Squibb and Parke-Davis provided the medication. LifeScan, Health o meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck, Nike Sports Marketing, Slim-Fast, and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson Corp., Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. P.W.F. was supported by grants from Novo Nordisk, the Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Association. J.C.F. has received consulting honoraria from Eli Lilly and Company and Pfizer. S.D.-J. has received research grants from AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, and Boehringer Ingelheim (all under contracts with his employer) and has received honoraria for serving as a consultant for Merck, Santarus, Amylin Pharmaceuticals, and Novo Nordisk. No other potential conflicts of interest relevant to this article were reported. NR 9 TC 3 Z9 3 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 909 EP 911 DI 10.2337/dc13-0700 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700018 PM 24271189 ER PT J AU Garvey, WT Ryan, DH Henry, R Bohannon, NJV Toplak, H Schwiers, M Troupin, B Day, WW AF Garvey, W. Timothy Ryan, Donna H. Henry, Robert Bohannon, Nancy J. V. Toplak, Hermann Schwiers, Michael Troupin, Barbara Day, Wesley W. TI Prevention of Type 2 Diabetes in Subjects With Prediabetes and Metabolic Syndrome Treated With Phentermine and Topiramate Extended Release SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; WEIGHT-LOSS; FOLLOW-UP; CARDIOVASCULAR-DISEASE; OBESE ADULTS; RISK; OVERWEIGHT; MANAGEMENT; REDUCTION AB OBJECTIVE To evaluate over 108 weeks the effect of phentermine and topiramate extended release (PHEN/TPM ER) treatment on progression to type 2 diabetes and/or cardiometabolic disease in subjects with prediabetes and/or metabolic syndrome (MetS) at baseline. RESEARCH DESIGN AND METHODS Subanalysis of a phase 3, randomized, placebo-controlled, double-blind study of overweight/obese subjects (BMI >= 27 to <= 45 kg/m(2)) with two or more comorbidities. Subjects were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92 mg (15/92) plus lifestyle modifications for 108 weeks. Percent weight loss in the intent-to-treat population using multiple imputation (ITT-MI), annualized incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid parameters, blood pressure, and waist circumference were evaluated. RESULTS At baseline, 475 subjects met the criteria for prediabetes and/or MetS. After 108 weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92 groups experienced mean percent weight loss of 2.5, 10.9, and 12.1%, respectively (ITT-MI; P < 0.0001 vs. placebo), associated with reductions of 70.5 and 78.7% in the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and 15/92, respectively (ITT, P < 0.05), versus placebo. The ability of PHEN/TPM ER to prevent diabetes was related to degree of weight lost and was accompanied by significant improvements in cardiometabolic parameters. PHEN/TPM ER was well tolerated by this subgroup over 2 years. CONCLUSIONS PHEN/TPM ER plus lifestyle modification produced significant weight loss and markedly reduced progression to type 2 diabetes in overweight/obese patients with prediabetes and/or MetS, accompanied by improvements in multiple cardiometabolic disease risk factors. C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Henry, Robert] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Henry, Robert] San Diego VA Med Ctr, San Diego, CA USA. [Bohannon, Nancy J. V.] Monteagle Med Ctr, San Francisco, CA USA. [Toplak, Hermann] Med Univ Graz, Graz, Austria. [Schwiers, Michael] Medpace, Cincinnati, OH USA. [Troupin, Barbara; Day, Wesley W.] VIVUS Inc, Mountain View, CA USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU VIVUS, Inc.; Merck; Calibra Medical; Intuity Medical; Halozyme Therapeutics; Johnson Johnson; Eli Lilly and Company; Novartis; Sanofi; Valeritus Medical Solutions; Boehringer Ingelheim; Bristol-Myers Squibb; AstraZeneca; Novo Nordisk; Takeda Pharmaceutical Company FX Funding for the study and for editorial assistance was provided by VIVUS, Inc. VIVUS, Inc. was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. W.T.G. has participated in clinical trials with Merck, Weight Watchers, National Institutes of Health, the Veterans Administration, Amylin Pharmaceuticals, VIVUS, Inc., Abbott Laboratories, and Daiichi-Sankyo, Inc. He has served as an advisor, consultant, and/or speaker for Alkermes, Daiichi-Sankyo, Inc., LipoScience, VIVUS, Inc., Janssen Pharmaceuticals, Inc., and Tethys Bioscience. He is a scientific advisory board member at Daiichi-Sankyo, Inc., Tethys Bioscience, LipoScience, and Alkermes; he holds stock in Bristol-Myers Squibb, Isis/Genzyme, Merck, Pfizer, Eli Lilly and Company, and VIVUS, Inc. He has grants/grants pending with Merck, Amylin Pharmaceuticals, and Weight Watchers. He has received payment for lectures, including service on speakers' bureaus, from Merck. He has received payment from VIVUS, Inc. for consulting fee/honorarium and support for travel to meetings for the current study or for other purposes. D.H.R. has received payment from VIVUS, Inc. for consulting fee/honorarium and support for travel to meetings for the current study or for other purposes. She is a board member for Nutrisystem and Alere Wellbeing and a consultant for VIVUS, Inc., Novo Nordisk, Eisai Pharmaceuticals, Dainippon Sumitoma Pharma, and Scientific Intake. She holds stock in Scientific Intake. She has received honoraria from the Cleveland Clinic Foundation, Medical Exchange International, CME Incite, Academy of Nutrition and Dietetics, American Society of Bariatric Physicians, Continuing Education Alliance, American Heart Association, Vindico, Obesity Action Coalition, George Washington University, American Society of Bariatric Physicians, Minimally Invasive Surgery Symposium, Professional TV Network, National Institutes of Health, and the European Union Innovative Medicines Initiative. R.H. has served as a consultant and/or an advisor for Amgen, Inc., AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Inc., Elcelyx Therapeutics, Inc., Gilead Sciences, Inc., Intarcia Therapeutics, Inc., Isis Pharmaceuticals, Inc., Eli Lilly and Company, Johnson & Johnson, Janssen Pharmaceuticals, Inc., Merck, Novo Nordisk, Roche/Genentech, Sanofi, and VIVUS, Inc. He has grants/grants pending for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Medtronic, Inc., and Sanofi. N.J.V.B.'s institution has received payment from VIVUS, Inc. for a research grant and an investigators' meeting. N.J.V.B. has grants from Calibra Medical, Intuity Medical, Halozyme Therapeutics, Johnson & Johnson, Eli Lilly and Company, Novartis, Sanofi, and Valeritus Medical Solutions. She has received payment for lectures and consulting and advisory boards, including service on speakers' bureaus, from VIVUS, Inc., Amylin Pharmaceuticals, Bristol-Myers Squibb, Daiichi-Sankyo, Inc., Eli Lilly and Company, Johnson & Johnson, Janssen, Merck, Merck/Schering-Plough, Novartis, Quest Diagnostics, Santarus, Sanofi, and Tethys Bioscience. She holds stock in VIVUS, Inc., Eli Lilly and Company, Johnson & Johnson, Merck, Novartis, Pfizer, Santarus, and Sanofi. H.T. has received consulting fees/honoraria from VIVUS, Inc., Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company, Merck, and Novartis.; He has grants/grants pending with Merck, Takeda Pharmaceutical Company, and Novartis. He has received payment for lectures, including service on speakers' bureaus, for Merck, Takeda Pharmaceutical Company, Novartis, Novo Nordisk, and Sanofi. He has received travel/accommodations/meeting expenses from VIVUS, Inc. unrelated to the current study. M.S. was employed as the lead statistician for Medpace, the study clinical research organization, throughout the study design, execution, and analysis; he was paid for his statistical analysis of all data presented in the manuscript by VIVUS, Inc. B.T. and W.W.D. are employees of VIVUS, Inc. No other potential conflicts of interest relevant to this article were reported. NR 39 TC 38 Z9 38 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 912 EP 921 DI 10.2337/dc13-1518 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700019 PM 24103901 ER PT J AU Sosenko, JM Skyler, JS Mahon, J Krischer, JP Greenbaum, CJ Rafkin, LE Beam, CA Boulware, DC Matheson, D Cuthbertson, D Herold, KC Eisenbarth, G Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Mahon, Jeffrey Krischer, Jeffrey P. Greenbaum, Carla J. Rafkin, Lisa E. Beam, Craig A. Boulware, David C. Matheson, Della Cuthbertson, David Herold, Kevan C. Eisenbarth, George Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp Diabet Prevention Trial-Type 1 TI Use of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for Improving the Accuracy of the Risk Classification of Type 1 Diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; ZINC TRANSPORTER 8; NATURAL-HISTORY; CLINICAL ONSET; RELATIVES; INSULIN; PREDICTION; AUTOANTIBODIES; TRIAL-TYPE-1; PARTICIPANTS AB OBJECTIVE We studied the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of type 1 diabetes (T1D) risk classification in TrialNet Natural History Study (TNNHS) participants. RESEARCH DESIGN AND METHODS The cumulative incidence of T1D was compared between normoglycemic individuals with DPTRS values > 7.00 and dysglycemic individuals in the TNNHS (n = 991). It was also compared between individuals with DPTRS values < 7.00 or > 7.00 among those with dysglycemia and those with multiple autoantibodies in the TNNHS. DPTRS values > 7.00 were compared with dysglycemia for characterizing risk in Diabetes Prevention Trial-Type 1 (DPT-1) (n = 670) and TNNHS participants. The reliability of DPTRS values > 7.00 was compared with dysglycemia in the TNNHS. RESULTS The cumulative incidence of T1D for normoglycemic TNNHS participants with DPTRS values > 7.00 was comparable to those with dysglycemia. Among those with dysglycemia, the cumulative incidence was much higher (P < 0.001) for those with DPTRS values > 7.00 than for those with values < 7.00 (3-year risks: 0.16 for < 7.00 and 0.46 for > 7.00). Dysglycemic individuals in DPT-1 were at much higher risk for T1D than those with dysglycemia in the TNNHS (P < 0.001); there was no significant difference in risk between the studies among those with DPTRS values > 7.00. The proportion in the TNNHS reverting from dysglycemia to normoglycemia at the next visit was higher than the proportion reverting from DPTRS values > 7.00 to values < 7.00 (36 vs. 23%). CONCLUSIONS DPTRS thresholds can improve T1D risk classification accuracy by identifying high-risk normoglycemic and low-risk dysglycemic individuals. The 7.00 DPTRS threshold characterizes risk more consistently between populations and has greater reliability than dysglycemia. C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.; Matheson, Della] Univ Miami, Div Endocrinol, Miami, FL USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada. [Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Virginia Mason, Benaroya Res Inst, Seattle, WA USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Eisenbarth, George] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA. [Palmer, Jerry P.] Univ Washington, Div Endocrinol Metab & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Research Resources; Juvenile Diabetes Research Foundation International; American Diabetes Association FX This work was funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Research Resources; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 21 TC 9 Z9 9 U1 3 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 979 EP 984 DI 10.2337/dc13-2359 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700027 PM 24550217 ER PT J AU Simonetti, JA Fine, MJ Chen, YF Simak, D Hess, R AF Simonetti, Joseph A. Fine, Michael J. Chen, Yi-Fan Simak, Deborah Hess, Rachel TI Racial Comparisons of Diabetes Care and Intermediate Outcomes in a Patient-Centered Medical Home SO DIABETES CARE LA English DT Article ID QUALITY-OF-CARE; BLOOD-PRESSURE CONTROL; RACIAL/ETHNIC DIFFERENCES; INFLUENZA VACCINATION; HEALTH LITERACY; MANAGED CARE; DISPARITIES; CONTINUITY; ETHNICITY; ADHERENCE AB OBJECTIVE To assess racial differences in diabetes processes and intermediate outcomes of care in an internal medicine, patient-centered medical home (PCMH) group practice. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study of 1,457 adults with diabetes receiving care from 89 medical providers within a PCMH-designated academic practice between 1 July 2009 and 31 July 2010. We used mixed models to assess independent associations between patient race (non-Hispanic white or black) and 1) receipt of processes of care (A1C and LDL testing, foot and retinal examination, and influenza and pneumococcal vaccination) and 2) achievement of intermediate outcomes (LDL < 100 mg/dL, blood pressure [BP] < 140/90 mmHg, A1C < 7.0% [< 53 mmol/mol], and A1C > 9.0% [> 75 mmol/mol]), controlling for sociodemographic factors, health status, treatment intensity, and clinical continuity. RESULTS Compared with non-Hispanic white patients, black patients were younger, were more often single, had lower educational attainment, and were less likely to have commercial insurance. In unadjusted analyses, fewer black patients received a retinal examination and influenza vaccination during the study period or any lifetime pneumococcal vaccination (P < 0.05 [all comparisons]). Fewer black patients achieved an LDL < 100 mg/dL, BP < 140/90 mmHg, or A1C < 7.0% (< 53 mmol/mol), while more black patients had an A1C > 9.0% (> 75 mmol/mol) (P < 0.05 [all comparisons]). In multivariable models, black patients were less likely to receive A1C testing (odds ratio [OR] 0.57 [95% CI 0.34-0.95]) or influenza vaccination (OR 0.75 [95% CI 0.57-0.99]) or to achieve an LDL < 100 mg/dL (OR 0.74 [95% CI 0.55-0.99]) or BP < 140/90 mmHg (OR 0.64 [95% CI 0.49-0.84]). CONCLUSIONS Racial differences in processes and intermediate outcomes of diabetes care were present within this PCMH-designated practice, controlling for differences in sociodemographic, clinical, and treatment factors. C1 [Simonetti, Joseph A.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Fine, Michael J.; Hess, Rachel] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chen, Yi-Fan] Univ Illinois, Ctr Clin & Translat Sci, Chicago, IL USA. [Simak, Deborah] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Simonetti, JA (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. EM simonja@uw.edu OI simonetti, joseph/0000-0002-1092-160X FU National Institutes of Health [UL1-RR-024153, UL1-TR-000005] FX This project was supported by National Institutes of Health grants UL1-RR-024153 and UL1-TR-000005. NR 42 TC 6 Z9 6 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 993 EP 1001 DI 10.2337/dc13-1332 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700029 PM 24255103 ER PT J AU Wei, N Zheng, H Nathan, DM AF Wei, Nancy Zheng, Hui Nathan, David M. TI Empirically Establishing Blood Glucose Targets to Achieve HbA(1c) Goals SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; ASSOCIATION; GUIDELINES; CARE AB OBJECTIVE To determine the average fasting, postprandial, and bedtime self-monitored blood glucose (SMBG) concentrations associated with specified HbA(1c) levels using data from the A1c-Derived Average Glucose (ADAG) study. RESEARCH DESIGN AND METHODS The ADAG study was a multicenter observational study that used continuous glucose monitoring and SMBG testing to determine the relationship between mean average glucose and HbA(1c). We used the SMBG data from 470 of the ADAG study participants (237 with type 1 diabetes and 147 with type 2 diabetes) to determine the average fasting, premeal, 90-min postmeal, and bedtime blood glucose (BG) for predefined target HbA(1c) groups between 5.5 and 8.5% (37-69 mmol/mol). t Tests were used to compare mean BG values between type 1 and type 2 diabetes groups. RESULTS The average fasting BG needed to achieve predefined HbA(1c) target levels of 5.5-6.49% (37-47 mmol/mol), 6.5-6.99% (48-52 mmol/mol), 7.0-7.49% (52-58 mmol/mol), 7.5-7.99% (58-64 mmol/mol), and 8.0-8.5% (64-69 mmol/mol) were 122 mg/dL with 95% CI 117-127, 142 mg/dL (135-150), 152 mg/dL (143-162), 167 mg/dL (157-177), and 178 mg/dL (164-192), respectively. Postmeal BG to achieve the HbA(1c) level of 6.5-6.99% (48-52 mmol/mol) and 7.0-7.49% (52-58 mmol/mol) were 139 mg/dL (134-144) and 152 mg/dL (147-157), respectively. Bedtime BG was 153 mg/dL (145-161) and 177 mg/dL (166-188), respectively. CONCLUSIONS We have determined the average BG at premeal, postmeal, and bedtime to achieve a variety of HbA(1c) targets. These results, based on empirical data, will help patients and providers set realistic day-to-day SMBG targets to achieve individualized HbA(1c) goals. C1 [Wei, Nancy; Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02115 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Wei, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02115 USA. EM ncwei@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK-007-028]; Charlton Fund for Innovative Research in Diabetes FX N.W. was supported by a National Institute of Diabetes and Digestive and Kidney Diseases training grant (T32 DK-007-028). D.M.N. is supported in part by the Charlton Fund for Innovative Research in Diabetes. NR 8 TC 14 Z9 16 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 1048 EP 1051 DI 10.2337/dc13-2173 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700036 PM 24513588 ER PT J AU Orban, T Bundy, B Becker, DJ DiMeglio, LA Gitelman, SE Goland, R Gottlieb, PA Greenbaum, CJ Marks, JB Monzavi, R Moran, A Peakman, M Raskin, P Russell, WE Schatz, D Wherrett, DK Wilson, DM Krischer, JP Skyler, JS AF Orban, Tihamer Bundy, Brian Becker, Dorothy J. DiMeglio, Linda A. Gitelman, Stephen E. Goland, Robin Gottlieb, Peter A. Greenbaum, Carla J. Marks, Jennifer B. Monzavi, Roshanak Moran, Antoinette Peakman, Mark Raskin, Philip Russell, William E. Schatz, Desmond Wherrett, Diane K. Wilson, Darrell M. Krischer, Jeffrey P. Skyler, Jay S. CA Type 1 Diabet TrialNet Abatacept TI Costimulation Modulation With Abatacept in Patients With Recent-Onset Type 1 Diabetes: Follow-up 1 Year After Cessation of Treatment SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; TRIAL; INTERVENTIONS; COMPLICATIONS; NEPHROPATHY; MELLITUS; THERAPY AB OBJECTIVE We previously reported that 2 years of costimulation modulation with abatacept slowed decline of beta-cell function in recent-onset type 1 diabetes (T1D). Subsequently, abatacept was discontinued and subjects were followed to determine whether there was persistence of effect. RESEARCH DESIGN AND METHODS Of 112 subjects (ages 6-36 years) with T1D, 77 received abatacept and 35 received placebo infusions intravenously for 27 infusions over 2 years. The primary outcome-baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 2 years-showed higher C-peptide with abatacept versus placebo. Subjects were followed an additional year, off treatment, with MMTTs performed at 30 and 36 months. RESULTS C-peptide AUC means, adjusted for age and baseline C-peptide, at 36 months were 0.217 nmol/L (95% CI 0.168-0.268) and 0.141 nmol/L (95% CI 0.071-0.215) for abatacept and placebo groups, respectively (P = 0.046). The C-peptide decline from baseline remained parallel with an estimated 9.5 months' delay with abatacept. Moreover, HbA(1c) levels remained lower in the abatacept group than in the placebo group. The slightly lower (nonsignificant) mean total insulin dose among the abatacept group reported at 2 years was the same as the placebo group by 3 years. CONCLUSIONS Costimulation modulation with abatacept slowed decline of beta-cell function and improved HbA(1c) in recent-onset T1D. The beneficial effect was sustained for at least 1 year after cessation of abatacept infusions or 3 years from T1D diagnosis. C1 [Orban, Tihamer] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bundy, Brian; Krischer, Jeffrey P.] Univ S Florida, Tampa, FL USA. [Becker, Dorothy J.] Univ Pittsburgh, Pittsburgh, PA USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Gitelman, Stephen E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goland, Robin] Columbia Univ, New York, NY USA. [Gottlieb, Peter A.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA USA. [Marks, Jennifer B.; Skyler, Jay S.] Univ Miami, Diabet Res Inst, Miami, FL USA. [Monzavi, Roshanak] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Moran, Antoinette] Univ Minnesota, Minneapolis, MN USA. [Peakman, Mark] Kings Coll London, London WC2R 2LS, England. [Raskin, Philip] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Russell, William E.] Vanderbilt Univ, Nashville, TN 37235 USA. [Schatz, Desmond] Univ Florida, Gainesville, FL USA. [Wherrett, Diane K.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA. RP Skyler, JS (reprint author), Univ Miami, Diabet Res Inst, Miami, FL USA. EM jskyler@miami.edu RI Skyler, Jay/F-4211-2016; OI DiMeglio, Linda/0000-0002-8033-6078 FU Type 1 Diabetes TrialNet Study Group; National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources, through Clinical and Translational Science Awards [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986]; General Clinical Research Center [M01-RR-00400]; Juvenile Diabetes Research Foundation International; American Diabetes Association FX The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509; contract HHSN267200800019C, the National Center for Research Resources, through Clinical and Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, and UL1-RR-031986; and General Clinical Research Center Award M01-RR-00400, the Juvenile Diabetes Research Foundation International, and the American Diabetes Association. Bristol-Myers Squibb (Princeton, NJ) provided abatacept (Orencia). LifeScan Division of Johnson & Johnson provided blood glucose monitoring meters and strips to research subjects. NR 13 TC 43 Z9 43 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 1069 EP 1075 DI 10.2337/dc13-0604 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700039 PM 24296850 ER PT J AU Barzilay, JI Jablonski, KA Fonseca, V Shoelson, SE Goldfine, AB Strauch, C Monnier, VM AF Barzilay, Joshua I. Jablonski, Kathleen A. Fonseca, Vivian Shoelson, Steven E. Goldfine, Allison B. Strauch, Christopher Monnier, Vincent M. CA TINSAL-T2D Res Consortium TI The Impact of Salsalate Treatment on Serum Levels of Advanced Glycation End Products in Type 2 Diabetes SO DIABETES CARE LA English DT Article ID N-EPSILON-CARBOXYMETHYLLYSINE; RANDOMIZED-TRIAL; PENTOSIDINE; PLASMA; COMPLICATIONS; METHYLGLYOXAL; ENDPRODUCTS; INHIBITION; SALICYLATE; METFORMIN AB OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A(1c) (HbA(1c)) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA(1c) and fructoselysine [measured as furosine]) and AGE levels (glyoxal and methylglyoxal hydroimidazolones [G-H-1, MG-H-1], carboxymethyllysine [CML], carboxyethyllysine [CEL], pentosidine) were measured in patient serum samples. RESULTS Forty-eight weeks of salsalate treatment lowered levels of HbA(1c) and serum furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G-H-1 and MG-H-1 levels were unchanged, whereas pentosidine levels increased more than twofold (P < 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA(1c) levels during follow-up (P < 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines. CONCLUSIONS Salsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of pentosidine precursor. C1 [Barzilay, Joshua I.] Emory Univ, Sch Med, Div Endocrinol, Kaiser Permanente Georgia, Atlanta, GA 30322 USA. [Barzilay, Joshua I.] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Fonseca, Vivian] Tulane Univ, Hlth Sci Ctr, Dept Med, Endocrinol Sect, New Orleans, LA 70118 USA. [Shoelson, Steven E.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Shoelson, Steven E.; Goldfine, Allison B.] Joslin Diabet Ctr, Dept Res, Boston, MA 02215 USA. [Strauch, Christopher; Monnier, Vincent M.] Case Western Reserve Univ, Dept Pathol & Biochem, Cleveland, OH 44106 USA. RP Barzilay, JI (reprint author), Emory Univ, Sch Med, Div Endocrinol, Kaiser Permanente Georgia, Atlanta, GA 30322 USA. EM joshua.barzilay@kp.org FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [1R01DK-081373-01A2, U01 DK-74556] FX This study was supported by grants 1R01DK-081373-01A2 (J.I.B.) and U01 DK-74556 (S.E.S. and A.B.G.) from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 26 TC 11 Z9 11 U1 3 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP 1083 EP 1091 DI 10.2337/dc13-1527 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700041 PM 24255104 ER PT J AU Goodstein, G Milanesi, A Weinreb, JE AF Goodstein, Gelsey Milanesi, Anna Weinreb, Jane E. TI Ketosis-Prone Type 2 Diabetes in a Veteran Population SO DIABETES CARE LA English DT Letter C1 [Goodstein, Gelsey] Cedars Sinai Med Ctr, Dept Internal Med, Los Angeles, CA 90048 USA. [Goodstein, Gelsey] VA Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. [Milanesi, Anna; Weinreb, Jane E.] VA Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA 90073 USA. [Milanesi, Anna; Weinreb, Jane E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. RP Weinreb, JE (reprint author), VA Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA 90073 USA. EM jane.weinerb@va.gov FU NIDDK NIH HHS [K08 DK097295] NR 4 TC 6 Z9 7 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2014 VL 37 IS 4 BP E74 EP E75 DI 10.2337/dc13-2824 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7BB UT WOS:000333414700007 PM 24652736 ER PT J AU Iezzoni, LI Yu, J Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Yu, Jun Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffrey L. TI General health, health conditions, and current pregnancy among US women with and without chronic physical disabilities SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Disability; Pregnancy; Mobility; Comorbidities; National health interview survey ID DISEASE AB Background: Although increasing numbers of reproductive-age U. S. women with chronic physical disabilities (CPD) are becoming pregnant, little is known about their general health or comorbid health conditions. Objectives: To explore general health and comorbid health conditions among women with and without CPD by current pregnancy status. Methods: We analyzed responses of 47,629 civilian, noninstitutionalized women ages 18-49 from the 2006-2011 National Health Interview Surveys. The survey asks about: various movement difficulties; selected adult health conditions; self-reported general health; and current pregnancy. We identified women with CPD using responses from 8 movement difficulty questions. Results: 6043 (12.7%) women report CPD. Among nondisabled women, 3.8% report current pregnancy, as do 2.0% of women with CPD. Among currently pregnant women with CPD, 29.1% report fair or poor health, compared with only 3.2% of nondisabled pregnant women. Currently pregnant women both with and without CPD are significantly less likely to report coexisting health conditions than nonpregnant women. Nonetheless, among currently pregnant women with CPD, only 24.5% report no coexisting conditions, while 28.7% report 1, 22.8% report 2, 13.2% report 3, and 10.8% report 4-6 health conditions. In a multivariable regression controlling for age category, health status, and health conditions, CPD is not statistically significantly associated with current pregnancy. Conclusions: According to national survey data, it appears that pregnant women with CPD may have a complex mix of health problems and often experience fair or poor health. Better understanding the obstetrical and subspecialty needs of these women with multimorbidities requires additional investigation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.; Yu, Jun; 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, Dept Med, 50 Staniford St,901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU National Institute for Child Health and Human Development [5R21HD068756-02] FX This work was funded by the National Institute for Child Health and Human Development, Grant no. 5R21HD068756-02. NR 23 TC 10 Z9 10 U1 2 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 APR PY 2014 VL 7 IS 2 BP 181 EP 188 DI 10.1016/j.dhjo.2013.12.002 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 AD7FM UT WOS:000333427800008 PM 24680047 ER PT J AU Tirumani, SH Shinagare, AB Jagannathan, JP Krajewski, KM Ramaiya, NH Raut, CP AF Tirumani, S. H. Shinagare, A. B. Jagannathan, J. P. Krajewski, K. M. Ramaiya, N. H. Raut, C. P. TI Radiologic assessment of earliest, best, and plateau response of gastrointestinal stromal tumors to neoadjuvant imatinib prior to successful surgical resection SO EJSO LA English DT Article DE Gastrointestinal stromal tumor; Neoadjuvant imatinib; Surgery; Imaging; RECIST ID PHASE-II TRIAL; PROGNOSTIC-FACTORS; GIST; MANAGEMENT; THERAPY; MESYLATE; SURVIVAL; CRITERIA; SURGERY; RECIST AB Background: To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST. Materials and methods: In this IRB-approved retrospective study, we included all 20 patients (10 women; mean age 61 years, range 30-83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and Underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter [LAD] and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (rime point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging. Results: Median tumor size at baseline was 7.2 cm (range, 3.0-31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16-36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7-26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7-26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31-48%) and 83% (IQR, 63-87%), (median interval = 28 weeks; IQR, 18-37 weeks), at which point 10 tumors were resected. Plateau response (45% [IQR, 35-45%] LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26-41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response. Conclusion: Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, S. H.; Shinagare, A. B.; Jagannathan, J. P.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Raut, C. P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org; ashinagare@partners.org; jjagannathan@partners.org; kmkrajewski@partners.org; nramaiya@partners.org; craut@partners.org NR 27 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD APR PY 2014 VL 40 IS 4 BP 420 EP 428 DI 10.1016/j.ejso.2013.10.021 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA AE3CU UT WOS:000333855400008 PM 24238762 ER PT J AU Zadra, G Photopoulos, C Tyekucheva, S Heidari, P Weng, QP Fedele, G Liu, H Scaglia, N Priolo, C Sicinska, E Mahmood, U Signoretti, S Birnberg, N Loda, M AF Zadra, Giorgia Photopoulos, Cornelia Tyekucheva, Svitlana Heidari, Pedram Weng, Qing Ping Fedele, Giuseppe Liu, Hong Scaglia, Natalia Priolo, Carmen Sicinska, Ewa Mahmood, Umar Signoretti, Sabina Birnberg, Neal Loda, Massimo TI A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis SO EMBO MOLECULAR MEDICINE LA English DT Article DE AMPK direct activation; MT 63-78; de novo lipogenesis; androgen signaling inhibitors; prostate cancer ID FATTY-ACID SYNTHASE; PROTEIN-KINASE ACTIVATORS; ELEMENT-BINDING PROTEINS; ANTINEOPLASTIC THERAPY; LKB1-AMPK PATHWAY; UPSTREAM KINASE; MTOR INHIBITION; UP-REGULATION; IN-VITRO; METFORMIN AB 5 ' AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63-78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63-78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment. C1 [Zadra, Giorgia; Photopoulos, Cornelia; Fedele, Giuseppe; Scaglia, Natalia; Priolo, Carmen; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zadra, Giorgia; Signoretti, Sabina; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tyekucheva, Svitlana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tyekucheva, Svitlana] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Weng, Qing Ping; Liu, Hong; Birnberg, Neal] Mercury Pharmaceut Inc, Woburn, MA USA. [Sicinska, Ewa; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU Prostate Cancer Foundation; DF/HCC SPORE in Prostate Cancer [NIH/NCI P50 CA90381]; NIH [RO1CA131945]; University of Milan; American Italian Cancer Foundation; Andrea e Libi Lorini Foundation FX We thank Dr. Benoit Viollet for providing AMPK alpha 1-/-/alpha 2-/- MEFs and AMPK alpha 2-/- mice, Dr. Nabeel El-Bardeesy for LKB1-/- MEFs, all the researchers at DFCI, BIDMC, and MGH that provided us the cancer cell lines described in the manuscript, and Dr. John Blenis for the constitutive active S6K1 plasmid. We thank Joshua Rose, Debora C Bastos, John Clohessy, Bhavik Padmani, and Sudeepa Syamala for their support with the in vivo studies. We thank Michael Peterson for his support with immunofluorescence experiments, Jane Hayward for graphical support, and Stefano Cacciatore for statistical support. Finally, we are grateful to Drs. Arkaitz Carracedo and Nabeel El-Bardeesy for their critical reading of the manuscript and to Dr. Emanuele Palescandolo for the helpful discussions. This work was supported by the Prostate Cancer Foundation, the DF/HCC SPORE in Prostate Cancer (NIH/NCI P50 CA90381), and NIH grant RO1CA131945 to ML. GZ was supported by fellowships from University of Milan, American Italian Cancer Foundation, and Andrea e Libi Lorini Foundation. NR 72 TC 40 Z9 43 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD APR PY 2014 VL 6 IS 4 BP 519 EP 538 DI 10.1002/emmm.201302734 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE1PR UT WOS:000333742100011 PM 24497570 ER PT J AU Astin, F Carroll, D Ruppar, T Uchmanowicz, I Hinterbuchner, L Kletsiou, E Serafin, A AF Astin, F. Carroll, D. Ruppar, T. Uchmanowicz, I. Hinterbuchner, L. Kletsiou, E. Serafin, A. TI A learning framework for the continuing education of cardiovascular nurses in europe SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Meeting Abstract C1 [Astin, F.] Univ Salford, Salford M5 4WT, Lancs, England. [Carroll, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruppar, T.] Univ Missouri, Columbia, MO 65211 USA. [Uchmanowicz, I.] Med Univ, Dept Publ Hlth, Wroclaw, Poland. [Hinterbuchner, L.] Salzburg Univ Hosp, Salzburg, Austria. [Kletsiou, E.] Univ Athens, Athens, Greece. [Serafin, A.] Maria Sklodowska Curie Warsaw Acad, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 EI 1873-1953 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD APR PY 2014 VL 13 SU 1 MA P8 BP S2 EP S2 PG 1 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA AE0QW UT WOS:000333672200004 ER PT J AU Carroll, DL AF Carroll, D. L. TI Use of temporal artery thermometry to identify fevers in critically ill cardiac surgery patients SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Meeting Abstract C1 [Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 EI 1873-1953 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD APR PY 2014 VL 13 SU 1 MA P212 BP S84 EP S84 PG 1 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA AE0QW UT WOS:000333672200163 ER PT J AU Burgess, JF Hockenberry, JM AF Burgess, James F., Jr. Hockenberry, Jason M. TI Can all cause readmission policy improve quality or lower expenditures? A historical perspective on current initiatives SO HEALTH ECONOMICS POLICY AND LAW LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HOSPITAL READMISSIONS; ELDERLY-PATIENTS; HEART-FAILURE; INTERNATIONAL VARIATION; MEDICARE POPULATION; 30-DAY READMISSIONS; POSTDISCHARGE CARE; REDUCTION PROGRAM; COST AB All-cause readmission to inpatient care is of wide policy interest in the United States and a number of other countries (Centers for Medicare and Medicaid Services, in the United Kingdom by the National Centre for Health Outcomes Development, and in Australia by the Australian Institute of Health and Welfare). Contemporary policy efforts, including high powered incentives embedded in the current US Hospital Readmission Reduction Program, and the organizationally complex interventions derived in anticipation of this policy, have been touted based on potential cost savings. Strong incentives and resulting interventions may not enjoy the support of a strong theoretical model or the empirical research base that are typical of strong incentive schemes. We examine the historical broad literature on the issue, lay out a 'full' conceptual organizational model of patient transitions as they relate to the hospital, and discuss the strengths and weaknesses of previous and proposed policies. We use this to set out a research and policy agenda on this critical issue rather than attempt to conduct a comprehensive structured literature review. We assert that researchers and policy makers should consider more fundamental societal issues related to health, social support and health literacy if progress is going to be made in reducing readmissions. C1 [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Jamaica Plain, MA USA. [Burgess, James F., Jr.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Hockenberry, Jason M.] Emory Univ, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Hockenberry, Jason M.] NBER, Cambridge, MA 02138 USA. RP Hockenberry, JM (reprint author), 1518 Clifton Rd, Atlanta, GA 30322 USA. EM jason.hockenberry@emory.edu NR 84 TC 9 Z9 9 U1 7 U2 26 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1744-1331 EI 1744-134X J9 HEALTH ECON POLICY L JI Health Econ. Policy Law PD APR PY 2014 VL 9 IS 2 BP 193 EP 213 DI 10.1017/S1744133113000340 PG 21 WC Health Policy & Services SC Health Care Sciences & Services GA AE0PE UT WOS:000333667400004 PM 23987089 ER PT J AU Field, JJ Nathan, DG Linden, J AF Field, Joshua J. Nathan, David G. Linden, Joel TI The Role of Adenosine Signaling in Sickle Cell Therapeutics SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Sickle cell disease; Adenosine; Adenosine A(2A) receptor; Adenosine A(2B) receptor; NKT cells ID PULMONARY INFLAMMATION; A(2B) RECEPTOR; RISK-FACTORS; NKT CELLS; IN-VIVO; DISEASE; PRIAPISM; ASTHMA; CONTRIBUTES; DYSFUNCTION AB Data suggest a role for adenosine signaling in the pathogenesis of sickle cell disease (SOD). Signaling through the adenosine A(2A) receptor (A(2A)R) has demonstrated beneficial effects. Activation of A(2A)Rs decreases inflammation with SCD by blocking activation of invariant natural killer T cells. Decreased inflammation may reduce the severity of vasoocclusive crises. Adenosine signaling through the adenosine A(2B) receptor (A(2B)R) may be detrimental in SCD. Whether adenosine signaling predominantly occurs through A(2A)Rs or A(2B)Rs may depend on differing levels of adenosine and disease state (steady state versus crisis). There may be opportunities to develop novel therapeutic approaches targeting A(2A)Rs and/or A(2B)Rs for patients with SCD. C1 [Field, Joshua J.] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA. [Field, Joshua J.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Nathan, David G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Nathan, David G.] Boston Childrens Hosp, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. [Nathan, David G.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Linden, Joel] La Jolla Inst Allergy & Immunol, San Diego, CA 92037 USA. RP Field, JJ (reprint author), BloodCtr Wisconsin, 8733 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM joshua.field@bcw.edu FU NHLBI NIH HHS [R01 HL095704, R01 HL111969, P50 HL110790, R34 HL108757, RC2 HL101367] NR 44 TC 10 Z9 10 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2014 VL 28 IS 2 BP 287 EP + DI 10.1016/j.hoc.2013.11.003 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA AD8VH UT WOS:000333543300009 PM 24589267 ER PT J AU Dubin, RF Beatty, AL Teerlink, JR Schiller, NB Bolger, AF Alokozai, D Peralta, CA Johansen, KL AF Dubin, Ruth F. Beatty, Alexis L. Teerlink, John R. Schiller, Nelson B. Bolger, Ann F. Alokozai, Dean Peralta, Carmen A. Johansen, Kirsten L. TI Determinants of hemodialysis-induced segmental wall motion abnormalities SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Heart failure; hemodialysis; end-stage renal disease ID STAGE RENAL-DISEASE; FILLING PRESSURES; DIALYSIS PATIENTS; TROPONIN-T; ECHOCARDIOGRAPHY; ASSOCIATION; DYSFUNCTION; PREVALENCE; VALSARTAN; FAILURE AB Patients who demonstrate worsening of cardiac wall motion (WM) during hemodialysis have higher 1-year mortality. We sought to identify risk factors for dialysis-induced WM abnormalities. Additionally, we examined the effects of hemodialysis on other parameters of cardiac function. Forty patients underwent echocardiography directly before dialysis and during the last hour of dialysis (79 dialysis sessions). Candidate predictors for intradialytic worsening of WM included age, a history of heart failure (HF) or coronary artery disease, changes in blood pressure or heart rate, high sensitivity cardiac troponin T and N-terminal brain natriuretic peptide. Among 40 patients, WM worsened segmentally in eight patients (20%), worsened globally in one patient (3%), and improved segmentally in four patients (10%). Diastolic function worsened in 44% of patients, and left ventricular ejection fraction was largely unchanged during dialysis. The case of globally worsened WM occurred in the setting of intradialytic hypertension in a patient without HF. Surprisingly, history of coronary artery disease, hemodynamics, and serologic factors were not associated with worsened segmental WM during dialysis. After adjustment for history of coronary artery disease and other cardiac risk factors, patients with a history of HF had a threefold higher risk of worsening segmental WM during dialysis (RR 3.1, 95% CI [1.1, 9], p = 0.04). In conclusion, patients with a history of clinical HF were at higher risk of intradialytic worsening of segmental WM. Further studies are needed to determine the mechanism of this association and whether cardioprotective medications could ameliorate this adverse cardiac effect of hemodialysis. C1 [Dubin, Ruth F.; Peralta, Carmen A.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med Nephrol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Beatty, Alexis L.; Teerlink, John R.; Schiller, Nelson B.] Univ Calif San Francisco, Dept Med Cardiol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Bolger, Ann F.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med Cardiol, San Francisco, CA USA. [Alokozai, Dean] Cardiocore, San Francisco, CA USA. RP Dubin, RF (reprint author), San Francisco VA Med Ctr, 4150 Clement St Box 111A1, San Francisco, CA 94121 USA. EM ruth.dubin@ucsf.edu FU University of California San Francisco Academic Senate, San Francisco, CA; Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA; National Institute of Diabetes and Digestive and Kidney Diseases [1K24-DK085153-02, 1K23-DK092354-01A1]; UCSF Clinical and Translational Science Institute [UL1 TR000004] FX Funding for this project came from the following sources: 1. Individual Investigator Grant, University of California San Francisco Academic Senate, San Francisco, CA; 2. Grant Huntington Fund provided by the Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA; 3. National Institute of Diabetes and Digestive and Kidney Diseases, 1K24-DK085153-02; 4. National Institute of Diabetes and Digestive and Kidney Diseases 1K23-DK092354-01A1; 5. UCSF Clinical and Translational Science Institute Grant Number UL1 TR000004. Roche Diagnostics Corporation (Indianapolis, Indiana) supplied reagents for the hs-TnT and NT-proBNP assays, but did not provide study funding. NR 21 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD APR PY 2014 VL 18 IS 2 BP 396 EP 405 DI 10.1111/hdi.12111 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AE1QF UT WOS:000333743600006 PM 24224868 ER PT J AU Williams, ME Garg, R Wang, WL Lacson, R Maddux, F Lacson, E AF Williams, Mark E. Garg, Rajesh Wang, Weiling Lacson, Ronilda Maddux, Franklin Lacson, Eduardo, Jr. TI High Hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Hypoglycemia; dialysis; diabetes; hemoglobin A1c ID MYOCARDIAL-INFARCTION; GLYCATED ALBUMIN; ASSOCIATION; MORTALITY; DEATH; SURVIVAL; FAILURE AB While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end-stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time-lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD. C1 [Williams, Mark E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Garg, Rajesh; Lacson, Ronilda] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wang, Weiling; Maddux, Franklin; Lacson, Eduardo, Jr.] Fresenius Med Care, Waltham, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 31 TC 2 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD APR PY 2014 VL 18 IS 2 BP 423 EP 432 DI 10.1111/hdi.12110 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AE1QF UT WOS:000333743600009 PM 24274900 ER PT J AU Albert, TJ Swenson, ER AF Albert, Tyler J. Swenson, Erik R. TI Peripheral Chemoreceptor Responsiveness and Hypoxic Pulmonary Vasoconstriction in Humans SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE hypoxic ventilatory response; peripheral chemoreceptor responsiveness; hypoxic pulmonary vasoconstriction ID AUTONOMIC NERVOUS-SYSTEM; PRESSURE-FLOW PLOTS; VENTILATORY RESPONSES; CONSCIOUS DOGS; BODY CHEMORECEPTORS; HIGH-ALTITUDE; RAT LUNG; STIMULATION; MODULATION; REFLEX AB Albert, Tyler J., and Erik R. Swenson. Peripheral chemoreceptor responsiveness and hypoxic pulmonary vasoconstriction in humans. High Alt Med Biol. 15:1520, 2014.Objective: Studies in animals have shown that interruption of carotid body afferent hypoxic signaling or efferent CNS activity to the lung enhances hypoxic pulmonary vasoconstriction (HPV). Whether a similar influence of the CNS on HPV strength is present in humans has never been studied, owing to the invasive nature of physical neural ablation or nonspecific systemic effects of pharmacological blockade of putative neural pathways. In order to demonstrate a peripheral chemoreceptor-mediated modulation of HPV in man, we hypothesized that individuals with high hypoxic ventilatory responsiveness, indicative of strong peripheral hypoxic chemosensitivity, should have less HPV in response to inspired hypoxia. Methods: In 15 healthy men and women, we measured the normobaric poikilocapnic hypoxic ventilatory response (HVR; L min(-1) % S(P)o(2)(-1)) during 15min of hypoxia (F(I)o(2)=0.12). On the following day, we then measured pulmonary artery systolic pressure (PASP) using echosonography while subjects randomly breathed 0.21, 0.18, 0.15, and 0.12 F(I)o(2), each for periods of 15min. We chose this strategy to obtain an equivalent stimulus for HPV in all subjects, using S(P)o(2) as a surrogate for alveolar Po-2. HPV was assessed as PASP at a common interpolated arterial oxygen saturation (S(P)o(2)) of 85%. Results: We recorded a sufficient six-fold range of HVR (0.05-0.30, mean 0.13L min(-1) % S(P)o(2)(-1)) similar to previously published data on normobaric, poikilocapnic HVR. HPV at S(P)o(2) of 85% was 28.5mmHg (range 21.7-41.3). There was a significant inverse relationship between poikilocapnic HVR and HPV (p=0.006, R-2=0.38). Discussion: Previous studies of individuals with susceptibility to high altitude pulmonary edema (HAPE) have suggested that both low HVR and high HPV are important risk factors. We show that these two responses are inversely correlated and conclude that a greater magnitude of peripheral chemoreceptor response to hypoxia limits hypoxic pulmonary vasoconstriction in healthy subjects. C1 [Albert, Tyler J.; Swenson, Erik R.] Univ Washington, Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, Seattle, WA USA. RP Albert, TJ (reprint author), Univ Washington, Med Ctr, Div Pulm & Crit Care Med, 1959 NE Pacific St,Box 366522, Seattle, WA 98195 USA. EM talbert@uw.edu NR 40 TC 8 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD APR 1 PY 2014 VL 15 IS 1 BP 15 EP 20 DI 10.1089/ham.2013.1072 PG 6 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA AD7RW UT WOS:000333464100003 PM 24444139 ER PT J AU Goris, A van Setten, J Diekstra, F Ripke, S Patsopoulos, NA Sawcer, SJ van Es, M Andersen, PM Melki, J Meininger, V Hardiman, O Landers, JE Brown, RH Shatunov, A Leigh, N Al-Chalabi, A Shaw, CE Traynor, BJ Chio, A Restagno, G Mora, G Ophoff, RA Oksenberg, JR Van Damme, P Compston, A Robberecht, W Dubois, B van den Berg, LH De Jager, PL Veldink, JH Bakker, PIW AF Goris, An van Setten, Jessica Diekstra, Frank Ripke, Stephan Patsopoulos, Nikolaos A. Sawcer, Stephen J. van Es, Michael Andersen, Peter M. Melki, Judith Meininger, Vincent Hardiman, Orla Landers, John E. Brown, Robert H., Jr. Shatunov, Aleksey Leigh, Nigel Al-Chalabi, Ammar Shaw, Christopher E. Traynor, Bryan J. Chio, Adriano Restagno, Gabriella Mora, Gabriele Ophoff, Roel A. Oksenberg, Jorge R. Van Damme, Philip Compston, Alastair Robberecht, Wim Dubois, Benedicte van den Berg, Leonard H. De Jager, Philip L. Veldink, Jan H. de Bakker, Paul I. W. CA Int Multiple Sclerosis Genetics Co Australia New Zealand MS Genetic C TI No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; HEXANUCLEOTIDE REPEAT; AUTOIMMUNE; NEURODEGENERATION; INFLAMMATION; METAANALYSIS; STATISTICS; ACTIVATION; MECHANISMS AB Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS. C1 [Goris, An; Dubois, Benedicte] Katholieke Univ Leuven, Lab Neuroimmunol, B-3000 Louvain, Belgium. [Goris, An; Van Damme, Philip; Robberecht, Wim; Dubois, Benedicte] Katholieke Univ Leuven, LIND, B-3000 Louvain, Belgium. [van Setten, Jessica; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Diekstra, Frank; van Es, Michael; van den Berg, Leonard H.; Veldink, Jan H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Patsopoulos, Nikolaos A.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Patsopoulos, Nikolaos A.; De Jager, Philip L.; de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Patsopoulos, Nikolaos A.; De Jager, Philip L.] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. [Sawcer, Stephen J.; Compston, Alastair] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 0QQ, England. [Andersen, Peter M.] Umea Univ, Dept Clin Neurosci, SE-90185 Umea, Sweden. [Melki, Judith] Univ Paris, Bicetre Hosp, Dept Neuropediat, F-94275 Paris, France. [Meininger, Vincent] Univ Paris 06, Hop La Salpetriere, Dept Neurol, F-75013 Paris, France. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, Orla] Univ Dublin Trinity Coll, Dept Neurol, Dublin 2, Ireland. [Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Landers, John E.; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Shatunov, Aleksey; Leigh, Nigel; Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Chio, Adriano] Univ Turin, Azienda Osped Citta Salute & Sci, Dept Neurosci, I-10126 Turin, Italy. [Restagno, Gabriella] Azienda Osped Citta Salute & Sci, Dept Lab Med, I-10126 Turin, Italy. [Mora, Gabriele] Sci Inst Milan, Fdn Salvatore Maugeri, I-20138 Milan, Italy. [Ophoff, Roel A.] UMC, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Oksenberg, Jorge R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Oksenberg, Jorge R.] Univ Calif San Francisco, Sch Med, Inst Human Genet, San Francisco, CA 94143 USA. [Van Damme, Philip; Robberecht, Wim; Dubois, Benedicte] Katholieke Univ Leuven Hosp, Dept Neurol, Louvain, Belgium. [Van Damme, Philip; Robberecht, Wim] Katholieke Univ Leuven, Lab Neurobiol Expt Neurol, B-3000 Louvain, Belgium. [Van Damme, Philip; Robberecht, Wim] VIB, VRC, Louvain, Belgium. [De Jager, Philip L.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. RP Goris, A (reprint author), Katholieke Univ Leuven, Sect Expt Neurol, Lab Neuroimmunol, Herestr 49 Bus 1022, B-3000 Louvain, Belgium. EM an.goris@med.kuleuven.be RI Van Damme, Philip/A-6464-2009; D'Alfonso, Sandra/K-7295-2014; de Bakker, Paul/B-8730-2009; MOSCATO, PABLO/G-7668-2013; Goris, An/F-2943-2010; Zipp, Frauke/C-9968-2015; OI Hardiman, Orla/0000-0003-2610-1291; Van Damme, Philip/0000-0001-6384-0611; D'Alfonso, Sandra/0000-0002-3983-9925; de Bakker, Paul/0000-0001-7735-7858; Goris, An/0000-0002-1276-6682; Zipp, Frauke/0000-0002-1231-1928; Field, Judith/0000-0002-7089-0999; Chio, Adriano/0000-0001-9579-5341; Saarela, Janna/0000-0002-0853-6219; Butzkueven, Helmut/0000-0003-3940-8727 FU Belgian Charcot Foundation; Wetenschappelijk Onderzoek Multiple Sclerose (WOMS); Belgian Neurological Society (BNS); Research Fund KU Leuven [OT/11/087]; National Multiple Sclerosis Society [FG 1938-A-1]; National Institutes of Health [R01 NSO49477]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01 NS073873]; National Institute for Health Research (NIHR) Dementia Biomedical Research Unit at South London; Maudsley NHS Foundation Trust and King's College London; Belgian Federal Science Policy Office [P6/43]; University of Leuven [GOA 11/014]; E von Behring Chair for Neuromuscular and Neurodegenerative Disorders; Thierry Latran Foundation; VIDI Award from the Netherlands Organization for Scientific Research (NWO) [016.126.354]; Association pour la Recherche sur la SLA; Association Roseau SLA Ile de France; ALS Therapy Alliance; Angel Fund; Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable Foundation; National Institute of Neurological Disorders and Stroke [NS050557]; Muscular Dystrophy Association (USA); Health Research Board of Ireland; Irish Neurological Association; Irish Motor Neuron Disease Research Foundation; Italian Ministry of Health [RF-PIE-2007-63565, RF-2010-2309849]; Regione Piemonte [2004-A317]; Fondazione Vialli c Mauro per la SLA Onlus [obiettivo 7]; Federazione Italiana Giuoco Calcio (FIGC); Prinses Beatrix Fonds (Kersten Foundation); VSB fonds; Netherlands ALS Foundation; Adessium Foundation; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; European Community's Health Seventh Framework Programme [259867]; Swedish Brain Research Foundation; WIllstens Research Foundation; Swedish Medical Society; Bjorklund Foundation; Swedish Association for the Neurologically Disabled; US National Institutes of Health (NIH), National Institute on Aging [Z01-AG000949-02]; National Institute of Neurological Disorders and Stroke (NINDS) FX A.G. is supported by the Belgian Charcot Foundation. A.G. and B.D. are supported by Wetenschappelijk Onderzoek Multiple Sclerose (WOMS), the Belgian Neurological Society (BNS) and the Research Fund KU Leuven (OT/11/087). Computational resources used in this work were provided by the Hercules Foundation and the Flemish Government department EWI. This investigation was supported in part by a postdoctoral fellowship from the National Multiple Sclerosis Society to N.A.P. (FG 1938-A-1) and by National Institutes of Health funding to the International Multiple Sclerosis Genetics Consortium (R01 NSO49477). J.E,L, received funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS073873). A.A.C. receives salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health, P,V,D, and B.D. are clinical investigators of the Research Foundation Flanders (FWO-Vlaanderen), B,D, is supported by TEVA PHARMA NEDERLAND BV. W.R. is supported by Interuniversity Attraction Poles (IUAP) program P6/43 of the Belgian Federal Science Policy Office, the University of Leuven (GOA 11/014 and Methusalem) and the E von Behring Chair for Neuromuscular and Neurodegenerative Disorders. J.V. is supported by the Thierry Latran Foundation. P.I.W.d.B. is the recipient of a VIDI Award from the Netherlands Organization for Scientific Research (NWO project 016.126.354). For the ALS GWA study, we thank all patients and healthy volunteers who participated in the project; general practitioners and pharmacists, In France, this study was funded by the Association pour la Recherche sur la SLA; and the Association Roseau SLA Ile de France, Support was also provided by the ALS Therapy Alliance; Project ALS; the Angel Fund; the Pierre L. de Bourgknecht ALS Research Foundation; the Al-Athel ALS Research Foundation; the ALS Family Charitable Foundation and the National Institute of Neurological Disorders and Stroke (NS050557). The Irish ALS study was funded by The Muscular Dystrophy Association (USA); The Health Research Board of Ireland; The Irish Neurological Association Travel Award and The Irish Motor Neuron Disease Research Foundation. The ALS Study in Italy was funded by the Italian Ministry of Health (RF-PIE-2007-63565 and RF-2010-2309849); Regione Piemonte (2004-A317); the Fondazione Vialli c Mauro per la SLA Onlus (obiettivo 7) and the Federazione Italiana Giuoco Calcio (FIGC). The ALS study in the Netherlands was supported by the Prinses Beatrix Fonds (Kersten Foundation); VSB fonds; the Netherlands ALS Foundation and J.R. van Dijk; the Adessium Foundation to L.v.d.B.; the Netherlands Organization of Scientific Research NWO Investments (grant numbers 175.010.2005.011, 911-03-012): the Research Institute for Diseases in the Elderly (014-93-015; RIDE) and the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (project number 050-060-810).; In addition, the research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) (grant agreement number 259867), In Sweden, the ALS study was supported by the Swedish Brain Research Foundation; the WIllstens Research Foundation; the Swedish Medical Society; the Bjorklund Foundation for ALS Research and the Swedish Association for the Neurologically Disabled to P.A. For the ALS UK study, we thank the Motor Neurone Disease Association of Great Britain and Ireland, the Medical Research Council (UK), the Wellcome Trust and the Psychiatry Research Trust (Tim Perkins Fund and Charcot Fund). This work was supported in part by the Intramural Research Programs of the US National Institutes of Health (NIH), National Institute on Aging (Z01-AG000949-02) and National Institute of Neurological Disorders and Stroke (NINDS), Members of the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Australia and New Zealand MS Genetics Consortium (ANZGenc) are listed in the supplementary file. NR 43 TC 5 Z9 5 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2014 VL 23 IS 7 BP 1916 EP 1922 DI 10.1093/hmg/ddt574 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AD5CA UT WOS:000333267900020 PM 24234648 ER PT J AU Wang, ED Papavassiliou, P Wang, AR Louissaint, A Wang, J Hutchinson, CB Huang, Q Reddi, D Wei, Q Sebastian, S Rehder, C Brynes, R Siddiqi, I AF Wang, Endi Papavassiliou, Paulie Wang, Alun R. Louissaint, Abner, Jr. Wang, Jun Hutchinson, Charles Blake Huang, Qin Reddi, Deepti Wei, Qiang Sebastian, Siby Rehder, Catherine Brynes, Russell Siddiqi, Imran TI Composite lymphoid neoplasm of B-cell and T-cell origins: a pathologic study of 14 cases SO HUMAN PATHOLOGY LA English DT Article DE Composite lymphoma; Lymphoid neoplasm; B cell; T cell ID EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; MYCOSIS-FUNGOIDES; CLINICOPATHOLOGICAL ANALYSIS; LYMPHOCYTIC LYMPHOMA; EBV; PROLIFERATION; GENE AB We retrospectively analyzed 14 composite lymphoma/lymphoid neoplasms (CL) of B-cell/T-cell origins. These consisted of a spectrum of T-cell neoplasms in combination with different B-cell lymphomas/leukemias, with peripheral T-cell lymphoma and diffuse large B-cell lymphoma encountered most frequently for each respective neoplastic lineage. Histopathologic evaluation demonstrated 6 patterns of neoplastic distribution, including zone, inverted zone, diffuse mixed, regional/nodular mixed, compartmental, and segmental distributions. Four of 9 cases studied were positive for Epstein-Ban virus, all with a mixed pattern, suggesting that this pattern may predict an Epstein-Ban virus association. None of 14 cases was considered CL at the initial histologic evaluation. Only 6 (46.2%) of 13 cases had coexisting B-cell/T-cell neoplasms highlighted by immunohistochemistry, and the other 7 (53.8%) cases had 1 or both of the neoplastic components hidden. Flow cytometry detected both neoplastic lineages in 4 (44%) but failed to detect a clonal B-cell population in 4 (44%) and missed neoplastic T cells in 1 (11.1%) of 9 cases. Molecular testing detected clonal rearrangement of IGH/K gene in 11(84.6%) of 13 cases, and clonal rearrangement of the TCRG/B gene in 13 (92.9%) of 14 cases, including 8 with identical amplicons detected in separate samples. CLs of B-cell/T-cell origin are heterogeneous in subtype combination and topographic pattern, often with one of the components histologically occult. A multidisciplinary approach is emphasized to establish a definitive diagnosis in these challenging cases. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wang, Endi; Papavassiliou, Paulie; Hutchinson, Charles Blake; Reddi, Deepti; Wei, Qiang; Sebastian, Siby; Rehder, Catherine] Duke Univ, Dept Pathol, Durham, NC 27710 USA. [Wang, Alun R.] Tulane Univ, Dept Pathol, New Orleans, LA 70118 USA. [Louissaint, Abner, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Wang, Jun] Loma Linda Univ, Dept Pathol, Loma Linda, CA 92350 USA. [Huang, Qin] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Brynes, Russell; Siddiqi, Imran] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. RP Wang, ED (reprint author), Duke Hosp South, Dept Pathol, DUMC Box 3712,M-345 Davison Bldg Green Zone, Durham, NC 27710 USA. EM endi.wang@duke.edu NR 35 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 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2014 VL 45 IS 4 BP 768 EP 784 DI 10.1016/j.humpath.2013.11.008 PG 17 WC Pathology SC Pathology GA AE0MG UT WOS:000333659800013 PM 24565206 ER PT J AU Zhang, Z Adappa, ND Lautenbach, E Chiu, AG Doghramji, L Howland, TJ Cohen, NA Palmer, JN AF Zhang, Zi Adappa, Nithin D. Lautenbach, Ebbing Chiu, Alexander G. Doghramji, Laurel Howland, Timothy J. Cohen, Noam A. Palmer, James N. TI The effect of diabetes mellitus on chronic rhinosinusitis and sinus surgery outcome SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE diabetes mellitus; Pseudomonas aeruginosa; quality of life; chronic rhinosinusitis; infection ID GASTROESOPHAGEAL-REFLUX DISEASE; SOFT-TISSUE INFECTIONS; QUALITY-OF-LIFE; ANTIMICROBIAL RESISTANCE; NASAL POLYPS; TYPE-2 DIABETICS; ASTHMA; RISK; BACTERIOLOGY; INFLAMMATION AB Background Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS). Methods We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis. Results Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p= 0.004) and Gram-negative rods (26.32% vs 8.96%; p= 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS. Conclusion DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM. C1 [Zhang, Zi; Lautenbach, Ebbing] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Adappa, Nithin D.; Doghramji, Laurel; Howland, Timothy J.; Cohen, Noam A.; Palmer, James N.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Lautenbach, Ebbing] Univ Penn, Dept Med, Div Infect Dis, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chiu, Alexander G.] Univ Arizona, Dept Surg, Tucson, AZ USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Zhang, Z (reprint author), 8th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM zizhang@mail.med.upenn.edu RI Chiu, Alexander/J-1230-2014; OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (NIH HHS/United States) [K24 AI080942/AI/NIAID] FX National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (K24 AI080942/AI/NIAID NIH HHS/United States). NR 44 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD APR PY 2014 VL 4 IS 4 BP 315 EP 320 DI 10.1002/alr.21269 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA AD8VA UT WOS:000333542600010 PM 24415555 ER PT J AU Rajabali, A Heist, EK AF Rajabali, A. Heist, E. K. TI Sudden cardiac death: a critical appraisal of the implantable cardioverter defibrillator SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Review ID QUALITY-OF-LIFE; HEART-FAILURE; COST-EFFECTIVENESS; PROPHYLACTIC USE; ICD; PREVENTION; THERAPY; TRIAL; SURGERY; CARDIOVERTER/DEFIBRILLATOR AB ImportanceApproximately 350,000 Americans still die of sudden cardiac death each year. This exceeds the number of patients who die annually from stroke, lung cancer, breast cancer and AIDS combined. ObjectiveThis review aims to trace the history of implantable cardioverter defibrillators (ICD) with reference to landmark trials and their influence on the formulation of Medicare guidelines for ICD implantation criteria. This paper will also discuss the cost-effectiveness of ICDs and the quality of life after implantation. The reasons for the disparity between guidelines for implantation and actual clinical practice will be elucidated, with suggestions for improving overall clinical performance. Results and conclusionThe ICD has been shown to be cost-effective in reducing sudden cardiac death and all-cause mortality. However, the existing recommendations for ICD implantation have yet to translate completely into clinical practice. Barriers to implementation of existing guidelines include knowledge gaps in the referring physician practices, lack of validated screening tools to assess patient candidacy for the device and patient understanding of the need for the device. Future strategies to increase compliance with the existing guidelines and improve clinical performance are areas of potential research focus. C1 [Rajabali, A.; Heist, E. K.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Rajabali, A (reprint author), Massachusetts Gen Hosp, Wang Bldg 6th Floor IMA 4B,55 Fruit St, Boston, MA 02114 USA. EM arajabali@partners.org FU BiotroniK; Boston Scientific; St. Jude Medical FX Alefiyah Rajabali, MBBS: No disclosures. E. Kevin Heist, MD PhD: BiotroniK (research grant, honoraria) Boston Scientific (research grant, honoraria, consultant), Medtronic (honoraria), Sanofi (consultant), Sorin (consultant, honoraria) St. Jude Medical (research grant, consultant, honoraria). No conflicts of interest for any of the authors on this manuscript. All authors meet criteria for authorship including acceptance of responsibility for the scientific content of the manuscript. NR 45 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1368-5031 EI 1742-1241 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD APR PY 2014 VL 68 IS 4 BP 458 EP 464 DI 10.1111/ijcp.12306 PG 7 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA AD6PI UT WOS:000333382900009 PM 24372939 ER PT J AU Gray, PJ Lin, CC Jemal, A Shipley, WU Fedewa, SA Kibel, AS Rosenberg, JE Kamat, AM Virgo, KS Blute, ML Zietman, AL Efstathiou, JA AF Gray, Phillip J. Lin, Chun Chieh Jemal, Ahmedin Shipley, William U. Fedewa, Stacey A. Kibel, Adam S. Rosenberg, Jonathan E. Kamat, Ashish M. Virgo, Katherine S. Blute, Michael L. Zietman, Anthony L. Efstathiou, Jason A. TI Clinical-Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Results From the National Cancer Data Base SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID INVASIVE UROTHELIAL CARCINOMA; NEOADJUVANT CHEMOTHERAPY; MUSCLE; SURVIVAL; IMPACT; OUTCOMES; PRESERVATION; METASTASES; PROGNOSIS; THERAPY AB Purpose: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. Methods and Materials: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical-pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. Results: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for >= 10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute-designated cancer center (HR 0.90, P=.042). Conclusions: Clinical-pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC. (C) 2014 Elsevier Inc. C1 [Gray, Phillip J.; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA USA. [Lin, Chun Chieh; Jemal, Ahmedin; Fedewa, Stacey A.] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Atlanta, GA 30329 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol, Boston, MA 02115 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Kamat, Ashish M.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Div Surg, Houston, TX 77030 USA. [Virgo, Katherine S.] Emory Univ, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org OI Rosenberg, Jonathan/0000-0003-2637-4249 FU NCI NIH HHS [P30 CA016672] NR 36 TC 16 Z9 16 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 APR 1 PY 2014 VL 88 IS 5 BP 1048 EP 1056 DI 10.1016/j.ijrobp.2014.01.001 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AD7QR UT WOS:000333460200011 PM 24661658 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI We Need Better Figures! In Regard to Lee Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2014 VL 88 IS 5 BP 1213 EP 1213 DI 10.1016/j.ijrobp.2014.01.004 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AD7QR UT WOS:000333460200034 PM 24661676 ER PT J AU Foray, N Badie, C Alsbeih, G Lambin, P Geara, F Taghian, AG Deschavanne, P Gueulette, J Courdi, A Chavaudra, N Fertil, B AF Foray, Nicolas Badie, Christophe Alsbeih, Ghazi Lambin, Philippe Geara, Fady Taghian, Alphonse G. Deschavanne, Patrick Gueulette, John Courdi, Adel Chavaudra, Nicole Fertil, Bernard TI Edmond-Philippe Malaise (1930-2013): A Lifetime of Perseverance Leads to the Cellular Definition of Intrinsic Radiosensitivity OBITUARY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Biographical-Item C1 [Foray, Nicolas] INSERM, UMR1052, Canc Res Ctr Lyon, Radiobiol Grp, F-69008 Lyon, France. [Badie, Christophe] Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Canc Genet & Cytogenet Grp, Biol Effects Dept, Didcot, Oxon, England. [Alsbeih, Ghazi] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Lambin, Philippe] Maastro Clin, Maastricht, Netherlands. [Geara, Fady] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Deschavanne, Patrick] Univ Paris Diderot, INSERM, U973, Paris, France. [Gueulette, John] Catholic Univ Louvain, Louvain, Belgium. [Courdi, Adel] Ctr Antoine Lacassagne, F-06054 Nice, France. [Chavaudra, Nicole] Inst Gustave Roussy, INSERM, U647, F-94805 Villejuif, France. [Fertil, Bernard] CNRS, UMR 7296, Marseille, France. RP Foray, N (reprint author), INSERM, UMR 1052, Ctr Rech Cancerol Lyon, Radiobiol Grp, Bat Cheney A-1er Etage,28 Rue Laennec, F-69008 Lyon, France. EM Nicolas.foray@inserm.fr NR 1 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2014 VL 88 IS 5 BP 1215 EP 1217 DI 10.1016/j.ijrobp.2013.12.049 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AD7QR UT WOS:000333460200037 PM 24661678 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Challenges Faced by Patients in Gout Treatment SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID NOMINAL GROUP TECHNIQUE; GENERAL-PRACTICE; MEDICATION; CARE; ADHERENCE; BELIEFS C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Division of Rheumatology at the University of Alabama at Birmingham; Agency for Health Quality and Research Center for Education and Research on Therapeutics; National Institute of Arthritis, Musculoskeletal and Skin Diseases; National Institute of Aging; National Cancer Institute; Takeda; Savient; Regeneron; Allergan FX This material is the result of work supported by research funds from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics; National Institute of Arthritis, Musculoskeletal and Skin Diseases; National Institute of Aging; and National Cancer Institute.; J.A.S. has received research and travel grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron and Allergan. J.A.S. is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. NR 12 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD APR PY 2014 VL 20 IS 3 BP 172 EP 174 DI 10.1097/RHU.0000000000000091 PG 3 WC Rheumatology SC Rheumatology GA AE2MF UT WOS:000333806400013 PM 24662562 ER PT J AU Shearer, WT Dunn, E Notarangelo, LD Dvorak, CC Puck, JM Logan, BR Griffith, LM Kohn, DB O'Reilly, RJ Fleisher, TA Pai, SY Martinez, CA Buckley, RH Cowan, MJ AF Shearer, William T. Dunn, Elizabeth Notarangelo, Luigi D. Dvorak, Christopher C. Puck, Jennifer M. Logan, Brent R. Griffith, Linda M. Kohn, Donald B. O'Reilly, Richard J. Fleisher, Thomas A. Pai, Sung-Yun Martinez, Caridad A. Buckley, Rebecca H. Cowan, Morton J. TI Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allogeneic hematopoietic cell transplantation; gene therapy; primary immunodeficiency; clinical trial ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; GENE-THERAPY; LIGASE-IV; MUTATIONS; RECONSTITUTION; OUTCOMES; COMPLEX; ANTIGEN; HUMANS AB Background: The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries. Objectives: The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America. Methods: Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group. Results: Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%). Conclusion: Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis. C1 [Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA. [Dunn, Elizabeth; Dvorak, Christopher C.; Puck, Jennifer M.; Cowan, Morton J.] Univ Calif San Francisco, Div Pediat Allergy Immunol & Blood & Marrow Trans, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Notarangelo, Luigi D.] Med Coll Wisconsin, Div Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Logan, Brent R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Logan, Brent R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. [Logan, Brent R.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA USA. [O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Div Hematol & Oncol, Boston Childrens Hosp, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Martinez, Caridad A.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Ctr Canc, Houston, TX 77030 USA. [Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Pediat & Immunol, Durham, NC 27706 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Baylor Coll Med, Immunol Allergy & Rheumatol Serv, 1102 Bates St,Suite FC330, Houston, TX 77030 USA. EM wtshearer@texaschildrens.org RI Notarangelo, Luigi/F-9718-2016; Kohn, Donald/N-5085-2016 OI Notarangelo, Luigi/0000-0002-8335-0262; Kohn, Donald/0000-0003-1840-6087 FU Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT-NIAID); Intramural Research Programs of the National Human Genome Research Institute (NHGRI); National Institute of Allergy and Infectious Diseases; Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health (ORDR-NACTS-NIH), Bethesda, Maryland [U54-AI082973, U54-NS064808, R13-AI094943]; Immune Deficiency Foundation, Towson, Md; Jeffrey Modell Foundation, New York, NY; Robert A. Good Immunology Society, St Petersburg, Fla; John P. McGovern Foundation, Houston, Tex; David Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex; Baxter International, Deerfield, Ill; CSL Behring, King of Prussia, Pa; Sigma-Tau Pharmaceuticals, Gaithersburg, Md; DAIT-NIAID; NHGRI NIAID; ORDR-NCATS-NIH; National Institutes of Health (NIH); NIH; March of Dimes; Jeffrey Modell Foundation; NIAID; NIH-Gene Therapy Resource Program; [NCI23766] FX The Primary Immune Deficiency Treatment Consortium (PIDTC) is supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT-NIAID); the Intramural Research Programs of the National Human Genome Research Institute (NHGRI) and the National Institute of Allergy and Infectious Diseases; and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health (ORDR-NACTS-NIH), Bethesda, Maryland: U54-AI082973 (PI: M. J. Cowan), U54-NS064808 (PI: J. P. Krischer), and R13-AI094943 (PIs: M. J. Cowan and L. D. Notarangelo). This manuscript was presented at the PIDTC Third Annual Scientific Workshop, Houston, Tex, May 2-4, 2013, supported in part by the Immune Deficiency Foundation, Towson, Md; the Jeffrey Modell Foundation, New York, NY; the Robert A. Good Immunology Society, St Petersburg, Fla; the John P. McGovern Foundation, Houston, Tex; the David Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex; Baxter International, Deerfield, Ill; CSL Behring, King of Prussia, Pa; and Sigma-Tau Pharmaceuticals, Gaithersburg, Md. The opinions expressed are those of the authors and do not represent the position of the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the Office of Rare Diseases Research, the National Center for Advancing Translational Sciences, the National Institutes of Health, or the US Government.; W. T. Shearer has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop; is employed by Baylor College of Medicine; and has grants/grants pending with the National Institutes of Health (NIH). E. Dunn has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Scientific Workshop; is employed by the University of California-San Francisco (UCSF); and has grants/grants pending from the NIH. L. D. Notarangelo has received research support from the NIH, March of Dimes, and the Jeffrey Modell Foundation; is a board member on the Immune Disease Institute, the Meyer Pediatric Hospital, DMC, Watermark and DMC, NovImmune, Board of Scientific Counselors for the NIAID and NIH, is an Associate Editor for the Journal of Allergy and Clinical Immunology, is an Associate Editor for Clinical Immunology; is employed by Children's Hospital Boston; and receives royalties from UpToDate. C. C. Dvorak has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH and has received travel support from DAIT-NIAID, NHGR NIAID, and ORDR-NCATS-NIH. J. M. Puck has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop; is employed by UCSF; has grants/grants pending from the NIH; and receives royalties from a published textbook. B. R. Logan has received research support from the NIAID. L. M. Griffith is a medical officer for the NIAID and is employed by the NIH. D. B. Kohn has received travel support from the PIDTC. R. J. O'Reilly has received research support from the NIAID for the PIDTC and NCI23766, is employed by MSKCC, has provided expert testimony for Miltenyi Biotech, and has patents pending for WT1 peptides. S.-Y. Pai has received grants from DAIT-NIAID, has received support for travel to meetings for study or other purposes from the PIDTC Workshop, is employed by the Boston Children's Hospital, and has grants/grants pending from NIH-Gene Therapy Resource Program. R. H. Buckley has received grants from the NIAID, has received support for travel to meetings from the PIDTC, is employed by the Duke University Medical Center, receives royalties from UpToDate, has stock/stock option in TIAA/CREF, and receives travel expenses from the Foundation for Primary immunodeficiency disease. M. J. Cowan has received research support from DAIT-NIAID, NHGRI NIAID, ORDR-NCATS-NIH, and the NIH; has received travel support to PIDTC workshops; and is employed by the University of California. These authors declare that they have no relevant conflicts of interest. NR 44 TC 48 Z9 48 U1 3 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2014 VL 133 IS 4 BP 1092 EP 1098 DI 10.1016/j.jaci.2013.09.044 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA AD8QW UT WOS:000333531700020 PM 24290292 ER PT J AU Lee, YN Frugoni, F Dobbs, K Walter, JE Giliani, S Gennery, AR Al-Herz, W Haddad, E LeDeist, F Bleesing, JH Lauren, AH Pai, SY Nelson, RP El-Ghoneimy, DH El-Feky, RA Reda, SM Hossny, E Soler-Palacin, P Fuleihan, RL Patel, NC Massaad, MJ Geha, RS Puck, JM Palma, P Cancrini, C Chen, K Vihinen, M Alt, FW Notarangelo, LD AF Lee, Yu Nee Frugoni, Francesco Dobbs, Kerry Walter, Jolan E. Giliani, Silvia Gennery, Andrew R. Al-Herz, Waleed Haddad, Elie LeDeist, Francoise Bleesing, Jack H. Henderson, Lauren A. Pai, Sung-Yun Nelson, Robert P. El-Ghoneimy, Dalia H. El-Feky, Reem A. Reda, Shereen M. Hossny, Elham Soler-Palacin, Pere Fuleihan, Ramsay L. Patel, Niraj C. Massaad, Michel J. Geha, Raif S. Puck, Jennifer M. Palma, Paolo Cancrini, Caterina Chen, Karin Vihinen, Mauno Alt, Frederick W. Notarangelo, Luigi D. TI A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Recombination-activating gene 1; V(D)J recombination; severe combined immune deficiency; Omenn syndrome; autoimmunity; genotype-phenotype correlation; immune repertoire ID SEVERE COMBINED IMMUNODEFICIENCY; HYPOMORPHIC RAG1 MUTATIONS; COMBINED IMMUNE-DEFICIENCY; B-CELL; V(D)J RECOMBINATION; OMENN-SYNDROME; GRANULOMATOUS-DISEASE; T-CELLS; REPERTOIRE; AUTOIMMUNITY AB Background: The recombination-activating gene (RAG) 1/2 proteins play a critical role in the development of T and B cells by initiating the VDJ recombination process that leads to generation of a broad T-cell receptor (TCR) and B-cell receptor repertoire. Pathogenic mutations in the RAG1/2 genes result in various forms of primary immunodeficiency, ranging from T 2 B 2 severe combined immune deficiency to delayed-onset disease with granuloma formation, autoimmunity, or both. It is not clear what contributes to such heterogeneity of phenotypes. Objective: We sought to investigate the molecular basis for phenotypic diversity presented in patients with various RAG1 mutations. Methods: We have developed a flow cytometry-based assay that allows analysis of RAG recombination activity based on green fluorescent protein expression and have assessed the induction of the Ighc locus rearrangements in mouse Rag1(-/-) pro-B cells reconstituted with wild-type or mutant human RAG1 (hRAG1) using deep sequencing technology. Results: Here we demonstrate correlation between defective recombination activity of hRAG1 mutant proteins and severity of the clinical and immunologic phenotype and provide insights on the molecular mechanisms accounting for such phenotypic diversity. Conclusions: Using a sensitive assay to measure the RAG1 activity level of 79 mutations in a physiologic setting, we demonstrate correlation between recombination activity of RAG1 mutants and the severity of clinical presentation and show that RAG1 mutants can induce specific abnormalities of the VDJ recombination process. C1 [Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry; Walter, Jolan E.; Henderson, Lauren A.; Massaad, Michel J.; Geha, Raif S.; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Boston, MA USA. [Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry; Walter, Jolan E.; Henderson, Lauren A.; Massaad, Michel J.; Geha, Raif S.; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Boston, MA USA. [Walter, Jolan E.] Massachusetts Gen Hosp Children, Div Pediat Allergy Immunol, Boston, MA USA. [Giliani, Silvia] Univ Brescia, A Nocivelli Inst Mol Med, Pediat Clin, Brescia, Italy. [Giliani, Silvia] Genet Sect, Dept Pathol Spedali Civili, Brescia, Italy. [Gennery, Andrew R.] NHS Fdn Trust, Newcastle Upon Tyne Hosp, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England. [Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait. [Haddad, Elie; LeDeist, Francoise] Univ Montreal, Dept Pediat, CHU St Justine Res Ctr, Montreal, PQ H3C 3J7, Canada. [Haddad, Elie; LeDeist, Francoise] Univ Montreal, Dept Microbiol Infectiol & Immunol, CHU St Justine Res Ctr, Montreal, PQ, Canada. [Bleesing, Jack H.] Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Nelson, Robert P.] Indiana Univ, Sch Med, Div Hematol & Oncol, Indianapolis, IN USA. [El-Ghoneimy, Dalia H.; El-Feky, Reem A.; Reda, Shereen M.; Hossny, Elham] Ain Shams Univ, Dept Pediat Allergy & Immunol, Childrens Hosp, Fac Med, Cairo, Egypt. [Soler-Palacin, Pere] Vall Hebron Univ Hosp, Paediat Infect Dis & Immunodeficiencies Unit, Barcelona, Spain. [Fuleihan, Ramsay L.] Northwestern Univ, Feinberg Sch Med, Div Allergy & Immunol, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Patel, Niraj C.] Levine Childrens Hosp, Carolinas Med Ctr, Immunol Clin, Charlotte, NC USA. [Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Puck, Jennifer M.] UCSF Benioff Childrens Hosp, San Francisco, CA USA. [Palma, Paolo; Cancrini, Caterina] Bambino Gesu Pediat Hosp, DPUO, Univ Dept Pediat, Rome, Italy. [Palma, Paolo; Cancrini, Caterina] Univ Roma Tor Vergata, Sch Med, Rome, Italy. [Chen, Karin] Univ Utah, Dept Pediat, Div Allergy Immunol & Rheumatol, Salt Lake City, UT USA. [Vihinen, Mauno] Lund Univ, Dept Expt Med Sci, S-22100 Lund, Sweden. [Alt, Frederick W.] Boston Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Alt, FW (reprint author), Boston Childrens Hosp, Program Mol & Cellular Med, Karp Res Bldg,9th Floor,One Blackfan Circle, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; luigi.notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; Soler-Palacin, Pere/N-2373-2014; OI Notarangelo, Luigi/0000-0002-8335-0262; Soler-Palacin, Pere/0000-0002-0346-5570; Palma, Paolo/0000-0002-3066-4719; Vihinen, Mauno/0000-0002-9614-7976; cancrini, caterina/0000-0001-8410-9617; Frugoni, Francesco/0000-0002-1769-8121 FU National Institutes of Health [U54AI082973, 1P01AI076210-01A1]; March of Dimes [1-FY-13-500]; Jeffrey Modell Foundation; Translational Research Program [TRP 2009 042809]; Dubai Harvard Foundation for Medical Research; Manton Foundation; March of Dimes; National Institutes of Health (NIH); National Institute of Allergy and Infectious Disease; Translational Investigator Service Award from Boston Children's Hospital; Baxter; CSL Behring; Octapharma; NIH FX Supported in part by National Institutes of Health grants U54AI082973 (to L.D.N.) and 1P01AI076210-01A1 (to L.D.N., F. W. A., and R. S. G.). F. W. A is an investigator of the Howard Hughes Medical Institute. This work received additionally contributions from the March of Dimes (grant 1-FY-13-500 to L.D.N.), the Jeffrey Modell Foundation (to L.D.N.), the Translational Research Program grant TRP 2009 042809 (to L.D.N.), the Dubai Harvard Foundation for Medical Research (to L.D.N. and R. S. G.), and the Manton Foundation (to Y.N.L. and L.D.N.).; Y.N. Lee has received research support from the Manton Foundation and the March of Dimes and is employed by Boston Children's Hospital. F. Frugoni, J. Puck, and F. Alt have received research support from the National Institutes of Health (NIH). J. E. Walter is employed by Massachusetts General Hospital and receives research support from the National Institute of Allergy and Infectious Disease. L. A. Henderson has received travel support from the American College of Rheumatology and the American Academy of Pediatrics. S.-Y. Pai is employed by Boston Children's Hospital and receives research support from the Translational Investigator Service Award from Boston Children's Hospital. P. Soler-Palacin has consultant arrangements with CSL Behring; has provided expert testimony on behalf of CSL Behring; has received research support from Baxter, CSL Behring, and Octapharma; has received payment for lectures from CSL Behring; and has received travel support from the European Society of Immunodeficiencies. R. S. Geha has received research support from the NIH and the Dubai Harvard Foundation for Medical Research. L. D. Notarangelo has received research support from the NIH, the Jeffrey Modell Foundation, the March of Dimes, the Dubai Harvard Foundation for Medical Research, and the Manton Foundation; has board memberships with the Program in Molecular and Cellular Medicine and Pediatric University Hospital "Meyer" in Florence, Italy; is employed by Boston Children's Hospital; and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. NR 43 TC 39 Z9 39 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2014 VL 133 IS 4 BP 1099 EP + DI 10.1016/j.jaci.2013.10.007 PG 22 WC Allergy; Immunology SC Allergy; Immunology GA AD8QW UT WOS:000333531700021 PM 24290284 ER PT J AU Hyde, ER Petrosino, JF Piedra, PA Camargo, CA Espinola, JA Mansbach, JM AF Hyde, Embriette R. Petrosino, Joseph F. Piedra, Pedro A. Camargo, Carlos A., Jr. Espinola, Janice A. Mansbach, Jonathan M. TI Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID DISEASE; ASTHMA C1 [Hyde, Embriette R.; Petrosino, Joseph F.] Baylor Coll Med, Integrat Mol & Biomed Sci Grad Program, Houston, TX 77030 USA. [Hyde, Embriette R.; Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA. [Petrosino, Joseph F.; Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol & Pediat, Houston, TX 77030 USA. [Petrosino, Joseph F.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.; Espinola, Janice A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Hyde, ER (reprint author), Baylor Coll Med, Integrat Mol & Biomed Sci Grad Program, Houston, TX 77030 USA. EM jonathan.mansbach@childrens.harvard.edu FU NIAID NIH HHS [K23 AI077801, U01 AI-67693, U01 AI067693, K23 AI-77801]; NIGMS NIH HHS [T32 GM008231] NR 10 TC 8 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2014 VL 133 IS 4 BP 1220 EP 1222 DI 10.1016/j.jaci.2013.10.049 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA AD8QW UT WOS:000333531700038 PM 24365140 ER PT J AU Walcott, BP Peterson, RT AF Walcott, Brian P. Peterson, Randall T. TI Zebrafish models of cerebrovascular disease SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE aneurysm; arteriovenous malformation; cavernous malformation; moyamoya; stroke; zebrafish ID CEREBRAL CAVERNOUS MALFORMATION; BRAIN ARTERIOVENOUS-MALFORMATIONS; UNRUPTURED INTRACRANIAL ANEURYSMS; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; MOYAMOYA-DISEASE; NATURAL-HISTORY; IN-VIVO; VASCULAR DEVELOPMENT; PEDIATRIC-PATIENTS AB Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish (Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Walcott, Brian P.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Walcott, Brian P.; Peterson, Randall T.] Harvard Univ, Sch Med, Charlestown, MA USA. [Peterson, Randall T.] Broad Inst, Cambridge, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 125 TC 4 Z9 5 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2014 VL 34 IS 4 BP 571 EP 577 DI 10.1038/jcbfm.2014.27 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AE2AE UT WOS:000333774900003 PM 24517974 ER PT J AU Calin, A Kumaraswamy, VM Braver, D Nair, DG Moldovan, M Simon, MV AF Calin, Alexandru Kumaraswamy, Vishakhadatta M. Braver, Diana Nair, Dinesh G. Moldovan, Mihai Simon, Mirela V. TI Intraoperative Somatosensory Evoked Potential Monitoring Decreases EEG Burst Suppression Ratio During Deep General Anesthesia SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG burst suppression; SSEP monitoring; Anesthesia ID ISOFLURANE ANESTHESIA; SEVOFLURANE ANESTHESIA; BISPECTRAL INDEX; PROPOFOL; ELECTROENCEPHALOGRAM; ACTIVATION AB Purpose: The burst suppression (BS) EEG patterns induced by general anesthesia can react to somatosensory stimuli. We investigated this reactivity by studying the effect of peripheral nerve stimulation used for routine intraoperative spinal cord monitoring by somatosensory evoked potentials on BS patterns. Methods: The relative time spent in suppression expressed as BS ratio (BSR) and mean burst duration were measured before (BSRPre), during (BSRStim), and after (BSRPost) a 60-second repetitive electrical ulnar nerve stimulation in nine patients under total intravenous general anesthesia with propofol. The BS reactivity was measured as BSRPre-BSRStim. Results: Overall, 27 trials were included with BSRPre up to 77%, indistinguishable from BSRPost. During stimulation, the mean BSR transiently decreased from 42% to 35%. For each 1% increase in BSRPre, the BS reactivity increased with 0.6%, whereas the burst duration remained approximately 3 seconds. For BSRPre below 30%, the BS reactivity was negligible. Conclusions: Data from this study show that somatosensory input can evoke bursts, altering the "spontaneous" deep BS patterns (BSRPre >30%). Further studies are necessary to objectively assess the clinical relevance of stimulus-induced BS reactivity during deep general anesthesia. C1 [Calin, Alexandru; Moldovan, Mihai] Carol Davila Univ Med & Pharm, Dept Funct Sci, Div Physiol & Fundamental Neurosci, Bucharest, Romania. [Calin, Alexandru; Kumaraswamy, Vishakhadatta M.; Braver, Diana; Nair, Dinesh G.; Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, Intraoperat Neurophysiol Unit, Boston, MA 02114 USA. [Calin, Alexandru; Kumaraswamy, Vishakhadatta M.; Braver, Diana; Nair, Dinesh G.; Simon, Mirela V.] Harvard Univ, Sch Med, Boston, MA USA. [Kumaraswamy, Vishakhadatta M.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Moldovan, Mihai] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurol, Intraoperat Neurophysiol Unit, WACC 739G,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org RI Moldovan, Mihai/C-4215-2011 OI Moldovan, Mihai/0000-0003-2512-3499 FU Romanian National Authority for Scientific Research; National Research Council-Executive Agency for Higher Education, Research, Development and Innovation [PN-II-ID-PCE-2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290] FX Supported by grants of the Romanian National Authority for Scientific Research, National Research Council-Executive Agency for Higher Education, Research, Development and Innovation Funding (project number PN-II-ID-PCE-2011-3-0847 and PN-II-PT-PCCA-2011-3.2-1290 to M.M.). NR 37 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD APR PY 2014 VL 31 IS 2 BP 133 EP 137 DI 10.1097/WNP.0000000000000034 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AE0JL UT WOS:000333650500008 PM 24691230 ER PT J AU Joynt, KE AF Joynt, Karen E. TI The Ninety-Nine Percent: Focusing on the Patient to Reduce Readmissions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID HEART-FAILURE; MORTALITY; IMPACT; TRIAL; CARE; RISK; HOME C1 [Joynt, Karen E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Joynt, Karen E.] VA Boston Healthcare Syst, Med Serv, Cardiol Serv, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org NR 10 TC 1 Z9 1 U1 3 U2 7 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 APR PY 2014 VL 29 IS 4 BP 556 EP 557 DI 10.1007/s11606-013-2732-6 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AD8RF UT WOS:000333532600004 PM 24442335 ER PT J AU Guyatt, GH Mulla, SM Scott, IA Jackevicius, CA You, JJ AF Guyatt, Gordon H. Mulla, Sohail M. Scott, Ian A. Jackevicius, Cynthia A. You, John J. TI Patient Engagement and Shared Decision-Making SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Guyatt, Gordon H.; Mulla, Sohail M.; You, John J.] McMaster Univ, Fac Hlth Sci, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada. [Guyatt, Gordon H.; You, John J.] McMaster Univ, Fac Hlth Sci, Dept Med, Hamilton, ON L8N 3Z5, Canada. [Scott, Ian A.] Princess Alexandra Hosp, Dept Internal Med & Clin Epidemiol, Brisbane, Qld 4102, Australia. [Jackevicius, Cynthia A.; You, John J.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Guyatt, GH (reprint author), McMaster Univ, Fac Hlth Sci, Dept Clin Epidemiol & Biostat, 1200 Main St West,Room 2C12, Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Scott, Ian/F-1482-2011 NR 3 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 IS 4 BP 562 EP 562 DI 10.1007/s11606-013-2727-3 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AD8RF UT WOS:000333532600007 PM 24464283 ER PT J AU Michaelidis, CI Zimmerman, RK Nowalk, MP Fine, MJ Smith, KJ AF Michaelidis, Constantinos I. Zimmerman, Richard K. Nowalk, Mary Patricia Fine, Michael J. Smith, Kenneth J. TI Cost-Effectiveness of Procalcitonin-Guided Antibiotic Therapy for Outpatient Management of Acute Respiratory Tract Infections in Adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE procalcitonin; antibiotics; respiratory tract infection; cost-effectiveness ID C-REACTIVE PROTEIN; UNITED-STATES; PRIMARY-CARE; RESISTANCE; COMMUNITY; IMPACT AB Two clinical trials suggest that procalcitonin-guided antibiotic therapy can safely reduce antibiotic prescribing in outpatient management of acute respiratory tract infections (ARTIs) in adults. Yet, it remains unclear whether procalcitonin testing is cost-effective in this setting. To evaluate the cost-effectiveness of procalcitonin-guided antibiotic therapy in outpatient management of ARTIs in adults. Cost-effectiveness model based on results from two published European clinical trials, with all parameters varied widely in sensitivity analyses. Two hypothetical cohorts were modeled in separate trial-based analyses: adults with ARTIs judged by their physicians to require antibiotics and all adults with ARTIs. Procalcitonin-guided antibiotic therapy protocols versus usual care. Costs and cost per antibiotic prescription safely avoided. We estimated the health care system willingness-to-pay threshold as $43 (range $0-$333) per antibiotic safely avoided, reflecting the estimated cost of antibiotic resistance per outpatient antibiotic prescribed. In the cohort including all adult ARTIs judged to require antibiotics by their physicians, procalcitonin cost $31 per antibiotic prescription safely avoided and the likelihood of procalcitonin use being favored compared to usual care was 58.4 % in a probabilistic sensitivity analysis. In the analysis that included all adult ARTIs, procalcitonin cost $149 per antibiotic prescription safely avoided and the likelihood of procalcitonin use being favored was 2.8 %. Procalcitonin-guided antibiotic therapy for outpatient management of ARTIs in adults would be cost-effective when the costs of antibiotic resistance are considered and procalcitonin testing is limited to adults with ARTIs judged by their physicians to require antibiotics. C1 [Michaelidis, Constantinos I.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. [Zimmerman, Richard K.; Nowalk, Mary Patricia] Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, Pittsburgh, PA 15261 USA. [Fine, Michael J.; Smith, Kenneth J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15261 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Michaelidis, CI (reprint author), Univ Pittsburgh, Sch Med, M240 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM michaelidis.constant@medstudent.pitt.edu OI Zimmerman, Richard/0000-0001-5941-6092 FU National Institute of Allergy and Infectious Diseases [R01AI076256]; National Institute of Health [AG21885]; Doris Duke Charitable Foundation FX This study was supported by the National Institute of Allergy and Infectious Diseases (Grant No. R01AI076256), the National Institute of Health (T32 Grant No. AG21885) and the Doris Duke Charitable Foundation. This study has not previously been presented in part or in full at any prior conference. NR 31 TC 13 Z9 13 U1 1 U2 6 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 APR PY 2014 VL 29 IS 4 BP 579 EP 586 DI 10.1007/s11606-013-2679-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AD8RF UT WOS:000333532600010 PM 24234394 ER PT J AU Uhlig, K Leff, B Kent, D Dy, S Brunnhuber, K Burgers, JS Greenfield, S Guyatt, G High, K Leipzig, R Mulrow, C Schmader, K Schunemann, H Walter, LC Woodcock, J Boyd, CM AF Uhlig, Katrin Leff, Bruce Kent, David Dy, Sydney Brunnhuber, Klara Burgers, Jako S. Greenfield, Sheldon Guyatt, Gordon High, Kevin Leipzig, Rosanne Mulrow, Cynthia Schmader, Kenneth Schunemann, Holger Walter, Louise C. Woodcock, James Boyd, Cynthia M. TI A Framework for Crafting Clinical Practice Guidelines that are Relevant to the Care and Management of People with Multimorbidity SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE guidelines; multimorbidity; comorbidity; grading evidence ID MULTIPLE CHRONIC CONDITIONS; SERVICES TASK-FORCE; ED AMERICAN-COLLEGE; OLDER-ADULTS; HEALTH-CARE; ANTITHROMBOTIC THERAPY; RECOMMENDATIONS; QUALITY; TRIALS; GRADE AB Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement. C1 [Uhlig, Katrin] Tufts Univ, Sch Med, Ctr Clin Evidence Synth, Tufts Med Ctr,Dept Med,Div Nephrol, Boston, MA 02111 USA. [Uhlig, Katrin] Tufts Univ, Sch Med, Ctr Clin Evidence Synth, Tufts Med Ctr,Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Leff, Bruce; Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Kent, David] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Leff, Bruce; Dy, Sydney; Boyd, Cynthia M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Brunnhuber, Klara] BMJ Evidence Ctr, London, England. [Burgers, Jako S.] Dutch Coll Gen Practitioners, Dept Guideline Dev & Res, Utrecht, Netherlands. [Greenfield, Sheldon] Univ Calif Irvine, Sch Med, Hlth Policy Res Inst, Irvine, CA 92717 USA. [Guyatt, Gordon; Schunemann, Holger] McMaster Univ, Hamilton, ON, Canada. [High, Kevin] Wake Forest Sch Med, Infect Dis Sect, Winston Salem, NC USA. [Leipzig, Rosanne] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Mulrow, Cynthia] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Schmader, Kenneth] Durham VA Med Ctr, GRECC, Durham, NC USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Woodcock, James] Univ Cambridge, Inst Publ Hlth, UKCRC Ctr Diet & Act Res CEDAR, Cambridge, England. RP Boyd, CM (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. EM cyboyd@jhmi.edu FU AHRQ [R21 HS018597-01, R21 HS017653]; Johns Hopkins Bayview Center for Innovative Medicine, The Robert Wood Johnson Foundation Physician Faculty Scholars Program; Paul Beeson Career Development Award Program [NIA K23 AG032910]; AFAR, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation; National Cancer Institute [R01 CA134425]; National Institute on Aging [K24 AG041180] FX Funding: This work was funded by AHRQ R21 HS018597-01 (PI Boyd) and AHRQ R21 HS017653. Dr. Boyd's effort was supported in part by the Johns Hopkins Bayview Center for Innovative Medicine, The Robert Wood Johnson Foundation Physician Faculty Scholars Program, and the Paul Beeson Career Development Award Program (NIA K23 AG032910, AFAR, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation, and an anonymous donor). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Walter's effort was supported by the National Cancer Institute (grant number R01 CA134425) and the National Institute on Aging (grant number K24 AG041180). NR 57 TC 30 Z9 31 U1 2 U2 15 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 APR PY 2014 VL 29 IS 4 BP 670 EP 679 DI 10.1007/s11606-013-2659-y PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AD8RF UT WOS:000333532600028 PM 24442332 ER PT J AU Bakan, J Chen, B Medeiros-Nancarrow, C Hu, JC Kantoff, PW Recklitis, CJ AF Bakan, Jennifer Chen, Bing Medeiros-Nancarrow, Cheryl Hu, Jim C. Kantoff, Philip W. Recklitis, Christopher J. TI Effects of a gift certificate incentive and specialized delivery on prostate cancer survivors' response rate to a mailed survey: A randomized-controlled trial SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Mailed surveys; Response rates; Cancer survivorship; Prostate cancer; Mailing methods ID UNCONDITIONAL INCENTIVES; INCREASING RESPONSE AB Objectives: Most men diagnosed with prostate cancer become long-term survivors, but are at risk for medical late-effects that can affect their long-term health. Mailed surveys are well suited to study late-effects in this population, but low response rates can compromise survey validity. This study investigated whether an unconditional $5.00 gift certificate incentive or Priority Mail delivery increased prostate cancer survivors' response to mailed surveys. Materials and Methods: 976 participants (mean age = 66.8 years), 2-8 years post-diagnosis, were randomized to one of four groups: Incentive; Priority Mail; Incentive & Priority Mail; or Control. After an introductory letter, initial study packets were mailed based on randomization; 46 days later, a second study packet was mailed to all non-responders by First-Class Mail. Results: The first mailing yielded a significant variation in response rates across groups (chi(2) = 9.34; p = 0.025). Priority Mail (64.7%; p = 0.008) and Incentive & Priority Mail (63.6%; p = 0.016) groups had significantly higher response rates than Controls (52.9%). After the second mailing, the overall response rate increased significantly from 59.6% to 71.4% (p < 0.001); however, response rates no longer differed across groups (range, 69.3% [Incentive group] to 73.9% [Priority Mail group]). Conclusions: Long-term prostate cancer survivors' response rates to mailed surveys increased with the use of Priority Mail and a repeat survey mailing, but the unconditional gift certificate incentive was not supported in this population. By identifying and applying specialized survey methods, studies targeting survivors of prostate cancer and other geriatric cancers may improve response rates, thus limiting a source of potential bias. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Bakan, Jennifer; Chen, Bing; Medeiros-Nancarrow, Cheryl; Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Hu, Jim C.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Div Solid Tumor Oncol, Boston, MA 02215 USA. RP Bakan, J (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_bakan@dfci.harvard.edu FU American Foundation for Suicide Prevention [PRG-1-10-156] FX Research support was provided by a grant from the American Foundation for Suicide Prevention (PRG-1-10-156; Recklitis). NR 10 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD APR PY 2014 VL 5 IS 2 BP 127 EP 132 DI 10.1016/j.jgo.2013.11.005 PG 6 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA AD8IB UT WOS:000333508600002 PM 24495697 ER PT J AU Moye, J June, A Martin, LA Gosian, J Herman, LI Naik, AD AF Moye, Jennifer June, Andrea Martin, Lindsey Ann Gosian, Jeffrey Herman, Levi I. Naik, Aanand D. TI Pain is prevalent and persisting in cancer survivors: Differential factors across age groups SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Cancer survivorship; Pain; Depression ID QUALITY-OF-LIFE; PRIMARY-CARE; DEPRESSION; MANAGEMENT; ADULTS; BREAST AB Objective: The Institute of Medicine documents a significant gap in care for long term side effects of cancer treatment, including pain. This paper characterizes age differences in the prevalence and predictive characteristics of pain to guide clinicians in identification and treatment. Materials and Methods: A sample of 170 adults with head and neck, esophageal, gastric, or colorectal cancers were recruited from two regional Veterans Administration Medical Centers. Face to face interviews were conducted 6, 12, and 18 months after diagnosis with the PROMIS scale to assess pain and PHQ-9 scale to assess depression. Descriptive statistics characterized incidence and prevalence of pain impact and intensity ratings. Multivariate linear hierarchical regression identified clinical characteristics associated with pain in older versus younger age groups. Results: Clinically significant pain was endorsed in one third (32%) of the sample, with younger adults reporting higher levels of the impact of pain on daily activities and work, and also higher pain intensity ratings than older adults. In younger adults, pain ratings were most associated with lower social support and higher depression, as well as advanced cancer stage. In older adults, pain was multifactorial, associated with baseline comorbidities, adjuvant treatment, and both combat post-traumatic stress disorder (PTSD) and depression. Conclusions: Pain is a significant persisting problem for one in three cancer survivors, requiring ongoing assessment, even months later. Important differences in pain's determinants and impact are present by age group. Identification and treatment of pain, as well as associated conditions such as depression, may improve the quality of life in cancer survivors. Published by Elsevier Ltd. C1 [Moye, Jennifer; Gosian, Jeffrey] VA Boston Hlth Care Syst, Jamaica Plain, MA USA. [Moye, Jennifer; Gosian, Jeffrey] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Martin, Lindsey Ann; Herman, Levi I.; Naik, Aanand D.] Michael E DeBakey VAMC, Hlth Serv Res & Dev, Houston, TX USA. [Martin, Lindsey Ann; Herman, Levi I.; Naik, Aanand D.] Baylor Coll Med, Houston, TX 77030 USA. [June, Andrea] Cent Connecticut State Univ, New Britain, CT USA. RP Moye, J (reprint author), VA Boston Healthcare Syst Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Houston VA Health Services Research & Development Center of Excellence at the Michael E DeBakey VA Medical Center [HFP90-020]; Department of Veterans Affairs Rehabilitation Research and Development Service [5I01RX000104-02] FX This material is the result of work supported with the resources and the use of facilities at the Boston VA Medical Center and the Houston VA Health Services Research & Development Center of Excellence (HFP90-020) at the Michael E DeBakey VA Medical Center. We thank the members of the Veterans Cancer Rehabilitation Study (Vetcares) Research team for their contributions. We are indebted to the Veterans who have participated in our research studies and allowed us to contribute to their healthcare. Funding was provided by the Department of Veterans Affairs Rehabilitation Research and Development Service #5I01RX000104-02. NR 32 TC 6 Z9 6 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD APR PY 2014 VL 5 IS 2 BP 190 EP 196 DI 10.1016/j.jgo.2013.12.006 PG 7 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA AD8IB UT WOS:000333508600011 PM 24495701 ER PT J AU Shoeb, M Khanna, R Fang, M Sharpe, B Finn, K Ranji, S Monash, B AF Shoeb, Marwa Khanna, Raman Fang, Margaret Sharpe, Brad Finn, Kathleen Ranji, Sumant Monash, Brad TI Internal medicine rounding practices and the accreditation council for graduate medical education core competencies SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID BEDSIDE CASE PRESENTATIONS; ATTENDING ROUNDS; RESIDENT; STUDENT AB BACKGROUND The Accreditation Council for Graduate Medical Education (ACGME) has established the requirement for residency programs to assess trainees' competencies in 6 core domains (patient care, medical knowledge, practice-based learning, interpersonal skills, professionalism, and systems-based practice). As attending rounds serve as a primary means for educating trainees at academic medical centers, our study aimed to identify current rounding practices and attending physician perceived capacity of different rounding models to promote teaching within the ACGME core competencies. METHODS We disseminated a 24-question survey electronically using educational and hospital medicine leadership mailing lists. We assessed attending physician demographics and the frequency with which they used various rounding models, as defined by the location of the discussion of the patient and care plan: bedside rounds (BR), hallway rounds (HR), and card-flipping rounds (CFR). Using the ACGME framework, we assessed the perceived educational value of each model. RESULTS We received 153 completed surveys from attending physicians representing 34 institutions. HR was used most frequently for both new and established patients (61% and 43%), followed by CFR for established patients (36%) and BR for new patients (22%). Most attending physicians indicated that BR and HR were superior to CFR in promoting the following ACGME competencies: patient care, systems-based practice, professionalism, and interpersonal skills. CONCLUSIONS HR is the most commonly employed rounding model. BR and HR are perceived to be valuable for teaching patient care, systems-based practice, professionalism, and interpersonal skills. CFR remains prevalent despite its perceived inferiority in promoting teaching across most of the ACGME core competencies. Journal of Hospital Medicine 2014;9:239-243. (c) 2014 Society of Hospital Medicine C1 [Shoeb, Marwa; Khanna, Raman; Fang, Margaret; Sharpe, Brad; Ranji, Sumant; Monash, Brad] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Finn, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shoeb, M (reprint author), 533 Parnassus Ave,Suite U149,Box 0131, San Francisco, CA 94143 USA. EM mshoeb@medicine.ucsfedu NR 21 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2014 VL 9 IS 4 BP 239 EP 243 DI 10.1002/jhm.2164 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AE1BE UT WOS:000333699600007 PM 24493566 ER PT J AU Kalscheuer, H Onoe, T Dahmani, A Li, HW Holzl, M Yamada, K Sykes, M AF Kalscheuer, Hannes Onoe, Takashi Dahmani, Alexander Li, Hao-Wei Hoelzl, Markus Yamada, Kazuhiko Sykes, Megan TI Xenograft Tolerance and Immune Function of Human T Cells Developing in Pig Thymus Xenografts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID XENOGENEIC PORCINE; ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; HOMEOSTATIC PROLIFERATION; NEGATIVE SELECTION; POSITIVE SELECTION; NONHUMAN-PRIMATES; DENDRITIC CELLS; KNOCKOUT PIGS; TRANSPLANTATION; SURVIVAL AB Transplantation of xenogeneic thymus tissue allows xenograft tolerance induction in the highly disparate pig-to-mouse model. Fetal swine thymus (SW THY) can support the generation of a diverse human T cell repertoire that is tolerant of the pig in vitro. We demonstrate that SW THY generates all human T cell subsets, including regulatory T cells (Tregs), in similar numbers as fetal human thymus (HU THY) grafts in immunodeficient mice receiving the same human CD34(+) cells. Peripheral T cells are specifically tolerant to the mouse and to the human and porcine donors, with robust responses to nondonor human and pig Ags. Specific tolerance is observed to pig skin grafts sharing the THY donor MHC. SW THY-generated peripheral Tregs show similar function, but include lower percentages of naive-type Tregs compared with HU THY-generated Tregs. Tregs contribute to donor-pig specific tolerance. Peripheral human T cells generated in SW THY exhibit reduced proportions of CD8(+) T cells and reduced lymphopenia-driven proliferation and memory-type conversion, accelerated decay of memory-type cells, and reduced responses to protein Ags. Thus, SW thymus transplantation is a powerful xenotolerance approach for human T cells. However, immune function may be further enhanced by strategies to permit positive selection by autologous HLA molecules. C1 [Kalscheuer, Hannes; Onoe, Takashi; Li, Hao-Wei; Yamada, Kazuhiko; Sykes, Megan] Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Dept Surg,Med Sch, Boston, MA 02114 USA. [Kalscheuer, Hannes; Dahmani, Alexander; Li, Hao-Wei; Hoelzl, Markus; Sykes, Megan] Columbia Univ, Coll Phys & Surg, Columbia Ctr Translat Immunol, Dept Med Surg & Microbiol Immunol, New York, NY 10032 USA. RP Sykes, M (reprint author), Columbia Ctr Translat Immunol, 622 West 168th St,PH 17-111, New York, NY 10032 USA. EM megan.sykes@columbia.edu FU National Institutes of Health [P01 AI045897, R01 AI084903]; Japan Society for the Promotion of Science; Uehara Memorial Foundation FX This work was supported by National Institutes of Health Grants P01 AI045897 and R01 AI084903. T.O. was supported in part by a Postdoctoral Fellowship for Research Abroad of the Japan Society for the Promotion of Science and a Postdoctoral Fellowship for study abroad from the Uehara Memorial Foundation. NR 49 TC 3 Z9 4 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2014 VL 192 IS 7 BP 3442 EP 3450 DI 10.4049/jimmunol.1302886 PG 9 WC Immunology SC Immunology GA AD6CY UT WOS:000333342800054 PM 24591363 ER PT J AU Smith, KM Chesin, MS Jeglic, EL AF Smith, Kellie M. Chesin, Megan S. Jeglic, Elizabeth L. TI Minority College Student Mental Health: Does Majority Status Matter? Implications for College Counseling Services SO JOURNAL OF MULTICULTURAL COUNSELING AND DEVELOPMENT LA English DT Article DE estudiantes universitarios de minorias; salud mental; mental health; minority college students ID DEPRESSION INVENTORY-II; BARRATT IMPULSIVENESS SCALE; AFRICAN-AMERICAN; SUICIDAL IDEATION; BINGE DRINKING; ACCULTURATIVE STRESS; NATIONAL-SURVEY; SOCIAL SUPPORT; YOUNG-ADULTS; PREVALENCE AB This study compared mental health among diverse college students to understand whether majority status buffered hypothesized relationships between poor mental health outcomes and minority status. Contrary to expectations, students at the majority-minority college (i.e., the college in which the majority of students were ethnic minorities), regardless of race or ethnicity, reported poorer mental health than their White peers at the predominantly White college. Internalizing symptoms were associated with minority race or ethnicity. These findings may inform the adaptation of college mental health services for diverse student bodies. C1 [Smith, Kellie M.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Smith, Kellie M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chesin, Megan S.; Jeglic, Elizabeth L.] CUNY John Jay Coll Criminal Justice, Dept Psychol, New York, NY 10019 USA. RP Jeglic, EL (reprint author), CUNY John Jay Coll Criminal Justice, Dept Psychol, 445 West 59th St, New York, NY 10019 USA. EM ejeglic@jjay.cuny.edu NR 89 TC 3 Z9 3 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0883-8534 EI 2161-1912 J9 J MULTICULT COUNS D JI J. Multicult. Couns. Dev. PD APR PY 2014 VL 42 IS 2 SI SI BP 77 EP 92 DI 10.1002/j.2161-1912.2014.00046.x PG 16 WC Psychology, Applied SC Psychology GA AE1DD UT WOS:000333705700003 ER PT J AU Rizzo, JF Ayton, LN AF Rizzo, Joseph F., III Ayton, Lauren N. TI Psychophysical testing of visual prosthetic devices: a call to establish a multi-national joint task force SO JOURNAL OF NEURAL ENGINEERING LA English DT Editorial Material C1 [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Neuroophthalmol Serv, Boston, MA 02115 USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ayton, Lauren N.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, East Melbourne 3002, Australia. RP Rizzo, JF (reprint author), Harvard Univ, Sch Med, Neuroophthalmol Serv, Boston, MA 02115 USA. EM Joseph_Rizzo@MEEI.Harvard.edu; lnayton@unimelb.edu.au OI Ayton, Lauren/0000-0001-9907-084X NR 0 TC 4 Z9 4 U1 2 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2014 VL 11 IS 2 AR 020301 DI 10.1088/1741-2560/11/2/020301 PG 2 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA AD7CQ UT WOS:000333419400002 PM 24556526 ER PT J AU Twyford, P Cai, C Fried, S AF Twyford, Perry Cai, Changsi Fried, Shelley TI Differential responses to high-frequency electrical stimulation in ON and OFF retinal ganglion cells SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID RETINITIS-PIGMENTOSA; CONDUCTION BLOCK; AUDITORY-NERVE; PULSE TRAINS; MACULAR DEGENERATION; MAMMALIAN RETINA; ACTIVATION; REPRESENTATIONS; VARIABILITY; PREVALENCE AB Objective. The field of retinal prosthetics for artificial vision has advanced considerably in recent years, however clinical outcomes remain inconsistent. The performance of retinal prostheses is likely limited by the inability of electrical stimuli to preferentially activate different types of retinal ganglion cell (RGC). Approach. Here we examine the response of rabbit RGCs to high-frequency stimulation, using biphasic pulses applied at 2000 pulses per second. Responses were recorded using cell-attached patch clamp methods, and stimulation was applied epiretinally via a small cone electrode. Main results. When prolonged stimulus trains were applied to OFF-brisk transient (BT) RGCs, the cells exhibited a non-monotonic relationship between response strength and stimulus amplitude; this response pattern was different from those elicited previously by other electrical stimuli. When the amplitude of the stimulus was modulated transiently from a non-zero baseline amplitude, ON-BT and OFF-BT cells exhibited different activity patterns: ON cells showed an increase in activity while OFF cells exhibited a decrease in activity. Using a different envelope to modulate the amplitude of the stimulus, we observed the opposite effect: ON cells exhibited a decrease in activity while OFF cells show an increase in activity. Significance. As ON and OFF RGCs often exhibit opposing activity patterns in response to light stimulation, this work suggests that high-frequency electrical stimulation of RGCs may be able to elicit responses that are more physiological than traditional pulsatile stimuli. Additionally, the prospect of an electrical stimulus capable of cell-type specific selective activation has broad applications throughout the fields of neural stimulation and neuroprostheses. C1 [Twyford, Perry; Cai, Changsi; Fried, Shelley] VA Boston Healthcare Syst, Boston, MA USA. [Twyford, Perry; Cai, Changsi; Fried, Shelley] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Twyford, Perry; Cai, Changsi; Fried, Shelley] Harvard Univ, Sch Med, Boston, MA USA. [Cai, Changsi] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China. [Cai, Changsi] Aarhus Univ, CFIN, Aarhus, Denmark. RP Fried, S (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM Fried.Shelley@mgh.harvard.edu FU Veterans Administration [1I01RX000350-01A1]; National Institute of Health [1R01 EY019967-01] FX This work was supported by the Veterans Administration (1I01RX000350-01A1) and by the National Institute of Health (1R01 EY019967-01). NR 58 TC 15 Z9 16 U1 2 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2014 VL 11 IS 2 AR 025001 DI 10.1088/1741-2560/11/2/025001 PG 10 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA AD7CQ UT WOS:000333419400004 PM 24556536 ER PT J AU Sampson, JH Barker, FG AF Sampson, John H. Barker, Fred G., II TI Methodology and reporting of meta-analyses in the neurosurgical literature SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID SYSTEMATIC REVIEWS; QUALITY; IMPROVEMENT; JOURNALS; SURGERY; AMSTAR C1 [Sampson, John H.] Duke Univ, Med Ctr, Durham, NC 27708 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Durham, NC 27708 USA. NR 23 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2014 VL 120 IS 4 BP 791 EP 794 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AD7IZ UT WOS:000333438800001 PM 24460491 ER PT J AU Helmer, KG Pasternak, O Fredman, E Preciado, RI Koerte, IK Sasaki, T Mayinger, M Johnson, AM Holmes, JD Forwell, LA Skopelja, EN Shenton, ME Echlin, PS AF Helmer, Karl G. Pasternak, Ofer Fredman, Eli Preciado, Ronny I. Koerte, Inga K. Sasaki, Takeshi Mayinger, Michael Johnson, Andrew M. Holmes, Jeffrey D. Forwell, Lorie A. Skopelja, Elaine N. Shenton, Martha E. Echlin, Paul S. TI Hockey Concussion Education Project, Part 1. Susceptibility-weighted imaging study in male and female ice hockey players over a single season SO JOURNAL OF NEUROSURGERY LA English DT Article DE susceptibility-weighted imaging; ice hockey; sex-based difference; concussion; mild traumatic brain injury ID TRAUMATIC BRAIN-INJURY; PHYSICIAN-OBSERVED CONCUSSION; WHITE-MATTER INTEGRITY; DIFFUSE AXONAL INJURY; PROFESSIONAL BOXERS; MICROSTRUCTURAL DAMAGE; COGNITIVE DYSFUNCTION; SPORTS CONCUSSION; FOOTBALL PLAYERS; ANISOTROPY AB Object. Concussion, or mild traumatic brain injury (mTBI), is a commonly occurring sports-related injury, especially in contact sports such as hockey. Cerebral microbleeds (CMBs), which appear as small, hypointense lesions on T-2*-weighted images, can result from TBI. The authors use susceptibility-weighted imaging (SWI) to automatically detect small hypointensities that may be subtle signs of chronic and acute damage due to both subconcussive and concussive injury. The goal was to investigate how the burden of these hypointensities changes over time, over a playing season, and postconcussion, in comparison with subjects who did not suffer a medically observed and diagnosed concussion. Methods. Images were obtained in 45 university-level adult male and female ice hockey players before and after a single Canadian Interuniversity Sports season. In addition, 11 subjects (5 men and 6 women) underwent imaging at 72 hours, 2 weeks, and 2 months after concussion. To identify subtle changes in brain tissue and potential CMBs, nonvessel clusters of hypointensities on SWI were automatically identified, and a hypointensity burden index was calculated for all subjects at the beginning of the season (BUS), the end of the season (EOS), and at postconcussion time points (where applicable). Results. A statistically significant increase in the hypointensity burden, relative to the BOS, was observed for male subjects with concussions at the 2-week postconcussion time point. A smaller, nonsignificant rise in the burden for female subjects with concussions was also observed within the same time period. There were no significant changes in burden for nonconcussed subjects of either sex between the BUS and BUS time points. However, there was a statistically significant difference in the burden between male and female subjects in the nonconcussed group at both the BUS and BUS time points, with males having a higher burden. Conclusions. This method extends the utility of SWI from the enhancement and detection of larger (> 5 mm) CMBs, which are often observed in more severe cases of TBI, to cases involving smaller lesions in which visual detection of injury is difficult. The hypointensity burden metric proposed here shows statistically significant changes over time in the male subjects. A smaller, nonsignificant increase in the burden metric was observed in the female subjects. C1 [Helmer, Karl G.] Massachusetts Gen Hosp Massachusetts Inst Technol, Charlestown, MA USA. [Preciado, Ronny I.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Pasternak, Ofer; Fredman, Eli; Koerte, Inga K.; Sasaki, Takeshi; Mayinger, Michael; Shenton, Martha E.; Echlin, Paul S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA. [Koerte, Inga K.; Mayinger, Michael] Univ Munich, Inst Clin Radiol, Munich, Germany. [Sasaki, Takeshi] Tokyo Med & Dent Univ, Grad Sch, Dept Psychiat & Behav Sci, Tokyo, Japan. [Johnson, Andrew M.] Univ Western Ontario, Sch Hlth Studies, London, ON, Canada. [Holmes, Jeffrey D.] Univ Western Ontario, Sch Occupat Therapy, London, ON, Canada. [Forwell, Lorie A.] Univ Western Ontario, Fowler Kennedy Sport Med Clin, London, ON, Canada. [Forwell, Lorie A.] Univ Western Ontario, Sch Phys Therapy, London, ON, Canada. [Skopelja, Elaine N.] Indiana Univ, Ruth Lilly Med Lib, Indianapolis, IN 46204 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Echlin, Paul S.] Elliott Sports Med Clin, Burlington, ON L7N 2G3, Canada. RP Echlin, PS (reprint author), Elliott Sports Med Clin, 1100 Walkers Line,Ste 2, Burlington, ON L7N 2G3, Canada. EM psechlin@gmail.com RI Holmes, Jeffrey/M-6484-2015 OI Holmes, Jeffrey/0000-0002-5744-8338 FU Ontario Trillium Foundation; Dave Irwin Foundation for Brain Injury; Ontario Neurotrauma Foundation; Air Canada; The Ontario Ministry of Health and Long-Term Care; The Ontario Ministry of Tourism, Culture and Sport; The Ontario Ministry of Education; Japan Society for the Promotion of Science [S2301]; NIH [P41RR013218, P41EB015902, R01MH074794]; Department of Defense [X81XWH-07-CC-CSDoD]; NARSAD (National Alliance for Research on Schizophrenia and Depression); Brain & Behavior Research Foundation; Else Kroner-Fresenius Foundation, Germany; Petraeic Legate Foundation; Henry Jackson Foundation FX Funding for this work was provided to the HCEP and Dr. Echlin by the Ontario Trillium Foundation, the Dave Irwin Foundation for Brain Injury, the Ontario Neurotrauma Foundation, Air Canada, The Ontario Ministry of Health and Long-Term Care, The Ontario Ministry of Tourism, Culture and Sport, and The Ontario Ministry of Education. Dr. Sasaki is supported by Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation from the Japan Society for the Promotion of Science (S2301). This work was partially funded by grants from the NIH (Grant Nos. P41RR013218, P41EB015902, and R01MH074794), the Department of Defense (No. X81XWH-07-CC-CSDoD), and a VA merit grant. Dr. Pasternak was partially supported by a NARSAD (National Alliance for Research on Schizophrenia and Depression) Young Investigator grant from the Brain & Behavior Research Foundation. Dr. Koerte is supported by the Else Kroner-Fresenius Foundation, Germany. Mr. Mayinger is supported by the Petraeic Legate Foundation. This work was part of Mr. Mayinger's doctoral thesis. Dr. Shenton is a consultant on an NIH grant to the State University of New York on velocardiofascial syndrome and on a grant supported by the Henry Jackson Foundation. NR 52 TC 24 Z9 24 U1 1 U2 11 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2014 VL 120 IS 4 BP 864 EP 890 DI 10.3171/2013.12.JNS132093 PG 27 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AD7IZ UT WOS:000333438800011 PM 24490839 ER PT J AU Sadat, K Ather, S Aljaroudi, W Heo, J Iskandrian, AE Hage, FG AF Sadat, Kamel Ather, Sameer Aljaroudi, Wael Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI The effect of bone marrow mononuclear stem cell therapy on left ventricular function and myocardial perfusion SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Bone marrow stem cell; myocardial perfusion imaging; single-photon emission computed tomography; cardiac magnetic resonance imaging; echocardiography; myocardial infarction; stable coronary artery disease; heart failure ID CHRONIC HEART-FAILURE; ENDOTHELIAL PROGENITOR CELLS; CHRONIC ISCHEMIC CARDIOMYOPATHY; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; EJECTION FRACTION; DOUBLE-BLIND; INTRAMYOCARDIAL INJECTION; FOLLOW-UP; INTRACORONARY INJECTION AB Bone morrow stem cell (BMC) transfer is an emerging therapy with potential to salvage cardiomyocytes during acute myocardial infarction and promote regeneration and endogenous repair of damaged myocardium in patients with left ventricular (LV) dysfunction. We performed a meta-analysis to examine the association between administration of BMC and LV functional recovery as assessed by imaging. Our meta-analysis included data from 32 trials comprising information on 1,300 patients in the treatment arm and 1,006 patients in the control arm. Overall, BMC therapy was associated with a significant increase in LV ejection fraction by 4.6% +/- A 0.7% (P < .001) (control-adjusted increase of 2.8% +/- A 0.9%, P = .001), and a significant decrease in perfusion defect size by 9.5% +/- A 1.4% (P < .001) (control-adjusted decrease of 3.8% +/- A 1.2%, P = .002). The effect of BMC therapy was similar whether the cells were administered via intra-coronary or intra-myocardial routes and was not influenced by baseline ejection fraction or perfusion defect size. BMC transfer appears to have a positive impact on LV recovery in patients with acute coronary syndrome and those with stable coronary disease with or without heart failure. Most studies were small and a minority used a core laboratory for image analysis. C1 [Sadat, Kamel; Ather, Sameer; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aljaroudi, Wael] Amer Univ Beirut Med Ctr, Div Cardiovasc Dis, Beirut, Lebanon. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Sadat, K (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1900 Univ Blvd, Birmingham, AL 35294 USA. EM ksadat01@gmail.com OI ather, sameer/0000-0002-5579-0658; Hage, Fadi/0000-0002-1397-4942 NR 77 TC 10 Z9 11 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2014 VL 21 IS 2 BP 351 EP 367 DI 10.1007/s12350-013-9846-4 PG 17 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD8SL UT WOS:000333535800013 PM 24379128 ER PT J AU Van Dyke, TE AF Van Dyke, Thomas E. TI Periodontitis Is Characterized by an Immuno-Inflammatory Host-Mediated Destruction of Bone and Connective Tissues That Support the Teeth SO JOURNAL OF PERIODONTOLOGY LA English DT Editorial Material ID NEUTROPHIL CHEMOTAXIS; DISEASE; RESOLUTION; PATHOGENESIS; ANTIGENS C1 [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA 02142 USA. [Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA 02142 USA. RP Van Dyke, TE (reprint author), Forsyth Inst, 245 First St,Room 1756,17th Floor, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org NR 16 TC 6 Z9 6 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD APR PY 2014 VL 85 IS 4 BP 509 EP 511 DI 10.1902/jop.2014.130701 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AE1SS UT WOS:000333750800004 PM 24678865 ER PT J AU Herrera, BS Bastos, AS Coimbra, LS Teixeira, SA Rossa, C Van Dyke, TE Muscara, MN Spolidorio, LC AF Herrera, Bruno S. Bastos, Alliny S. Coimbra, Leila S. Teixeira, Simone A. Rossa, Carlos, Jr. Van Dyke, Thomas E. Muscara, Marcelo N. Spolidorio, Luis C. TI Peripheral Blood Mononuclear Phagocytes From Patients With Chronic Periodontitis Are Primed for Osteoclast Formation SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Chronic periodontitis; cytokines; macrophage colony-stimulating factor; monocytes; nitric oxide; osteoclasts ID NITRIC-OXIDE SYNTHASE; CARDIOVASCULAR-DISEASE; BONE-RESORPTION; CELLS; INFLAMMATION; EXPRESSION; INFECTION; GENDER; RISK; AGE AB Background: During inflammatory periodontal disease, peripheral blood mononuclear cells (PBMCs) are attracted to bone and differentiate into active bone-resorbing osteoclasts (OCs), thus providing evidence that the impact of chronic periodontitis (CP) on the activity of circulating mononuclear cells is of central importance. The authors test the hypothesis that peripheral blood mononuclear phagocytes (PBMPs) from patients with CP are activated and more susceptible to differentiation into OCs, which in turn would lead to more intense bone resorption. Methods: In vitro cytokine production by both unstimulated and lipopolysaccharide-stimulated PBMCs from individuals with (n = 10) or without (n = 12) periodontitis was determined by cytokine array. OC differentiation from CD14(+) PBMCs was induced by receptor activator of nuclear factor-kappa B ligand (RANKL), either alone or in the presence of macrophage colony-stimulating factor (M-CSF). PBMC differentiation to OCs was confirmed by tartrate-resistant acid phosphatase staining; bone resorbing activity was assessed by using an osteologic plate assay (bone resorption pit formation). Results: PBMCs from patients with CP produced tumor necrosis factor-a and higher amounts of interferon-gamma, interleukin (IL)-1 alpha, IL-1 beta, IL-1r alpha, CXC motif chemokine 10, macrophage migration inhibitory factor, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta than the control cells. OC differentiation was induced by RANKL alone in PBMCs from patients with CP, but not in PBMCs from the healthy controls, which required the addition of M-CSF. In addition, PBMC-derived OCs from patients with CP showed significantly higher resorption activity than that observed in the healthy controls. Also, the circulating concentrations of M-CSF were significantly higher in patients with CP than in the control participants. Conclusions: These data indicate that in patients with CP, circulating PBMCs are primed for increased proinflammatory activity and that M-CSF plays a central role in this process by increasing OC formation and the consequent bone resorption activity. C1 [Herrera, Bruno S.; Coimbra, Leila S.; Spolidorio, Luis C.] State Univ Sao Paulo, Araraquara Dent Sch, Dept Physiol, Araraquara, Brazil. [Herrera, Bruno S.; Coimbra, Leila S.; Spolidorio, Luis C.] State Univ Sao Paulo, Araraquara Dent Sch, Dept Pathol, Araraquara, Brazil. [Herrera, Bruno S.; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Bastos, Alliny S.; Rossa, Carlos, Jr.] State Univ Sao Paulo, Araraquara Dent Sch, Dept Diag, Araraquara, Brazil. [Bastos, Alliny S.; Rossa, Carlos, Jr.] State Univ Sao Paulo, Araraquara Dent Sch, Dept Surg, Araraquara, Brazil. [Teixeira, Simone A.; Muscara, Marcelo N.] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, Brazil. RP Herrera, BS (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. EM bherrera@forsyth.org RI Muscara, Marcelo/F-3250-2012; Rossa Jr, Carlos/D-8328-2012; Spolidorio, Luis Carlos/G-1857-2012; Teixeira, Simone/K-3991-2016 OI Muscara, Marcelo/0000-0002-8342-5586; Rossa Jr, Carlos/0000-0003-1705-5481; Teixeira, Simone/0000-0002-8515-5030 FU Sao Paulo Research Foundation (FAPESP), Sao Paulo, SP, Brazil [08/02893-4, 09/1515-0, 11/17800-4]; National Council for Scientific and Technological Development, CNPq, Brasilia, DF, Brazil FX This study was supported by Sao Paulo Research Foundation (FAPESP), Sao Paulo, SP, Brazil, grants 08/02893-4, 09/1515-0, and 11/17800-4. The authors report no conflicts of interest related to this study. Authors MNM and LCS are recipients of fellowships from the National Council for Scientific and Technological Development, CNPq, Brasilia, DF, Brazil. The authors report no conflicts of interest related to this study. NR 38 TC 2 Z9 3 U1 0 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD APR PY 2014 VL 85 IS 4 BP E72 EP E81 DI 10.1902/jop.2013.130280 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AE1SS UT WOS:000333750800003 PM 24059638 ER PT J AU Buffum, MD Buccheri, RK Trygstad, LN Dowling, GA AF Buffum, Martha D. Buccheri, Robin Kay Trygstad, Louise Nigh Dowling, Glenna A. TI Disseminating an Evidence-Based Course to Teach Self-Management of Auditory Hallucinations SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID COMMAND HALLUCINATIONS; INTERVENTION FIDELITY; BEHAVIORAL-MANAGEMENT; IMPLEMENTATION; HARM AB This multi-site project extended course dissemination of the 10-session Behavioral Management of Auditory Hallucinations Course to U. S. Department of Veterans Affairs (VA) mental health outpatient settings. The VA Quality Enhancement Research Initiative (QUERI) model and Rogers' theory of diffusion of innovations served as the theoretical framework. The course was taught to mental health professionals using teleconferencing, electronic media, and monthly conference calls across 24 VA mental health outpatient sites. Twenty course leaders provided feedback. One hundred percent reported being better able to communicate with patients about their voices and 96% reported improved understanding of the voice-hearing experience. Thirty-three course participants provided feedback. Ninety-four percent would recommend the course, 85% reported being better able to communicate with staff about their voices, and 66% reported being better able to manage their voices. Facilitators and barriers to course implementation are described. C1 [Buffum, Martha D.] San Francisco VA Med Ctr, San Francisco, CA USA. [Buffum, Martha D.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Buccheri, Robin Kay; Trygstad, Louise Nigh] Univ Calif San Francisco, Sch Nursing & Hlth Profess, San Francisco, CA 94143 USA. [Dowling, Glenna A.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. RP Buffum, MD (reprint author), 655 Bamboo Terrace, San Rafael, CA 94903 USA. EM marti.buffum@gmail.com FU University of San Francisco Faculty Development Funds FX The authors have disclosed no potential conflicts of interest, financial or otherwise. This material is the result of work supported with resources and the use of facilities at San Francisco VA Medical Center. This project was funded in part by a grant from University of San Francisco Faculty Development Funds. NR 16 TC 2 Z9 2 U1 1 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 EI 1938-2413 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD APR PY 2014 VL 52 IS 4 BP 32 EP 41 DI 10.3928/02793695-20131029-04 PG 10 WC Nursing SC Nursing GA AE1NM UT WOS:000333736100009 PM 24200916 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI COGNITIVE FUNCTION SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID DEMENTIA; LIFE; NUN C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] UCLA Dent Sch, Los Angeles, CA USA. [Friedlander, Arthur H.] Ronald Reagan Univ, Calif Med Ctr, Qual Assurance Hosp Dent Serv, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2014 VL 145 IS 4 BP 324 EP 327 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AE2OG UT WOS:000333812000003 ER PT J AU Friedlander, AH El-Saden, SM Aghazadehsanai, N Chang, TI Harada, ND Garrett, NR AF Friedlander, Arthur H. El-Saden, Suzie M. Aghazadehsanai, Nona Chang, Tina I. Harada, Nancy D. Garrett, Neal R. TI Association of calcified carotid atheromas visualized on panoramic images and aortic arch calcifications seen on chest radiographs of postmenopausal women SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Atherosclerosis; panoramic radiography ID CORONARY-ARTERY CALCIFICATION; RISK-FACTORS; CARDIOVASCULAR RISK; VASCULAR-DISEASE; HEART-DISEASE; BONE LOSS; X-RAY; ATHEROSCLEROSIS; PROGRESSION; POPULATION AB Background. Occult atherosclerotic disease is the leading cause of death among older women. The authors hypothesized that women with calcified carotid artery plaque (CCAP) visualized on panoramic images were more likely to have aortic arch calcifications (AAC) that were visible on chest radiographs (CRs), a risk indicator of experiencing cardiovascular events, than would matched cohorts who did not have atheromas. Methods. The authors obtained the CRs of 36 female veterans (>= 50 years) who had CCAP and atherogenically risk-matched them to those of 36 women without CCAP. A radiologist evaluated the CRs for AAC. Other study variables included age, ethnicity, body mass index and presence or absence of hypertension, diabetes and dyslipidemia. The authors computed descriptive and bivariate statistics. Results. Women 60 years or older who had evidence of CCAP on their panoramic radiographs were significantly (P =. 022; 95 percent confidence interval, 1.29826.223) more likely to have evidence of AAC on their CRs than were similarly aged women who did not have evidence of CCAP. This association was not evident in women younger than 60 years. Among women who were both younger and older than 60 years, there was no evident association between the presence of CCAP and the severity (on a four point scale [0-3]) of AAC calcification. Conclusion. Prevalence of carotid plaque on panoramic images of women 60 years or older is significantly associated with presence of aortic arch calcifications on CRs. Practical Implications. Panoramic images of women 60 years or older must be evaluated for CCAP, given their association with AAC. Patients with atheromas should be referred to their physicians for further evaluation given the systemic implications. C1 [Friedlander, Arthur H.; El-Saden, Suzie M.; Aghazadehsanai, Nona; Chang, Tina I.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Ronald Reagan Univ Calif Los Angeles, Hosp Dent Serv, Med Ctr, Los Angeles, CA USA. [Friedlander, Arthur H.; Chang, Tina I.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [El-Saden, Suzie M.; Harada, Nancy D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 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 FU Research Facilities Improvement Program grant from the National Center for Research Resources, National Institutes of Health [CO6 RR-14529-01] FX Elements of the study described in this article were conducted in a facility constructed with support from Research Facilities Improvement Program grant CO6 RR-14529-01 from the National Center for Research Resources, National Institutes of Health. NR 37 TC 0 Z9 0 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2014 VL 145 IS 4 BP 345 EP 351 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AE2OG UT WOS:000333812000012 PM 24686967 ER PT J AU McLaughlin, PM Wright, MJ LaRocca, M Nguyen, PT Teng, E Apostolova, LG Ringman, JM Zhou, Y Cummings, JL Woo, E AF McLaughlin, Paula M. Wright, Matthew J. LaRocca, Michael Nguyen, Peter T. Teng, Edmond Apostolova, Liana G. Ringman, John M. Zhou, Yan Cummings, Jeffrey L. Woo, Ellen TI The "Alzheimer's Type" Profile of Semantic Clustering in Amnestic Mild Cognitive Impairment SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Dementia; Memory disorders; Verbal learning; Diagnosis; Disease progression; Memory ID VERBAL-LEARNING TEST; MEMORY IMPAIRMENT; FREE-RECALL; WORKING-MEMORY; DISEASE; PATTERNS; PERFORMANCE; KNOWLEDGE; DEMENTIA; DEFICITS AB Impairments in learning and recall have been well established in amnestic mild cognitive impairment (aMCI). However, a relative dearth of studies has examined the profiles of memory strategy use in persons with aMCI relative to those with Alzheimer's disease (AD). Participants with aMCI, nonamnestic MCI, AD, and healthy older adults were administered the California Verbal Learning Test-II (CVLT-II). Measures of semantic clustering and recall were obtained across learning and delayed recall trials. In addition, we investigated whether deficits in semantic clustering were related to progression from healthy aging to aMCI and from aMCI to AD. The aMCI group displayed similar semantic clustering performance as the AD participants, whereas the AD group showed greater impairments on recall relative to the aMCI participants. Control participants who progressed to aMCI showed reduced semantic clustering at the short delay at baseline compared to individuals who remained diagnostically stable across follow-up visits. These findings show that the ability to engage in an effective memory strategy is compromised in aMCI, before AD has developed, suggesting that disruptions in semantic networks are an early marker of the disease. (JINS, 2014, 20, 1-11) C1 [McLaughlin, Paula M.; Teng, Edmond; Apostolova, Liana G.; Ringman, John M.; Zhou, Yan; Woo, Ellen] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [McLaughlin, Paula M.; Wright, Matthew J.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Wright, Matthew J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Psychiat, Los Angeles, CA USA. [LaRocca, Michael] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Nguyen, Peter T.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cummings, Jeffrey L.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA. RP Woo, E (reprint author), 10911 Weyburn Ave,Ste 200, Los Angeles, CA 90095 USA. EM ewoo@mednet.ucla.edu OI Zhou, Yan/0000-0002-1659-1672 FU National Institutes of Health [NIH P50 AG016570]; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation; Jim Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers at UCLA FX This work was funded by the National Institutes of Health (NIH P50 AG016570), the Alzheimer's Disease Research Centers of California, the Sidell-Kagan Foundation, and the Jim Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers at UCLA. None of the authors have potential conflicts of interest. NR 47 TC 2 Z9 2 U1 5 U2 21 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD APR PY 2014 VL 20 IS 4 BP 402 EP 412 DI 10.1017/S135561771400006X PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA AD9CI UT WOS:000333561900006 PM 24521694 ER PT J AU Singh, R Patel, V Mureithi, MW Naranbhai, V Ramsuran, D Tulsi, S Hiramen, K Werner, L Mlisana, K Altfeld, M Luban, J Kasprowicz, V Dheda, K Karim, SSA Ndung'u, T AF Singh, Ravesh Patel, Vinod Mureithi, Marianne W. Naranbhai, Vivek Ramsuran, Duran Tulsi, Sahil Hiramen, Keshni Werner, Lise Mlisana, Koleka Altfeld, Marcus Luban, Jeremy Kasprowicz, Victoria Dheda, Keertan Karim, Salim S. Abdool Ndung'u, Thumbi TI TRIM5 alpha and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-ALPHA; DISEASE PROGRESSION; CEREBROSPINAL-FLUID; GENE-EXPRESSION; I INTERFERON; LIPID RAFTS; E3 LIGASES; PROTEIN; CELLS AB The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5 alpha and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5 alpha, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P<0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5 alpha than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5 alpha (P = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r = -0.40; P = 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5 alpha and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4(+) lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5 alpha and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo. C1 [Singh, Ravesh; Mureithi, Marianne W.; Ramsuran, Duran; Hiramen, Keshni; Kasprowicz, Victoria; Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV K RITH, Nelson R Mandela Sch Med, Durban, South Africa. [Singh, Ravesh; Mureithi, Marianne W.; Naranbhai, Vivek; Tulsi, Sahil; Hiramen, Keshni; Altfeld, Marcus; Kasprowicz, Victoria; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Pathogenesis Programme, Durban, South Africa. [Patel, Vinod] Univ KwaZulu Natal, Dept Neurol, Durban, South Africa. [Mureithi, Marianne W.; Altfeld, Marcus; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Mureithi, Marianne W.; Altfeld, Marcus; Ndung'u, Thumbi] Harvard Univ, Boston, MA USA. [Naranbhai, Vivek; Tulsi, Sahil; Werner, Lise; Karim, Salim S. Abdool; Ndung'u, Thumbi] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa. [Mlisana, Koleka] Univ KwaZulu Natal Durban, Sch Lab Med & Med Sci, Durban, South Africa. [Mlisana, Koleka] Natl Hlth Lab Serv, Durban, South Africa. [Luban, Jeremy] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. [Luban, Jeremy] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA USA. [Dheda, Keertan] UCL, Dept Infect, London, England. [Dheda, Keertan] Univ Cape Town, Div Pulmonol, Lung Infect & Immun Unit, ZA-7925 Cape Town, South Africa. [Dheda, Keertan] Univ Cape Town, Dept Med, UCT Lung Inst, ZA-7925 Cape Town, South Africa. [Dheda, Keertan] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV K RITH, Nelson R Mandela Sch Med, Durban, South Africa. EM ndungu@ukzn.ac.za FU South African Department of Science and Technology/National Research Foundation Research Chairs Initiative (SARChI); Swiss South Africa Joint Research Programme (SSAJRP); NIDA/NIH [DP1DA034990]; Howard Hughes Medical Institute; Columbia University-Southern African Fogarty AIDS International Training and Research Program (AITRP) through the Fogarty International Center, National Institutes of Health [D43TW000231] FX This study was supported by South African Department of Science and Technology/National Research Foundation Research Chairs Initiative (SARChI) grants to T.N. and K. D., a grant from the Swiss South Africa Joint Research Programme (SSAJRP) to T.N. and J.L., and NIDA/NIH grant DP1DA034990 to J.L. The research of T.N. was supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute. R. S. was supported by the Columbia University-Southern African Fogarty AIDS International Training and Research Program (AITRP) through the Fogarty International Center, National Institutes of Health (grant no. D43TW000231). NR 54 TC 5 Z9 6 U1 1 U2 2 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 APR PY 2014 VL 88 IS 8 BP 4291 EP 4303 DI 10.1128/JVI.03603-13 PG 13 WC Virology SC Virology GA AE0SL UT WOS:000333676400032 PM 24478420 ER PT J AU Hung, JY Horn, D Woodruff, K Prihoda, T LeSaux, C Peters, J Tio, F Abboud-Werner, SL AF Hung, Jaclyn Y. Horn, Diane Woodruff, Kathleen Prihoda, Thomas LeSaux, Claude Peters, Jay Tio, Fermin Abboud-Werner, Sherry L. TI Colony-stimulating factor 1 potentiates lung cancer bone metastasis SO LABORATORY INVESTIGATION LA English DT Article DE bone; cancer; CSF1; lung; metastasis ID FACTOR CSF-1; CELL-LINES; TUMOR PROGRESSION; STEM-CELLS; RECEPTOR; MODELS; GROWTH; EXPRESSION; OSTEOCLASTS; XENOGRAFTS AB Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that mediates osteolysis in metastatic tumors. Patients with lung cancer have increased CSF1 in serum and high levels are associated with poor survival. Adenocarcinomas metastasize rapidly and many patients suffer from bone metastasis. Lung cancer stem-like cells sustain tumor growth and potentiate metastasis. The purpose of this study was to determine the role of CSF1 in lung cancer bone metastasis and whether inhibition of CSF1 ameliorates the disease. Human lung adenocarcinoma A549 cells were examined in vitro for CSF1/CSF1R. A549-luc cells were injected intracardiac in NOD/SCID mice and metastasis was assessed. To determine the effect of CSF1 knockdown (KD) in A549 cells on bone metastasis, cells were stably transfected with a retroviral vector containing short-hairpin CSF1 (KD) or empty vector (CT). Results showed that A549 cells express CSF1/CSF1R; CSF1 increased their proliferation and invasion, whereas soluble CSF1R inhibited invasion. Mice injected with A549-luc cells showed osteolytic bone lesions 3.5 weeks after injection and lesions increased over 5 weeks. Tumors recapitulated adenocarcinoma morphology and showed osteoclasts along the tumor/bone interface, trabecular, and cortical bone loss. Analyses of KD cells showed decreased CSF1 protein levels, reduced colony formation in soft agar assay, and decreased fraction of stem-like cells. In CSF1KD mice, the incidence of tumor metastasis was similar to controls, although fewer CSF1KD mice had metastasis in both hind limbs. KD tumors showed reduced CSF1 expression, Ki-67 + cells, and osteoclasts. Importantly, there was a low incidence of large tumors >0.1 mm(2) in CSF1KD mice compared with control mice (10% vs 62.5%). This study established a lung osteolytic bone metastasis model that resembles human disease and suggests that CSF1 is a key determinant of cancer stem cell survival and tumor growth. Results may lead to novel strategies to inhibit CSF1 in lung cancer and improve management of bone metastasis. C1 [Hung, Jaclyn Y.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Dept Pediat, Div Hematol & Oncol, San Antonio, TX 78229 USA. [Horn, Diane; Woodruff, Kathleen; Prihoda, Thomas; Tio, Fermin; Abboud-Werner, Sherry L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Horn, Diane; Woodruff, Kathleen; Prihoda, Thomas; Peters, Jay; Tio, Fermin; Abboud-Werner, Sherry L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [LeSaux, Claude] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Peters, Jay] Univ Texas Hlth Sci Ctr San Antonio, Dept Pulm Med, San Antonio, TX 78229 USA. RP Abboud-Werner, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboudwerner@uthscsa.edu FU Biomedical Research Foundation of South Texas FX We thank Roberto Fajardo, PhD, and James Schmitz at RAYO, the Daniel W Carlisle Center for Bone and Mineral Imaging at UTHSCSA for their assistance in analyzing the skeletal tissues. We also thank the Flow Cytometry Shared Resource Facility at UTHSCSA, which is supported by NIH-NCI P30CA54174 (CTRC at UTHSCSA) for fluorescence-activated cell-sorting analysis. This work was supported by the Biomedical Research Foundation of South Texas (SA-W, FT). NR 43 TC 7 Z9 8 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD APR PY 2014 VL 94 IS 4 BP 371 EP 381 DI 10.1038/labinvest.2014.1 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA AD9HB UT WOS:000333574900002 PM 24468794 ER PT J AU Ganjoo, K Hong, FX Horning, SJ Gascoyne, RD Natkunam, Y Swinnen, LJ Habermann, TM Kahl, BS Advani, RH AF Ganjoo, Kristen Hong, Fangxin Horning, Sandra J. Gascoyne, Randy D. Natkunam, Yasodha Swinnen, Lode J. Habermann, Thomas M. Kahl, Brad S. Advani, Ranjana H. TI Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative Oncology Group study (E2404) SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoma and Hodgkin disease; chemotherapeutic approaches; immunotherapeutic approaches ID NON-HODGKIN-LYMPHOMA; ANGIOGENIC GROWTH-FACTORS; PHASE-2 TRIAL; EXPRESSION; CHOP; CHEMOTHERAPY; INSTITUTION; PROGNOSIS; RITUXIMAB; CANCER AB Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Forty-six patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median follow-up of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia (n = 8), anemia (n = 3), thrombocytopenia (n = 5), congestive heart failure (n = 4), venous thrombosis (n = 3), gastrointestinal hemorrhage/perforation (n = 2), infection (n = 8) and fatigue (n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor. C1 [Ganjoo, Kristen; Natkunam, Yasodha; Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Swinnen, Lode J.] Johns Hopkins Univ, Baltimore, MD USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. RP Ganjoo, K (reprint author), Stanford Univ, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM kganjoo@stanford.edu FU NCI NIH HHS [U10 CA066636, P30 CA014520, P30 CA124435, U10 CA013650, U10 CA016116, U10 CA021076, U10 CA021115, U10 CA023318, U10 CA180794, U10 CA180799, U10 CA180820, U24 CA114737] NR 31 TC 13 Z9 14 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2014 VL 55 IS 4 BP 768 EP 772 DI 10.3109/10428194.2013.816700 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AD9JZ UT WOS:000333582600008 PM 23786456 ER PT J AU Houldsworth, J Guttapalli, A Thodima, V Yan, XJ Mendiratta, G Zielonka, T Nanjangud, G Chen, WY Patil, S Mato, A Brown, JR Rai, K Chiorazzi, N Chaganti, RSK AF Houldsworth, Jane Guttapalli, Asha Thodima, Venkata Yan, Xiao Jie Mendiratta, Geetu Zielonka, Tania Nanjangud, Gouri Chen, Weiyi Patil, Sujata Mato, Anthony Brown, Jennifer R. Rai, Kanti Chiorazzi, Nicholas Chaganti, R. S. K. TI Genomic imbalance defines three prognostic groups for risk stratification of patients with chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoid leukemia; molecular genetics; prognostication ID IN-SITU HYBRIDIZATION; MICROARRAY ANALYSIS; CLONAL EVOLUTION; 13Q14 DELETION; FOLLOW-UP; MUTATIONS; CLL; SURVIVAL; NUMBER; NOTCH1 AB Array comparative genomic hybridization (aCGH) has yet to be fully leveraged in a prognostic setting in chronic lymphocytic leukemia (CLL). Genomic imbalance was assessed in 288 CLL specimens using a targeted array. Based on 20 aberrations in a hierarchical manner, all 228 treatment-naive specimens were classified into a group with poor outcome (20.6%) exhibiting at least one aberration that was univariately associated with adverse outcome (gain: 2p, 3q, 8q, 17q, loss: 7q, 8p, 11q, 17p, 18p), good outcome (32.5%) showing 13q14 loss without any of the other 10 aberrations (gain: 1p, 7p, 12, 18p, 18q, 19, loss: 4p, 5p, 6q, 7p) or intermediate outcome (remainder). The three groups were significantly separated with respect to time to first treatment and overall survival (p < 0.001), and validation of the stratification scheme was performed in two independent datasets. Gain of 3q and 8q, and 17p loss were determined to be independent unfavorable prognostic biomarkers. TP53, NOTCH1 and SF3B1 mutations correlated with the presence of one poor outcome aCGH marker, at a considerably higher frequency than when only considering poor risk aberrations routinely detected by fluorescence in situ hybridization (FISH). These data support genomic imbalance evaluation in CLL by aCGH to assist in risk stratification. C1 [Houldsworth, Jane; Guttapalli, Asha; Thodima, Venkata; Mendiratta, Geetu; Chen, Weiyi] Canc Genet Inc, Rutherford, NJ 07070 USA. [Yan, Xiao Jie; Rai, Kanti; Chiorazzi, Nicholas] Feinstein Inst Med Res, Manhasset, NY USA. [Zielonka, Tania; Mato, Anthony] Hackensack Univ, Lymphoma Div, John Theurer Canc Ctr, Med Ctr, Hackensack, NJ USA. [Nanjangud, Gouri; Chaganti, R. S. K.] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. [Patil, Sujata] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Chaganti, R. S. K.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, Jennifer R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Houldsworth, J (reprint author), Canc Genet Inc, 201 Route 17 North, Rutherford, NJ 07070 USA. EM jhouldsworth@cancergenetics.com NR 43 TC 8 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2014 VL 55 IS 4 BP 920 EP 928 DI 10.3109/10428194.2013.845882 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA AD9JZ UT WOS:000333582600029 PM 24047479 ER PT J AU Hasegawa, K Brown, DFM Tsugawa, Y Camargo, CA AF Hasegawa, Kohei Brown, David F. M. Tsugawa, Yusuke Camargo, Carlos A., Jr. TI Epidemiology of Emergency Department Visits for Opioid Overdose: A Population-Based Study SO MAYO CLINIC PROCEEDINGS LA English DT Article ID UNITED-STATES; CHRONIC PAIN; DRUG OVERDOSE; HOSPITALIZATIONS; DEATHS; ASTHMA; PREDICTORS; PATTERNS; OUTCOMES; THERAPY AB Objectives: To evaluate the rate of emergency department (ED) visits for opioid overdose and to examine whether frequent ED visits for opioid overdose are associated with more hospitalizations, near-fatal events, and health care spending. Patients and Methods: Retrospective cohort study of adults with at least 1 ED visit for opioid overdose between January 1, 2010, and December 31, 2011, derived from population-based data of State Emergency Department Databases and State Inpatient Databases for 2 large and diverse states: California and Florida. Main outcome measures were hospitalizations for opioid overdose, near-fatal events (overdose involving mechanical ventilation), and hospital charges during the year after the first ED visit. Results: The analytic cohort comprised 19,831 unique patients with 21,609 ED visits for opioid overdose. During a 1-year period, 7% (95% CI, 7%-7%; n = 1389 patients) of the patients had frequent (2 or more) ED visits, accounting for 15% (95% CI, 14%-15%; n = 3167) of all opioid overdose ED visits. Middle age, male sex, public insurance, lower household income, and comorbidities (such as chronic pulmonary disease and neurological diseases) were associated with frequent ED visits (all P < .01). Overall, 53% (95% CI, 52%-54%; n = 11,412) of the ED visits for opioid overdose resulted in hospitalizations; patients with frequent ED visits for opioid overdose had a higher likelihood of hospitalization (adjusted odds ratio, 3.98; 95% CI, 3.38-4.69). In addition, 10.0% (95% CI, 10%-10%; n = 2161) of the ED visits led to near-fatal events; patients with frequent ED visits had a higher likelihood of a near-fatal event (adjusted odds ratio, 2.27; 95% CI, 1.96-2.66). Total charges in Florida were $ 208 million (95% CI, $200-$219 million). Conclusion: In this population-based cohort, we found that frequent ED visits for opioid overdose were associated with a higher likelihood of future hospitalizations and near-fatal events. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Hasegawa, Kohei; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Tsugawa, Yusuke] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. RP Hasegawa, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Eleanor and Miles Shore Fellowship Program (Boston, MA); Honjo International Scholarship Foundation (Tokyo, Japan) FX Dr Hasegawa was supported, in part, by Eleanor and Miles Shore Fellowship Program (Boston, MA). Dr Tsugawa was supported, in part, by Honjo International Scholarship Foundation (Tokyo, Japan). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication. NR 36 TC 20 Z9 20 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2014 VL 89 IS 4 BP 462 EP 471 DI 10.1016/j.mayocp.2013.12.008 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AD8PS UT WOS:000333528700011 PM 24629443 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Physician-Poet William Carlos Williams-"No Ideas But In Things" SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2014 VL 89 IS 4 BP E35 EP E36 DI 10.1016/j.mayocp.2013.04.035 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AD8PS UT WOS:000333528700002 PM 24684882 ER PT J AU Liang, SH Yokell, DL Jackson, RN Rice, PA Callahan, R Johnson, KA Alagille, D Tamagnan, G Collier, TL Vasdev, N AF Liang, Steven H. Yokell, Daniel L. Jackson, Raul N. Rice, Peter A. Callahan, Ronald Johnson, Keith A. Alagille, David Tamagnan, Gilles Collier, Thomas Lee Vasdev, Neil TI Microfluidic continuous-flow radiosynthesis of [F-18]FPEB suitable for human PET imaging SO MEDCHEMCOMM LA English DT Article ID RECEPTOR 5 MGLUR5; TRACER; BRAIN; METABOTROPIC-GLUTAMATE-RECEPTOR-SUBTYPE-5; RADIOTRACERS; MODULATION; REACTORS AB The synthesis of fluorine-18 labeled 3-fluoro-5-[(pyridin-3-yl) ethynyl] benzonitrile ([F-18] FPEB) for imaging metabotropic glutamate receptor subtype type 5 (mGluR5) was achieved with a commercial continuousflow microfluidics device. This work represents the first positron emission tomography (PET) radiopharmaceutical that is suitable for human use with this technology. We also describe a validated synthesis of [18F] FPEB with a commercial reactor-based system. C1 [Liang, Steven H.; Callahan, Ronald; Johnson, Keith A.; Collier, Thomas Lee; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Liang, Steven H.; Yokell, Daniel L.; Jackson, Raul N.; Rice, Peter A.; Callahan, Ronald; Johnson, Keith A.; Collier, Thomas Lee; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Alagille, David; Tamagnan, Gilles] Mol Neuroimaging LLC, New Haven, CT 06510 USA. [Alagille, David; Tamagnan, Gilles] Inst Neurodegenerat Disorders, New Haven, CT 06510 USA. [Collier, Thomas Lee] Advion Inc, Ithaca, NY 14850 USA. RP Collier, TL (reprint author), Harvard Univ, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM collierl@advion.com; vasdev.neil@mgh.harvard.edu FU Alzheimer's Drug Discovery Foundation; Advion, Inc FX We thank the Alzheimer's Drug Discovery Foundation and Advion, Inc for generously providing funding and/or equipment for this research. We thank Kelvin Hammond for helpful discussions and David F. Lee Jr and Brian Bradshaw for isotope production and support. We thank Hogger & Co. for graphical abstract design. NR 24 TC 11 Z9 11 U1 0 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PD APR PY 2014 VL 5 IS 4 BP 432 EP 435 DI 10.1039/c3md00335c PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AD9JA UT WOS:000333580000002 PM 25431646 ER PT J AU Li, M Luo, XJ Rietschel, M Lewis, CM Mattheisen, M Muller-Myhsok, B Jamain, S Leboyer, M Landen, M Thompson, PM Cichon, S Nothen, MM Schulze, TG Sullivan, PF Bergen, SE Donohoe, G Morris, DW Hargreaves, A Gill, M Corvin, A Hultman, C Toga, AW Shi, L Lin, Q Shi, H Gan, L Meyer-Lindenberg, A Czamara, D Henry, C Etain, B Bis, JC Ikram, MA Fornage, M Debette, S Launer, LJ Seshadri, S Erk, S Walter, H Heinz, A Bellivier, F Stein, JL Medland, SE Vasquez, AA Hibar, DP Franke, B Martin, NG Wright, MJ Su, B AF Li, M. Luo, X-j Rietschel, M. Lewis, C. M. Mattheisen, M. Mueller-Myhsok, B. Jamain, S. Leboyer, M. Landen, M. Thompson, P. M. Cichon, S. Noethen, M. M. Schulze, T. G. Sullivan, P. F. Bergen, S. E. Donohoe, G. Morris, D. W. Hargreaves, A. Gill, M. Corvin, A. Hultman, C. Toga, A. W. Shi, L. Lin, Q. Shi, H. Gan, L. Meyer-Lindenberg, A. Czamara, D. Henry, C. Etain, B. Bis, J. C. Ikram, M. A. Fornage, M. Debette, S. Launer, L. J. Seshadri, S. Erk, S. Walter, H. Heinz, A. Bellivier, F. Stein, J. L. Medland, S. E. Vasquez, A. Arias Hibar, D. P. Franke, B. Martin, N. G. Wright, M. J. Su, B. CA MooDS Bipolar Consortium Swedish Bipolar Study Group Alzheimer's Dis Neuroimaging ENIGMA Consortium CHARGE Consortium TI Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility SO MOLECULAR PSYCHIATRY LA English DT Article DE association; bipolar disorder; CREB1; gene expression; intermediate phenotype; natural selection ID GENOME-WIDE ASSOCIATION; MAJOR DEPRESSIVE DISORDER; HUMAN PREFRONTAL CORTEX; COMMON VARIANTS; STATISTICAL TESTS; SPATIAL LOCATION; SCHIZOPHRENIA; POPULATION; TRANSCRIPTION; LANDSCAPE AB Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P = 6.32 x 10(-5), odds ratio (OR) = 1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P < 0.005) and the prefrontal cortex (P < 1.0 x 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations. C1 [Li, M.; Shi, L.; Lin, Q.; Shi, H.; Su, B.] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China. [Li, M.; Gan, L.] Univ Chinese Acad Sci, Beijing, Peoples R China. [Luo, X-j] Univ Rochester, Flaum Eye Inst, Rochester, NY USA. [Rietschel, M.; Schulze, T. G.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany. [Rietschel, M.; Walter, H.] Univ Bonn, Dept Psychiat, Bonn, Germany. [Lewis, C. M.] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London WC2R 2LS, England. [Mattheisen, M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Mattheisen, M.] Harvard Univ, Sch Med, Boston, MA USA. [Mueller-Myhsok, B.; Czamara, D.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Jamain, S.; Leboyer, M.; Henry, C.; Etain, B.; Bellivier, F.] Hop Henri Mondor, INSERM, U955, IMRB, F-94010 Creteil, France. [Jamain, S.; Leboyer, M.; Henry, C.; Etain, B.; Bellivier, F.] Fdn Fondamental, Creteil, France. [Leboyer, M.; Henry, C.; Etain, B.] Hop H Mondor A Chenevier, AP HP, Creteil, France. [Leboyer, M.; Henry, C.] Univ Paris Est, Fac Med, Creteil, France. [Landen, M.] Gothenburg Univ, Sahlgrenska Acad, Sect Psychiat & Neurochem, Gothenburg, Sweden. [Landen, M.; Hultman, C.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Thompson, P. M.; Toga, A. W.; Stein, J. L.; Hibar, D. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Imaging Genet Ctr,Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, S.; Noethen, M. M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, S.; Noethen, M. M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Noethen, M. M.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Schulze, T. G.] Univ Gottingen, Sect Psychiat Genet, Dept Psychiat & Psychotherapy, Univ Med Ctr, D-37073 Gottingen, Germany. [Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, P. F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, P. F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Bergen, S. E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Bergen, S. E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Neuropsychiat Genet Grp, Dublin 2, Ireland. [Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Dept Psychiat, Inst Mol Med, Dublin 2, Ireland. [Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Inst Neurosci, Dublin 2, Ireland. [Meyer-Lindenberg, A.] Heidelberg Univ, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany. [Bis, J. C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Ikram, M. A.] Erasmus MC Univ Med Ctr, Dept Radiol & Epidemiol, Rotterdam, Netherlands. [Ikram, M. A.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. [Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Debette, S.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Debette, S.] INSERM, U708, Paris, France. [Debette, S.] Univ Versailles St Quentin En Yvelines, Dept Epidemiol, Paris, France. [Launer, L. J.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Erk, S.; Walter, H.; Heinz, A.] Charite, Dept Psychiat, D-13353 Berlin, Germany. [Erk, S.; Walter, H.] Charite, Div Mind & Brain Res, D-13353 Berlin, Germany. [Bellivier, F.] Hop St Louis Lariboisiere F Widal, AP HP, Serv Univ Psychiat, Paris, France. [Bellivier, F.] Univ Paris 07, Fac Med, Paris, France. [Stein, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA. [Medland, S. E.; Martin, N. G.; Wright, M. J.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia. [Medland, S. E.] Queensland Inst Med Res, Quantitat Genet Lab, Brisbane, Qld 4006, Australia. [Medland, S. E.] Broad Inst Harvard & MIT, Boston, MA USA. [Vasquez, A. Arias; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Vasquez, A. Arias; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. RP Su, B (reprint author), Chinese Acad Sci, Kunming Inst Zool, 32 East Jiao Chang Rd, Kunming 650223, Peoples R China. EM sub@mail.kiz.ac.cn RI Lewis, Cathryn/A-5225-2010; Franke, Barbara/D-4836-2009; Medland, Sarah/C-7630-2013; Walter, Henrik/O-2612-2013; Li, Ming/K-7455-2013; Mattheisen, Manuel/B-4949-2012; Wright, Margaret/A-4560-2016; Arias Vasquez, Alejandro/E-4762-2012; BELLIVIER, FRANK/H-5197-2012; OI Corvin, Aiden/0000-0001-6717-4089; Morris, Derek/0000-0002-3413-570X; Landen, Mikael/0000-0002-4496-6451; Gill, Michael/0000-0003-0206-5337; Ikram, Mohammad Arfan/0000-0003-0372-8585; Stein, Jason/0000-0003-4829-0513; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Jamain, Stephane/0000-0002-4321-4100; Lewis, Cathryn/0000-0002-8249-8476; Seshadri, Sudha/0000-0001-6135-2622; Franke, Barbara/0000-0003-4375-6572; Medland, Sarah/0000-0003-1382-380X; Li, Ming/0000-0002-8197-6552; Mattheisen, Manuel/0000-0002-8442-493X; Wright, Margaret/0000-0001-7133-4970; Arias Vasquez, Alejandro/0000-0002-4786-0169; Bergen, Sarah/0000-0002-5888-0034; Etain, Bruno/0000-0002-5377-1488; Martin, Nicholas/0000-0003-4069-8020 FU National 973 project of China [2011CBA00401]; National Natural Science Foundation of China [U1202225, 31130051, 31071101]; German Federal Ministry of Education and Research (BMBF); National Genome Research Network (NGFN); Integrated Genome Research Network (IG) MooDS [01GS08144]; MMR [01GS08147]; TGS FX We acknowledge the Bipolar Disorder Working Group of Psychiatric GWAS Consortium for their efforts. We are deeply grateful for Stacy Steinberg, Hreinn Stefansson, Kari Stefansson (deCODE genetics, Reykjavik, Iceland) and Engilbert Sigurdsson (Landspitali University Hospital, Reykjavi ' k, Iceland) for their results in the Icelandic samples, Angelika Erhardt (Max Planck Institute of Psychiatry, Kraepelinstr, Munich, Germany) for her assistance in this study, Andrew Willden (Kunming Institute of Zoology, China) for the language editing of the manuscript. We wish to thank Xiaosen Guo, Shanshan Dong and Jun Wang (Shenzhen Key Laboratory of Transomics Biotechnologies, BGI-Shenzhen, China) for providing sequence data of CREB1 from the 1000-Human-Genome project. We would like to thank Daniel R. Weinberger (Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, USA) for his very helpful review of the manuscript. This work was supported by grants from the National 973 project of China (2011CBA00401), the National Natural Science Foundation of China (U1202225, 31130051 and 31071101), the German Federal Ministry of Education and Research (BMBF), the National Genome Research Network (NGFN), and the Integrated Genome Research Network (IG) MooDS (grant 01GS08144 to SC and MMR, grant 01GS08147 to MR and TGS). NR 75 TC 23 Z9 23 U1 8 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2014 VL 19 IS 4 BP 452 EP 461 DI 10.1038/mp.2013.37 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AD6ZB UT WOS:000333409100011 PM 23568192 ER PT J AU Shrestha, A Hamblin, MR Kishen, A AF Shrestha, Annie Hamblin, Michael R. Kishen, Anil TI Photoactivated rose bengal functionalized chitosan nanoparticles produce antibacterial/biofilm activity and stabilize dentin-collagen SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Functionalized nanoparticles; Chitosan; Biofilms; Collagen; Dentin; Photodynamic therapy ID CROSS-LINKING; PHOTODYNAMIC THERAPY; LETHAL PHOTOSENSITIZATION; ANTIMICROBIAL AGENT; BACTERIA; TISSUE; PERIODONTITIS; DISINFECTION; ANTIBIOFILM; MEMBRANES AB Treatment of infected teeth presents two major challenges: persistence of the bacterial-biofilm within root canals after treatment and compromised structural integrity of the dentin hard-tissue. In this study bioactive polymeric chitosan nanoparticles functionalized with rose-bengal, CSRBnp were developed to produce antibiofilm effects as well as stabilize structural-integrity by photocrosslinking dentin-collagen. CSRBnp were less toxic to fibroblasts and had significant antibacterial activity even in the presence of bovine serum albumin. CSRBnp exerted antibacterial mechanism by adhering to bacterial cell surface, permeabilizing the membrane and lysing the cells subsequent to photodynamic treatment. Photoactivated CSRBnp resulted in reduced viability of Enterococcus faecalis biofilms and disruption of biofilm structure. Incorporation of CSRBnp and photocrosslinking significantly improved resistance to degradation and mechanical strength of dentin-collagen (P < 0.05). The functionalized chitosan nanoparticles provided a single-step treatment of infected root dentin by combining the properties of chitosan and that of photosensitizer to eliminate bacterial-biofilms and stabilize dentin-matrix. From the Clinical Editor: In this study, bioactive polymeric chitosan nanoparticles functionalized with rose-bengal (a photosensitizer), CSRBnp were developed to produce antibiofilm effects as well as stabilize structural-integrity of dental root dentin by photocrosslinking dentin-collagen, leading to efficient elimination of bacterial-biofilms and stabilization of dentin-matrix. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shrestha, Annie; Kishen, Anil] Univ Toronto, Fac Dent, Discipline Endodont, Toronto, ON M5G 1G6, Canada. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kishen, A (reprint author), Univ Toronto, Fac Dent, Discipline Endodont, 124 Edward St, Toronto, ON M5G 1G6, Canada. EM anil.kishen@utoronto.ca OI Hamblin, Michael/0000-0001-6431-4605 FU University of Toronto; CIHR Training Fellowship [TGF-53877]; US National Institutes of Health [R01AI50875] FX This work is funded by the University of Toronto and CIHR Training Fellowship (TGF-53877). MRH was funded by the US National Institutes of Health (R01AI50875). NR 50 TC 25 Z9 25 U1 5 U2 53 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD APR PY 2014 VL 10 IS 3 BP 491 EP 501 DI 10.1016/j.nano.2013.10.010 PG 11 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA AE2OH UT WOS:000333812100001 PM 24200522 ER PT J AU Ghazani, AA Pectasides, M Sharma, A Castro, CM Mino-Kenudson, M Lee, H Shepard, JAO Weissleder, R AF Ghazani, Arezou A. Pectasides, Melina Sharma, Amita Castro, Cesar M. Mino-Kenudson, Mari Lee, Hakho Shepard, Jo-Anne O. Weissleder, Ralph TI Molecular characterization of scant lung tumor cells using iron-oxide nanoparticles and micro-nuclear magnetic resonance SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Bioorthogonal click chemistry; Circulating tumor cell; mu NMR; Iron-oxide nanoparticles; Point of care diagnosis ID PLEURAL EFFUSION; RAPID DETECTION; CANCER-PATIENTS; NEEDLE-BIOPSY; DIAGNOSIS; PULMONARY; SYSTEM; CARCINOMA; NAPSIN; TOOL AB Advances in nanotechnology and microfluidics are enabling the analysis of small amounts of human cells. We tested whether recently developed micro-nuclear magnetic resonance (mu NMR) technology could be leveraged for diagnosing pulmonary malignancy using fine needle aspirate (FNA) of primary lesions and/or peripheral blood samples. We enrolled a cohort of 35 patients referred for CT biopsy of primary pulmonary nodules, liver or adrenal masses and concurrently obtained FNA and peripheral blood samples. FNA sampling yielded sufficient material for mu NMR analysis in 91% of cases and had a sensitivity and specificity of 91.6% and 100% respectively. Interestingly, among blood samples with positive circulating tumor cells (CTC), mu NMR analysis of each patient's peripheral blood led to similar diagnosis (malignant vs benign) and differential diagnosis (lung malignancy subtype) in 100% and 90% (18/20) of samples, respectively. mu NMR appears to be a valuable, non-invasive adjunct in the diagnosis of lung cancer. From the Clinical Editor: The authors of this study established that recently developed micro-nuclear magnetic resonance (mu NMR) technology can be leveraged for diagnosing pulmonary malignancy using fine needle aspirate (FNA) of primary lesions and/or peripheral blood samples derived from 35 patients, suggesting practical clinical applicability of this technique. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ghazani, Arezou A.; Pectasides, Melina; Castro, Cesar M.; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pectasides, Melina; Sharma, Amita; Shepard, Jo-Anne O.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Shepard, JAO (reprint author), Massachusetts Gen Hosp, Div Chest Radiol, Boston, MA 02114 USA. EM JSHEPARD@PARTNERS.ORG; rweissleder@mgh.harvard.edu FU DOD [W81XWH-11-1-0706]; [K12CA087723] FX This work was funded in part by K12CA087723 and DOD W81XWH-11-1-0706. NR 35 TC 15 Z9 15 U1 5 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD APR PY 2014 VL 10 IS 3 BP 661 EP 668 DI 10.1016/j.nano.2013.10.008 PG 8 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA AE2OH UT WOS:000333812100018 PM 24200523 ER PT J AU Michor, F Weaver, VM AF Michor, Franziska Weaver, Valerie M. TI Understanding tissue context influences on intratumour heterogeneity SO NATURE CELL BIOLOGY LA English DT Editorial Material ID TUMOR HETEROGENEITY; CANCER; METASTASIS; DIVERSITY; EVOLUTION; INVASION; MATRIX; CELLS AB Although human cancers exhibit intratumour heterogeneity, the influence of the tumour environment on this property is unclear. Single basal-like mammary epithelial cells are now shown to engage a dynamic TGFBR3-JUND signalling circuit in an extracellular-matrix-dependent manner. Cell transition between the distinct gene expression states underlying this circuit alters their properties and may modulate their propensity to malignancy. C1 [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Ctr Bioengn & Tissue Regenerat, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Surg, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Anat, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Bioengn, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Therapeut, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu; Valerie.Weaver@ucsfmedctr.org FU NCI NIH HHS [U54 CA143798] NR 13 TC 5 Z9 5 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2014 VL 16 IS 4 BP 301 EP 302 DI 10.1038/ncb2942 PG 2 WC Cell Biology SC Cell Biology GA AD9AM UT WOS:000333556900002 PM 24691256 ER PT J AU Li, JF Zhang, DD Sheen, J AF Li, Jian-Feng Zhang, Dandan Sheen, Jen TI Epitope-tagged protein-based artificial miRNA screens for optimized gene silencing in plants SO NATURE PROTOCOLS LA English DT Article ID TRANSIENT EXPRESSION SYSTEM; ARABIDOPSIS-THALIANA; NICOTIANA-BENTHAMIANA; TARGETED MUTAGENESIS; CHLAMYDOMONAS-REINHARDTII; ALEURONE PROTOPLASTS; BIOTIC STRESSES; SMALL RNAS; MICRORNAS; RESISTANCE AB Artificial miRNA (amiRNA) technology offers highly specific gene silencing in diverse plant species. The principal challenge in amiRNA application is to select potent amiRNAs from hundreds of bioinformatically designed candidates to enable maximal target gene silencing at the protein level. To address this issue, we developed the epitope-tagged protein-based amiRNA (ETPamir) screens, in which single or multiple potential target genes encoding epitope-tagged proteins are constitutively or inducibly coexpressed with individual amiRNA candidates in plant protoplasts. Accumulation of tagged proteins, detected by immunoblotting with commercial tag antibodies, inversely and quantitatively reflects amiRNA efficacy in vivo. The core procedure, from protoplast isolation to identification of optimal amiRNA, can be completed in 2-3 d. The ETPamir screens circumvent the limited availability of plant antibodies and the complexity of plant amiRNA silencing at target mRNA and/or protein levels. The method can be extended to verify predicted target genes for endogenous plant miRNAs. C1 [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Li, JF (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM jli@molbio.mgh.harvard.edu FU Massachusetts General Hospital Executive Committee on Research Postdoctoral Fellowship; US National Science Foundation [IOS-0843244]; US National Institutes of Health [R01 GM60493, R01 GM70567] FX We thank the Weigel laboratory for developing the versatile WMD platform and members in the Sheen laboratory for their efforts to test and improve the ETPamir screens. This work has been supported by a Massachusetts General Hospital Executive Committee on Research Postdoctoral Fellowship for Medical Discovery to J.-F.L. and by grants from the US National Science Foundation (grant no. IOS-0843244) and the US National Institutes of Health (grant nos. R01 GM60493 and R01 GM70567) to J.S. NR 76 TC 9 Z9 9 U1 4 U2 30 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 APR PY 2014 VL 9 IS 4 BP 939 EP 949 DI 10.1038/nprot.2014.061 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AE1TE UT WOS:000333752100015 PM 24675734 ER PT J AU Stanford, FC Taveras, EM AF Stanford, Fatima Cody Taveras, Elsie M. TI The Massachusetts School-Based Body Mass Index Experiment-Gleaning Implementation Lessons for Future Childhood Obesity Reduction Efforts SO OBESITY LA English DT Article AB In 2009, Massachusetts (MA) Department of Public Health (DPH) implemented new regulations that required public schools in the state to measure height and weight, determine body mass index (BMI), and notify parents of children in grades 1, 4, 7, and 10 of their child's weight status. After 3 years of implementation, MA DPH recently abandoned parental notification of school-based BMI screening results citing several concerns including flaws in the ability to monitor the way that the BMI screening results were communicated from the schools to parents/guardians and some reports of breaches in confidentiality of students' measurements. In this article, we review implementation issues that could have impacted the success of the MA DPH regulation as well as lessons to be learned and potentially applied to future childhood obesity efforts. C1 [Stanford, Fatima Cody] Massachusetts Gen Hosp, Gastrointestinal Unit, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Stanford, Fatima Cody] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Stanford, Fatima Cody; Taveras, Elsie M.] Harvard Univ, Sch Med, Boston, MA USA. [Taveras, Elsie M.] Massachusetts Gen Hosp Children, Div Gen Acad Pediat, Boston, MA USA. RP Stanford, FC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Obes Metab & Nutr Inst, Boston, MA 02114 USA. EM fstanford@mgh.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X NR 6 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD APR PY 2014 VL 22 IS 4 BP 973 EP 975 DI 10.1002/oby.20707 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AE0OY UT WOS:000333666800001 PM 24458805 ER PT J AU Beech, RD Leffert, JJ Lin, A Sylvia, LG Umlauf, S Mane, S Zhao, H Bowden, C Calabrese, JR Friedman, ES Ketter, TA Iosifescu, DV Reilly-Harrington, NA Ostacher, M Thase, ME Nierenberg, A AF Beech, R. D. Leffert, J. J. Lin, A. Sylvia, L. G. Umlauf, S. Mane, S. Zhao, H. Bowden, C. Calabrese, J. R. Friedman, E. S. Ketter, T. A. Iosifescu, D. V. Reilly-Harrington, N. A. Ostacher, M. Thase, M. E. Nierenberg, A. TI Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS) SO PHARMACOGENOMICS JOURNAL LA English DT Article DE BCL2L1; bipolar disorder; gene expression; lithium-response; microarray ID MANIC-DEPRESSIVE ILLNESS; AMINO-ACID TRANSPORTER; RADIATION-INDUCED APOPTOSIS; NEUROTROPHIC FACTOR GENE; BIPOLAR DISORDER; PHOSPHOLIPASE C-GAMMA-1; PROPHYLACTIC LITHIUM; GLYCINE TRANSPORTERS; SIGNALING PATHWAYS; MOOD STABILIZERS AB This study was designed to identify genes whose expression in peripheral blood may serve as early markers for treatment response to lithium (Li) in patients with bipolar disorder. Although changes in peripheral blood gene-expression may not relate directly to mood symptoms, differences in treatment response at the biochemical level may underlie some of the heterogeneity in clinical response to Li. Subjects were randomized to treatment with (n= 28) or without (n= 32) Li. Peripheral blood gene-expression was measured before and 1month after treatment initiation, and treatment response was assessed after 6 months. In subjects treated with Li, 62 genes were differentially regulated in treatment responders and non-responders. Of these, BCL2L1 showed the greatest difference between Li responders and non-responders. These changes were specific to Li responders (n= 9), and were not seen in Li non-responders or patients treated without Li, suggesting that they may have specific roles in treatment response to Li. C1 [Beech, R. D.; Leffert, J. J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Lin, A.] Yale Univ, Sch Med, Keck Fdn Biotechnol Biostat Resource, New Haven, CT 06519 USA. [Sylvia, L. G.; Reilly-Harrington, N. A.; Nierenberg, A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Umlauf, S.; Mane, S.] Yale Univ, Sch Med, Ctr Genome Anal, New Haven, CT 06519 USA. [Zhao, H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06519 USA. [Bowden, C.] Univ Texas Hlth Sci, Dept Psychiat, San Antonio, TX USA. [Bowden, C.] Univ Texas Hlth Sci, Dept Pharmacol, San Antonio, TX USA. [Calabrese, J. R.] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Friedman, E. S.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Ketter, T. A.; Ostacher, M.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Iosifescu, D. V.] Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. [Iosifescu, D. V.] Mt Sinai Med Ctr, Dept Neurosci, New York, NY 10029 USA. [Thase, M. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Beech, RD (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St,4th Floor, New Haven, CT 06519 USA. EM robert.beech@yale.edu OI Ostacher, Michael/0000-0003-0353-7535 FU California Bipolar Foundation; National Institute of Mental Health [NO1MH80001]; National Library of Medicine's ClinicalTrials.gov website [NCT00667745]; Donaghue Foundation [DF08-009] FX This work was supported by grants from the California Bipolar Foundation (RDB) and Donaghue Foundation Grant number DF08-009 (RDB). LiTMUS was sponsored by National Institute of Mental Health (Contract number NO1MH80001) and is registered with the National Library of Medicine's ClinicalTrials.gov website (Record number: NCT00667745). NR 65 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD APR PY 2014 VL 14 IS 2 BP 182 EP 191 DI 10.1038/tpj.2013.16 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AE0OK UT WOS:000333665400012 PM 23670706 ER PT J AU Song, GJ Springer, TA AF Song, Gaojie Springer, Timothy A. TI Structures of the Toxoplasma gliding motility adhesin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMALIAN-CELLS; HOST-CELLS; INTEGRIN REGULATION; INVASION; COMPLEX; GONDII; PROTEINS; SECRETION; SYSTEM; DOMAIN AB Micronemal protein 2 (MIC2) is the key adhesin that supports gliding motility and host cell invasion by Toxoplasma gondii. With a von Willebrand factor A (VWA) domain and six thrombospondin repeat domains (TSR1-6) in its ectodomain, MIC2 connects to the parasite actomyosin system through its cytoplasmic tail. MIC2-associated protein (M2AP) binds noncovalently to the MIC2 ectodomain. MIC2 and M2AP are stored in micronemes as proforms. We find that the MIC2-M2AP ectodomain complex is a highly elongated 1: 1 monomer with M2AP bound to the TSR6 domain. Crystal structures of N-terminal fragments containing the VWA and TSR1 domains for proMIC2 and MIC2 reveal a closed conformation of the VWA domain and how it associates with the TSR1 domain. A long, proline-rich, disulfide-bonded pigtail loop in TSR1 overlaps the VWA domain. Mannose alpha-C-linked to Trp-276 in TSR1 has an unusual C-1(4) chair conformation. The MIC2 VWA domain includes a mobile alpha 5-helix and a 22-residue disordered region containing two disulfide bonds in place of an alpha 6-helix. A hydrophobic residue in the prodomain binds to a pocket adjacent to the alpha 7-helix that pistons in opening of the VWA domain to a putative high-affinity state. C1 [Song, Gaojie; Springer, Timothy A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Song, Gaojie; Springer, Timothy A.] Boston Childrens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. [Song, Gaojie; Springer, Timothy A.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. RP Springer, TA (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu FU National Institutes of Health Grant [AI095686] FX We thank beamlines X9A at National Synchotron Light Source and 24ID at Advanced Photon Source; Jianghai Zhu, Xianchi Dong, and Li-Zhi Mi for help with data collection and refinement; and Adem Koksal for help with SAXS data collection and processing. This work was supported by National Institutes of Health Grant AI095686. NR 36 TC 6 Z9 8 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 2014 VL 111 IS 13 BP 4862 EP 4867 DI 10.1073/pnas.1403059111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9IX UT WOS:000333579700049 PM 24639528 ER PT J AU Chinman, M George, P Dougherty, RH Daniels, AS Ghose, SS Swift, A Delphin-Rittmon, ME AF Chinman, Matthew George, Preethy Dougherty, Richard H. Daniels, Allen S. Ghose, Sushmita Shoma Swift, Anita Delphin-Rittmon, Miriam E. TI Peer Support Services for Individuals With Serious Mental Illnesses: Assessing the Evidence SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTENSIVE CASE-MANAGEMENT; CONSUMER CASE-MANAGEMENT; HEALTH-SERVICES; WELLNESS RECOVERY; CLIENT OUTCOMES; EVIDENCE BASE; PROVIDERS; COMMUNITY; EDUCATION AB Objective: This review assessed the level of evidence and effectiveness of peer support services delivered by individuals in recovery to those with serious mental illnesses or co-occurring mental and substance use disorders. Methods: Authors searched PubMed, PsycINFO, Applied Social Sciences Index and Abstracts, Sociological Abstracts, Social Services Abstracts, Published International Literature on Traumatic Stress, the Educational Resources Information Center, and the Cumulative Index to Nursing and Allied Health Literature for outcome studies of peer support services from 1995 through 2012. They found 20 studies across three service types: peers added to traditional services, peers in existing clinical roles, and peers delivering structured curricula. Authors judged the methodological quality of the studies using three levels of evidence (high, moderate, and low). They also described the evidence of service effectiveness. Results: The level of evidence for each type of peer support service was moderate. Many studies had methodological shortcomings, and outcome measures varied. The effectiveness varied by service type. Across the range of methodological rigor, a majority of studies of two service types peers added and peers delivering curricula showed some improvement favoring peers. Compared with professional staff, peers were better able to reduce inpatient use and improve a range of recovery outcomes, although one study found a negative impact. Effectiveness of peers in existing clinical roles was mixed. Conclusions: Peer support services have demonstrated many notable outcomes. However, studies that better differentiate the contributions of the peer role and are conducted with greater specificity, consistency, and rigor would strengthen the evidence. C1 [Chinman, Matthew] US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, Pittsburgh Med Ctr, Pittsburgh, PA 15206 USA. [George, Preethy; Daniels, Allen S.; Ghose, Sushmita Shoma] WESTAT Corp, Rockville, MD 20850 USA. [Dougherty, Richard H.] DMA Hlth Strategies, Lexington, MA USA. [Swift, Anita] Swift Consulting, Newport, KY USA. [Delphin-Rittmon, Miriam E.] SAMHSA, Off Policy Planning & Innovat, Rockville, MD USA. RP Chinman, M (reprint author), US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, Pittsburgh Med Ctr, Pittsburgh, PA 15206 USA. EM chinman@rand.org; preethygeorge@westat.com FU Substance Abuse and Mental Health Services Administration (SAMHSA) [HHSS283200700029I/HHSS28342002T HHSS283200700006I/HHSS28342003T, HHSS2832007000171/HHSS28300001T]; U.S. Department of Veterans Affairs [RRP 06-147]; Evidence-Based Review of Peer Support [IIR 06-227] FX Development of the Assessing the Evidence Base Series was supported by contracts HHSS283200700029I/HHSS28342002T, HHSS283200700006I/HHSS28342003T, and HHSS2832007000171/HHSS28300001T from 2010 through 2013 from the Substance Abuse and Mental Health Services Administration (SAMHSA). Development of this review was also partly supported by two grants from the U.S. Department of Veterans Affairs: grant RRP 06-147, Evidence-Based Review of Peer Support; and grant IIR 06-227 PEers Enhancing Recovery. The authors acknowledge the contributions of Wilma Townsend, M.S.W., Kevin Malone, B.A., and Suzanne Fields, M.S.W., from SAMHSA: John O'Brien, M.A., from the Centers for Medicare & Medicaid Services; Garrett Moran, Ph.D., from Westat; and John Easterday, Ph.D., Linda Lee, Ph.D., Rosanna Coffey, Ph.D., and Tami Mark, Ph.D., from Truven Health Analytics. The views expressed in this article are those of the authors and do not necessarily represent the views of SAMHSA. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States government. NR 52 TC 59 Z9 59 U1 6 U2 31 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2014 VL 65 IS 4 BP 429 EP 441 DI 10.1176/appi.ps.201300244 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AD8WE UT WOS:000333545600006 PM 24549400 ER PT J AU Slade, EP Wissow, LS Davis, M Abrams, MT Dixon, LB AF Slade, Eric P. Wissow, Lawrence S. Davis, Maryann Abrams, Michael T. Dixon, Lisa B. TI Medicaid Lapses and Low-Income Young Adults' Receipt of Outpatient Mental Health Care After an Inpatient Stay SO PSYCHIATRIC SERVICES LA English DT Article ID INSTRUMENTAL VARIABLES; UNITED-STATES; TRANSITION; SERVICES; ILLNESS; IDENTIFICATION; SCHIZOPHRENIA; DEPRESSION; INSURANCE; OUTCOMES AB Objective: This study examined low-income young adults' use of outpatient mental health services after an inpatient mental health stay, with a focus on Medicaid enrollment lapses and public mental health safety-net coverage. Methods: The sample included 1,174 young adults ages 18 to 26 who had been discharged from inpatient psychiatric care in a mid-Atlantic state. All were enrolled in Medicaid at the time of discharge, and all were eligible for continued outpatient public mental health services regardless of Medicaid enrollment Administrative claims data were used to examine outpatient mental health clinic use, psychotropic medication possession, inpatient readmission, and emergency department admission during the 365-day period after the index discharge. The main independent variable was a lapse in Medicaid enrollment. An instrumental-variables regression model was used to minimize estimation bias resulting from unmeasured confounding between lapses and service use. Results: Nearly a third (30%) of the young adults had an enrollment lapse. In instrumental-variables analysis, those whose coverage lapsed were less likely than those who had continuous Medicaid coverage to have at least two clinic visits (38% versus 80%); they also had a lower average psychotropic medication possession ratio (25% versus 55%). Conclusions: Age-related Medicaid enrollment lapses were common in this sample of young adults and were associated with receipt of less clinical care postdischarge despite continued eligibility for public services. States should examine opportunities to assist young adults with serious mental health problems who are aging out of Medicaid enrollment categories for children. C1 [Slade, Eric P.] US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, Capitol Healthcare Network VISN5, Baltimore, MD 21201 USA. [Slade, Eric P.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Wissow, Lawrence S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Davis, Maryann] Univ Massachusetts, Sch Med, Dept Psychiat, Syst & Psychosocial Adv Res Ctr,Adulthood Rehabil, Worcester, MA 01655 USA. [Abrams, Michael T.] Univ Maryland Baltimore Cty, HillTop Inst, Baltimore, MD 21228 USA. [Dixon, Lisa B.] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. [Dixon, Lisa B.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Slade, EP (reprint author), US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, Capitol Healthcare Network VISN5, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu FU National Institute of Mental Health [R34-MH081303]; Maryland's Medicaid authority; H. Lundbeck A/S FX This research was funded by the National Institute of Mental Health under grant number R34-MH081303. The authors thank Jack Clark, M.A., for expert database programming.; Dr. Slade has served as a paid consultant to H. Lundbeck A/S. Mr. Abrams has served as a paid consultant to Maryland's Medicaid authority. The other authors report no competing interests. NR 40 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2014 VL 65 IS 4 BP 454 EP 460 DI 10.1176/appi.ps.201200375 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AD8WE UT WOS:000333545600008 PM 24382558 ER PT J AU Davis, M Abrams, MT Wissow, LS Slade, EP AF Davis, Maryann Abrams, Michael T. Wissow, Lawrence S. Slade, Eric P. TI Identifying Young Adults at Risk of Medicaid Enrollment Lapses After Inpatient Mental Health Treatment SO PSYCHIATRIC SERVICES LA English DT Article ID INSURANCE-COVERAGE; CARE; MASSACHUSETTS; CHILDREN; REFORM; YOUTH; CLASSIFICATION; POPULATIONS; TRANSITION; DISORDERS AB Objective: This study sought to describe Medicaid disenrollment rates and risk factors among young adults after discharge from inpatient psychiatric treatment. Methods: The sample included 1,176 Medicaid-enrolled young adults ages 18 to 26 discharged from inpatient psychiatric care in a mid-Atlantic state. Medicaid disenrollment in the 365 days postdischarge and disenrollment predictors from the 180-day predischarge period (antecedent period) were identified from administrative records. Classification and regression free and probit regression analysis were used. Results: Thirty-two percent were disenrolled from Medicaid within a year of discharge. Both analytical approaches converged on four main risk factors: being in the Medicaid enrollment category for persons with a nondisabled low-income parent or for a child in a low-income household, being age 18 or 20 at discharge, having a Medicaid enrollment gap in the antecedent period, and having no primary care utilization in the antecedent period. For the 48% of the sample continuously enrolled in the antecedent period who were in the enrollment categories for disabled adults or foster care children, the disenrollment rate was 13%. Conclusions: A substantial minority of Medicaid-enrolled young adults discharged from inpatient care were disenrolled from Medicaid within a year. About half the sample had a low disenrollment risk, but the other half was at substantial risk. Risk factors largely reflected legal status changes that occur among these transition-age youths. Identifying inpatients at high risk of disenrollment and ensuring continuous coverage should improve access to needed postdischarge supports. Regular primary care visits may also help reduce unintended Medicaid disenrollment in this population. C1 [Davis, Maryann] Univ Massachusetts, Sch Med, Dept Psychiat, Ctr Mental Hlth Serv Res,Adulthood Rehabil Res &, Worcester, MA 01655 USA. [Abrams, Michael T.] Univ Maryland Baltimore Cty, Hilltop Inst, Baltimore, MD 21228 USA. [Wissow, Lawrence S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Slade, Eric P.] US Dept Vet Affairs, Capitol Healthcare Network VISN5, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Slade, Eric P.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Davis, M (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, Ctr Mental Hlth Serv Res,Adulthood Rehabil Res &, Worcester, MA 01655 USA. EM maryann.davis@umassmed.edu FU National Institutes of Health [R34-MH081303]; National Institute on Disability and Rehabilitation Research [H133B090018]; H. Lundbeck A/S; Maryland's Medicaid authority FX This work was funded by grants to Dr. Slade from the National Institutes of Health (R34-MH081303) and to Dr. Davis from the National Institute on Disability and Rehabilitation Research (H133B090018). The authors thank Jack Clark, M.A., for expert database programming, and Amanda Costa, A.A., for assistance.; Dr. Slade has served as a paid consultant to H. Lundbeck A/S. Mr. Abrams has served as a paid consultant to Maryland's Medicaid authority. The other authors report no competing interests. NR 44 TC 2 Z9 2 U1 4 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2014 VL 65 IS 4 BP 461 EP 468 DI 10.1176/appi.ps.201300199 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AD8WE UT WOS:000333545600009 PM 24382689 ER PT J AU Koiliari, E Roussos, P Pasparakis, E Lencz, T Malhotra, A Siever, LJ Giakoumaki, SG Bitsios, P AF Koiliari, Erasmia Roussos, Panos Pasparakis, Emmanouil Lencz, Todd Malhotra, Anil Siever, Larry J. Giakoumaki, Stella G. Bitsios, Panos TI The CSMD1 genome-wide associated schizophrenia risk variant rs10503253 affects general cognitive ability and executive function in healthy males SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Cognition; Executive function; Endophenotypes; CSMD1 gene; Schizophrenia ID HUMAN PREFRONTAL CORTEX; INHIBITED LIGHT REFLEX; WORKING-MEMORY; PERSONALITY-TRAITS; DECISION-MAKING; TASK; ABNORMALITIES; PERFORMANCE; COMPONENTS; DISORDER AB Background: The single-nucleotide polymorphism(SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, has reached genome-wide support as a risk factor for schizophrenia. There is initial but inconclusive evidence for a role of this variant in aspects of cognition. Methods: We investigated the neurocognitive effects of the CSMD1 rs10503253 (C/A) polymorphism in a large, demographically homogeneous sample of young, healthy Greek Caucasian males (n=1149) phenotyped for a wide range of neuropsychological measures, most of which have been shown to be reliable endophenotypes for schizophrenia. Results: The risk 'A' allele was associated with poorer performance on measures of general cognitive ability, strategy formation, spatial and visual working memory, set shifting, target detection and planning for problem solving but not for emotional decision making. Most of these effects were dependent on risk "A" allele dose, with AA and CC homozygotes being the worse and the best respectively, while CA individuals were intermediate. Potential genotype effects in Stroop and verbal memory performance were also suggested by our dataset. Discussion: These results underline the relevance of the risk "A" allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia. (C) 2014 Elsevier B. V. All rights reserved. C1 [Koiliari, Erasmia; Pasparakis, Emmanouil; Bitsios, Panos] Univ Crete, Fac Med, Dept Psychiat, Iraklion, Crete, Greece. [Roussos, Panos; Siever, Larry J.] Mt Sinai, Dept Psychiat, New York, NY USA. [Roussos, Panos] Mt Sinai, Inst Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA. [Roussos, Panos; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY USA. [Lencz, Todd; Malhotra, Anil] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. [Lencz, Todd; Malhotra, Anil] Feinstein Inst Med Res, Manhasset, NY USA. [Giakoumaki, Stella G.] Univ Crete, Dept Psychol, Rethimnon, Crete, Greece. RP Bitsios, P (reprint author), Univ Crete, Fac Med, Dept Psychiat, Iraklion, Crete, Greece. EM pbitsios@med.uoc.gr RI Roussos, Panos/J-7090-2013; Lencz, Todd/J-3418-2014 OI Roussos, Panos/0000-0002-4640-6239; Lencz, Todd/0000-0001-8586-338X NR 52 TC 8 Z9 9 U1 3 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2014 VL 154 IS 1-3 BP 42 EP 47 DI 10.1016/j.schres.2014.02.017 PG 6 WC Psychiatry SC Psychiatry GA AD7EU UT WOS:000333425800006 PM 24630139 ER PT J AU Bergen, SE O'Dushlaine, CT Lee, PH Fanous, AH Ruderfer, DM Ripke, S Sullivan, PF Smoller, JW Purcell, SM Corvin, A AF Bergen, Sarah E. O'Dushlaine, Colm T. Lee, Phil H. Fanous, Ayman H. Ruderfer, Douglas M. Ripke, Stephan Sullivan, Patrick F. Smoller, Jordan W. Purcell, Shaun M. Corvin, Aiden CA Int Schizophrenia Consortium Swedish Schizophrenia Consortium TI Genetic modifiers and subtypes in schizophrenia: Investigations of age at onset, severity, sex and family history SO SCHIZOPHRENIA RESEARCH LA English DT Article DE GWAS; Association; psychosis; Gender ID GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; SYMPTOM SEVERITY; OF-ONSET; RISK; CLASSIFICATION; HETEROGENEITY; METAANALYSIS; RELIABILITY; EXPRESSION AB Schizophrenia is a genetically and clinically heterogeneous disorder. Genetic risk factors for the disorder may differ between the sexes or between multiply affected families compared to cases with no family history. Additionally, limited data support a genetic basis for variation in onset and severity, but specific loci have not been identified. We performed genome-wide association studies (GWAS) examining genetic influences on age at onset (AAO) and illness severity as well as specific risk by sex or family history status using up to 2762 cases and 3187 controls from the International Schizophrenia Consortium (ISC). Subjects with a family history of schizophrenia demonstrated a slightly lower average AAO that was not significant following multiple testing correction (p=.048), but no differences in illness severity were observed by family history status (p=.51). Consistent with prior reports, we observed earlier AAO (p=.005) and a more severe course of illness for men (p=.002). Family history positive analyses showed the greatest association with KIF5C (p=1.96 x 10(-8)), however, genetic risk burden overall does not differ by family history. Separate association analyses for males and females revealed no significant sex-specific associations. The top GWAS hit for AAO was near the olfactory receptor gene OR2K2 (p=1.52 x 10(-7)). Analyses of illness severity (episodic vs. continuous) implicated variation in ST18 (p=8.24 x 10(-7)). These results confirm recognized demographic relationships but do not support a simplified genetic architecture for schizophrenia subtypes based on these variables. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bergen, Sarah E.; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Bergen, Sarah E.; O'Dushlaine, Colm T.; Lee, Phil H.; Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Fanous, Ayman H.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Fanous, Ayman H.] Washington VA Med Ctr, Washington, DC USA. [Fanous, Ayman H.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Fanous, Ayman H.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Fanous, Ayman H.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Ruderfer, Douglas M.] Mt Sinai Sch Med, New York, NY USA. [Lee, Phil H.; Ruderfer, Douglas M.; Ripke, Stephan; Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bergen, Sarah E.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Corvin, Aiden] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Bergen, Sarah E.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. RP Bergen, SE (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden. EM sbergen@gmail.com RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Bergen, Sarah/0000-0002-5888-0034; Corvin, Aiden/0000-0001-6717-4089; Sullivan, Patrick/0000-0002-6619-873X FU National Institute of Mental Health [R01 MH079799]; Science Foundation Ireland; National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator grant FX This work was supported by a National Institute of Mental Health grant, R01 MH079799, to JWS, a Science Foundation Ireland grant to AC, and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator grant to SEB. NR 44 TC 13 Z9 14 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2014 VL 154 IS 1-3 BP 48 EP 53 DI 10.1016/j.schres.2014.01.030 PG 6 WC Psychiatry SC Psychiatry GA AD7EU UT WOS:000333425800007 PM 24581549 ER PT J AU DeLisi, LE AF DeLisi, Lynn E. TI Re: Caution urged in interpreting a negative study of cannabis use and schizophrenia: A response to Dr. Christine Miller SO SCHIZOPHRENIA RESEARCH LA English DT Letter C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP DeLisi, LE (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02301 USA. FU NIDA NIH HHS [R01 DA 021576, R01 DA021576] NR 1 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2014 VL 154 IS 1-3 BP 121 EP 121 DI 10.1016/j.schres.2014.02.012 PG 1 WC Psychiatry SC Psychiatry GA AD7EU UT WOS:000333425800020 PM 24630137 ER PT J AU Blackwell, T Yaffe, K Laffan, A Ancoli-Israel, S Redline, S Ensrud, KE Song, Y Stone, KL AF Blackwell, Terri Yaffe, Kristine Laffan, Alison Ancoli-Israel, Sonia Redline, Susan Ensrud, Kristine E. Song, Yeonsu Stone, Katie L. CA Osteoporotic Fractures Men MrOS TI Associations of Objectively and Subjectively Measured Sleep Quality with Subsequent Cognitive Decline in Older Community-Dwelling Men: The MrOS Sleep Study SO SLEEP LA English DT Article DE Aging; cognitive function; disturbed sleep; total sleep time ID JAPANESE-AMERICAN MEN; OSTEOPOROTIC FRACTURES; DAYTIME SLEEPINESS; DEMENTIA; IMPAIRMENT; HEALTH; ADULTS; ACTIGRAPHY; WOMEN; SCALE AB Study Objectives: To examine associations of objectively and subjectively measured sleep with subsequent cognitive decline. Design: A population-based longitudinal study. Setting: Six centers in the United States. Participants: Participants were 2,822 cognitively intact community-dwelling older men (mean age 76.0 +/- 5.3 y) followed over 3.4 +/- 0.5 y. Interventions: None. Measurements and Results: Objectively measured sleep predictors from wrist actigraphy: total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of long wake episodes (LWEP). Self-reported sleep predictors: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline on the Modified Mini-Mental State examination (3MS), change score for the Trails B test time in the worse decile. Associations of sleep predictors and cognitive decline were examined with logistic regression and linear mixed models. After multivariable adjustment, higher levels of WASO and LWEP and lower SE were associated with an 1.4 to 1.5-fold increase in odds of clinically significant decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE >= 70%: 1.53 (1.07, 2.18); WASO >= 90 min versus WASO < 90 min: 1.47 (1.09, 1.98); eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to linear change in cognition over time. PSQI was related to decline in Trails B performance (3 sec/y per standard deviation increase). Conclusions: Among older community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness, greater number of long wake episodes, and poor self-reported sleep quality were associated with subsequent cognitive decline. C1 [Blackwell, Terri; Laffan, Alison; Song, Yeonsu; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat & Med, La Jolla, CA 92093 USA. [Ancoli-Israel, Sonia] Vet Affairs San Diego Ctr Excellence Stress & Men, San Diego, CA USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Blackwell, T (reprint author), San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM tblackwell@sfcc-cpmc.net; kstone@sfcc-cpmc.net FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Cancer Institute (NCI); National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]; NIA [K24 AG031155]; NIH; ResMed, Inc; Philips Respironics; ResMed Foundation FX This was not an industry supported study. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Cancer Institute (NCI), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. Dr. Yaffe is supported by a grant from the NIA, K24 AG031155; serves on DSMB's for Takeda, Inc and a study sponsored by the NIH; is a member of the Beeson Advisory Committee; and is a consultant for Novartis and Eli Lilly. Dr. Ancoli- Israel is a consultant or on the advisory board for Astra Zeneca, Ferring Pharmaceuticals Inc, GaxoSmithKline, Hypnocore, Johnson & Johnson, Merck, NeuroVigil Inc, and Purdue Pharma LP. Dr. Redline's institution has received grant funding from ResMed, Inc, Philips Respironics, and ResMed Foundation and equipment from them for use in NIH studies. The other authors have indicated no financial conflicts of interest. The analysis was performed at California Pacific Medical Center Research Institute, San Francisco, CA. NR 50 TC 21 Z9 21 U1 1 U2 12 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD APR 1 PY 2014 VL 37 IS 4 BP 655 EP 663 DI 10.5665/sleep.3562 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AE0RF UT WOS:000333673100004 PM 24899757 ER PT J AU Hicks, CW Weinstein, M Wakamatsu, M Savitt, L Pulliam, S Bordeianou, L AF Hicks, Caitlin W. Weinstein, Milena Wakamatsu, May Savitt, Lieba Pulliam, Samantha Bordeianou, Liliana TI In patients with rectoceles and obstructed defecation syndrome, surgery should be the option of last resort SO SURGERY LA English DT Article ID TRANSANAL RECTAL RESECTION; PELVIC FLOOR DISORDERS; EVACUATION PROCTOGRAPHY; NORMAL VOLUNTEERS; INTUSSUSCEPTION; BIOFEEDBACK; CONSTIPATION; MANAGEMENT; TRIAL; MULTICENTER AB Background. The indications for operation in patients with obstructed defecation syndrome (ODS) with rectocele are not well defined. Methods. A total of 90 female patients with ODS and rectocele were prospectively evaluated and treated with fiber supplements and biofeedback training. Univariate and multivariate regression was used to determine factors predictive of failing medical management. Results. Obstructive symptoms were the most prevalent Presenting complaint (82.2%). Ultimately, 71.1% of patients responded to medical management and biofeedback. Multivariate regression analysis suggested that the presence of internal intussusception was associated with a lower chance of undergoing surgery to address ODS symptoms [odds ratio 0.18; P = .05], whereas inability to expel balloon, contrast retention on defecography, and splinting were not (P >= .15). Conclusion. Rectoceles with concomitant intussusception in patients with ODS appear to portend a favorable response to biofeedback and medical management. We argue that all patients considered for surgery for rectoceles because of ODS should first undergo appropriate bowel retraining. C1 [Hicks, Caitlin W.; Savitt, Lieba; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Pelv Floor Disorders Serv, Boston, MA 02114 USA. [Weinstein, Milena; Wakamatsu, May; Pulliam, Samantha] Massachusetts Gen Hosp, Dept Gynecol, Pelv Floor Disorders Serv, Boston, MA 02114 USA. [Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, Pelv Floor Disorders Serv, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org OI Hicks, Caitlin/0000-0001-7638-1936 NR 43 TC 9 Z9 12 U1 0 U2 6 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 APR PY 2014 VL 155 IS 4 BP 659 EP 667 DI 10.1016/j.surg.2013.11.013 PG 9 WC Surgery SC Surgery GA AE0MV UT WOS:000333661300010 PM 24508117 ER PT J AU Wo, JY Dawson, LA Zhu, AX Hong, TS AF Wo, Jennifer Y. Dawson, Laura A. Zhu, Andrew X. Hong, Theodore S. TI An Emerging Role for Radiation Therapy in the Treatment of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Hepatobiliary cancers; Radiation therapy; Stereotactic body radiation therapy ID STEREOTACTIC BODY RADIOTHERAPY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; RANDOMIZED CONTROLLED TRIAL; PORTAL-VEIN THROMBOSIS; PROTON-BEAM THERAPY; CARBON ION THERAPY; TUMOR THROMBUS; PHASE-I; TRANSARTERIAL CHEMOEMBOLIZATION; FEASIBILITY AB Radiation therapy is emerging as a potentially effective treatment of locally advanced, unresectable hepatocellular carcinoma (HOC). Outcomes from early prospective studies seem promising, with improved survival compared with historical controls. Cure of early stage and unresectable HOC may be possible with high-quality radiation therapy. Many questions remain, including determination of the ideal radiation dose and fractionation schema, optimal patient selection criteria based on tumor size, tumor location, extent of vascular invasion, and baseline liver function, and the role of radiation therapy compared with other localized standard treatments including radiofrequency ablation or transarterial chemoembolization. C1 [Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dawson, Laura A.] Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada. [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Wo, JY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jwo@partners.org NR 46 TC 3 Z9 3 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 EI 1558-5042 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2014 VL 23 IS 2 BP 353 EP + DI 10.1016/j.soc.2013.10.007 PG 17 WC Oncology; Surgery SC Oncology; Surgery GA AD5UD UT WOS:000333317800012 PM 24560114 ER PT J AU Makela, KT Matilainen, M Pulkkinen, P Fenstad, AM Havelin, LI Engesaeter, L Furnes, O Overgaard, S Pedersen, AB Karrholm, J Malchau, H Garellick, G Ranstam, J Eskelinen, A AF Makela, Keijo T. Matilainen, Markus Pulkkinen, Pekka Fenstad, Anne M. Havelin, Leif I. Engesaeter, Lars Furnes, Ove Overgaard, Soren Pedersen, Alma B. Kaerrholm, Johan Malchau, Henrik Garellick, Goeran Ranstam, Jonas Eskelinen, Antti TI Countrywise results of total hip replacement An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database SO ACTA ORTHOPAEDICA LA English DT Article ID REGISTRATION; REVISIONS; FAILURE AB Background and purpose An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995-2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included. Material and methods 438,733 THRs performed during the period 1995-2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint. Results The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7-86.9) in Denmark, 88% (CI: 87.6-88.3) in Sweden, 87% (CI: 86.4-87.4) in Norway, and 84% (CI: 82.9-84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34-0.82), seventh (HR = 0.60, CI: 0.37-0.97), and ninth (HR = 0.59, CI: 0.36-0.98) year of follow-up. Interpretation The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required. C1 [Makela, Keijo T.] Turku Univ Hosp, Dept Orthopaed & Traumatol, FIN-20520 Turku, Finland. [Matilainen, Markus] Turku Univ, Dept Biostat, Turku, Finland. [Pulkkinen, Pekka] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Fenstad, Anne M.; Havelin, Leif I.; Engesaeter, Lars; Furnes, Ove] Haukeland Univ Hospita, Dept Orthopaed Surg, Bergen, Norway. [Havelin, Leif I.; Engesaeter, Lars; Furnes, Ove] Univ Bergen, Dept Clin Med, Bergen, Norway. [Overgaard, Soren; Pedersen, Alma B.] Aarhus Univ Hosp, Dept Clin Epidemiol, Ctr Clin Databases, DK-8000 Aarhus, Denmark. [Pedersen, Alma B.] Aarhus Univ Hosp, Dept Clin Epidemiol, Competence Ctr Clin Epidemiol & Biostat, DK-8000 Aarhus, Denmark. [Overgaard, Soren] Odense Univ Hosp, Dept Orthopaed Surg & Traumatol, DK-5000 Odense, Denmark. [Overgaard, Soren] Odense Univ Hosp, Inst Clin, DK-5000 Odense, Denmark. [Kaerrholm, Johan; Malchau, Henrik; Garellick, Goeran] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Orthopaed, Inst Surg Sci, Molndal, Sweden. [Kaerrholm, Johan; Malchau, Henrik; Garellick, Goeran] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. [Ranstam, Jonas] Skane Univ Hosp, Swedish Natl Competence Ctr Musculoskeletal Dis, Lund, Sweden. [Eskelinen, Antti] Coxa Hosp Joint Replacement, Tampere, Finland. RP Makela, KT (reprint author), Turku Univ Hosp, Dept Orthopaed & Traumatol, FIN-20520 Turku, Finland. EM keijo.makela@fimnet.fi RI Eskelinen, Antti/E-6433-2015; OI Eskelinen, Antti/0000-0003-0302-0253; Ranstam, Jonas/0000-0002-8287-7273 NR 24 TC 23 Z9 24 U1 1 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD APR PY 2014 VL 85 IS 2 BP 107 EP 116 DI 10.3109/17453674.2014.893498 PG 10 WC Orthopedics SC Orthopedics GA AD3ZP UT WOS:000333185500001 PM 24650019 ER PT J AU Brugada, J Brachmann, J Delnoy, PP Padeletti, L Reynolds, D Ritter, P Borri-Brunetto, A Singh, JP AF Brugada, Josep Brachmann, Johannes Delnoy, Peter Paul Padeletti, Luigi Reynolds, Dwight Ritter, Philippe Borri-Brunetto, Alberto Singh, Jagmeet P. TI Automatic Optimization of Cardiac Resynchronization Therapy Using SonR-Rationale and Design of the Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the Paradym RF SonR CRT-D (RESPOND CRT) Trial SO AMERICAN HEART JOURNAL LA English DT Article ID PEAK ENDOCARDIAL ACCELERATION; CHRONIC HEART-FAILURE; CARE-HF TRIAL; ATRIOVENTRICULAR DELAY; CONDUCTION DELAY; RANDOMIZED-TRIAL; TASK-FORCE; FOLLOW-UP; VALIDATION; ECHOCARDIOGRAPHY AB Although cardiac resynchronization therapy (CRT) is effective in most patients with heart failure (HF) and ventricular dyssynchrony, a significant minority of patients (approximately 30%) are non-responders. Optimal atrioventricular and interventricular delays often change over time and reprogramming these intervals might increase CRT effectiveness. The SonR algorithm automatically optimizes atrioventricular and interventricular intervals each week using an accelerometer to measure change in the SonR signal, which was shown previously to correlate with hemodynamic improvement (left ventricular [LV] dP/dt(max)). The RESPOND CRT trial will evaluate the effectiveness and safety of the SonR optimization system in patients with HF New York Heart Association class III or ambulatory IV eligible for a CRT-D device. Enrolled patients will be randomized in a 2:1 ratio to either SonR CRT optimization or to a control arm employing echocardiographic optimization. All patients will be followed for at least 24 months in a double-blinded fashion. The primary effectiveness end point will be evaluated for non-inferiority, with a nested test of superiority, based on the proportion of responders (defined as alive, free from HF-related events, with improvements in New York Heart Association class or improvement in Kansas City Cardiomyopathy Questionnaire quality of life score) at 12 months. The required sample size is 876 patients. The two primary safety end points are acute and chronic SonR lead-related complication rates, respectively. Secondary end points include proportion of patients free from death or HF hospitalization, proportion of patients worsened, and lead electrical performance, assessed at 12 months. The RESPOND CRT trial will also examine associated reverse remodeling at 1 year. C1 [Brugada, Josep] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Brachmann, Johannes] Coburg Hosp, Coburg, Germany. [Delnoy, Peter Paul] Isala Kliniken, Zwolle, Netherlands. [Padeletti, Luigi] Careggi Univ Hosp, Florence, Italy. [Reynolds, Dwight] Univ Oklahoma, Oklahoma City, OK USA. [Ritter, Philippe] Univ Hosp Bordeaux, Pessac, France. [Borri-Brunetto, Alberto] Sorin CRM SAS, Clamart, France. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugada, J (reprint author), Univ Barcelona, Hosp Clin, Barcelona, Spain. EM jbrugada@clinic.ub.es OI BRUGADA, JOSEP/0000-0002-5662-8302 FU Sorin CRM SAS FX Josep Brugada, Johannes Brachmann, Peter Paul Delnoy, Luigi Padeletti, Dwight Reynolds, Philippe Ritter and Jagmeet P. Singh have received research grants from Sorin CRM SAS for their participation to this study. Alberto Borri-Brunetto has received a salary from Sorin CRM SAS as an employee of the company. NR 47 TC 5 Z9 5 U1 0 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 APR PY 2014 VL 167 IS 4 BP 429 EP 436 DI 10.1016/j.ahj.2013.12.007 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD3UE UT WOS:000333170900003 PM 24655689 ER PT J AU Bonaca, MP Bhatt, DL Braunwald, E Cohen, M Steg, PG Storey, RF Held, P Jensen, EC Sabatine, MS AF Bonaca, Marc P. Bhatt, Deepak L. Braunwald, Eugene Cohen, Marc Steg, Philippe Gabriel Storey, Robert F. Held, Peter Jensen, Eva C. Sabatine, Marc S. TI Design and rationale for the Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; DUAL-ANTIPLATELET THERAPY; TRANSIENT ISCHEMIC ATTACK; DRUG-ELUTING STENTS; SECONDARY PREVENTION; RECEPTOR ANTAGONIST; DOUBLE-BLIND; ATHEROTHROMBOTIC EVENTS; CLOPIDOGREL AB Background P2Y(12) receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y(12) receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year. Study Design PEGASUS-TIMI 54 is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor in addition to aspirin (75-150 mg) for the prevention of major adverse cardiovascular events in patients with a history of myocardial infarction and risk factors. Patients with a history of spontaneous myocardial infarction within 1 to 3 years are randomized in a 1:1:1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or matching placebo, all with low dose ASA, until the end of the study. The primary endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. Recruitment began in October 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial is planned to continue until the latest of either 1,360 adjudicated primary end points are accrued or the last patient randomized has been followed for at least 12 months. Conclusions PEGASUS-TIMI 54 is investigating whether the addition of intensive antiplatelet therapy with ticagrelor to low-dose aspirin reduces major adverse cardiovascular events in high-risk patients with a history of myocardial infarction. C1 [Bonaca, Marc P.; Bhatt, Deepak L.; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, Cardiovasc Div, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Bonaca, Marc P.; Bhatt, Deepak L.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Marc] Mt Sinai Sch Med, Newark Beth Israel Med Ctr, Cardiovasc Div, Dept Med, New York, NY USA. [Steg, Philippe Gabriel] Univ Paris Diderot, INSERM, Dept Hosp Univ FIRE, Sorbonne Paris Cite,Hop Bichat,U698, Paris, France. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Held, Peter; Jensen, Eva C.] AstraZeneca, Molndal, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU AstraZeneca; Brigham and Women's Hospital from Abbott; Brigham and Women's Hospital from Amgen; Brigham and Women's Hospital from AstraZeneca; Brigham and Women's Hospital from Beckman Coulter; Brigham and Women's Hospital from BG Medicine; Brigham and Women's Hospital from BRAHMS; Brigham and Women's Hospital from Bristol-Myers Squibb; Brigham and Women's Hospital from Buhlmann; Brigham and Women's Hospital from Critical Diagnostics; Brigham and Women's Hospital from CV Therapeutics; Brigham and Women's Hospital from Daiichi Sankyo Co Ltd; Brigham and Women's Hospital from Eli Lilly and Co; Brigham and Women's Hospital from GlaxoSmithKline; Brigham and Women's Hospital from Genzyme; Brigham and Women's Hospital from Merck and Co; Brigham and Women's Hospital from Intarcia; Brigham and Women's Hospital from Merck; Brigham and Women's Hospital from Nanosphere; Brigham and Women's Hospital from Novartis Pharmaceuticals; Brigham and Women's Hospital from Ortho-Clinical Diagnostics; Brigham and Women's Hospital from Pfizer; Brigham and Women's Hospital from Randox; Brigham and Women's Hospital from Roche Diagnostics; Brigham and Women's Hospital from Sanofi-Aventis; Brigham and Women's Hospital from Siemens; Brigham and Women's Hospital from Singulex; Brigham and Women's Hospital from Takeda; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Roche; Sanofi Aventis; Bayer; Boehringer-Ingelheim; Bristol-Myers-Squibb; Daiichi-Sankyo; GlaxoSmithKline; Lilly; Merck-Sharpe-Dohme; Novartis; Otsuka; Pfizer; Sanofi; Servier; Genzyme; Amgen; AstraZeneca/Bristol-Myers Squibb Alliance; Bristol-Myers Squibb/Sanofi-aventis Joint Venture; Intarcia; Merck; Sanofi-aventis; Takeda; Abbott Laboratories; Critical Diagnostics; Nanosphere; Roche Diagnostics; National Health, Lung, and Blood Institute [R01 HL099692, R01 HL096738, HHSN268201000033C] FX The PEGASUS-TIMI 54 Study was funded through a grant from AstraZeneca.; The TIMI Study Group has received research grant support through Brigham and Women's Hospital from Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Buhlmann, Critical Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Genzyme, Merck and Co, Intarcia, Merck, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche Diagnostics, Sanofi-Aventis, Siemens, Singulex, and Takeda.; Dr Deepak L. Bhatt discloses the following relationships: Advisory Board: Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology); Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); Other: Clinical Cardiology (Associate Editor); Journal of the American College of Cardiology (Section Editor, Pharmacology); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda.; Dr Steg reports receiving honorarium from AstraZeneca for steering committee membership and support for travel to study meetings. In addition, he has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, and Vivus and research grants from Sanofi and Servier outside the submitted work.; Dr Storey reports receiving honorarium from AstraZeneca for steering committee membership and support for travel to study meetings. In addition, he has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, and Vivus and research grants from Sanofi and Servier outside the submitted work.; Dr Sabatine report the following financial disclosures over past 12 months and research grant support through Brigham and Women's Hospital from:; Pharmaceutical and biotechnology companies: Amgen; AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb/Sanofi-aventis Joint Venture, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Intarcia, Merck, Sanofi-aventis, and Takeda.; Medical diagnostic companies: Abbott Laboratories, Critical Diagnostics, Nanosphere, Roche Diagnostics.; Dr Sabatine was supported in part by grant R01 HL099692, grant R01 HL096738, and contract HHSN268201000033C from the National Health, Lung, and Blood Institute. NR 44 TC 39 Z9 42 U1 0 U2 17 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 APR PY 2014 VL 167 IS 4 BP 437 EP U44 DI 10.1016/j.ahj.2013.12.020 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD3UE UT WOS:000333170900004 PM 24655690 ER PT J AU Henriques, JPS Ouweneel, DM Naidu, SS Palacios, IF Popma, J Ohman, EM O'Neill, WW AF Henriques, Jose P. S. Ouweneel, Dagmar M. Naidu, Srihari S. Palacios, Igor F. Popma, Jeffrey Ohman, E. Magnus O'Neill, William W. TI Evaluating the learning curve in the prospective Randomized Clinical Trial of hemodynamic support with Impella 2.5 versus Intra-Aortic Balloon Pump in patients undergoing high-risk percutaneous coronary intervention: a prespecified subanalysis of the PROTECT II study SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOGENIC-SHOCK; DEVICE; COUNTERPULSATION; REGISTRY AB Background The introduction of new medical devices may be accompanied by a learning curve. Methods To evaluate the impact of the device learning curve on the outcomes of PROTECT II trial, comparing Impella 2.5 versus the intra-aortic balloon pump (IABP) during high-risk percutaneous coronary intervention, we report on a prespecified analysis, excluding the first Impella 2.5 and IABP patients at each site. Results A total of 448 patients were enrolled at 74 sites. Among these, 58 patients were the first to receive Impella 2.5 at their site, 62 were the first to receive IABP. A trend toward higher major adverse events (MAEs) at 30 days was observed for the subgroup of first versus remaining Impella 2.5 patients: 44.8% versus 31.7%, P = .072. MAE rates for the first and remaining IABP patients were similar at 30 days. After exclusion of the first patient in each group, MAE rates for Impella 2.5 and IABP were 31.7% versus 40.0% (P = .119) at 30 days and 38.0% versus 50.0% (P = .029) at 90 days. Conclusions Significantly lower 90-day MAE rates were observed with the use of Impella 2.5 compared to the use of IABP after excluding the first patient per group at each site. This prespecified analysis suggests a learning curve associated with initial introduction of the Impella 2.5. Clinical trials should better address the training aspect of new devices, especially when compared with more established devices. C1 [Henriques, Jose P. S.; Ouweneel, Dagmar M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Naidu, Srihari S.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Popma, Jeffrey] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA. [O'Neill, William W.] Henry Ford Hosp, Detroit, MI 48202 USA. RP Henriques, JPS (reprint author), Univ Amsterdam, Acad Med Ctr, AMC Heart Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.p.henriques@amc.uva.nl NR 15 TC 14 Z9 14 U1 0 U2 5 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 APR PY 2014 VL 167 IS 4 BP 472 EP U85 DI 10.1016/j.ahj.2013.12.018 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD3UE UT WOS:000333170900009 PM 24655695 ER PT J AU O'Brien, EC Holmes, DN Ansell, JE Allen, LA Hylek, E Kowey, PR Gersh, BJ Fonarow, GC Koller, CR Ezekowitz, MD Mahaffey, KW Chang, P Peterson, ED Piccini, JP Singer, DE AF O'Brien, Emily C. Holmes, DaJuanicia N. Ansell, Jack E. Allen, Larry A. Hylek, Elaine Kowey, Peter R. Gersh, Bernard J. Fonarow, Gregg C. Koller, Christopher R. Ezekowitz, Michael D. Mahaffey, Kenneth W. Chang, Paul Peterson, Eric D. Piccini, Jonathan P. Singer, Daniel E. TI Physician practices regarding contraindications to oral anticoagulation in atrial fibrillation: Findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry SO AMERICAN HEART JOURNAL LA English DT Article ID ANTITHROMBOTIC THERAPY; PREDICTING STROKE; RISK-FACTORS; REASONS AB Background Oral anticoagulation (OAC) therapy reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed OAC. The aim of this study is to describe the frequencies of and factors associated with OAC contraindications in contemporary clinical practice. Methods We analyzed data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. Oral anticoagulation contraindications were uniformly collected at enrollment by site personnel using a predefined list. Baseline patient and provider characteristics were compared between participants with and without documented OAC contraindications. Results From June 2010 to August 2011, 10,130 patients 18 years or older with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1,330 (13.1%) had contraindications documented at the baseline visit: prior bleed (27.7%), patient refusal/preference (27.5%), high bleeding risk (18.0%), frequent falls/frailty (17.6%), need for dual antiplatelet therapy (10.4%), unable to adhere/monitor warfarin (6.0%), comorbid illness (5.3%), prior intracranial hemorrhage (5.0%), allergy (2.4%), occupational risk (0.8%), pregnancy (0.2%), and other (12.6%). Among patients with reported contraindications, 30.3% were taking warfarin or dabigatran, as compared with 83.0% of those without reported contraindications. Besides "patient refusal/preference," being labeled as having frequent falls or being frail was associated with the lowest OAC use among patients with high stroke risk. Conclusions Contraindications to OAC therapy among patients with AF are common but subjective. Many patients with reported contraindications were receiving OAC, suggesting that the perceived benefit outweighed the potential harm posed by the relative contraindication. C1 [O'Brien, Emily C.; Holmes, DaJuanicia N.; Koller, Christopher R.; Peterson, Eric D.; Piccini, Jonathan P.] Duke Clin Res Inst, Durham, NC 27705 USA. [Ansell, Jack E.] NYU, Sch Med, Lenox Hill Hosp, New York, NY USA. [Allen, Larry A.] Univ Colorado, Sch Med, Aurora, CO USA. [Hylek, Elaine] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kowey, Peter R.; Ezekowitz, Michael D.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Gersh, Bernard J.] Mayo Clin, Rochester, MN USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Mahaffey, Kenneth W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Chang, Paul] Janssen Sci Affairs, Raritan, NJ USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Brien, EC (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM emily.obrien@duke.edu FU Janssen Scientific Affairs, LLC, Raritan, NJ; Agency of Healthcare Research and Quality [1U19 HS021092]; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA); Bristol Myers Squibb; Pfizer; Janssen; Daiichi; Boehringer Ingelheim; Alere; Amgen; JJ/Janssen; AstraZeneca; Bayer; Boehringer-Ingleheim; Bristol-Myers-Squibb; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Johnson Johnson; Merck; Novartis; Portola; POZEN Pharmaceutical; Schering-Plough; Eli Lilly Company; Boston Scientific Corporation; Johnson and Johnson FX The ORBIT-AF registry is sponsored by Janssen Scientific Affairs, LLC, Raritan, NJ. This project was supported (in part) by funding from the Agency of Healthcare Research and Quality through cooperative agreement number 1U19 HS021092. Dr. Singer was, in part, supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA). This work was performed at the Duke Clinical Research Institute, Durham, NC.; Dr. O'Brien and Ms. Holmes report no disclosures. Dr. Ansell reports that he has received Consultant/Advisory Board fees from Bristol Myers Squibb, Pfizer, Janssen, Daiichi, Boehringer Ingelheim, Alere (all modest). Dr. Allen reports consulting fees from Amgen and J&J/Janssen. Dr. Hylek reports that she is a member of the Speakers Bureau (modest) for Boehringer-Ingelheim, Bayer and a member of the Consultant/Advisory Boards (Modest) for Johnson & Johnson, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, Ortho-McNeil-Janssen. Dr. Kowey reports that he has served as a Consultant/Advisory Board for Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, Portola, Merck, Sanofi, Daiichi Sankyo (all modest). Dr. Gersh reports that he is a member of the advisory board for Boston Scientific and St. Jude Medical (both modest). Dr. Fonarow reports that he has served as a Consultant/Advisory Board member for Ortho McNeil. Dr. Ezekowitz is a member of the speakers bureau with Boehringer Ingelheim and consultancy with Boehringer Ingelheim, ARYx Therapeutics, Pfizer, Sanofi, Bristol-Myers-Squibb, Portola, Daiichi Sankyo, Medtronic, Merck, Gilead, and Janssen. Mr. Koller reports no disclosures. Dr. Mahaffey has received research support from AstraZeneca, Amgen, Bayer, Boehringer-Ingleheim, Bristol-Myers-Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Portola, POZEN Pharmaceutical, Schering-Plough, and The Medicines Company, and has consulting agreements with Amgen, AstraZeneca, Glaxo SmithKline, Johnson & Johnson, and Merck. Dr. Chang is an employee of Janssen. Dr. Peterson has received research support from Eli Lilly & Company and Janssen. Dr. Piccini has received research support from Boston Scientific Corporation and Janssen and consultancies to Forest Laboratories, Janssen, and Medtronic. Dr. Singer reports that he has received a research grant (significant) from Johnson and Johnson and served as a Consultant/Advisory Board member for Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson and Johnson, Pfizer (modest) and Daiichi Sankyo (significant). NR 22 TC 21 Z9 22 U1 1 U2 5 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 APR PY 2014 VL 167 IS 4 BP 601 EP U229 DI 10.1016/j.ahj.2013.12.014 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD3UE UT WOS:000333170900025 PM 24655711 ER PT J AU Shah, RV Abbasi, SA Heydari, B Farhad, H Dodson, JA Bakker, JP John, RM Veves, A Malhotra, A Blankstein, R Jerosch-Herold, M Kwong, RY Neilan, TG AF Shah, Ravi V. Abbasi, Siddique A. Heydari, Bobak Farhad, Hoshang Dodson, John A. Bakker, Jessie P. John, Roy M. Veves, Aristidis Malhotra, Atul Blankstein, Ron Jerosch-Herold, Michael Kwong, Raymond Y. Neilan, Tomas G. TI Obesity and sleep apnea are independently associated with adverse left ventricular remodeling and clinical outcome in patients with atrial fibrillation and preserved ventricular function SO AMERICAN HEART JOURNAL LA English DT Article ID POSITIVE AIRWAY PRESSURE; CATHETER ABLATION; ARTERIAL STIFFNESS; RECURRENCE; IMPACT; THERAPY; ATHEROSCLEROSIS; HYPERTENSION; RISK; MASS AB Aims Obesity is associated with the development of atrial fibrillation (AF), and both obesity and AF are independently associated with the development of heart failure with preserved ejection fraction. We tested the hypothesis that sleep apnea (SA) would have a body mass index (BMI) independent association with adverse left ventricular (LV) remodeling and clinical outcomes in patients with AF and preserved LV function. Methods and results From 720 consecutive patients with AF, 403 patients without myocardial disease (preserved LV function) were identified and followed up for 3.3 +/- 1.5 years. The primary outcome was a combination of all-cause mortality/heart failure hospitalization. Left ventricular mass and LV mass-to-volume ratio were higher in patients with SA and obesity (P < .0001 for all). Body mass index (beta per log = .47; P < .0001) and SA (beta = .05; P = .045) were independently associated with LV mass index. Patients with treated SA had a lower LV mass index (but not LV mass-to-volume ratio) compared with untreated (P = .002). In a best overall multivariable model, SA therapy (beta = -. 129; P =.001) and BMI (beta per log = .373; P = .0007) had opposing associations with LV mass index. Sleep apnea (hazard ratio [HR] = 2.94; P = .0004) and BMI (HR per 1 kg/m(2) = 1.08; P = .004) were associated with clinical outcome in unadjusted analysis. Only SA was associated with clinical outcome in a best overall multivariable model (HR = 2.14; P = .02). Conclusion Sleep apnea and obesity are independently associated with adverse LV remodeling and clinical outcomes in patients with preserved LV function, whereas continuous positive airway pressure therapy is associated with a beneficial effect on LV remodeling. Research investigating SA therapies in patients at high risk for LV remodeling and heart failure is warranted. C1 [Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Farhad, Hoshang; John, Roy M.; Blankstein, Ron; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Shah, Ravi V.; Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Dodson, John A.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Bakker, Jessie P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Veves, Aristidis] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Malhotra, Atul] Univ Calif San Diego, Div Pulm & Crit Care, La Jolla, CA 92093 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Neilan, TG (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac MR PET CT Program,Div Radiol, Boston, MA 02114 USA. EM tneilan@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 FU RVS-American Heart Association [11POST000002]; Heart Failure Clinical Research Network [U01-HL084877]; SAA-National Institutes of Health [T32HL094301-02]; MJH-National Institutes of Health [RO1HL090634]; RYK-National Institutes of Health [RO1HL091157]; JAD-National Institutes of Health [T32 AG000158-24]; TGN-American Heart Association [12FTF12060588]; AM-National Institutes of Health [R01HL090897, K24HL093218, P01HL095491, R01HL110350, UM1HL108724, R01AG035117, R01HL085188] FX External sources of funding: RVS-American Heart Association (11POST000002) and Heart Failure Clinical Research Network (U01-HL084877). SAA-National Institutes of Health (T32HL094301-02). MJH-National Institutes of Health (RO1HL090634). RYK-National Institutes of Health (RO1HL091157). JAD-National Institutes of Health (T32 AG000158-24). TGN-American Heart Association (12FTF12060588). AM-National Institutes of Health (R01HL090897, K24HL093218, P01HL095491, R01HL110350, UM1HL108724, R01AG035117, and R01HL085188). NR 27 TC 9 Z9 10 U1 1 U2 5 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 APR PY 2014 VL 167 IS 4 BP 620 EP 626 DI 10.1016/j.ahj.2014.01.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD3UE UT WOS:000333170900027 PM 24655713 ER PT J AU Gonzalez-Quesada, CJ Giugliano, RP AF Gonzalez-Quesada, Carlos J. Giugliano, Robert P. TI Comparison of the Phase III Clinical Trial Designs of Novel Oral Anticoagulants Versus Warfarin for the Treatment of Nonvalvular Atrial Fibrillation: Implications for Clinical Practice SO AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS LA English DT Review ID FACTOR-XA INHIBITOR; INTERNATIONAL NORMALIZED RATIO; STROKE RISK STRATIFICATION; DIRECT THROMBIN INHIBITOR; HEALTHY MALE-SUBJECTS; RE-LY TRIAL; DABIGATRAN ETEXILATE; PREDICTING STROKE; CHADS(2) SCORE; RIVAROXABAN AB Although vitamin K antagonists (VKAs) have been the backbone of thromboprophylaxis in nonvalvular atrial fibrillation, their limitations have encouraged the development of a new generation of oral anticoagulants. This review compares the different designs and procedures used to conduct four phase III trials that tested dabigatran, rivaroxaban, apixaban, and edoxaban versus VKAs. Although pharmacologic characteristics and results of the main trials are briefly discussed, this review mainly focuses on study designs, enrollment criteria, populations studied, quality metrics, and transition strategies between oral anticoagulants. While each of the trials was of high quality, performed independently, and led by independent academic groups, substantial differences exist in terms of drug pharmacology and trial characteristics. Caution is advised when comparing results across trials as practicing clinicians strive to personalize anticoagulation treatments for their individual patients. We believe that the differences in the pharmacokinetic and pharmacodynamic profiles of the available novel oral anticoagulants (NOACs), coupled with substantial heterogeneity in the trial populations and designs and procedures used to conduct the trials, support an important role for each of the NOACs dependent upon the specific clinical scenario faced by the practicing clinician. C1 [Gonzalez-Quesada, Carlos J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Giugliano, Robert P.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Daiichi Sankyo FX We would like to thank Colville Brown, MD, from AlphaBioCom for his technical assistance and formatting of this manuscript. Daiichi Sankyo provided funding for this technical assistance. NR 66 TC 9 Z9 9 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-3277 EI 1179-187X J9 AM J CARDIOVASC DRUG JI Am. J. Cardiovasc. Drugs PD APR PY 2014 VL 14 IS 2 BP 111 EP 127 DI 10.1007/s40256-013-0062-z PG 17 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA AD4EG UT WOS:000333199200004 PM 24504768 ER PT J AU Berkowitz, SA Seligman, HK Choudhry, NK AF Berkowitz, Seth A. Seligman, Hilary K. Choudhry, Niteesh K. TI Treat or Eat: Food Insecurity, Cost-related Medication Underuse, and Unmet Needs SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Chronic disease; Medication adherence; Socioeconomic factors; Population health; Underserved populations ID SOCIOECONOMIC DISPARITIES; CHRONIC DISEASE; NONADHERENCE; ADULTS; HEALTH; COVERAGE; HUNGER; CARE AB BACKGROUND: Adults with chronic disease are often unable to meet medication and food needs, but no study has examined the relationship between cost-related medication underuse and food insecurity in a nationally representative sample. We examined which groups most commonly face unmet food and medication needs. METHODS: Cross-sectional analysis of data from chronically ill participants (self-report of arthritis, diabetes mellitus, cancer, asthma, chronic obstructive pulmonary disease, stroke, hypertension, coronary heart disease, or presence of a "psychiatric problem") aged >= 20 years, in the 2011 National Health Interview Survey. We fit logistic regression models to identify factors associated with food insecurity, cost-related medication underuse, or both. RESULTS: There were 9696 adult National Health Interview Survey (NHIS) participants who reported chronic illness; 23.4% reported cost-related medication underuse; 18.8% reported food insecurity; and 11% reported both. Adults who reported food insecurity were significantly more likely to report cost-related medication underuse (adjusted odds ratio [aOR] 4.03). Participants with both cost-related medication underuse and food insecurity were more likely to be Hispanic (aOR 1.58), non-Hispanic black (aOR 1.58), and have more chronic conditions (aOR per additional chronic condition 1.56) than patients reporting neither. They also were less likely to have public, non-Medicare insurance (aOR 0.70) and report participation in the Special Supplemental Nutrition Assistance Program for Woman, Infants, and Children (aOR 0.39). CONCLUSIONS: Approximately 1 in 3 chronically ill NHIS participants are unable to afford food, medications, or both. WIC and public health insurance participation are associated with less food insecurity and cost-related medication underuse. (C) 2014 Elsevier Inc. All rights reserved. C1 [Berkowitz, Seth A.] Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02141 USA. [Berkowitz, Seth A.; Choudhry, Niteesh K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Seligman, Hilary K.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA 94143 USA. [Choudhry, Niteesh K.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02141 USA. EM SABerkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU Institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; General Medicine Division at Massachusetts General Hospital FX SAB was supported by an Institutional National Research Service Award #T32HP10251, the Ryoichi Sasakawa Fellowship Fund, and by the General Medicine Division at Massachusetts General Hospital. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; or preparation, review, decision to submit for publication, or approval of the manuscript. NR 24 TC 27 Z9 29 U1 6 U2 20 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 APR PY 2014 VL 127 IS 4 BP 303 EP + DI 10.1016/j.amjmed.2014.01.002 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AD4ZN UT WOS:000333261000020 PM 24440543 ER PT J AU Simon, HB AF Simon, Harvey B. TI Reading Fiction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hsimon@mgh.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD APR PY 2014 VL 127 IS 4 BP 356 EP 357 DI 10.1016/j.amjmed.2013.11.017 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AD4ZN UT WOS:000333261000028 PM 24355350 ER PT J AU Blosnich, JR Farmer, GW Lee, JGL Silenzio, VMB Bowen, DJ AF Blosnich, John R. Farmer, Grant W. Lee, Joseph G. L. Silenzio, Vincent M. B. Bowen, Deborah J. TI Health Inequalities Among Sexual Minority Adults Evidence from Ten US States, 2010 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; BISEXUAL POPULATIONS; SUBSTANCE USE; ORIENTATION; GAY; PREVALENCE; BEHAVIORS; RISK; DISPARITIES; DISORDERS AB Background: Improving the health of lesbian, gay, and bisexual (LGB) individuals is a Healthy People 2020 goal; however, the IOM highlighted the paucity of information currently available about LGB populations. Purpose: To compare health indicators by gender and sexual orientation statuses. Methods: Data are from Behavioral Risk Factor Surveillance System surveys conducted January-December of 2010 with population-based samples of non-institutionalized U. S. adults aged over 18 years (N=93,414) in ten states that asked about respondents' sexual orientation (response rates=41.1%-65.6%). Analyses were stratified by gender and sexual orientation to compare indicators of mental health, physical health, risk behaviors, preventive health behaviors, screening tests, health care utilization, and medical diagnoses. Analyses were conducted in March 2013. Results: Overall, 2.4% (95% CI=2.2, 2.7) of the sample identified as LGB. All sexual minority groups were more likely to be current smokers than their heterosexual peers. Compared with heterosexual women, lesbian women had more than 30% decreased odds of having an annual routine physical exam, and bisexual women had more than 2.5 times the odds of not seeking medical care owing to cost. Compared with heterosexual men, gay men were less likely to be overweight or obese, and bisexual men were twice as likely to report a lifetime asthma diagnosis. Conclusions: This study represents one of the largest samples of LGB adults and finds important health inequalities, including that bisexual women bear particularly high burdens of health disparities. Further work is needed to identify causes of and intervention for these disparities. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Blosnich, John R.; Silenzio, Vincent M. B.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Farmer, Grant W.] St Louis Univ, Coll Publ Hlth & Social Justice, Dept Epidemiol, St Louis, MO 63103 USA. [Lee, Joseph G. L.] Univ N Carolina, Dept Hlth Behav, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Bowen, Deborah J.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov RI Lee, Joseph/B-7475-2009 OI Lee, Joseph/0000-0001-9698-649X FU Institutional National Research Service Award from the National Institute of Mental Health [5T32MH020061]; predoctoral National Research Service Award from the National Institute on Drug Abuse [F31DA032220] FX This work was supported partially by a postdoctoral fellowship to John R. Blosnich in an Institutional National Research Service Award from the National Institute of Mental Health (5T32MH020061) and a predoctoral National Research Service Award to Grant W. Farmer from the National Institute on Drug Abuse (F31DA032220). The opinions expressed in this work are those of the authors and do not represent those of the funders, institutions, the Department of Veterans Affairs, or the U.S. Government. NR 35 TC 37 Z9 37 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2014 VL 46 IS 4 BP 337 EP 349 DI 10.1016/j.amepre.2013.11.010 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AD4YM UT WOS:000333257900003 PM 24650836 ER PT J AU Cohen, JFW Richardson, S Parker, E Catalano, PJ Rimm, EB AF Cohen, Juliana F. W. Richardson, Scott Parker, Ellen Catalano, Paul J. Rimm, Eric B. TI Impact of the New US Department of Agriculture School Meal Standards on Food Selection, Consumption, and Waste SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID VEGETABLE CONSUMPTION; PLATE WASTE; FRUIT; CHILDREN AB Background: The U.S Department of Agriculture (USDA) recently made substantial changes to the school meal standards. The media and public outcry have suggested that this has led to substantially more food waste. Purpose: School meal selection, consumption, and waste were assessed before and after implementation of the new school meal standards. Methods: Plate waste data were collected in four schools in an urban, low-income school district. Logistic regression and mixed-model ANOVA were used to estimate the differences in selection and consumption of school meals before (fall 2011) and after implementation (fall 2012) of the new standards among 1030 elementary and middle school children. Analyses were conducted in 2013. Results: After the new standards were implemented, fruit selection increased by 23.0% and entree and vegetable selection remained unchanged. Additionally, post-implementation entree consumption increased by 15.6%, vegetable consumption increased by 16.2%, and fruit consumption remained the same. Milk selection and consumption decreased owing to an unrelated milk policy change. Conclusions: Although food waste levels were substantial both pre- and post-implementation, the new guidelines have positively affected school meal selection and consumption. Despite the increased vegetable portion size requirement, consumption increased and led to significantly more cups of vegetables consumed. Significantly more students selected a fruit, whereas the overall percentage of fruit consumed remained the same, resulting in more students consuming fruits. Contrary to media reports, these results suggest that the new school meal standards have improved students' overall diet quality. Legislation to weaken the standards is not warranted. (C) 2014 American Journal of Preventive Medicine C1 [Cohen, Juliana F. W.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Richardson, Scott; Parker, Ellen] Brigham & Womens Hosp, Project Bread, Boston, MA 02115 USA. [Catalano, Paul J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rimm, Eric B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cohen, JFW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave, Boston, MA 02115 USA. EM jcohen@hsph.harvard.edu FU NCI NIH HHS [R25 CA 098566, R25 CA098566] NR 17 TC 42 Z9 42 U1 4 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2014 VL 46 IS 4 BP 388 EP 394 DI 10.1016/j.amepre.2013.11.013 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AD4YM UT WOS:000333257900008 PM 24650841 ER PT J AU Batki, SL Pennington, DL AF Batki, Steven L. Pennington, David L. TI Toward Personalized Medicine in the Pharmacotherapy of Alcohol Use Disorder: Targeting Patient Genes and Patient Goals SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID FUNCTIONAL POLYMORPHISM; NALTREXONE RESPONSE; DEPENDENT PATIENTS; HEAVY DRINKERS; TOPIRAMATE; RISK C1 [Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, Addict Res Program, San Francisco, CA 94121 USA. RP Batki, SL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM steven.batki@ucsf.edu NR 15 TC 4 Z9 5 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2014 VL 171 IS 4 BP 391 EP 394 DI 10.1176/appi.ajp.2014.14010061 PG 4 WC Psychiatry SC Psychiatry GA AD8FD UT WOS:000333501000004 PM 24687193 ER PT J AU Basturk, O Tang, L Hruban, RH Adsay, V Yang, ZH Krasinskas, AM Vakiani, E La Rosa, S Jang, KT Frankel, WL Liu, XL Zhang, LZ Giordano, TJ Bellizzi, AM Chen, JH Shi, CJ Allen, P Reidy, DL Wolfgang, CL Saka, B Rezaee, N Deshpande, V Klimstra, DS AF Basturk, Olca Tang, Laura Hruban, Ralph H. Adsay, Volkan Yang, Zhaohai Krasinskas, Alyssa M. Vakiani, Efsevia La Rosa, Stefano Jang, Kee-Taek Frankel, Wendy L. Liu, Xiuli Zhang, Lizhi Giordano, Thomas J. Bellizzi, Andrew M. Chen, Jey-Hsin Shi, Chanjuan Allen, Peter Reidy, Diane L. Wolfgang, Christopher L. Saka, Burcu Rezaee, Neda Deshpande, Vikram Klimstra, David S. TI Poorly Differentiated Neuroendocrine Carcinomas of the Pancreas A Clinicopathologic Analysis of 44 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE neuroendocrine; high grade; carcinoma; poorly differentiated; large cell; pancreas; small cell ID SMALL-CELL-CARCINOMA; PROGNOSTIC-FACTORS; UNDIFFERENTIATED CARCINOMA; GASTROINTESTINAL-TRACT; ENDOCRINE NEOPLASMS; LUNG-TUMORS; GRADE; CISPLATIN; ETOPOSIDE; DISTINCT AB Background: In the pancreas, poorly differentiated neuroendocrine carcinomas include small cell carcinoma and large cell neuroendocrine carcinoma and are rare; data regarding their pathologic and clinical features are very limited. Design: A total of 107 pancreatic resections originally diagnosed as poorly differentiated neuroendocrine carcinomas were reassessed using the classification and grading (mitotic rate/Ki67 index) criteria put forth by the World Health Organization in 2010 for the gastroenteropancreatic system. Immunohistochemical labeling for neuroendocrine and acinar differentiation markers was performed. Sixty-three cases were reclassified, mostly as well-differentiated neuroendocrine tumor (NET) or acinar cell carcinoma, and eliminated. The clinicopathologic features and survival of the remaining 44 poorly differentiated neuroendocrine carcinomas were further assessed. Results: The mean patient age was 59 years (range, 21 to 82 y), and the male/female ratio was 1.4. Twenty-seven tumors were located in the head of the pancreas, 3 in the body, and 11 in the tail. The median tumor size was 4 cm (range, 2 to 18 cm). Twenty-seven tumors were large cell neuroendocrine carcinomas, and 17 were small cell carcinomas (mean mitotic rate, 37/10 and 51/10 HPF; mean Ki67 index, 66% and 75%, respectively). Eight tumors had combined components, mostly adenocarcinomas. In addition, 2 tumors had components of well-differentiated NET. Eighty-eight percent of the patients had nodal or distant metastatic disease at presentation, and an additional 7% developed metastases subsequently. Follow-up information was available for 43 patients; 33 died of disease, with a median survival of 11 months (range, 0 to 104 mo); 8 were alive with disease, with a median follow-up of 19.5 months (range, 0 to 71 mo). The 2- and 5-year survival rates were 22.5% and 16.1%, respectively. Conclusions: Poorly differentiated neuroendocrine carcinoma of the pancreas is a highly aggressive neoplasm, with frequent metastases and poor survival. Most patients die within less than a year. Most (61%) are large cell neuroendocrine carcinomas. Well-differentiated NET and acinar cell carcinoma are often misdiagnosed as poorly differentiated neuroendocrine carcinoma, emphasizing that diagnostic criteria need to be clearly followed to ensure accurate diagnosis. C1 [Basturk, Olca; Tang, Laura; Vakiani, Efsevia; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Allen, Peter] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. [Reidy, Diane L.] Mem Sloan Kettering Canc Ctr, Dept Oncol, New York, NY 10065 USA. [Hruban, Ralph H.; Wolfgang, Christopher L.; Rezaee, Neda] Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA. [Wolfgang, Christopher L.; Rezaee, Neda] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Adsay, Volkan; Saka, Burcu] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Yang, Zhaohai] Penn State Hershey MC, Dept Pathol, Hershey, PA USA. [Krasinskas, Alyssa M.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Frankel, Wendy L.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Liu, Xiuli] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA. [Zhang, Lizhi] Mayo Clin, Dept Pathol, Rochester, MN USA. [Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Bellizzi, Andrew M.] Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA. [Chen, Jey-Hsin] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. [Shi, Chanjuan] Vanderbilt Univ, Dept Pathol, Nashville, TN USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [La Rosa, Stefano] Osped Circolo Varese, Dept Pathol, Varese, Italy. [Jang, Kee-Taek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM klimstrd@mskcc.org FU National Cancer Institute Specialized Program in Research Excellence (SPORE) [CA62924]; National Institutes of Health [5P50 CA62924] FX Supported in part by the National Cancer Institute Specialized Program in Research Excellence (SPORE) CA62924. R.H.H. and N.V.A. have a grant from National Institutes of Health (#5P50 CA62924); Z.Y. has received honoraria from UpToDate Inc.; W.L.F. has been an alliance for Clinical Trials in Oncology and received honoraria from Frozen Section Library: Pancreas: Springer; D.S.K. was on the speaker's bureau for Novartis and has received honoraria from UpToDate. For the remaining authors none were declared. NR 42 TC 34 Z9 36 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2014 VL 38 IS 4 BP 437 EP 447 DI 10.1097/PAS.0000000000000169 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA AD6SN UT WOS:000333391300001 PM 24503751 ER PT J AU Hawkins, AT Henry, AJ Crandell, DM Nguyen, LL AF Hawkins, Alexander T. Henry, Antonia J. Crandell, David M. Nguyen, Louis L. TI A Systematic Review of Functional and Quality of Life Assessment after Major Lower Extremity Amputation SO ANNALS OF VASCULAR SURGERY LA English DT Review ID LOWER-LIMB AMPUTEES; SICKNESS IMPACT PROFILE; PHYSICAL-ACTIVITY QUESTIONNAIRE; PROSTHESIS EXPERIENCE SCALES; FRENCHAY ACTIVITIES INDEX; RIVERMEAD MOBILITY INDEX; TEST-RETEST RELIABILITY; TRANS-TIBIAL AMPUTEES; HEALTH STATUS MEASURE; 2-MINUTE WALK TEST AB Background: When judging the success or failure of major lower extremity (MLE) amputation, the assessment of appropriate functional and quality of life (QOL) outcomes is paramount. The heterogeneity of the scales and tests in the current literature is confusing and makes it difficult to compare results. We provide a primer for outcome assessment after amputation and assess the need for the additional development of novel instruments. Methods: MEDLINE, EMBASE, and Google Scholar were searched for all studies using functional and QOL instruments after MLE amputation. Assessment instruments were divided into functional and QOL categories. Within each category, they were subdivided into global and amputation-specific instruments. An overall assessment of instrument quality was obtained. Results: The initial search revealed 746 potential studies. After a review of abstracts, 102 were selected for full review, and 40 studies were then included in this review. From the studies, 21 different assessment instruments were used 63 times. There were 14 (67%) functional measures and 7 (33%) QOL measures identified. Five (36%) of the functional instruments and 3 (43%) of the QOL measures were specific for MLE amputees. Sixteen instruments were used > 1 time, but only 5 instruments were used > 3 times. An additional 5 instruments were included that were deemed important by expert opinion. The 26 assessment instruments were rated. Fourteen of the best-rated instruments were then described. Conclusions: The heterogeneity of instruments used to measure both functional and QOL outcomes make it difficult to compare MLE amputation outcome studies. Future researchers should seek to use high-quality instruments. Clinical and research societies should endorse the best validated instruments for future use in order to strengthen overall research in the field. C1 [Hawkins, Alexander T.; Nguyen, Louis L.] Ctr Surg & Publ Hlth, Boston, MA USA. [Hawkins, Alexander T.; Henry, Antonia J.; Nguyen, Louis L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hawkins, Alexander T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crandell, David M.] Spaulding Rehabil Hosp, Charlestown, MA USA. [Crandell, David M.; Nguyen, Louis L.] Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, LL (reprint author), Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. EM llnguyen@partners.org FU Arthur Tracy Cabot Fellowship though the Brigham & Women's Hospital Center for Surgery and Public Health; Harvard-Longwood T-32 Vascular Training Grant [NIH 5T32HL007734] FX Supported by the Arthur Tracy Cabot Fellowship though the Brigham & Women's Hospital Center for Surgery and Public Health and the Harvard-Longwood T-32 Vascular Training Grant (to A.T.H.; NIH 5T32HL007734). NR 113 TC 6 Z9 8 U1 3 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD APR PY 2014 VL 28 IS 3 BP 763 EP 780 DI 10.1016/j.avsg.2013.07.011 PG 18 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AD4WR UT WOS:000333252600058 PM 24495325 ER PT J AU Novick, DM Allbaugh, L Zhao, Z Henshaw, E Vazquez, DM Armitage, R Flynn, H AF Novick, Danielle M. Allbaugh, Lucy Zhao, Zhuo Henshaw, Erin Vazquez, Delia M. Armitage, Roseanne Flynn, Heather CA Womens Mental Hlth Infants Program TI Representativeness of obstetric patients who participate in perinatal depression research: findings from the Women's Mental Health and Infants Program (WMHIP) integrated dataset SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Perinatal; Depression; Selection bias; Validity; Recruitment ID TRIALS; RECRUITMENT; SYMPTOMS; IMPACT AB The aims of this study were to evaluate the feasibility of integrating archival datasets from depression projects involving pregnant women recruited from obstetric clinics and then assess the representativeness of the integrated dataset. Datasets from six studies were standardized and integrated. Chi-square, t-, and Wilcoxon rank-sum tests were used to compare characteristics between women who completed a depression screening questionnaire (DSQ) and were (1) eligible and ineligible for research participation and (2) eligible women who accepted and declined participation. The integrated dataset comprises 9,112 pregnant women, of whom 71.0 % (n = 6,472) were ineligible for participation because their DSQ scores indicated no-to-minimal depressive symptoms (NDS). Among the 23.9 % (2,176) of women identified as eligible, in part, because their DSQ scores indicated elevated levels of depressive symptoms (EDS), 29.6 % (644) of women participated (P-EDS) and 47.6 % (1,036) of women did not participate (D-EDS). While the NDS and EDS groups were significantly different on almost all variables, the P-EDS and D-EDS groups were significantly different on only a few variables. Compared to the D-EDS group, the P-EDS group was earlier in pregnancy and, on the Edinburgh Postnatal Depression Screen, was more likely to endorse impaired "ability to laugh" and "enjoy oneself", and endorse at greater severity "ability to laugh." It is a reasonable and feasible strategy to integrate thematically similar datasets to increase statistical power. Additionally, typical recruitment strategies for minimal risk perinatal depression research at obstetric clinics, during routine prenatal care visits, appear to produce an externally valid study cohort. C1 [Novick, Danielle M.; Zhao, Zhuo; Armitage, Roseanne; Flynn, Heather; Womens Mental Hlth Infants Program] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Novick, Danielle M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Allbaugh, Lucy] Miami Univ, Dept Psychol, Oxford, OH 45056 USA. [Henshaw, Erin] Denison Univ, Granville, OH 43023 USA. [Vazquez, Delia M.] Univ Michigan, Dept Pediat Endocrinol, Ann Arbor, MI 48109 USA. [Flynn, Heather] Florida State Univ, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA. RP Novick, DM (reprint author), Univ Michigan, Dept Psychiat, 4250 Plymouth Rd,SPC 5769, Ann Arbor, MI 48109 USA. EM dnovick@med.umich.edu FU Department of Psychiatry at University of Michigan; National Institute of Mental Health [MH065062, MH063880]; Psychiatry Research Council; Rachel Upjohn Scholars Award, University of Michigan Depression Center FX The Women's Mental Health and Infants Program (WMHIP) was established with support from the Department of Psychiatry at University of Michigan. Original research was supported with grants from the National Institute of Mental Health MH065062 and MH063880, Psychiatry Research Council, and Rachel Upjohn Scholars Award, University of Michigan Depression Center. The authors gratefully acknowledge feedback on a previous draft from Cynthia Battle. NR 22 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD APR PY 2014 VL 17 IS 2 BP 97 EP 105 DI 10.1007/s00737-013-0385-4 PG 9 WC Psychiatry SC Psychiatry GA AD3HY UT WOS:000333130200002 PM 24248412 ER PT J AU Gandy, S AF Gandy, Sam TI Alzheimer's Disease: New Data Highlight Nonneuronal Cell Types and the Necessity for Presymptomatic Prevention Strategies SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Amyloid plaques; amyloidosis; microglia; neuro-degeneration; systems biology; tauopathy ID AMYLOID-BETA PEPTIDE; MICE; ANTIBODIES; MICROGLIA; PATHOLOGY; VARIANTS; CD33; APOE; CR-1 AB Despite compelling genetic evidence indicating that cerebral amyloidosis can be, at least sometimes, the primary cause of Alzheimer's disease (AD), clinical trials for symptomatic AD with amyloid-reducing agents have succeeded at target engagement but failed to cause clinical benefit. In a landmark shift, the U.S. Food and Drug Administration now proposes to approve prophylaxis that alters the trajectory of what is now believed to be typical AD biomarker evolution. The first prevention trials are now beginning in patients with genetic guarantees for or high genetic risks for AD. The expectation is that clues to their outcomes will begin to emerge from these trials in approximately 2018. In the meantime, new strategies point to nonneuronal cells and to system pathology. A review of the current state of the art of AD science follows herein. C1 [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Mt Sinai Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, One Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU National Institute of Neurological Disorders and Stroke; National Institute on Aging; Veterans Administration; American Health Assistance Foundation; Cure Alzheimer's Fund FX SG acknowledges the support of National Institute of Neurological Disorders and Stroke, National Institute on Aging, the Veterans Administration, the American Health Assistance Foundation, and the Cure Alzheimer's Fund. NR 24 TC 4 Z9 4 U1 2 U2 11 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 APR 1 PY 2014 VL 75 IS 7 BP 553 EP 557 DI 10.1016/j.biopsych.2013.11.019 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AD2RD UT WOS:000333081900006 PM 24373429 ER PT J AU Rorije, NMG Shea, MM Satyanarayana, G Hammond, SP Ho, VT Baden, LR Antin, JH Soiffer, RJ Marty, FM AF Rorije, Nienke M. G. Shea, Margaret M. Satyanarayana, Gowri Hammond, Sarah P. Ho, Vincent T. Baden, Lindsey R. Antin, Joseph H. Soiffer, Robert J. Marty, Francisco M. TI BK Virus Disease after Allogeneic Stem Cell Transplantation: A Cohort Analysis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE BK virus; Allogeneic stem cell transplantation; Cord blood transplantation; Graft-versus-host disease; Human BK polyomavirus ID BONE-MARROW-TRANSPLANTATION; ONSET HEMORRHAGIC CYSTITIS; CORD BLOOD TRANSPLANTATION; VERSUS-HOST-DISEASE; RISK-FACTORS; RECIPIENTS; ASSOCIATION; PROPHYLAXIS; INTENSITY; SIROLIMUS AB The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BIN disease after HSCT. BIN disease was defined as BIN detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of.47/1000 patient-days (95% confidence interval [CI],.37 to .59); BIN disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades ll to IV (adjusted hazard ratio [aHR14.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Rorije, Nienke M. G.; Shea, Margaret M.; Satyanarayana, Gowri; Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Rorije, Nienke M. G.] Univ Groningen, Univ Med Ctr Groningen, Sch Med, Groningen, Netherlands. [Hammond, Sarah P.; Ho, Vincent T.; Baden, Lindsey R.; Antin, Joseph H.; Soiffer, Robert J.; Marty, Francisco M.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org FU Dutch Kidney Foundation; Dutch Cancer Society; Marco Polo fund; J.K. de Cock foundation FX The Dutch Kidney Foundation, the Dutch Cancer Society, the Marco Polo fund, and the J.K. de Cock foundation provided financial support for N.M.G.R. NR 46 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2014 VL 20 IS 4 BP 564 EP 570 DI 10.1016/j.bbmt.2014.01.014 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AD5VX UT WOS:000333322400019 PM 24462984 ER PT J AU DeCensi, A Sun, ZX Guerrieri-Gonzaga, A Thurlimann, B McIntosh, C Tondini, C Monnier, A Campone, M Debled, M Schonenberger, A Zaman, K Johansson, H Price, KN Gelber, RD Goldhirsch, A Coates, AS Aebi, S AF DeCensi, Andrea Sun, Zhuoxin Guerrieri-Gonzaga, Aliana Thuerlimann, Beat McIntosh, Christina Tondini, Carlo Monnier, Alain Campone, Mario Debled, Marc Schoenenberger, Astrid Zaman, Khalil Johansson, Harriet Price, Karen N. Gelber, Richard D. Goldhirsch, Aron Coates, Alan S. Aebi, Stefan TI Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Adjuvant drug therapy; Aromatase inhibitor; Bone density; Bone turnover ID EARLY BREAST-CANCER; HEALTHY POSTMENOPAUSAL WOMEN; INTERGROUP EXEMESTANE; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; ANASTROZOLE; FRACTURES; TURNOVER; OSTEOPOROSIS; PREDICTS AB The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence. C1 [DeCensi, Andrea] EO Osped Galliera, Div Med Oncol, I-16128 Genoa, Italy. [DeCensi, Andrea; Guerrieri-Gonzaga, Aliana; Johansson, Harriet] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. [Sun, Zhuoxin] Harvard Univ, Sch Publ Hlth, Int Breast Canc Study Grp IBCSG Stat Ctr, Dept Biostat & Computat Biol,Dana Farber Canc Ins, Boston, MA 02115 USA. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [McIntosh, Christina] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tondini, Carlo] Osped Papa Giovanni XXIII, Bergamo, Italy. [Monnier, Alain] Univ Franche Comte, IRMA Team, CNRS, UMR 6249, Montbeliard, France. [Campone, Mario] Inst Cancerol OUEST, Dept Med Oncol, Nantes, France. [Debled, Marc] Inst Bergonie, Dept Med, Bordeaux, France. [Schoenenberger, Astrid] Spital Langenthal SRO AG, Langenthal, Switzerland. [Zaman, Khalil] Univ Hosp CHUV, Breast Ctr, Lausanne, Switzerland. [Zaman, Khalil] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Dana Farber Canc Inst, Int Breast Canc Study Grp IBCSG Stat Ctr, Boston, MA 02215 USA. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth,Harvard Med Sch, Int Breast Canc Study Grp IBCSG Stat Ctr, Dept Biostat & Computat Biol,Dana Farber Canc Ins, Boston, MA 02115 USA. [Goldhirsch, Aron] European Inst Oncol, Div Med Oncol, Milan, Italy. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Darlington, NSW, Australia. [Aebi, Stefan] Luzerner Kantonsspital, Luzern, Switzerland. [Aebi, Stefan] Univ Bern, Bern, Switzerland. [Aebi, Stefan] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. RP DeCensi, A (reprint author), EO Osped Galliera, Div Med Oncol, Mura Cappuccine 14, I-16128 Genoa, Italy. EM andrea.decensi@galliera.it; zhuoxin@jimmy.harvard.edu; aliana.guerrieri-gonzaga@ieo.it; beat.thuerlimann@kssg.ch; cmm862@mail.harvard.edu; carlo.tondini@ospedaliriuniti.bergamo.it; dramonnier@orange.fr; Mario.Campone@ico.unicancer.fr; m.debled@bordeaux.unicancer.fr; a.schoenenberger@sro.ch; Khalil.Zaman@chuv.ch; harriet.johansson@ieo.it; gelber@jimmy.harvard.edu; alan.coates@ibcsg.org; stefan.aebi@onkologie.ch RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU Novartis; Swedish Cancer Society; Cancer Council Australia; Australia and New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Institutes of Health [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX This work was supported by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society; the Cancer Council Australia; Australia and New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Institutes of Health [grant number CA-75362] to [RDG], Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). We thank the patients, physicians, investigators, nurses, and data managers who participated in the BIG 1-98 Bone Sub-study NR 31 TC 1 Z9 1 U1 0 U2 3 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 APR PY 2014 VL 144 IS 2 BP 321 EP 329 DI 10.1007/s10549-014-2849-2 PG 9 WC Oncology SC Oncology GA AD0XY UT WOS:000332959000011 PM 24487691 ER PT J AU Ruddy, KJ O'Neill, A Miller, KD Schneider, BP Baker, E Sparano, JA Dang, C Northfelt, DW Sledge, GW Partridge, AH AF Ruddy, Kathryn J. O'Neill, Anne Miller, Kathy D. Schneider, Bryan P. Baker, Emily Sparano, Joseph A. Dang, Chau Northfelt, Donald W. Sledge, George W., Jr. Partridge, Ann H. TI Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast neoplasms; Fertility; Biomarkers; Chemotherapy; Adjuvant ID ANTI-MULLERIAN HORMONE; OVARIAN RESERVE; BEVACIZUMAB AVASTIN; THERAPY AB This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25-55), and median serum AMH level was 0.11 ng/mL (range 0.01-8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted. C1 [Ruddy, Kathryn J.] Mayo Clin, Rochester, MN 55905 USA. [O'Neill, Anne; Baker, Emily; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Kathy D.; Schneider, Bryan P.] Indiana Univ Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. [Sparano, Joseph A.] Montefiore Hosp & Med Ctr, Bronx, NY USA. [Dang, Chau] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Northfelt, Donald W.] Mayo Clin, Scottsdale, AZ USA. [Sledge, George W., Jr.] Stanford Univ, Palo Alto, CA 94304 USA. RP Ruddy, KJ (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM ruddy.kathryn@mayo.edu FU Public Health Service Grants [CA23318, CA66636, CA21115, CA49883, CA14958, CA77651, CA25224, CA32291]; Komen Promise Grant; Breast Cancer Research Foundation; Roche/Genentech; GlaxoSmithKline; Genentech FX This study was supported by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, CA14958, CA77651, CA25224, CA32291, as well as a Komen Promise Grant (PI: Schneider) and funds from the Breast Cancer Research Foundation. Chau Dang receives research funding from Roche/Genentech and GlaxoSmithKline and also serves as a consultant/advisor for Pfizer. Kathy Miller, Bryan Schneider, and Joseph Sparano have consultant/advisory roles Genentech, and Dr. Schneider is on the Genentech Speaker's Bureau. George Sledge receives remuneration from Genentech. NR 25 TC 7 Z9 7 U1 0 U2 9 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 APR PY 2014 VL 144 IS 3 BP 591 EP 597 DI 10.1007/s10549-014-2891-0 PG 7 WC Oncology SC Oncology GA AD6IF UT WOS:000333360700014 PM 24584876 ER PT J AU Kim, B Hing, ZA Wu, A Schiller, T Struble, EB Liuwantara, D Kempert, PH Broxham, EJ Edwards, NC Marder, VJ Simhadri, VL Sauna, ZE Howard, TE Kimchi-Sarfaty, C AF Kim, Benjamin Hing, Zachary A. Wu, Andrew Schiller, Tal Struble, Evi B. Liuwantara, David Kempert, Pamela H. Broxham, Eric J. Edwards, Nathan C. Marder, Victor J. Simhadri, Vijaya L. Sauna, Zuben E. Howard, Tom E. Kimchi-Sarfaty, Chava TI Single-nucleotide variations defining previously unreported ADAMTS13 haplotypes are associated with differential expression and activity of the VWF-cleaving protease in a Salvadoran congenital thrombotic thrombocytopenic purpura family SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE haplotypes; congenital thrombotic thrombocytopenic purpura; phenotypes; quantitative trait nucleotides; ADAMTS13 ID MUTATIONS; DISEASE C1 [Kim, Benjamin] Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. [Hing, Zachary A.; Wu, Andrew; Schiller, Tal; Edwards, Nathan C.; Simhadri, Vijaya L.; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, CBER, Bethesda, MD 20014 USA. [Struble, Evi B.] US FDA, Lab Plasma Derivat, Div Hematol, CBER, Bethesda, MD 20014 USA. [Liuwantara, David; Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Kempert, Pamela H.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Pediat, Los Angeles, CA 90095 USA. [Broxham, Eric J.; Howard, Tom E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Marder, Victor J.; Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. RP Kim, B (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. EM tom.howard@va.gov; chava.kimchi-sarfaty@fda.hhs.gov FU NHLBI NIH HHS [HL-72533, 1RC2-HL101851, HL-71130] NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2014 VL 165 IS 1 BP 154 EP 158 DI 10.1111/bjh.12713 PG 5 WC Hematology SC Hematology GA AC8BH UT WOS:000332757500020 PM 24433405 ER PT J AU Shields, HM Stoffel, EM Chung, DC Sequist, TD Li, JW Pelletier, SR Spencer, J Silk, JM Austin, BL Diguette, S Furbish, JE Lederman, R Weingart, SN AF Shields, Helen M. Stoffel, Elena M. Chung, Daniel C. Sequist, Thomas D. Li, Justin W. Pelletier, Stephen R. Spencer, Justin Silk, Jean M. Austin, Bonita L. Diguette, Susan Furbish, Jean E. Lederman, Ruth Weingart, Saul N. TI Disparities in Evaluation of Patients With Rectal Bleeding 40 Years and Older SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Early Detection; Colorectal Cancer; Age; Patient Management ID COLORECTAL-CANCER; GENERAL-PRACTICE; UNITED-STATES; AFRICAN-AMERICAN; DECISION-MAKING; BOWEL-CANCER; PRIMARY-CARE; HEALTH-CARE; COLONOSCOPY; RISK AB BACKGROUND & AIMS: Rectal bleeding is associated with colorectal cancer. We characterized the evaluation of patients aged 40 years and older with rectal bleeding and identified characteristics associated with inadequate evaluation. METHODS: We conducted a retrospective review of records of outpatient visits that contained reports of rectal bleeding for patients aged 40 years and older (N = 480). We studied whether patient characteristics affected whether or not they received a colonoscopy examination within 90 days of presentation with rectal bleeding. Patient characteristics included demographics; family history of colon cancer and polyps; and histories of screening colonoscopies, physical examinations, referrals to specialists at the index visit, and communication of laboratory results. Data were collected from medical records, and patient income levels were estimated based on Zip codes. RESULTS: Nearly half of the patients presenting with rectal bleeding received colonoscopies (48.1%); 81.7% received the procedure within 90 days. A history of a colonoscopy examination was more likely to be reported in white patients compared with Hispanic or Asian patients (P = .012 and P = .006, respectively), and in high-income compared with low-income patients (P = .022). A family history was more likely to be documented among patients with private insurance than those with Medicaid or Medicare (P = .004). A rectal examination was performed more often for patients who were white or Asian, male, and with high or middle incomes, compared with those who were black, Hispanic, female, or with low incomes (P = .027). White patients were more likely to have their laboratory results communicated to them than black patients (P = .001). CONCLUSIONS: Sex, race, ethnicity, patient income, and insurance status were associated with disparities in evaluation of rectal bleeding. There is a need to standardize the evaluation of patients with rectal bleeding. C1 [Shields, Helen M.; Furbish, Jean E.; Weingart, Saul N.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Shields, Helen M.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Shields, Helen M.; Chung, Daniel C.; Sequist, Thomas D.] Harvard Univ, Sch Med, Boston, MA USA. [Stoffel, Elena M.; Sequist, Thomas D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Stoffel, Elena M.; Silk, Jean M.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Sequist, Thomas D.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Sequist, Thomas D.] Brigham & Womens Hosp, Dept Hlth Care Policy, Boston, MA 02115 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Li, Justin W.; Spencer, Justin; Weingart, Saul N.] Harvard Vanguard Med Associates, Boston, MA USA. [Lederman, Ruth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pelletier, Stephen R.] Harvard Univ, Sch Med, Ctr Evaluat, Boston, MA USA. RP Shields, HM (reprint author), Brigham & Womens Hosp, Div Gastroenterol & Hepatol, 1620 Tremont St, Boston, MA 02120 USA. EM hmshields@partners.org FU Risk Management Foundation of the Harvard Medical Institutions FX This study was funded by a grant from theRisk Management Foundation of the Harvard Medical Institutions. NR 48 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2014 VL 12 IS 4 BP 669 EP 675 DI 10.1016/j.cgh.2013.07.008 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD2IF UT WOS:000333057500025 PM 23891918 ER PT J AU Walling, AM Wenger, NS AF Walling, Anne M. Wenger, Neil S. TI Palliative Care and End-Stage Liver Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID TRANSPLANT; CIRRHOSIS; BURDEN; LIFE C1 [Walling, Anne M.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Walling, Anne M.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Wenger, Neil S.] UCLA, Hlth Eth Ctr, Los Angeles, CA USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. FU NCATS NIH HHS [KL2 TR000122, UL1 TR000124, KL2TR000122] NR 10 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2014 VL 12 IS 4 BP 699 EP 700 DI 10.1016/j.cgh.2013.11.010 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD2IF UT WOS:000333057500030 PM 24246765 ER PT J AU Castillo, JJ Ingham, RR Reagan, JL Furman, M Dalia, S Mitri, J AF Castillo, Jorge J. Ingham, Randall R. Reagan, John L. Furman, Michael Dalia, Samir Mitri, Joanna TI Obesity Is Associated With Increased Relative Risk of Diffuse Large B-Cell Lymphoma: A Meta-Analysis of Observational Studies SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE Body mass index; Epidemiology; Lymphoma; Meta-analysis; Obesity ID NON-HODGKIN-LYMPHOMA; BODY-MASS INDEX; PHYSICAL-ACTIVITY; ANTHROPOMETRIC CHARACTERISTICS; PROSPECTIVE COHORT; UNITED-STATES; CANCER; HEIGHT; OVERWEIGHT; LEUKEMIA AB Our study aimed at evaluating the relation, if any, between obesity and diffuse large B-cell lymphoma (DLBCL). We pooled and analyzed data from 16 studies accounting for approximately 7500 cases of DLBCL. We found an approximately 30% increase in the relative risk of DLBCL in obese individuals; this increase was consistent among men and women. Background: The relation between body mass index (BMI) and incidence of diffuse large B-cell lymphoma (DLBCL) has been suggested, but no systematic review has been undertaken. Material and Methods: We performed a literature search through December 2012. Meta-analyses were performed to quantify the relative risk (RR) of DLBCL incidence in overweight and obese persons compared with normal weight individuals using the random-effects model. Subset analyses were performed according to study design, sex, and geographic region. Overweight was defined as a BMI 25 to 29.9 kg/m(2), and obesity was defined as a BMI of 30 kg/m(2). Meta-regression, using an unrestricted maximum likelihood model, was performed to evaluate the linear association between BMI and odds of DLBCL. Results: Our study included 6 case-control and 10 cohort studies. The RR of DLBCL in overweight individuals was 1.14 (95% confidence interval [Cl], 1.04-1.24; P = .004), and in obese individuals, RR was 1.29 (95% Cl, 1.16-1.43; P < .001). The RR of DLBCL in overweight men and women was 1.22 and 1.27, respectively. In overweight individuals, both prospective and case-control studies showed an RR of 1.13. The RR of DLBCL in obese men and women was 1.40 and 1.34, respectively. In obese individuals, the RR in prospective studies was 1.25 and in case-control studies it was 1.33. Meta-regression analysis showed a 14% increase in DLBCL incidence for each 10 kg/m(2) increase in BMI. Conclusion: An increased BMI is associated with higher RR of DLBCL regardless of sex. Also, there seems to be a linear association between BMI and DLBCL incidence. C1 [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ingham, Randall R.; Reagan, John L.] Rhode Isl Hosp, Div Hematol & Oncol, Providence, RI USA. [Furman, Michael] Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. [Dalia, Samir] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Hematol & Oncol, Tampa, FL 33612 USA. [Mitri, Joanna] Prima CARE, Serv Endocrinol, Fall River, MA USA. RP Castillo, JJ (reprint author), M221,450 Brookline Ave, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 43 TC 9 Z9 9 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2014 VL 14 IS 2 BP 122 EP 130 DI 10.1016/j.dml.2013.10.005 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA AD8IQ UT WOS:000333510100006 PM 24360912 ER PT J AU Layfield, LJ Pitman, MB AF Layfield, Lester James Pitman, Martha Bishop TI The papanicolaou society of cytopathology guidelines for pancreaticobiliary tract cytology: A new installment in the "Bethesda" style of guidelines from the papanicolaou society of cytopathology SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material ID FINE-NEEDLE-ASPIRATION; INTERNATIONAL CONSENSUS GUIDELINES; PAPILLARY MUCINOUS NEOPLASMS; OF-CYTOPATHOLOGY; EPITHELIAL ATYPIA; SPECIMENS; MANAGEMENT; STATE C1 [Layfield, Lester James] Univ Missouri, Dept Pathol & Anat Sci, Columbia, MO 65211 USA. [Pitman, Martha Bishop] Massachusetts Gen Hosp, Cytopathol Lab, Boston, MA 02114 USA. [Pitman, Martha Bishop] Harvard Univ, Sch Med, Boston, MA USA. RP Layfield, LJ (reprint author), Univ Missouri, Dept Pathol & Anat Sci, Columbia, MO 65211 USA. 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 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 283 EP 284 DI 10.1002/dc.23129 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600001 PM 24554423 ER PT J AU Adler, D Max Schmidt, C Al-Haddad, M Barthel, JS Ljung, BM Merchant, NB Romagnuolo, J Shaaban, AM Simeone, D Bishop Pitman, M Field, A Layfield, LJ AF Adler, Douglas Max Schmidt, C. Al-Haddad, Mohammad Barthel, James S. Ljung, Britt-Marie Merchant, Nipun B. Romagnuolo, Joseph Shaaban, Akram M. Simeone, Diane Bishop Pitman, Martha Field, Andrew Layfield, Lester J. TI Clinical evaluation, imaging studies, indications for cytologic study, and preprocedural requirements for duct brushing studies and pancreatic FNA: The papanicolaou society of cytopathology recommendations for pancreatic and biliary cytology SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE indications; pancreas; guidelines; bile duct; cytology; fine-needle aspiration; PSC ID PHASE HELICAL CT; INTERNATIONAL CONSENSUS GUIDELINES; PRIMARY SCLEROSING CHOLANGITIS; PAPILLARY MUCINOUS NEOPLASMS; EUS-GUIDED FNA; COMPUTED-TOMOGRAPHY; INFORMED-CONSENT; ENDOSCOPIC ULTRASONOGRAPHY; SPIRAL CT; MR CHOLANGIOPANCREATOGRAPHY AB The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreaticobiliary cytology including indications for endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) biopsy, techniques for EUS-FNA, terminology and nomenclature to be used for pancreaticobiliary disease, ancillary testing, and post-biopsy management. All documents are based on expertise of the authors, literature review, discussions of the draft document at national and international meetings, and synthesis of online comments of the draft document. This document selectively presents the results of these discussions. This document summarizes recommendations for the clinical and imaging work-up of pancreatic and biliary tract lesions along with indications for cytologic study of these lesions. Prebrushing and FNA requirements are also discussed. Diagn. Cytopathol. 2014;42:325-332. (c) 2014 Wiley Periodicals, Inc. C1 [Adler, Douglas] Univ Utah, Sch Med, Dept Med, Div Gastroenterol, Salt Lake City, UT USA. [Max Schmidt, C.] Indiana Univ, Indiana Univ Hlth Pancreat Cyst & Canc Early Dete, Indianapolis, IN 46204 USA. [Max Schmidt, C.] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. [Al-Haddad, Mohammad] Indiana Univ, Dept Med, Div Gastroenterol, Indianapolis, IN 46204 USA. [Barthel, James S.] Florida Digest Hlth Specialists, Bradenton, FL USA. [Ljung, Britt-Marie] Univ Calif San Francisco, Dept Pathol & Lab Med, San Francisco, CA 94143 USA. [Merchant, Nipun B.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA. [Romagnuolo, Joseph] Med Univ S Carolina, Dept Med, Div Gastroenterol, Charleston, SC 29425 USA. [Shaaban, Akram M.] Univ Utah, Sch Med, Dept Radiol, Salt Lake City, UT USA. [Simeone, Diane] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Bishop Pitman, Martha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Field, Andrew] St Vincents Hosp, Dept Anat Pathol, Sydney, NSW 2010, Australia. [Layfield, Lester J.] Univ Missouri, Dept Pathol & Anat Sci, Columbia, MO 65211 USA. RP Layfield, LJ (reprint author), Univ Missouri, Dept Pathol & Anat Sci, M263 Med Sci Bldg,1 Hosp Dr, Columbia, MO 65211 USA. EM layfieldl@helath.missouri.edu OI Adler, Douglas/0000-0003-3214-6285 NR 70 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 325 EP 332 DI 10.1002/dc.23095 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600009 PM 24554480 ER PT J AU Brugge, W DeWitt, J Klapman, JB Ashfaq, R Shidham, V Chhieng, D Kwon, R Baloch, Z Zarka, M Staerkel, G AF Brugge, William DeWitt, John Klapman, Jason B. Ashfaq, Raheela Shidham, Vinod Chhieng, David Kwon, Richard Baloch, Zubair Zarka, Matthew Staerkel, Gregg TI Techniques for cytologic sampling of pancreatic and bile duct lesions SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE cytology; techniques; pancreas; bile duct; FNA ID FINE-NEEDLE-ASPIRATION; MALIGNANT BILIARY OBSTRUCTION; BRUSH CYTOLOGY; STRICTURE DILATION; DIAGNOSTIC-ACCURACY; 25-GAUGE NEEDLES; CANCER-DETECTION; ERCP; BIOPSY; 22-GAUGE AB The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound guided fine-needle aspiration biopsy, techniques of the endoscopic retrograde cholangiopancreatography, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18-month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology website []. This document presents the results of these discussions regarding the use of ancillary testing in the cytological diagnosis of biliary and pancreatic lesions. This document summarizes the current state of the art for techniques in acquiring cytology specimens from the biliary tree as well as solid and cystic lesions of the pancreas. Diagn. Cytopathol. 2014;42:333-337. (c) 2014 Wiley Periodicals, Inc. C1 [Brugge, William] Mass Gen Hosp, Div Gastroenterol, Boston, MA USA. [DeWitt, John] Indiana Univ, Div Gastroenterol, Bloomington, IN 47405 USA. [Klapman, Jason B.] H Lee Moffitt Canc Ctr & Res Inst, Sect Endoscop Oncol, Tampa, FL USA. [Shidham, Vinod] Wayne State Univ, Div Cytopathol, Detroit, MI 48202 USA. [Chhieng, David] Yale Univ, Div Cytopathol, New Haven, CT 06520 USA. [Kwon, Richard] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Zarka, Matthew] Mayo Clin, Div Cytopathol, Scottsdale, AZ USA. [Staerkel, Gregg] MD Anderson Ctr, Sect Cytopathol, Houston, TX USA. RP Brugge, W (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM wbrugge@partners.org NR 36 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 333 EP 337 DI 10.1002/dc.23096 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600010 PM 24554498 ER PT J AU Pitman, MB Centeno, BA Ali, SZ Genevay, M Stelow, E Mino-Kenudson, M Fernandez-del Castillo, C Schmidt, CM Brugge, W Layfield, L AF Pitman, Martha B. Centeno, Barbara A. Ali, Syed Z. Genevay, Muriel Stelow, Ed Mino-Kenudson, Mari Fernandez-del Castillo, Carlos Schmidt, C. Max Brugge, William Layfield, Lester TI Standardized terminology and nomenclature for pancreatobiliary cytology: The Papanicolaou Society of Cytopathology guidelines SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE guidelines; pancreas; terminology; nomenclature; PSC ID FINE-NEEDLE-ASPIRATION; PAPILLARY MUCINOUS NEOPLASMS; ACINAR-CELL CARCINOMA; CYST FLUID ANALYSIS; DUCT BRUSHING CYTOLOGY; INTERNATIONAL CONSENSUS GUIDELINES; ATYPICAL EPITHELIAL-CELLS; INTRAEPITHELIAL NEOPLASIA; DIFFERENTIAL-DIAGNOSIS; NEUROENDOCRINE TUMORS AB The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy treatment and management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18-month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology web site (). This document selectively presents the results of these discussions and focuses on a proposed standardized terminology scheme for pancreatobiliary specimens that correlate cytological diagnosis with biological behavior and increasingly conservative patient management of surveillance only. The proposed terminology scheme recommends a six-tiered system: Nondiagnostic, Negative, Atypical, Neoplastic (benign or other), Suspicious and Positive. Unique to this scheme is the "Neoplastic" category separated into "benign" (serous cystadenoma), or "Other" (premalignant mucinous cysts, neuroendocrine tumors, and solid-pseudopapillary neoplasms). The positive or malignant category is reserved for high-grade, aggressive malignancies including ductal adenocarcinoma, acinar cell carcinoma, poorly differentiated neuroendocrine carcinomas, pancreatoblastoma, lymphoma, and metastases. Interpretation categories do not have to be used. Some pathology laboratory information systems require an interpretation category, which places the cytological diagnosis into a general category. This proposed scheme provides terminology that standardizes the category of the various diseases of the pancreas, some of which are difficult to diagnose specifically by cytology. In addition, this terminology scheme attempts to provide maximum flexibility for patient management, which has become increasingly conservative for some neoplasms. Diagn. Cytopathol. 2014;42:338-350. (c) 2014 Wiley Periodicals, Inc. C1 [Pitman, Martha B.; Mino-Kenudson, Mari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Centeno, Barbara A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Ali, Syed Z.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Genevay, Muriel] Hosp Pathol Clin, Dept Pathol, Geneva, Switzerland. [Stelow, Ed] Univ Virginia, Med Ctr, Dept Pathol, Charlottesville, VA USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Schmidt, C. Max] Indiana Univ, Med Ctr, Dept Surg, Indianapolis, IN 46202 USA. [Brugge, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA USA. [Layfield, Lester] Univ Missouri, Dept Pathol & Anatom Sci, Columbia, MO USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 86 TC 31 Z9 32 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 338 EP 350 DI 10.1002/dc.23092 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600011 PM 24554455 ER PT J AU Layfield, LJ Ehya, H Filie, AC Hruban, RH Jhala, N Joseph, L Vielh, P Pitman, MB AF Layfield, Lester J. Ehya, Hormoz Filie, Armando C. Hruban, Ralph H. Jhala, Nirag Joseph, Loren Vielh, Philippe Pitman, Martha B. TI Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: The papanicolaou society of cytopathology guidelines for pancreatobiliary cytology SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE pancreas; biliary tract; molecular diagnosis; EUS; ancillary studies; fine-needle aspiration ID FINE-NEEDLE-ASPIRATION; IN-SITU HYBRIDIZATION; CYST FLUID ANALYSIS; ACINAR CELL-CARCINOMA; TUMOR-SUPPRESSOR GENE; K-RAS MUTATIONS; PAPILLARY MUCINOUS NEOPLASMS; ENDOBILIARY BRUSH CYTOLOGY; DIGITAL IMAGE-ANALYSIS; BILE-DUCT STRICTURES AB The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound-guided fine-needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in situ hybridization (FISH) appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta-catenin supports a diagnosis of solid-pseudopapilary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the preoperative classification of pancreatic cysts. Many gene mutations (KRAS, GNAS, VHL, RNF43, and CTNNB1) may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs. Diagn. Cytopathol. 2014;42:351-362. (c) 2014 Wiley Periodicals, Inc. C1 [Layfield, Lester J.] Univ Missouri, Dept Pathol & Anatom Sci, Columbia, MO USA. [Ehya, Hormoz] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Filie, Armando C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [Jhala, Nirag] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Joseph, Loren] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Vielh, Philippe] Inst Gustave Roussy, Villejuif, France. [Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Layfield, LJ (reprint author), Dept Pathol & Anatom Sci, M263 Med Sci Bldg,One Hosp Dr, Columbia, MO 65212 USA. EM layfieldl@health.missouri.edu FU NCI NIH HHS [P30 CA006973] NR 117 TC 26 Z9 26 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 351 EP 362 DI 10.1002/dc.23093 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600012 PM 24639398 ER PT J AU Kurtycz, D Tabatabai, ZL Michaels, C Young, N Schmidt, CM Farrell, J Gopal, D Simeone, D Merchant, NB Field, A Pitman, MB AF Kurtycz, Daniel Tabatabai, Z. Laura Michaels, Claire Young, Nancy Schmidt, C. Max Farrell, James Gopal, Deepak Simeone, Diane Merchant, Nipun B. Field, Andrew Pitman, Martha Bishop TI Postbrushing and fine-needle aspiration biopsy follow-up and treatment options for patients with pancreatobiliary lesions: The papanicolaou society of cytopathology guidelines SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE PSC; cytology; management; pancreas; guidelines; treatment ID INTERNATIONAL CONSENSUS GUIDELINES; EUS-GUIDED FNA; ENDOSCOPIC ULTRASOUND; NEUROENDOCRINE TUMORS; MUCINOUS CYSTS; PATHOLOGICAL CLASSIFICATION; LYMPHOEPITHELIAL CYSTS; BRUSH CYTOLOGY; PANCREAS; DIAGNOSIS AB The papanicolaou society of cytopathology (PSC) has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomenclature for pancreatobiliary cytology, ancillary testing, and postprocedure management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18 month period and synthesis of online comments of the draft document on the PSC web site []. This document selectively presents the results of these discussions and focuses on the follow-up and treatment options for patients after procedures performed for obtaining cytology samples for the evaluation of biliary strictures and solid and cystic masses in the pancreas. These recommendations follow the six-tiered terminology and nomenclature scheme proposed by Committee III. Diagn. Cytopathol. 2014;42:363-371. (c) 2014 Wiley Periodicals, Inc. C1 [Kurtycz, Daniel] Univ Wisconsin, Dept Pathol, Wisconsin State Lab Hyg, Madison, WI 53706 USA. [Tabatabai, Z. Laura] UCSF, Dept Pathol, San Francisco, CA USA. [Michaels, Claire] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Young, Nancy] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Schmidt, C. Max] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. [Farrell, James] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Gopal, Deepak] Univ Wisconsin, Dept Med, Div Gastroenterol, Madison, WI USA. [Simeone, Diane] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Merchant, Nipun B.] Vanderbilt Univ, Dept Med, Div Surg Oncol, Nashville, TN USA. [Field, Andrew] St Vincents Hosp, Dept Pathol, Sydney, NSW 2010, Australia. [Pitman, Martha Bishop] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Kurtycz, D (reprint author), Univ Wisconsin, Dept Pathol, Wisconsin State Lab Hyg, 465 Henry Mall,Off 429a, Madison, WI 53706 USA. EM dkurtycz@wisc.edu NR 57 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2014 VL 42 IS 4 BP 363 EP 371 DI 10.1002/dc.23121 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA AC8OI UT WOS:000332792600013 PM 24639399 ER PT J AU Patel, SA Chen, YH Hornick, JL Catalano, P Nowak, JA Zukerberg, LR Bleday, R Shellito, PC Hong, TS Mamon, HJ AF Patel, Sagar A. Chen, Yu-Hui Hornick, Jason L. Catalano, Paul Nowak, Jonathan A. Zukerberg, Lawrence R. Bleday, Ronald Shellito, Paul C. Hong, Theodore S. Mamon, Harvey J. TI Early- Stage Rectal Cancer: Clinical and Pathologic Prognostic Markers of Time to Local Recurrence and Overall Survival After Resection SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Rectal cancer; Recurrence; Survival; Prognosis ID TOTAL MESORECTAL EXCISION; COLORECTAL-CANCER; CURATIVE RESECTION; POSTOPERATIVE CHEMORADIOTHERAPY; PREOPERATIVE CHEMORADIOTHERAPY; T2 CANCERS; CARCINOMA; RISK; RADIOTHERAPY; INVOLVEMENT AB BACKGROUND: Resection without adjuvant therapy results in a low recurrence rate for patients with stage I (T1/2 N0) rectal cancer in the range of 4% to 16% at 5 years. There are limited data, however, regarding clinical or pathologic prognostic markers for recurrence in this population. OBJECTIVE: The aim of this study is to assess the clinical and pathologic factors associated with local recurrence and overall survival in patients with early-stage rectal cancer after resection. DESIGN: This is a retrospective study. SETTING: This study was conducted at 2 tertiary care centers in Boston, Massachusetts. PATIENTS: From 2000 to 2008, 175 patients with stage I rectal cancer treated with local or total mesorectal excision without adjuvant therapy were identified. MAIN OUTCOME MEASURES: Time to local recurrence after resection and overall survival were evaluated for all patients with complete follow-up data. Perioperative data were reviewed to identify staging method, preoperative CEA, type of surgery, tumor size, number of lymph nodes resected, histological grade, circumferential resection margin, perineural invasion, lymphovascular invasion, and tumor ulceration. Data were analyzed by using a Cox proportional hazards regression model. RESULTS: Of the eligible cohort, 137 patients had complete follow-up data for analysis of time to local recurrence, and only 23 (16.8%) patients had local recurrence. Among these 23 patients, the median time to recurrence was 1.1 years (0.1-7.8). On multivariate analysis, male sex, current alcohol use, and tumor ulceration were associated with heightened risk of local recurrence. Of the original cohort, 173 patients had complete follow-up for overall survival analysis. Among these patients, the median overall survival was 12 years. On multivariable analysis, age at diagnosis >65 years and T2 pathologic stage were associated with decreased survival. LIMITATIONS: As in any retrospective study, there is a potential for selection bias. Several patients were excluded from the analysis due to inadequate follow-up data. These results from two academic medical centers with specialized colorectal surgeons may not be generally applicable. The relatively small number of events, ie, recurrences, suggest the findings should be validated in a larger study. CONCLUSIONS: For patients with stage I rectal cancer treated with resection alone, these results provide important prognostic information and may help identify those who could benefit from additional therapy. C1 [Patel, Sagar A.; Mamon, Harvey J.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Yu-Hui; Catalano, Paul] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hornick, Jason L.; Nowak, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bleday, Ronald] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Shellito, Paul C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Mamon, HJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM hmamon@lroc.harvard.edu FU NCI NIH HHS [P30 CA006516] NR 31 TC 9 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD APR PY 2014 VL 57 IS 4 BP 449 EP 459 DI 10.1097/DCR.0b013e3182a70709 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AD1MS UT WOS:000332998700007 PM 24608301 ER PT J AU Ananthakrishnan, AN Chan, AT AF Ananthakrishnan, Ashwin N. Chan, Andrew T. TI Dietary Fiber and Risk of Inflammatory Bowel Disease: Fact or Hype? Reply SO GASTROENTEROLOGY LA English DT Letter ID CROHNS-DISEASE C1 [Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2014 VL 146 IS 4 BP 1134 EP 1135 DI 10.1053/j.gastro.2014.02.035 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4XH UT WOS:000333254500045 PM 24576728 ER PT J AU McManus, DD Lin, HH Tanriverdi, K Quercio, M Yin, XY Larson, MG Elinor, PT Levy, D Freedman, JE Benjamin, EJ AF McManus, David D. Lin, Honghuang Tanriverdi, Kahraman Quercio, Michael Yin, Xiaoyan Larson, Martin G. Elinor, Patrick T. Levy, Daniel Freedman, Jane E. Benjamin, Emelia J. TI Relations between circulating microRNAs and atrial fibrillation: Data from the Framingham Offspring Study SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Epidemiology; Circulation; microRNA; Risk factors ID HEART-FAILURE; CARDIAC-HYPERTROPHY; RISK-FACTORS; FIBROSIS; CONTRIBUTES; PREVALENCE; EXPRESSION; PREVENTION; PROTECTS; STROKE AB BACKGROUND MicroRNA (miRNA) expression in atrial tissue has been implicated in pathologic susceptibility to atrial fibrillation (AF). Nevertheless, data on how circulating levels relate to AF are limited. OBJECTIVE The purpose of this study was to test the hypothesis that circulating miRNAs are associated with AF. METHODS Among 2445 Framingham Heart Study Offspring participants, we measured the expression of 385 circulating whole blood miRNAs by high-throughput quantitative reverse transcriptase polymerase chain reaction. We related miRNA Levels with prevalent and new-onset AF. RESULTS Mean age of the cohort was 66.3 +/- 8.9 years, and 56% were women; 153 participants had clinically apparent AF at baseline, and 107 developed AF during median follow-up of 5.4 years. miRNA-328 (miR-328) expression was lower among participants with prevalent AF (8.76 cycle threshold) compared to individuals with no AF (7.75 cycle threshold, P < .001). The association between miR-328 and prevalent AF persisted after adjustment for age, sex, and technical covariates (odds ratio 1.21, P = 1.8 x 10(-4)) but was attenuated in analyses adjusting for clinical AF risk factors (odds ratio 1.14, P = .017). In contrast to the associations between miR-328 and prevalent AF, none of the circulating miRNAs were associated with incident AF. CONCLUSION Circulating levels of miR-328, a miRNA known to promote atrial electrical remodeling by reducing L-type Ca2+ channel density, were associated with prevalent AF. Adjustment for risk factors that promote atrial remodeling, including hypertension, attenuated the association between miR-328 and AF, potentially implicating miR-328 as a potential mediator of atrial remodeling and AF vulnerability. C1 [McManus, David D.; Lin, Honghuang; Tanriverdi, Kahraman; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Freedman, Jane E.] NHLBI, Framingham, MA USA. [McManus, David D.; Lin, Honghuang; Tanriverdi, Kahraman; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Freedman, Jane E.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [McManus, David D.; Tanriverdi, Kahraman; Quercio, Michael; Freedman, Jane E.] Univ Massachusetts, Dept Med, Sch Med, Div Cardiol, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Med Sch Worcester, Dept Quantitat Hlth Sci, Epidemiol Div, Worcester, MA 01605 USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Computat Biomed Sect, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Elinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Elinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Levy, Daniel] NHLBI, Populat Res Branch, NIH, Bethesda, MD 20892 USA. [Levy, Daniel] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP McManus, DD (reprint author), Univ Massachusetts, Sch Med, Div Cardiol, 55 Lake Ave North, Worcester, MA 01655 USA. EM mcmanusd@ummhc.org OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [N01-HC 25195, 6R01-NS 17950, RFA-HL-12-008, R01 HL087201A, 1R01 HL64753, R01 HL076784, 1R01 AG028321]; Division of Intramural Research, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD; National Institute of Health [1U01HL105268-01, KL2RR031981] FX This work was supported by N01-HC 25195, 6R01-NS 17950; RFA-HL-12-008 to Dr. Freedman; R01 HL087201A to Drs. Freedman and Taariverdi; RFA-HL-12-008 to Dr. Freedman; and 1R01 HL64753; R01 HL076784; 1R01 AG028321 to Dr. Benjamin from the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the Division of Intramural Research, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD. Partial salary support is additionally provided by National Institute of Health Grants 1U01HL105268-01 and KL2RR031981 to Dr. McManus. NR 26 TC 21 Z9 24 U1 0 U2 4 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 APR PY 2014 VL 11 IS 4 BP 663 EP 669 DI 10.1016/j.hrthm.2014.01.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD6WL UT WOS:000333401800023 PM 24444445 ER PT J AU La Fountaine, MF Toda, M Testa, A Bauman, WA AF La Fountaine, Michael F. Toda, Michita Testa, Anthony Bauman, William A. TI Cardioautonomic instability following a sports-related concussion in a 20-year-old male SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Concussion; Electrocardiogram; Wandering atrial pacemaker; Atrial ectopy ID QT INTERVAL VARIABILITY C1 [La Fountaine, Michael F.; Toda, Michita; Testa, Anthony] Seton Hall Univ, S Orange, NJ 07079 USA. [La Fountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Bauman, William A.] Icahn Sch Med Mt Sinai, New York, NY USA. RP La Fountaine, MF (reprint author), Seton Hall Univ, Sch Hlth & Med Sci, 400 South Orange Ave, S Orange, NJ 07079 USA. EM michael.lafountaine@shu.edu NR 10 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 1 PY 2014 VL 172 IS 3 BP E511 EP E512 DI 10.1016/j.ijcard.2014.01.095 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD2XU UT WOS:000333101000050 PM 24491870 ER PT J AU Sutton, MY Lasswell, SM Lanier, Y Miller, KS AF Sutton, Madeline Y. Lasswell, Sarah M. Lanier, Yzette Miller, Kim S. TI Impact of Parent-Child Communication Interventions on Sex Behaviors and Cognitive Outcomes for Black/African-American and Hispanic/Latino Youth: A Systematic Review, 1988-2012 SO JOURNAL OF ADOLESCENT HEALTH LA English DT Review DE Youth; Black/African-American; Hispanic/Latino; Parent-child communication; Sex outcomes; Disparities ID SEXUALLY-TRANSMITTED-DISEASES; PREGNANCY PREVENTION PROGRAM; AFRICAN-AMERICAN; HIV PREVENTION; RISK BEHAVIORS; RANDOMIZED-TRIAL; MONITORING INTERVENTION; ADOLESCENT PREGNANCY; FAMILIES PROGRAM; REDUCTION AB Purpose: We reviewed human immunodeficiency virus (HIV) and sexually transmitted infection (STI)- behavioral interventions implemented with disproportionately affected black/African-American and Hispanic/Latino youth and designed to improve parent-child communications about sex. We compared their effectiveness in improving sex-related behavior or cognitive outcomes. Methods: A search of electronic databases identified peer-reviewed studies published between 1988 and 2012. Eligible studies were U. S.-based parent-child communication interventions with active parent components, experimental and quasiexperimental designs, measurement of youth sexual health outcomes, and enrollment of >= 50% black/African-American or Hispanic/Latino youth. We conducted systematic, primary reviews of eligible papers to abstract data on study characteristics and youth outcomes. Results: Fifteen studies evaluating 14 interventions were eligible. Although youth outcome measures and follow-up times varied, 13 of 15 studies (87%) showed at least one significantly improved youth sexual health outcome compared with controls (p < .05). Common components of effective interventions included joint parent and child session attendance, promotion of parent/family involvement, sexuality education for parents, developmental and/or cultural tailoring, and opportunities for parents to practice new communication skills with their youth. Conclusions: Parent-child communication interventions that include parents of youth disproportionately affected by HIV/STIs can effectively reduce sexual risk for youth. These interventions may help reduce HIV/STI-related health disparities and improve sexual health outcomes. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Sutton, Madeline Y.; Lasswell, Sarah M.; Lanier, Yzette; Miller, Kim S.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Lanier, Yzette] Univ Penn, Sch Nursing, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Lanier, Yzette] Ctr Hlth Equ Res, Philadelphia, PA USA. RP Sutton, MY (reprint author), DHAP NCHHSTP CDC, 1600 Clifton Rd NE MS E-45, Atlanta, GA 30333 USA. EM msutton@cdc.gov NR 74 TC 11 Z9 11 U1 5 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 2014 VL 54 IS 4 BP 369 EP 384 DI 10.1016/j.jadohealth.2013.11.004 PG 16 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA AD4YT UT WOS:000333258700003 PM 24388108 ER PT J AU Katz, I Pichelin, M Montesantos, S Majoral, C Martin, A Conway, J Fleming, J Venegas, J Greenblatt, E Caillibotte, G AF Katz, I. Pichelin, M. Montesantos, S. Majoral, C. Martin, A. Conway, J. Fleming, J. Venegas, J. Greenblatt, E. Caillibotte, G. TI Using Helium-Oxygen to Improve Regional Deposition of Inhaled Particles: Mechanical Principles SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Article DE CFD; particle deposition; helium; imaging; heliox; aerosol ID HUMAN RESPIRATORY-TRACT; HETEROGENEOUS AIRWAY OBSTRUCTIONS; DRIVEN ALBUTEROL NEBULIZATION; AEROSOL DRUG-DELIVERY; ASTHMA EXACERBATIONS; MIXTURES; VENTILATION; THROAT; TOMOGRAPHY; PRESSURE AB Background: Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in a heterogeneous pathological lung. It is in this context that it is hypothesized that helium-oxygen can improve regional deposition, leading to more homogeneous deposition by increasing deposition in ventilation-deficient lung regions. Methods: Analytical models of inertial impaction, sedimentation, and diffusion are examined to illustrate the importance of gas property values on deposition distribution through both fluid mechanics- and particle mechanics-based mechanisms. Also considered are in vitro results from a bench model for a heterogeneously obstructed lung. In vivo results from three-dimensional (3D) imaging techniques provide visual examples of changes in particle deposition patterns in asthmatics that are further analyzed using computational fluid dynamics (CFD). Results and Conclusions: Based on analytical modeling, it is shown that deeper particle deposition is expected when breathing helium-oxygen, as compared with breathing air. A bench model has shown that more homogeneous ventilation distribution is possible breathing helium-oxygen in the presence of heterogeneous obstructions representative of central airway obstructions. 3D imaging of asthmatics has confirmed that aerosol delivery with a helium-oxygen carrier gas results in deeper and more homogeneous deposition distributions. CFD results are consistent with the in vivo imaging and suggest that the mechanics of gas particle interaction are the source of the differences seen in deposition patterns. However, intersubject variability in response to breathing helium-oxygen is expected, and an example of a nonresponder is shown where regional deposition is not significantly changed. C1 [Katz, I.; Pichelin, M.; Montesantos, S.; Majoral, C.; Caillibotte, G.] Air Liquide Sante Int, R&D Med Gases Grp, Les Loges En Josas, France. [Katz, I.] Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA. [Martin, A.] Amer Air Liquide, Med Gases Delaware Res & Technol Ctr, Newark, DE USA. [Conway, J.] Univ Southampton, Fac Hlth Sci, Southampton, Hants, England. [Conway, J.; Fleming, J.] NHS Fdn Trust, Southampton Univ Hosp, NIHR Southampton Resp Biomed Res Unit, Southampton, Hants, England. [Venegas, J.; Greenblatt, E.] Massachusetts Gen Hosp Harvard, Dept Anesthesia Bioengn, Boston, MA USA. RP Katz, I (reprint author), Air Liquide Sante Int, R&D Med Gases Grp, Les Loges En Josas, France. EM ira.katz@airliquide.com OI Conway, Joy/0000-0001-6464-1526 FU Southampton Respiratory Biomedical Research Unit; UK National Institute for Health Research; Air Liquide FX John Fleming and Joy Conway acknowledge the support of the Southampton Respiratory Biomedical Research Unit funded by the UK National Institute for Health Research. Southampton University Hospital Trust and Massachusetts General Hospital have received funding from Air Liquide. NR 47 TC 7 Z9 7 U1 0 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 EI 1941-2703 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR 1 PY 2014 VL 27 IS 2 BP 71 EP 80 DI 10.1089/jamp.2013.1072 PG 10 WC Respiratory System SC Respiratory System GA AD6XV UT WOS:000333405700001 PM 24383961 ER PT J AU Nguyen, HM Shier, KL Graber, CJ AF Nguyen, Hien M. Shier, Kileen L. Graber, Christopher J. TI Determining a clinical framework for use of cefepime and -lactam/-lactamase inhibitors in the treatment of infections caused by extended-spectrum--lactamase-producing Enterobacteriaceae SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Review DE ESBLs; antimicrobial resistance; pharmacokinetics; pharmacodynamics; piperacillin; tazobactam ID BLOOD-STREAM INFECTIONS; MONTE-CARLO-SIMULATION; BETA-LACTAMASE; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; PIPERACILLIN-TAZOBACTAM; CTX-M; CLAVULANIC ACID; RISK-FACTORS; BREAKPOINTS AB Traditionally, physicians have not used cefepime (a fourth-generation cephalosporin with greater stability against -lactamases) or -lactam/-lactamase inhibitors (BLBLIs) for infections caused by bacteria (generally Escherichia coli and Klebsiella species) that produce an extended-spectrum -lactamase (ESBL). Many microbiology laboratories have historically labelled these ESBL-producing organisms as resistant to all cephalosporins regardless of their MIC. The recommendation to eliminate ESBL identification started with EUCAST in 2009, followed by CLSI in 2010. As a consequence, many ESBL-producing organisms that were previously labelled as resistant to all cephalosporins may be reclassified as susceptible to some (particularly cefepime), depending on their MICs. Because there are limited treatment options against ESBL-producing organisms, there is growing interest in using cefepime and BLBLIs. In this review, we examine the clinical outcomes of therapy directed against ESBL-producing Enterobacteriaceae and the pharmacokinetics/pharmacodynamics of cefepime and BLBLIs to construct a clinical framework for how physicians can best employ these carbapenem-sparing alternatives for the treatment of infections caused by ESBL-producing Enterobacteriaceae. We conclude that standard-dose cefepime is a reasonable option for the definitive therapy of invasive infections resulting from ESBL-producing E. coli and Klebsiella species when the MIC for the organism is 2 mg/L (CLSI) or 1 mg/L (EUCAST), although higher doses may be considered for MICs in the 48 mg/L range. Piperacillin/tazobactam is also a reasonable option when the MIC is 16 mg/L. C1 [Nguyen, Hien M.] Northwest Permanente, Portland, OR 97227 USA. [Shier, Kileen L.] Quest Diagnost Nichols Inst, Chantilly, VA USA. [Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Nguyen, HM (reprint author), Northwest Permanente, Portland, OR 97227 USA. EM hien.m.nguyen@kp.org NR 85 TC 25 Z9 25 U1 3 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2014 VL 69 IS 4 BP 871 EP 880 DI 10.1093/jac/dkt450 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AD5EQ UT WOS:000333275000002 PM 24265230 ER PT J AU Weiner, M Egelund, EF Engle, M Kiser, M Prihoda, TJ Gelfond, JAL Mac Kenzie, W Peloquin, CA AF Weiner, Marc Egelund, Eric F. Engle, Melissa Kiser, Melissa Prihoda, Thomas J. Gelfond, Jonathan A. L. Mac Kenzie, William Peloquin, Charles A. TI Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE rifamycin; latent tuberculosis infection; antiretroviral therapy; integrase strand transfer inhibitor; HIV ID HIV-INFECTED PATIENTS; PLASMA-CONCENTRATIONS; LATENT TUBERCULOSIS; RIFAMPIN; VARIABILITY; METABOLISM; INHIBITOR; REGIMENS; ATORVASTATIN; INDUCTION AB Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir. In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 14 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 1215 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 48 and 1114 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 1114 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718. In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC(012)) being increased by 71; the peak concentration increased by 89 and the trough concentration decreased by 12. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC(012) or the peak concentration, but it decreased the trough concentration by 41. Raltegravir coadministered with rifapentine was generally well tolerated. The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV. C1 [Weiner, Marc] Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX 78229 USA. [Weiner, Marc; Engle, Melissa] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Egelund, Eric F.; Peloquin, Charles A.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Kiser, Melissa] Bioanalyt Syst Inc, Mcminnville, OR USA. [Prihoda, Thomas J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Mac Kenzie, William] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. RP Weiner, M (reprint author), Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU Investigator-Initiated Studies Program of Merck Co., Inc.; Veterans Administration, United States Centers for Disease Control and Prevention (Tuberculosis Trials Consortium); National Center for Advancing Translational Sciences [8UL1TR000149] FX This study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck & Co., Inc. Support was also provided by the Veterans Administration, United States Centers for Disease Control and Prevention (Tuberculosis Trials Consortium), and National Center for Advancing Translational Sciences, through Grant 8UL1TR000149. NR 40 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2014 VL 69 IS 4 BP 1079 EP 1085 DI 10.1093/jac/dkt483 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AD5EQ UT WOS:000333275000031 PM 24343893 ER PT J AU Villet, RA Truong-Bolduc, QC Wang, Y Estabrooks, Z Medeiros, H Hooper, DC AF Villet, Regis A. Truong-Bolduc, Que Chi Wang, Yin Estabrooks, Zoe Medeiros, Heidi Hooper, David C. TI Regulation of Expression of abcA and Its Response to Environmental Conditions SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; BINDING PROTEIN 4; BIOSYNTHETIC GENE-CLUSTER; EFFLUX PUMP; TRANSPORTER; MGRA; INFECTIONS; SARA; TRANSCRIPTION; VIRULENCE AB The ATP-dependent transporter gene abcA in Staphylococcus aureus confers resistance to hydrophobic beta-lactams. In strain ISP794, abcA is regulated by the transcriptional regulators MgrA and NorG and shares a 420-nucleotide intercistronic region with the divergently transcribed pbp4 gene, which encodes the transpeptidase Pbp4. Exposure of exponentially growing cells to iron-limited media, oxidative stress, and acidic pH (5.5) for 0.5 to 2 h had no effect on abcA expression. In contrast, nutrient limitation produced a significant increase in abcA transcripts. We identified three additional regulators (SarA, SarZ, and Rot) that bind to the overlapping promoter region of abcA and pbp4 in strain MW2 and investigated their role in the regulation of abcA expression. Expression of abcA is decreased by 10.0-fold in vivo in a subcutaneous abscess model. In vitro, abcA expression depends on rot and sarZ regulators. Moenomycin A exposure of strain MW2 produced an increase in abcA transcripts. Relative to MW2, the MIC of moenomycin was decreased 8-fold for MW2 Delta abcA and increased 10-fold for the MW2 abcA overexpresser, suggesting that moenomycin is a substrate of AbcA. C1 [Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis & Med Serv, Boston, MA 02130 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis & Med Serv, Boston, MA 02130 USA. EM dhooper@partners.org FU NIH-NIAID National Institute of Allergy and Infectious Diseases [2P01AI083214-04] FX This work was supported by the NIH-NIAID National Institute of Allergy and Infectious Diseases (Antimicrobial and Efflux Pumps in S. aureus/Harvard-wide Program on Antibiotic Resistance number 2P01AI083214-04). NR 46 TC 5 Z9 5 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2014 VL 196 IS 8 BP 1532 EP 1539 DI 10.1128/JB.01406-13 PG 8 WC Microbiology SC Microbiology GA AD7ML UT WOS:000333447900007 PM 24509312 ER PT J AU Barteneva, NS Ponomarev, ED Tsytsykova, A Armant, M Vorobjev, IA AF Barteneva, Natasha S. Ponomarev, Eugeny D. Tsytsykova, Alla Armant, Myriam Vorobjev, Ivan A. TI Mitochondrial Staining Allows Robust Elimination of Apoptotic and Damaged Cells during Cell Sorting SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE TMRE; mitochondrial dye; caspase; cell sorting; Click-IT; viability; apoptotic cell elimination ID FLOW-CYTOMETRY; SPERM PREPARATION; LYMPHOMA-CELLS; IN-VIVO; DEATH; SPERMATOZOA; VIABILITY; PROBES; ASSAY; PH AB High-speed fluorescence-activated cell sorting is relevant for a plethora of applications, such as PCR-based techniques, microarrays, cloning, and propagation of selected cell populations. We suggest a simple cell-sorting technique to eliminate early and late apoptotic and necrotic cells, with good signal-to-noise ratio and a high-purity yield. The mitochondrial potential dye, TMRE (tetramethylrhodamine ethyl ester perchlorate), was used to separate viable and non-apoptotic cells from the cell sorting samples. TMRE staining is reversible and does not affect cell proliferation and viability. Sorted TMRE+ cells contained a negligible percentage of apoptotic and damaged cells and had a higher proliferative potential as compared with their counterpart cells, sorted on the basis of staining with DNA viability dye. This novel sorting technique using TMRE does not interfere with subsequent functional assays and is a method of choice for the enrichment of functionally active, unbiased cell populations. C1 [Barteneva, Natasha S.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Barteneva, Natasha S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ponomarev, Eugeny D.] Chinese Univ Hong Kong, Sch Biomed Sci, Themat Res Program Neurodegenerat Dev & Repair, Shatin, Hong Kong, Peoples R China. [Tsytsykova, Alla; Armant, Myriam] Childrens Hosp, Program Cellular & Mol Med, Ctr Human Cell Therapy, Boston, MA 02115 USA. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Fac Biol, AN Belozersky Inst Physicochem Biol, Moscow, Russia. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Fac Biol, Moscow, Russia. RP Barteneva, NS (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, 200 Longwood Ave,D-239, Boston, MA 02115 USA. EM natasha.barteneva@childrens.harvard.edu FU NIH [S10 RR023459]; Harvard Pilot grant; Russian Foundation for Basic Research [11-04-01749a, 13-04-40189-H]; Program in Cellular and Molecular Medicine, Boston Children's Hospital FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported in part by NIH S10 RR023459 grant, Harvard Pilot grant, Russian Foundation for Basic Research grants 11-04-01749a and 13-04-40189-H and Program in Cellular and Molecular Medicine, Boston Children's Hospital. NR 36 TC 5 Z9 5 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD APR PY 2014 VL 62 IS 4 BP 265 EP 275 DI 10.1369/0022155413520404 PG 11 WC Cell Biology SC Cell Biology GA AD5WK UT WOS:000333323700003 PM 24394470 ER PT J AU Ebersole, JL Holt, SC Cappelli, D AF Ebersole, J. L. Holt, S. C. Cappelli, D. TI Periodontitis in pregnant baboons: systemic inflammation and adaptive immune responses and pregnancy outcomes in a baboon model SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE inflammation; baboons; periodontitis; pregnancy ID C-REACTIVE PROTEIN; GINGIVAL CREVICULAR FLUID; CHRONIC KIDNEY-DISEASE; PRETERM BIRTH; NONHUMAN-PRIMATES; FUSOBACTERIUM-NUCLEATUM; GESTATIONAL-AGE; PAPIO-HAMADRYAS; ORAL BACTERIA; HOST-RESPONSE AB Background/Objectives Chronic periodontal infections have been suggested to contribute to the risk of adverse pregnancy outcomes. Material and Methods This study describes the relationship of patterns of systemic inflammatory mediators and IgG antibody to 20 oral bacteria in pregnant female baboons (Papio anubis) coupled with clinical features of ligature-induced periodontitis, as risk indicators for adverse pregnancy outcomes. Animals showing a preterm delivery and/or low birth weight newborns, as well as those pregnancies resulting in spontaneous abortion, stillbirth, or fetal demise were tabulated as adverse pregnancy outcomes. Results A significantly greater frequency of the periodontitis group neonates had a low birth weight (18.1%; p=0.008) and decreased gestational age (9.8%). Spontaneous abortion/stillbirth/fetal demise were increased in the periodontitis (8.7%) versus the control group (3.8%) (p=0.054). The baseline oral clinical presentation of the experimental animals did not relate to the adverse pregnancy outcomes. Animals with the greatest extent/severity of periodontitis progression during the initial 1/2 of gestation (ie. to mid-pregnancy) had the greatest risk for adverse pregnancy outcomes. Baseline biological parameters indicating historical responses of the animals to periodontal challenge demonstrated individual variation in selected mediators, some of which became more differential during ligature-induced periodontitis. The relationship of clinical parameters to systemic inflammatory responses was consistent with a temporal contribution to adverse pregnancy outcomes in a subset of the animals. Conclusions These results support a link between periodontitis and adverse pregnancy outcomes in the baboons and provide a prospective experimental model for delineating the biologic parameters that contribute to a causal relationship between chronic oral infections and birth events. C1 [Ebersole, J. L.] Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY 40536 USA. [Holt, S. C.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Cappelli, D.] Univ Texas Hlth Sci Ctr San Antonio, Sch Dent Med, Dept Comprehens Dent, San Antonio, TX 78229 USA. RP Ebersole, JL (reprint author), Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, HSRB422 Bosomworth Bldg, Lexington, KY 40536 USA. EM jleber2@uky.edu FU U.S.P.H.S. grant from the National Institute for Dental and Craniofacial Research [DE013598]; U.S.P.H.S. grant of the National Primate Research Center at the Southwest Foundation for Biomedical Research [13986] FX This work was supported by U.S.P.H.S. grant DE013598 from the National Institute for Dental and Craniofacial Research. Additional support was derived from U.S.P.H.S. grant 13986 in support of the National Primate Research Center at the Southwest Foundation for Biomedical Research. NR 80 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD APR PY 2014 VL 49 IS 2 BP 226 EP 236 DI 10.1111/jre.12099 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AC8HE UT WOS:000332773300010 PM 23710643 ER PT J AU Sheen, J AF Sheen, Jen TI Master regulators in plant glucose signaling networks SO JOURNAL OF PLANT BIOLOGY LA English DT Review DE Energy sensor kinase; Glucose signaling networks; Hexokinase; Target of rapamycin kinase ID UNCOUPLES HEXOKINASE1-DEPENDENT SUGAR; SNF1-RELATED PROTEIN-KINASES; AMINO-ACID-METABOLISM; E2F TARGET GENES; ARABIDOPSIS-THALIANA; TRANSCRIPTION FACTOR; ABSCISIC-ACID; TREHALOSE METABOLISM; GLOBAL REGULATORS; VEGETATIVE GROWTH AB The daily life of photosynthetic plants revolves around sugar production, transport, storage and utilization, and the complex sugar metabolic and signaling networks integrate internal regulators and environmental cues to govern and sustain plant growth and survival. Although diverse sugar signals have emerged as pivotal regulators from embryogenesis to senescence, glucose is the most ancient and conserved regulatory signal that controls gene and protein expression, cell-cycle progression, central and secondary metabolism, as well as growth and developmental programs. Glucose signals are perceived and transduced by two principal mechanisms: direct sensing through glucose sensors and indirect sensing via a variety of energy and metabolite sensors. This review focuses on the comparative and functional analyses of three glucose-modulated master regulators in Arabidopsis thaliana, the hexokinase1 (HXK1) glucose sensor, the energy sensor kinases KIN10/KIN11 inactivated by glucose, and the glucoseactivated target of rapamycin (TOR) kinase. These regulators are evolutionarily conserved, but have evolved universal and unique regulatory wiring and functions in plants and animals. They form protein complexes with multiple partners as regulators or effectors to serve distinct functions in different subcellular locales and organs, and play integrative and complementary roles from cellular signaling and metabolism to development in the plant glucose signaling networks. C1 [Sheen, Jen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NSF [IOS-0843244]; NIH [R01 GM060493, R01 GM070567]; WJC Special Project RDA-Korea [PJ009106] FX I thank Q Hall, Li Li, Lei Li, K-H Liu, M Ramon, F Rolland, Y Xiong, P. Giavalisco and C. Caldana for unpublished information and discussions. I am grateful to the NSF (IOS-0843244), NIH (R01 GM060493 and R01 GM070567), and WJC Special Project (PJ009106) RDA-Korea for supporting the research in the Sheen lab. Former and current lab members are greatly appreciated for sharing their passion, knowledge and discoveries. NR 145 TC 33 Z9 33 U1 8 U2 122 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1226-9239 EI 1867-0725 J9 J PLANT BIOL JI J. Plant Biol. PD APR PY 2014 VL 57 IS 2 BP 67 EP 79 DI 10.1007/s12374-014-0902-7 PG 13 WC Plant Sciences SC Plant Sciences GA AD3OQ UT WOS:000333155900001 PM 25530701 ER PT J AU Magidson, JF Blashill, AJ Wall, MM Balan, IC Wang, S Lejuez, CW Blanco, C AF Magidson, Jessica F. Blashill, Aaron J. Wall, Melanie M. Balan, Ivan C. Wang, Shuai Lejuez, C. W. Blanco, Carlos TI Relationship between psychiatric disorders and sexually transmitted diseases in a nationally representative sample SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Externalizing; Internalizing; Sexually transmitted disease; Latent factors; Structural model ID SUBSTANCE USE DISORDERS; ENVIRONMENTAL RISK-FACTORS; COMMON MENTAL-DISORDERS; EPIDEMIOLOGIC-SURVEY; BEHAVIORAL INTERVENTIONS; HIV PREVENTION; ALCOHOL; ADOLESCENTS; PREVALENCE; INFECTION AB Objective: Sexually transmitted diseases (STDs) are a significant public health concern. Numerous internalizing and externalizing psychiatric disorders have been found to be related to STD risk. However, to date, no studies have examined several psychiatric disorders simultaneously to account for STD risk. Given that psychiatric disorders often co-occur and can be explained by a limited number of latent dimensions of psychopathology, it is important to examine whether the relationship between STDs and psychiatric disorders is best explained by broad dimensions of psychopathology. Methods: The current study examined the associations between a range of Axis land II psychiatric disorders at baseline and rates of STDs at a three-year follow-up in a large, nationally representative sample of adults in the United States (n = 34,434). A confirmatory factor analysis (CFA) was conducted to fit three factors, two internalizing and one externalizing. Structural equation modeling (SEM) was used to assess the relationships between and among the factors and STD status and to test for mediation. Results: In bivariate analyses, most Axis I and Axis II disorders were associated with STD diagnosis at Wave 2, whereas the results of the structural model showed that only the externalizing factor was significantly associated with STD diagnosis at Wave 2. Further, the externalizing factor mediated the relationship between one of the internalizing factors and STD diagnosis. Conclusion: Findings suggest the unique contribution of externalizing psychopathology to STD risk and the importance of examining latent dimensions of disorders when understanding this relationship between psychiatric disorders and STDs. (C) 2014 Elsevier Inc. All rights reserved. C1 [Magidson, Jessica F.; Blashill, Aaron J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Magidson, Jessica F.; Lejuez, C. W.] Univ Maryland, College Pk, MD 20742 USA. [Wall, Melanie M.; Balan, Ivan C.; Wang, Shuai; Blanco, Carlos] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. [Wall, Melanie M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. RP Magidson, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM JMAGIDSON@partners.org FU National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH [DA019606, DA023973, MH076051, MH082773, R36DA034513, T32MH093310]; New York State Psychiatric Institute; [K23MH096647] FX The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism with supplemental support from the National Institute on Drug Abuse. Dr. Blanco's work on this manuscript was supported by NIH grants DA019606, DA023973, MH076051 and MH082773 and the New York State Psychiatric Institute. Dr. Magidson's work on this manuscript was supported by NIH grants R36DA034513 and T32MH093310. Dr. Blashill was supported by K23MH096647. NR 51 TC 9 Z9 9 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD APR PY 2014 VL 76 IS 4 BP 322 EP 328 DI 10.1016/j.jpsychores.2013.12.009 PG 7 WC Psychiatry SC Psychiatry GA AD6NX UT WOS:000333378600010 PM 24630184 ER PT J AU Duggan, MJ Rago, A Marini, J Beagle, J Peev, M Velmahos, G Sharma, U King, DR AF Duggan, Michael J. Rago, Adam Marini, John Beagle, John Peev, Miroslav Velmahos, George Sharma, Upma King, David R. TI Development of a lethal, closed-abdomen, arterial hemorrhage model in noncoagulopathic swine SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Trauma; Bleeding; Hemorrhage; Iliac; Battlefield; Artery; Resuscitation; Exsanguination ID HYPERTONIC SALINE DEXTRAN; AORTOTOMY HEMORRHAGE; ANESTHETIZED SWINE; AORTIC HEMORRHAGE; INJURY; AFGHANISTAN; DRESSINGS; FLUID; WARS; IRAQ AB Background: Prehospital treatment for noncompressible abdominal bleeding, particularly due to large vascular injury, represents a significant unmet medical need on the battlefield and in civilian trauma. To date, few large animal models are available to assess new therapeutic interventions and hemostatic agents for prehospital hemorrhage control. Methods: We developed a novel, lethal, closed-abdomen injury model in noncoagulopathic swine by strategic placement of a cutting wire around the external iliac artery. The wire was externalized, such that percutaneous distraction would result in vessel transection leading to severe uncontrolled abdominal hemorrhage. Resuscitation boluses were administered at 5 and 12 min. Results: We demonstrated 86% mortality (12/14 animals) at 60 min, with a median survival time of 32 min. The injury resulted in rapid and massive hypotension and exsanguinating blood loss. The noncoagulopathic animal model incorporated clinically significant resuscitation and ventilation protocols based on best evidenced-based prehospital practices. Conclusion: A new injury model is presented that enables screening of prehospital interventions designed to control noncompressible arterial hemorrhage. (C) 2014 Elsevier Inc. All rights reserved. C1 [Duggan, Michael J.; Beagle, John; Peev, Miroslav; Velmahos, George; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02141 USA. [Duggan, Michael J.; Beagle, John; Peev, Miroslav; Velmahos, George; King, David R.] Harvard Univ, Sch Med, Boston, MA 02141 USA. [Rago, Adam; Marini, John; Sharma, Upma] Arsenal Med Inc, Watertown, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 FU DARPA; ARO [W911NF10-C-0089] FX This work was supported by DARPA and ARO contract W911NF10-C-0089. The authors thank Kyle Sims, Dr Julius Chang, Drs Bijan Kheirabadi, Jill Sondeen, Mike Dubick, John Holcomb, Martin Schreiber, and Peter Rhee for consultation and feedback. NR 15 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 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD APR PY 2014 VL 187 IS 2 BP 536 EP 541 DI 10.1016/j.jss.2013.12.005 PG 6 WC Surgery SC Surgery GA AC8GD UT WOS:000332770600024 PM 24398305 ER PT J AU Iyer, JG Storer, BE Paulson, KG Lemos, B Phillips, JL Bichakjian, CK Zeitouni, N Gershenwald, JE Sondak, V Otley, CC Yu, SS Johnson, TM Liegeois, NJ Byrd, D Sober, A Nghiem, P AF Iyer, Jayasri G. Storer, Barry E. Paulson, Kelly G. Lemos, Bianca Phillips, Jerri Linn Bichakjian, Christopher K. Zeitouni, Nathalie Gershenwald, Jeffrey E. Sondak, Vernon Otley, Clark C. Yu, Siegrid S. Johnson, Timothy M. Liegeois, Nanette J. Byrd, David Sober, Arthur Nghiem, Paul TI Relationships among primary tumor size, number of involved nodes, and survival for 8044 cases of Merkel cell carcinoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE average tumor size; Merkel cell carcinoma; National Cancer Data Base; neuroendocrine carcinoma of the skin; nodal spread; prognosis; regional node metastasis; sentinel lymph node biopsy ID CANCER DATA-BASE; STAGING SYSTEM; RELATIVE SURVIVAL; UNSTAGED CANCER; UNITED-STATES; LYMPH-NODES; BIOPSY; CARE; AGE AB Background: The effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not, to our knowledge, been examined in a national database of Merkel cell carcinoma (MCC). Objective: We sought to analyze a retrospective cohort of patients with MCC from the largest US national database to assess the relationships between these clinical parameters and survival. Methods: A total of 8044 MCC cases in the National Cancer Data Base were analyzed. Results: There was a 14% risk of regional nodal involvement for 0.5-cm tumors that increased to 25% for 1.7-cm (median-sized) tumors and to more than 36% for tumors 6 cm or larger. The number of involved nodes was strongly predictive of survival (0 nodes, 76% 5-year relative survival; 1 node, 50%; 2 nodes, 47%; 3-5 nodes, 42%; and >= 6 nodes, 24%; P<.0001 for trend). Younger and/or male patients were more likely to undergo pathological nodal evaluation. Limitations: The National Cancer Data Base does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival with age-and sex-matched US population data. Conclusion: Pathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management. C1 [Iyer, Jayasri G.; Paulson, Kelly G.; Lemos, Bianca; Nghiem, Paul] Univ Washington, Dept Med Dermatol, Seattle, WA 98109 USA. [Byrd, David] Univ Washington, Dept Surg, Seattle, WA 98109 USA. [Storer, Barry E.; Nghiem, Paul] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Lemos, Bianca] Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. [Phillips, Jerri Linn] Amer Coll Surg, Commiss Canc, Chicago, IL USA. [Sober, Arthur] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Bichakjian, Christopher K.; Johnson, Timothy M.] Univ Michigan Hlth Syst, Dept Dermatol, Ann Arbor, MI USA. [Zeitouni, Nathalie] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX USA. [Sondak, Vernon] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Sondak, Vernon] Univ S Florida, Tampa, FL 33620 USA. [Otley, Clark C.] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Yu, Siegrid S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Liegeois, Nanette J.] Johns Hopkins, Dept Oncol & Plast Surg, Baltimore, MD USA. [Byrd, David; Nghiem, Paul] Seattle Canc Care Alliance, Seattle, WA USA. RP Nghiem, P (reprint author), Univ Washington, Dept Med Dermatol, 850 Republican St, Seattle, WA 98109 USA. EM pnghiem@uw.edu RI Paulson, Kelly/E-5761-2010 OI Paulson, Kelly/0000-0002-0033-3708 FU National Institutes of Health (NIH) [K02-AR50993]; American Cancer Society [RSG-08-115-01-CCE]; NIH [K24-CA139052]; David and Rosalind Bloom Endowment for Merkel Cell Carcinoma Research; Michael Piepkorn Endowment; University of Washington FX Supported by National Institutes of Health (NIH) K02-AR50993, American Cancer Society RSG-08-115-01-CCE, NIH K24-CA139052, the David and Rosalind Bloom Endowment for Merkel Cell Carcinoma Research, the Michael Piepkorn Endowment, and the University of Washington Merkel Cell Carcinoma Patient Gift Fund. NR 24 TC 21 Z9 21 U1 1 U2 3 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 APR PY 2014 VL 70 IS 4 BP 637 EP 643 DI 10.1016/j.jaad.2013.11.031 PG 7 WC Dermatology SC Dermatology GA AC8FP UT WOS:000332769200018 PM 24521828 ER PT J AU Fett, N Haynes, K Propert, KJ Margolis, DJ AF Fett, Nicole Haynes, Kevin Propert, Kathleen Joy Margolis, David J. TI Five-year malignancy incidence in patients with chronic pruritus: A population-based cohort study aimed at limiting unnecessary screening practices SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE chronic pruritus; generalized pruritus; itch; paraneoplastic signs; pruritus; skin signs of systemic disease ID HEALTH IMPROVEMENT NETWORK; GENERALIZED PRURITUS; LUNG-CANCER; COMPUTED-TOMOGRAPHY; SYSTEMIC-DISEASE; ITCH; PREVALENCE; VALIDATION; RISK; EPIDEMIOLOGY AB Background: The incidence of malignancy in patients with chronic pruritus and nondiseased skin is unknown. Objective: We sought to assess the hazard ratio (HR) of incident overall malignancy and incident malignancy by subtype in patients with chronic pruritus during the 5 years after diagnosis. Methods: A population-based cohort study was performed in the Health Improvement Network. In all, 8744 patients with chronic pruritus were matched with 31,580 patients without chronic pruritus based on sex, age, and practice. Primary outcomes were HR of incident malignancy and HR of malignancy subtypes. Results: The fully adjusted HR for incident malignancy in patients with chronic pruritus was 1.14 (95% confidence interval 0.98-1.33). The fully adjusted HR for incident hematologic malignancy and incident bile duct malignancy in patients with chronic pruritus was 2.02 (95% confidence interval 1.48-2.75) and 3.73 (95% confidence interval 1.55-8.97), respectively. The incidence of hematologic malignancy and cholangiocarcinoma in patients with chronic pruritus was 0.0016 and 0.0003 per person-year, respectively. Limitations: Potential for misclassification and detection biases is a limitation. Conclusions: Chronic pruritus without concomitant skin changes is a risk factor for having undiagnosed hematologic and bile duct malignancies, but not other malignancies. The overall incidence of these malignancies in patients with chronic pruritus is very low. C1 [Fett, Nicole] Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA USA. [Fett, Nicole; Margolis, David J.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Haynes, Kevin; Propert, Kathleen Joy] Univ Penn, Ctr Pharmacoepidermiol Res & Training, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol,Perelman Sch Med, Philadelphia, PA 19104 USA. RP Fett, N (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, 3303 SW Bond Ave, Portland, OR 97239 USA. EM fett@ohsu.edu FU National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health (NIH) [UL1TR000003] FX The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through Grant UL1TR000003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 46 TC 11 Z9 11 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 APR PY 2014 VL 70 IS 4 BP 651 EP 658 DI 10.1016/j.jaad.2013.11.045 PG 8 WC Dermatology SC Dermatology GA AC8FP UT WOS:000332769200020 PM 24485529 ER PT J AU Ambrosy, AP Fonarow, GC Butler, J Chioncel, O Greene, SJ Vaduganathan, M Nodari, S Lam, CSP Sato, N Shah, AN Gheorghiade, M AF Ambrosy, Andrew P. Fonarow, Gregg C. Butler, Javed Chioncel, Ovidiu Greene, Stephen J. Vaduganathan, Muthiah Nodari, Savina Lam, Carolyn S. P. Sato, Naoki Shah, Ami N. Gheorghiade, Mihai TI The Global Health and Economic Burden of Hospitalizations for Heart Failure Lessons Learned From Hospitalized Heart Failure Registries SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID INITIATE LIFESAVING TREATMENT; VENTRICULAR EJECTION FRACTION; QUALITY-OF-CARE; OPTIMIZE-HF REGISTRY; EUROBSERVATIONAL RESEARCH-PROGRAM; STROKE STATISTICS-2012 UPDATE; PRESERVED SYSTOLIC FUNCTION; PHYSICIAN FOLLOW-UP; ONE-YEAR MORTALITY; ORGANIZED PROGRAM AB Heart failure is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction (EF) have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized heart failure (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last 2 decades. In addition, the proportion of HHF patients classified as having a preserved EF continues to grow and may overtake HF with a reduced EF in the near future. However, the prognosis for HF with a preserved EF is similar and there are currently no available diseasemodifying therapies. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. The authors review global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, they also propose a roadmap for the design and conduct of future HHF registries. (C) 2014 by the American College of Cardiology Foundation C1 [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Chioncel, Ovidiu] Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest, Romania. [Greene, Stephen J.; Shah, Ami N.; Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60601 USA. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Lam, Carolyn S. P.] Natl Univ Hlth Ctr, Singapore, Singapore. [Sato, Naoki] Musashi Kosugi Hosp, Nippon Med Sch, Kawasaki, Kanagawa, Japan. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron,Galter 3-150, Chicago, IL 60601 USA. EM mgheorghiade@nmff.org RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; chioncel, ovidiu/0000-0002-3197-3628 FU National Institutes of Health, Health Resources and Services Administration, European Commission, Amgen, Medtronic, Novartis, and Otsuka; Boston Scientific, Medtronic, Vifor Pharma, and the National Medical Research Council of Singapore; Roche Diagnostics Japan and Otsuka FX Dr. Butler has received research support from the National Institutes of Health, Health Resources and Services Administration, European Commission, Amgen, Medtronic, Novartis, and Otsuka; and is a consultant for Alere, Bayer, BG Medicine, Celladon, CardioMEMS, Gambro, Medpace, Ono, Reate, Takeda, and Trevena. Dr. Lam has received research support from Boston Scientific, Medtronic, Vifor Pharma, and the National Medical Research Council of Singapore; and is a consultant for Bayer and Novartis. Dr. Sato has received research support from Roche Diagnostics Japan and Otsuka; and is a consultant for Novartis. Dr. Gheorghiade is a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma, Bayer HealthCare, Cardiorentis, CorThera, Cytokinetics, CytoPherx, DebioPharm, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, Johnson & Johnson, Medtronic, Merck, Novartis Pharma, Ono Pharma USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, sanofi-aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals, and Trevena Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 87 TC 194 Z9 195 U1 10 U2 24 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 APR 1 PY 2014 VL 63 IS 12 BP 1123 EP 1133 DI 10.1016/j.jacc.2013.11.053 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD4XW UT WOS:000333256100003 PM 24491689 ER PT J AU Lubitz, SA Lunetta, KL Lin, HH Arking, DE Trompet, S Li, G Krijthe, BP Chasman, DI Barnard, J Kleber, ME Dorr, M Ozaki, K Smith, AV Muller-Nurasyid, M Walter, S Agarwal, SK Bis, JC Brody, JA Chen, LY Everett, BM Ford, I Franco, OH Harris, TB Hofman, A Kaab, S Mahida, S Kathiresan, S Kubo, M Launer, LJ Macfarlane, PW Magnani, JW McKnight, B McManus, DD Peters, A Psaty, BM Rose, LM Rotter, JI Silbernagel, G Smith, JD Sotoodehnia, N Stott, DJ Taylor, KD Tomaschitz, A Tsunoda, T Uitterlinden, AG Van Wagoner, DR Volker, U Volzke, H Murabito, JM Sinner, MF Gudnason, V Felix, SB Marz, W Chung, M Albert, CM Stricker, BH Tanaka, T Heckbert, SR Jukema, JW Alonso, A Benjamin, EJ Ellinor, PT AF Lubitz, Steven A. Lunetta, Kathryn L. Lin, Honghuang Arking, Dan E. Trompet, Stella Li, Guo Krijthe, Bouwe P. Chasman, Daniel I. Barnard, John Kleber, Marcus E. Doerr, Marcus Ozaki, Kouichi Smith, Albert V. Mueller-Nurasyid, Martina Walter, Stefan Agarwal, Sunil K. Bis, Joshua C. Brody, Jennifer A. Chen, Lin Y. Everett, Brendan M. Ford, Ian Franco, Oscar H. Harris, Tamara B. Hofman, Albert Kaab, Stefan Mahida, Saagar Kathiresan, Sekar Kubo, Michiaki Launer, Lenore J. Macfarlane, Peter W. Magnani, Jared W. McKnight, Barbara McManus, David D. Peters, Annette Psaty, Bruce M. Rose, Lynda M. Rotter, Jerome I. Silbernagel, Guenther Smith, Jonathan D. Sotoodehnia, Nona Stott, David J. Taylor, Kent D. Tomaschitz, Andreas Tsunoda, Tatsuhiko Uitterlinden, Andre G. Van Wagoner, David R. Voelker, Uwe Voelzke, Henry Murabito, Joanne M. Sinner, Moritz F. Gudnason, Vilmundur Felix, Stephan B. Maerz, Winfried Chung, Mina Albert, Christine M. Stricker, Bruno H. Tanaka, Toshihiro Heckbert, Susan R. Jukema, J. Wouter Alonso, Alvaro Benjamin, Emelia J. Ellinor, Patrick T. TI Novel Genetic Markers Associate With Atrial Fibrillation Risk in Europeans and Japanese SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; atrial flutter; genetic; prognosis; risk ID FAMILIAL AGGREGATION; CHROMOSOME 4Q25; VARIANTS; SUSCEPTIBILITY; POPULATION; METAANALYSIS; PREVALENCE; IDENTITY; ZFHX3; OLDER AB Objectives This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. Background AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. Methods We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). Results We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. Conclusions The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. (C) 2014 by the American College of Cardiology Foundation C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lunetta, Kathryn L.; Lin, Honghuang; Magnani, Jared W.; Murabito, Joanne M.; Benjamin, Emelia J.] Boston Univ, Boston, MA USA. [Lunetta, Kathryn L.; Lin, Honghuang; Magnani, Jared W.; Murabito, Joanne M.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Li, Guo; Bis, Joshua C.; Brody, Jennifer A.; Psaty, Bruce M.; Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.] NCHA, Leiden, Netherlands. [Chasman, Daniel I.; Everett, Brendan M.; Albert, Christine M.] Harvard Univ, Sch Med, Boston, MA USA. [Chasman, Daniel I.; Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Barnard, John] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Inst Publ Hlth Social & Prevent Med, Mannheim, Germany. [Doerr, Marcus; Felix, Stephan B.] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. [Doerr, Marcus; Voelker, Uwe; Voelzke, Henry; Felix, Stephan B.] DZHK German Ctr Cardiovasc Res, Greifswald, Germany. [Ozaki, Kouichi; Tanaka, Toshihiro] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Mueller-Nurasyid, Martina; Kaab, Stefan; Sinner, Moritz F.] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Walter, Stefan] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Agarwal, Sunil K.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA. [Everett, Brendan M.; Albert, Christine M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Kaab, Stefan; Peters, Annette] Partner Munich Heart Alliance, DZHK, Munich, Germany. [Mahida, Saagar] Leeds Gen Infirm, Leeds, W Yorkshire, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan. [Macfarlane, Peter W.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. [Rose, Lynda M.] Brigham & Womens Hosp, Div Prevent Med, Div Cardiovasc, Boston, MA 02115 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Silbernagel, Guenther] Univ Hosp Bern, Swiss Cardiovasc Ctr, Dept Angiol, CH-3010 Bern, Switzerland. [Smith, Jonathan D.] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Stott, David J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Tomaschitz, Andreas] Med Univ Graz, Dept Cardiol, Graz, Austria. [Tsunoda, Tatsuhiko] RIKEN Ctr Integrat Med Sci, Lab Med Sci Math, Yokohama, Kanagawa, Japan. [Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Van Wagoner, David R.; Chung, Mina] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA. [Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, Mannheim, Germany. [Chung, Mina] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands. [Tanaka, Toshihiro] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Div, Tokyo, Japan. [Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM slubitz@partners.org RI Tsunoda, Tatsuhiko/K-2061-2014; Gudnason, Vilmundur/K-6885-2015; Alonso, Alvaro/A-4917-2010; Tanaka, Toshihiro/J-9310-2014; Peters, Annette/A-6117-2011; Smith, Albert/K-5150-2015; Kubo, Michiaki/N-7947-2015; OI Kleber, Marcus/0000-0003-0663-7275; Gudnason, Vilmundur/0000-0001-5696-0084; Alonso, Alvaro/0000-0002-2225-8323; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU AstraZeneca and Amgen; Roche Diagnostics FX Dr. Chasman has received research grant suppport from AstraZeneca and Amgen. Dr. Everett has received an investigator-initiated research grant from Roche Diagnostics. Dr. Kathiresan has received research grant support from Celera totaling more than $10,000; and serves on scientific advisory boards for American Genomics and Catabasis. Dr. McManus has received grants from Biotronic, Philips Healthcare, and Otsuka Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Lubitz, Lunetta, Lin, Arking, Trompet, Li, Krijthe, Chasman, Barnard, Kleber, Dorr, Ozaki, Smith, Muller-Nurasyid, and Walter are joint first authors. Drs. Murabito, Sinner, Gudnason, Felix, Marz, Chung, Albert, Stricker, Tanaka, Heckbert, Jukema, Alonso, Benjamin, and Ellinor are joint senior authors. NR 38 TC 43 Z9 44 U1 0 U2 18 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 APR 1 PY 2014 VL 63 IS 12 BP 1200 EP 1210 DI 10.1016/j.jacc.2013.12.015 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD4XW UT WOS:000333256100014 PM 24486271 ER PT J AU Mohiuddin, K Haneuse, S Sofer, T Gill, R Jaklitsch, MT Colson, YL Wee, J Bueno, R Mentzer, SJ Sugarbaker, DJ Swanson, SJ AF Mohiuddin, Kamran Haneuse, Sebastien Sofer, Tamar Gill, Ritu Jaklitsch, Michael T. Colson, Yolonda L. Wee, Jon Bueno, Raphael Mentzer, Steven J. Sugarbaker, David J. Swanson, Scott J. TI Relationship between margin distance and local recurrence among patients undergoing wedge resection for small (<= 2 cm) non-small cell lung cancer SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID POOR-RISK PATIENTS; BRONCHOGENIC-CARCINOMA; LIMITED RESECTION; PROGNOSTIC-FACTORS; LOBECTOMY; SURVIVAL; EXCISION AB Objective: Successful pulmonary wedge resection for early-stage non-small cell lung cancer requires a pathologically confirmed negative margin. To date, however, no clear evidence is available regarding whether an optimal margin distance, defined as the distance from the primary tumor to the closest resection margin, exists. Toward addressing this gap, we investigated the relationship between the margin distance and local recurrence risk. Methods: We reviewed all adult patients who had undergone wedge resection for small (<= 2 cm) non-small cell lung cancer from January 2001 to August 2011, with follow-up through to December 31, 2011. The exclusion criteria included other active noncutaneous malignancies, bronchoalveolar carcinomas, lymph node or distant metastases at diagnosis, large cell cancer, adenosquamous cancer, multiple, multifocal, and/or metastatic disease, and previous chemotherapy or radiotherapy. Using Cox regression analysis, we examined the relationship between the margin distance and interval to local recurrence, adjusting for chronic obstructive pulmonary disease, forced expiratory volume in 1 second, smoking, diabetes, tumor size, tumor location, surgeon, open versus video-assisted thoracoscopic surgery, and whether the lymph nodes were sampled. Results: Of 557 consecutive adult patients, 479 met our inclusion criteria. The overall, unadjusted 1-and 2-year local recurrences rate was 5.7% and 11.0%, respectively. From the adjusted analyses, an increased margin distance was significantly associated with a lower risk of local recurrence (P = .033). Patients with a 10-mm margin distance had a 45% lower local recurrence risk than those with a 5-mm distance (hazard ratio, 0.55; 95% confidence interval, 0.35-0.86). Beyond 15 mm, no evidence of additional benefit was associated with an increased margin distance. Conclusions: In wedge resection for small non-small cell lung cancer, increasing the margin distance <= 15 mm significantly decreased the local recurrence risk, with no evidence of additional benefit beyond 15 mm. C1 [Mohiuddin, Kamran; Jaklitsch, Michael T.; Colson, Yolonda L.; Wee, Jon; Bueno, Raphael; Mentzer, Steven J.; Sugarbaker, David J.; Swanson, Scott J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Gill, Ritu] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Haneuse, Sebastien; Sofer, Tamar] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Swanson, SJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg,Dept Surg,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM sjswanson@partners.org OI Sofer, Tamar/0000-0001-8520-8860 FU Myriad; Genentech; Exosome FX Raphael Bueno reports consulting fees from Myriad, Genentech, and Exosome. All other authors have nothing to disclose with regard to commercial support. NR 27 TC 15 Z9 18 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2014 VL 147 IS 4 BP 1169 EP 1175 DI 10.1016/j.jtcvs.2013.11.056 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AC8GT UT WOS:000332772200020 PM 24507406 ER PT J AU Kang, JW Conrad, MF Patel, VI Mukhopadhyay, S Garg, A Cambria, MR LaMuraglia, GM Cambria, RP AF Kang, Jeanwan Conrad, Mark F. Patel, Virendra I. Mukhopadhyay, Shankha Garg, Ashu Cambria, Matthew R. LaMuraglia, Glenn M. Cambria, Richard P. TI Clinical and anatomic outcomes after carotid endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Spring Meeting of the Peripheral-Vascular-Surgery-Society CY JUN 06-09, 2012 CL National Harbor, MD SP Peripheral Vasc Surg Soc ID TERM-FOLLOW-UP; PATCH ANGIOPLASTY; RANDOMIZED-TRIAL; HIGH-RISK; CONTRALATERAL OCCLUSION; ASYMPTOMATIC STENOSIS; STROKE PREVENTION; ARTERY STENOSIS; PRIMARY CLOSURE; SURGERY TRIAL AB Objective: The purpose of this study was to examine 30-day and long-term outcomes after carotid endarterectomy (CEA) in a contemporary series and to identify variables associated with stroke and death after CEA. Methods: This was a retrospective review of patients undergoing an isolated CEA at a single institution between January 1989 and December 2005. Primary study end points were 30-day and long-term overall stroke, ipsilateral stroke, and death. Secondary end points were recurrent stenosis (>70% stenosis) and reintervention. Kaplan-Meier analysis was used to create survival curves for the long-term study end points. Multivariate models were created to identify variables associated with the study end points. Results: During the study period, 3014 CEAs were performed on 2644 patients (mean age, 71.0 +/- 8.9 years; 60.9% male; 33.5% symptomatic; 37% primary closure), with mean follow-up of 7.0 years. The 30-day ipsilateral stroke, death, and combined ipsilateral stroke/death rates were 1.3%, 1.1%, and 2.2%, respectively. Previous ipsilateral CEA or neck dissection for cancer (hazard ratio [HR], 3.68; P = .0081) and symptomatic disease (HR, 2.45; P = .0071) were predictive of 30-day ipsilateral stroke. Stroke-free survival was 93.8% at 4 years and 86.9% at 10 years. Diabetes (HR, 1.94; P < .0001), symptomatic disease (HR, 1.75; P < .0001), female gender (HR, 1.34; P = .035), and increasing age (HR, 1.02; P < .0001) were predictors of long-term overall stroke. Ipsilateral stroke-free survival was 97.6% at 5 years and 94.6% at 10 years, respectively. Contralateral occlusion (HR, 2.06; P = .025) and symptomatic disease (HR, 1.87; P = .003) were predictors of ipsilateral stroke, whereas antilipid therapy was protective (HR, 0.65; P = .049). Overall survival was 70.1% at 5 years and 42.2% at 10 years, with no difference between symptomatic and asymptomatic patients. Although a variety of comorbidities were associated with inferior late survival, as anticipated, female gender (HR, 0.89; P = .016) and lipid-lowering therapy (HR, 0.69; P < .0001) were protective. Reintervention was 3.4% at 5 years and 6.6% at 10 years, with primary closure (vs patch angioplasty/eversion) increasing the risk of reintervention (HR, 1.72; P = .007). Conclusions: CEA has favorable perioperative and long-term clinical and anatomic outcomes with respect to its goal of stroke prevention for symptomatic and asymptomatic patients. Adjuvant medical therapy (antilipid) has increased overall and ipsilateral stroke-free survival. C1 [Cambria, Richard P.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 410, Boston, MA 02114 USA. EM rcambria@partners.org NR 36 TC 17 Z9 19 U1 0 U2 2 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 APR PY 2014 VL 59 IS 4 BP 944 EP 949 DI 10.1016/j.jvs.2013.10.059 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AD6WR UT WOS:000333402400013 PM 24661892 ER PT J AU Gorfine, M Hsu, L Zucker, DM Parmigiani, G AF Gorfine, Malka Hsu, Li Zucker, David M. Parmigiani, Giovanni TI Calibrated predictions for multivariate competing risks models SO LIFETIME DATA ANALYSIS LA English DT Article DE Risk prediction; Competing risks; Frailty model; Multivariate survival model; Calibration; ROC analysis ID FAILURE TIME ASSOCIATIONS; BREAST-CANCER; KIN-COHORT; REGRESSION; DISEASE AB Prediction models for time-to-event data play a prominent role in assessing the individual risk of a disease, such as cancer. Accurate disease prediction models provide an efficient tool for identifying individuals at high risk, and provide the groundwork for estimating the population burden and cost of disease and for developing patient care guidelines. We focus on risk prediction of a disease in which family history is an important risk factor that reflects inherited genetic susceptibility, shared environment, and common behavior patterns. In this work family history is accommodated using frailty models, with the main novel feature being allowing for competing risks, such as other diseases or mortality. We show through a simulation study that naively treating competing risks as independent right censoring events results in non-calibrated predictions, with the expected number of events overestimated. Discrimination performance is not affected by ignoring competing risks. Our proposed prediction methodologies correctly account for competing events, are very well calibrated, and easy to implement. C1 [Gorfine, Malka] Technion Israel Inst Technol, Fac Ind Engn & Management, IL-32000 Haifa, Israel. [Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Zucker, David M.] Hebrew Univ Jerusalem, Dept Stat, IL-91905 Jerusalem, Israel. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Gorfine, M (reprint author), Technion Israel Inst Technol, Fac Ind Engn & Management, IL-32000 Haifa, Israel. EM gorfinm@ie.technion.ac.il; lih@fhcrc.org; mszucker@mscc.huji.ac.il; gp@jimmy.harvard.edu FU Israel Science Foundation (ISF) [2012898]; NIH [P01 CA53996, R01AG14358]; NIH/NCI [5P30 CA006516-46]; Komen [KG081303] FX Malka Gorfine's work was supported by Israel Science Foundation (ISF) Grant 2012898. Li Hsu's work was supported by NIH Grants P01 CA53996 and R01AG14358. Giovanni Parmigiani's work was supported by NIH/NCI 5P30 CA006516-46 and Komen KG081303. NR 19 TC 1 Z9 1 U1 2 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 EI 1572-9249 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD APR PY 2014 VL 20 IS 2 SI SI BP 234 EP 251 DI 10.1007/s10985-013-9260-x PG 18 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA AD6IZ UT WOS:000333363400005 PM 23737081 ER PT J AU Mathai, SK Miloslavsky, EM Contreras-Valdes, FM Milosh-Zinkus, T Hayden, EM Gordon, JA Currier, PF AF Mathai, Susan K. Miloslavsky, Eli M. Contreras-Valdes, Fernando M. Milosh-Zinkus, Tanya Hayden, Emily M. Gordon, James A. Currier, Paul F. TI How we implemented a resident-led medical simulation curriculum in a large internal medicine residency program SO MEDICAL TEACHER LA English DT Editorial Material ID DELIBERATE PRACTICE; EDUCATION AB Mannequin-based simulation in graduate medical education has gained widespread acceptance. Its use in non-procedural training within internal medicine (IM) remains scant, possibly due to the logistical barriers to implementation of simulation curricula in large residency programs. We report the Massachusetts General Hospital Department of Medicine's scale-up of a voluntary pilot program to a mandatory longitudinal simulation curriculum in a large IM residency program (n = 54). We utilized an eight-case curriculum implemented over the first four months of the academic year. An intensive care unit curriculum was piloted in the spring. In order to administer a comprehensive curriculum in a large residency program where faculty resources are limited, thirty second-year and third-year residents served as session facilitators and two senior residents served as chairpersons of the program. Post-session anonymous survey revealed high learner satisfaction scores for the mandatory program, similar to those of the voluntary pilot program. Most interns believed the sessions should continue to be mandatory. Utilizing residents as volunteer facilitators and program leaders allowed the implementation of a well-received mandatory simulation program in a large IM residency program and facilitated program sustainability. C1 [Mathai, Susan K.; Miloslavsky, Eli M.; Contreras-Valdes, Fernando M.; Milosh-Zinkus, Tanya; Hayden, Emily M.; Gordon, James A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hayden, Emily M.] Massachusetts Gen Hosp, Fac Lead Strateg Initiat & Operat, MGH Learning Lab, Boston, MA 02114 USA. [Currier, Paul F.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Mathai, Susan K.] Univ Colorado, Boulder, CO 80309 USA. [Contreras-Valdes, Fernando M.] Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Mathai, SK (reprint author), Univ Colorado Denver, 12700 East 19th Ave,RM 9023,Mail Stop C272, Aurora, CO 80045 USA. EM mathai@post.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X EI 1466-187X J9 MED TEACH JI Med. Teach. PD APR PY 2014 VL 36 IS 4 BP 279 EP 283 DI 10.3109/0142159X.2013.875619 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD3XH UT WOS:000333179300001 PM 24495251 ER PT J AU Richardson, RC Tarleton, JC Bird, TD Gospe, SM AF Richardson, Randal C. Tarleton, Jack C. Bird, Thomas D. Gospe, Sidney M., Jr. TI TRUNCATING CLCN1 MUTATIONS IN MYOTONIA CONGENITA: VARIABLE PATTERNS OF INHERITANCE SO MUSCLE & NERVE LA English DT Article DE allelic variability; CLC-1; CLCN1; myotonia; myotonia congenita ID CHLORIDE CHANNEL; DOMINANT; BECKER AB Introduction: Myotonia congenita due to protein truncating CLCN1 mutations is associated with variable patterns of inheritance. Methods: Three family kindreds are described, all of whom possess protein truncating mutations (Y33X, fs503X, R894X). One lineage also has coexistent R894X, A313T, and A320V mutations. Results: The Y33X mutation kinship has autosomal recessive inheritance and a severe phenotype when homozygous. The fs503X family has autosomal dominant inheritance and a moderate-to-severe phenotype. The A313T mutation kindred also has autosomal dominant inheritance but expresses a mild phenotype, except for the more severely affected compound heterozygotes. Conclusions: Early truncating mutations precluding dimerization are expected to be autosomal recessive and express a severe phenotype, while later mutations may be variable. The pedigrees presented here demonstrate that intrafamilial phenotypic variability may result from a dosage effect of an additional mutation, not necessarily variable expressivity. Mutations that have unexpected patterns of inheritance may represent allelic variability. Muscle Nerve 49:593-600, 2014 C1 [Richardson, Randal C.; Gospe, Sidney M., Jr.] Univ Washington, Div Pediat Neurol, Dept Neurol, Seattle, WA 98105 USA. [Richardson, Randal C.; Gospe, Sidney M., Jr.] Univ Washington, Div Pediat Neurol, Dept Pediat, Seattle, WA 98105 USA. [Richardson, Randal C.; Gospe, Sidney M., Jr.] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Tarleton, Jack C.] Mission Hosp, Fullerton Genet Lab, Asheville, NC USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ Clin Ctr, Seattle, WA USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98105 USA. RP Gospe, SM (reprint author), Univ Washington, Div Pediat Neurol, Dept Neurol, 4800 Sand Point Way NE,MB 7-420, Seattle, WA 98105 USA. EM sgospe@uw.edu OI Gospe Jr, Sidney/0000-0002-0099-109X FU Athena Diagnostics, Inc. FX Dr. Bird has received licensing fees from Athena Diagnostics, Inc. Mission Hospitals' Fullerton Genetics Laboratory has provided in-kind support for analysis and interpretation of DNA sequence data for patients included in the study. Dr. Tarleton is an employee of this nonprofit institution. All remaining authors have nothing to disclose. NR 19 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD APR PY 2014 VL 49 IS 4 BP 593 EP 600 DI 10.1002/mus.23976 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD4CE UT WOS:000333193100020 PM 23893571 ER PT J AU Kurachi, M Barnitz, RA Yosef, N Odorizzi, PM DiIorio, MA Lemieux, ME Yates, K Godec, J Klatt, MG Regev, A Wherry, EJ Haining, WN AF Kurachi, Makoto Barnitz, R. Anthony Yosef, Nir Odorizzi, Pamela M. DiIorio, Michael A. Lemieux, Madeleine E. Yates, Kathleen Godec, Jernej Klatt, Martin G. Regev, Aviv Wherry, E. John Haining, W. Nicholas TI The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8(+) T cells SO NATURE IMMUNOLOGY LA English DT Article ID PROBE LEVEL DATA; VIRAL-INFECTION; REGULATORY ELEMENT; CLONAL EXPANSION; IRF INTERACTIONS; MEMORY; EXPRESSION; NETWORK; T(H)17; GENOME AB The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) and follicular helper T cells (T-FH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells showed profound defects in effector population expansion and underwent proliferative and metabolic catastrophe early after encountering antigen. BATF, together with the transcription factors IRF4 and Jun proteins, bound to and promoted early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors while paradoxically repressing genes encoding effector molecules (IFN-gamma and granzyme B). Thus, BATF amplifies T cell antigen receptor (TCR)-dependent expression of transcription factors and augments the propagation of inflammatory signals but restrains the expression of genes encoding effector molecules. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved. C1 [Kurachi, Makoto; Odorizzi, Pamela M.; Wherry, E. John] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kurachi, Makoto; Odorizzi, Pamela M.; Wherry, E. John] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barnitz, R. Anthony; DiIorio, Michael A.; Yates, Kathleen; Godec, Jernej; Klatt, Martin G.; Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Yosef, Nir; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA USA. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA. [Haining, W. Nicholas] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Wherry, EJ (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM wherry@mail.med.upenn.edu; nicholas_haining@dfci.harvard.edu OI Lemieux, Madeleine/0000-0001-6355-8691; Barnitz, Tony/0000-0002-9634-4558 FU US National Institutes of Health [T32 AI00762, AI091493, AI083022, AI095608, HHSN266200500030C, AI082630]; US Government (Presidential Early Career Award for Science and Engineering); Ministry of Education, Culture, Sports, Science and Technology of Japan [22790453]; Uehara Memorial Foundation of Japan; German National Academic Foundation FX We thank M. Ali for animal care; K. Mansfield and J. Kurachi for technical assistance; the Center for Cancer Computational Biology Sequencing Core of the Dana-Farber Cancer Institute for sequencing services and advice; and members of the Haining and Wherry laboratories for discussions. Supported by the US National Institutes of Health (T32 AI00762 to P.M.O.; AI091493 to W.N.H.; AI083022, AI095608 and HHSN266200500030C to E.J.W.; and AI082630 to W.N.H. and E.J.W.), the US Government (Presidential Early Career Award for Science and Engineering to W.N.H.), The Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Young Scientists (B) 22790453 to M.K.), the Uehara Memorial Foundation of Japan (M.K.) and the German National Academic Foundation (M.G.K.). NR 64 TC 43 Z9 43 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2014 VL 15 IS 4 BP 373 EP + DI 10.1038/ni.2834 PG 13 WC Immunology SC Immunology GA AD4WL UT WOS:000333252000012 PM 24584090 ER PT J AU Hivert, MF Vassy, JL Meigs, JB AF Hivert, Marie-France Vassy, Jason L. Meigs, James B. TI Susceptibility to type 2 diabetes mellitus-from genes to prevention SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID LIFE-STYLE INTERVENTION; IMPAIRED GLUCOSE-TOLERANCE; SCALE ASSOCIATION ANALYSIS; INSULIN-RESISTANCE; AFRICAN-AMERICANS; HEALTH BEHAVIORS; DNA VARIANTS; RISK-FACTORS; PREDICTION; WOMEN AB Knowledge of the genetics of type 2 diabetes mellitus (T2DM) has evolved tremendously over the past few years. Following advances in technology and analytical approaches, collaborative case-control genome-wide association studies have revealed up to 65 loci credibly associated with T2DM. Prospective population studies have demonstrated that aggregated genetic risk scores, so-called because they sum the genetic risk attributed to each locus, can predict incident T2DM among individuals of various age ranges and diverse ethnic backgrounds. With each set of T2DM loci discovered, increasing the number of loci in these scores has improved their predictive ability, although a prediction plateau may already have been reached. The current literature shows that intensive lifestyle interventions are effective for preventing T2DM at any level of genetic risk and might be particularly efficacious among individuals with high genetic susceptibility. By contrast, counselling to inform patients about their personal T2DM genetic risk profiles does not seem to improve motivation or attitudes that lead to positive lifestyle behaviour changes. Future studies should investigate the role of genetics for both T2DM prediction and prevention in young populations in the hope of reducing disease burden for future generations. C1 [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02114 USA. [Vassy, Jason L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU NHGRI NIH HHS [U01 HG006500]; NIDDK NIH HHS [K24 DK080140, L30 DK089597, R01 DK078616, U01 DK078616] NR 60 TC 20 Z9 20 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD APR PY 2014 VL 10 IS 4 BP 198 EP 205 DI 10.1038/nrendo.2014.11 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD4VX UT WOS:000333250500005 PM 24535206 ER PT J AU Giustina, A Chanson, P Kleinberg, D Bronstein, MD Clemmons, DR Klibanski, A van der Lely, AJ Strasburger, CJ Lamberts, SW Ho, KKY Casanueva, FF Melmed, S AF Giustina, Andrea Chanson, Philippe Kleinberg, David Bronstein, Marcello D. Clemmons, David R. Klibanski, Anne van der Lely, Aart J. Strasburger, Christian J. Lamberts, Steven W. Ho, Ken K. Y. Casanueva, Felipe F. Melmed, Shlomo TI EXPERT CONSENSUS DOCUMENT A consensus on the medical treatment of acromegaly SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID SOMATOSTATIN ANALOG THERAPY; LONG-TERM; GROWTH-HORMONE; OCTREOTIDE LAR; TUMOR VOLUME; SLEEP-APNEA; PEGVISOMANT THERAPY; POSTOPERATIVE CURE; CLINICAL-PRACTICE; DISEASE-ACTIVITY AB In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus. C1 [Giustina, Andrea] Univ Brescia, Brescia, Italy. [Chanson, Philippe] Hop Univ Paris Sud, Paris, France. [Kleinberg, David] NYU, Sch Med, New York, NY USA. [Bronstein, Marcello D.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Clemmons, David R.] Univ N Carolina, Chapel Hill, NC USA. [Klibanski, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [van der Lely, Aart J.; Lamberts, Steven W.] Erasmus MC, Rotterdam, Netherlands. [Strasburger, Christian J.] Charite Campus Mitte, Berlin, Germany. [Ho, Ken K. Y.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Casanueva, Felipe F.] S Compostela Univ, Santiago De Compostela, Spain. [Casanueva, Felipe F.] CIBERobn, Santiago De Compostela, Spain. [Melmed, Shlomo] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. RP Melmed, S (reprint author), Cedars Sinai Med Ctr, Dept Med, Room 2015,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM melmed@csmc.edu RI Ho, Ken/E-5832-2011 FU Ipsen Ltd, Paris, France; Cedars-Sinai Medical Center FX The authors thank all participants in the Ninth Acromegaly Consensus Group meeting: Michel Aubert (Switzerland), John Ayuk (UK), Ariel Barkan (USA), Albert Beckers (Belgium), Paolo Beck-Peccoz (Italy), Anat Ben Shlomo (USA), Nienke Biermasz (Netherlands), Jens Bollerslev (Norway), Philippe Caron (France), Kazuo Chihara (Japan), Annamaria Colao (Italy), Ettore Degli Uberti (Italy), Eleni Dimarki (USA), William Drake (UK), Diego Ferone (Italy), Maria Fleseriu (USA), Hidenori Fukuoka (Japan), Monica Gadelha (Brazil), Yona Greenman (Israel), Ashley Grossman (UK), Peter Kamenicky (France), Larry Katznelson (USA), Marta Korbonits (UK), Andre Lacroix (Canada), Anton Luger (Austria), Gherardo Mazziotti (Italy), Moises Mercado (Mexico), Sebastian Neggers (Netherlands), Vera Popovic-Brkic (Serbia), Johannes Romijn (Netherlands), Jochen Schopohl (Germany), Gunther Stalla (Germany), Peter Trainer (UK), Jacqueline Trouillas (France), Stylianos Tsagarakis (Greece), Mary Lee Vance (USA), John Wass (UK), Susan Webb (Spain), Margaret Wierman (USA) and Whitney Woodmansee (USA). This study was sponsored by an unrestricted educational grant from Ipsen Ltd, Paris, France. Scientific sponsorship of the meeting was provided by Cedars-Sinai Medical Center. We also acknowledge the editorial assistance provided by Martin Gilmour (ESP Bioscience, Crowthorne, UK), who attended the workshop to take minutes that were used to assist the authors in writing. NR 75 TC 107 Z9 107 U1 6 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD APR PY 2014 VL 10 IS 4 BP 243 EP 248 DI 10.1038/nrendo.2014.21 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD4VX UT WOS:000333250500009 PM 24566817 ER PT J AU Plotkin, SR AF Plotkin, Scott R. TI Chemoprevention for neurofibromatosis 2: just over the horizon? SO NEURO-ONCOLOGY LA English DT Editorial Material ID PROGRESSIVE VESTIBULAR SCHWANNOMAS; MTORC1 INHIBITORS; PHASE-II; TYPE-2; BEVACIZUMAB; EVEROLIMUS; MENINGIOMA; NF2/MERLIN; GROWTH C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2014 VL 16 IS 4 BP 471 EP 472 DI 10.1093/neuonc/nou037 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AD5IS UT WOS:000333286400002 PM 24637549 ER PT J AU Wen, PY Chang, SM Lamborn, KR Kuhn, JG Norden, AD Cloughesy, TF Robins, HI Lieberman, FS Gilbert, MR Mehta, MP Drappatz, J Groves, MD Santagata, S Ligon, AH Yung, WKA Wright, JJ Dancey, J Aldape, KD Prados, MD Ligon, KL AF Wen, Patrick Y. Chang, Susan M. Lamborn, Kathleen R. Kuhn, John G. Norden, Andrew D. Cloughesy, Timothy F. Robins, H. Ian Lieberman, Frank S. Gilbert, Mark R. Mehta, Minesh P. Drappatz, Jan Groves, Morris D. Santagata, Sandro Ligon, Azra H. Yung, W. K. Alfred Wright, John J. Dancey, Janet Aldape, Kenneth D. Prados, Michael D. Ligon, Keith L. TI Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02 SO NEURO-ONCOLOGY LA English DT Article DE anaplastic glioma; clinical trial; epidermal growth factor; erlotinib; glioblastoma; temsirolimus ID GROWTH-FACTOR-RECEPTOR; EGFR KINASE INHIBITORS; GLIOBLASTOMA-MULTIFORME; MAMMALIAN TARGET; II TRIAL; RAPAMYCIN INHIBITION; ANTITUMOR-ACTIVITY; MTOR INHIBITORS; PLUS SIROLIMUS; PTEN-DEFICIENT AB Inhibition of epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin (mTOR) may have synergistic antitumor effects in high-grade glioma patients. We conducted a phase I/II study of the EGFR inhibitor erlotinib (150 mg/day) and the mTOR inhibitor temsirolimus. Patients initially received temsirolimus 50 mg weekly, and the dose adjusted based on toxicities. In the phase II component, the primary endpoint was 6-month progression-free survival (PFS6) among glioblastoma patients. Twenty-two patients enrolled in phase I, 47 in phase II. Twelve phase I patients treated at the maximum tolerated dosage were included in the phase II cohort for analysis. The maximum tolerated dosage was 15 mg temsirolimus weekly with erlotinib 150 mg daily. Dose-limiting toxicities were rash and mucositis. Among 42 evaluable glioblastoma patients, 12 (29) achieved stable disease, but there were no responses, and PFS6 was 13. Among 16 anaplastic glioma patients, 1 (6) achieved complete response, 1 (6) partial response, and 2 (12.5) stable disease, with PFS6 of 8. Tumor levels of both drugs were low, and posttreatment tissue in 3 patients showed no reduction in the mTOR target phosphorylated (phospho-)S6(S235/236) but possible compensatory increase in phospho-Akt(S473). Presence of EGFR variant III, phospho-EGFR, and EGFR amplification did not correlate with survival, but patients with elevated phosphoextracellular signal-regulated kinase or reduced phosphatase and tensin homolog protein expression had decreased progression-free survival at 4 months. Because of increased toxicity, the maximum tolerated dosage of temsirolimus in combination with erlotinib proved lower than expected. Insufficient tumor drug levels and redundant signaling pathways may partly explain the minimal antitumor activity noted. C1 [Wen, Patrick Y.; Norden, Andrew D.; Drappatz, Jan] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurol, Div Neurooncol, Los Angeles, CA 90024 USA. [Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Madison, WI USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Neurooncol Program, Div Hematol Oncol, Pittsburgh, PA USA. [Gilbert, Mark R.; Groves, Morris D.; Yung, W. K. Alfred; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Div Neurooncol, Houston, TX 77030 USA. [Santagata, Sandro; Ligon, Azra H.] Dana Farber Brigham & Womens Canc Ctr, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Santagata, Sandro; Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wright, John J.; Dancey, Janet] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU Ivy Foundation; Sontag Foundation; [U01 CA137443]; [P01CA095616] FX This study was funded by U01 CA137443. K. L. L. acknowledges support from P01CA095616, the Ivy Foundation, and the Sontag Foundation. NR 49 TC 36 Z9 37 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2014 VL 16 IS 4 BP 567 EP 578 DI 10.1093/neuonc/not247 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AD5IS UT WOS:000333286400011 PM 24470557 ER PT J AU Peereboom, DM Murphy, C Ahluwalia, MS Conlin, A Eichler, A Van Poznak, C Baar, J Elson, P Seidman, AD AF Peereboom, David M. Murphy, Conleth Ahluwalia, Manmeet S. Conlin, Alison Eichler, April Van Poznak, Catherine Baar, Joseph Elson, Paul Seidman, Andrew D. TI Phase II trial of patupilone in patients with brain metastases from breast cancer SO NEURO-ONCOLOGY LA English DT Article DE brain metastases; breast cancer; chemotherapy; epothilone; patupilone ID EPOTHILONE B; IN-VIVO; CARCINOMA; TEMOZOLOMIDE; CHEMOTHERAPY; MALIGNANCIES; RADIOTHERAPY; TRASTUZUMAB; RESISTANT; LAPATINIB AB For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the bloodbrain barrier. We hypothesized that patupilone would produce a 35 3-month CNS progression-free survival in women with BCBM after WBRT. This multicenter phase II trial included 2 cohorts. Group A included women with progressive BCBM after WBRT. Group B was an exploratory cohort of patients with either leptomeningeal metastases or untreated brain metastases. The primary goal was to observe a 35 3-month CNS progression-free survival in Group A. The sample size was 45 for Group A and 10 for Group B. Patients received patupilone 10 mg/m(2) once every 3 weeks until progression. Responses were scored according to the Macdonald criteria. Fifty-five patients (45 in Group A, 10 in Group B) enrolled. In Group A, the 3-month CNS progression-free survival was 27, the median overall survival was 12.7 months, and the overall response rate was 9. In Group B, which enrolled 5 patients with leptomeningeal disease and 5 with no prior WBRT, no responses occurred and 8 patients had CNS progression before 3 months. Systemic responses occurred in 15 of patients, including a complete response in liver metastases. Diarrhea occurred in 87 of patients; 25 had grade 3 and 4 adverse events. Patupilone in patients with BCBM did not meet the efficacy criteria and had significant gastrointestinal toxicity. Further study of brain-penetrant agents is warranted for patients with CNS metastases from breast cancer. C1 [Peereboom, David M.; Ahluwalia, Manmeet S.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Peereboom, David M.; Ahluwalia, Manmeet S.] Cleveland Clin, Neurol Inst, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Peereboom, David M.; Ahluwalia, Manmeet S.; Elson, Paul] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Elson, Paul] Cleveland Clin, Cleveland, OH 44106 USA. [Murphy, Conleth; Conlin, Alison; Seidman, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Eichler, April] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Van Poznak, Catherine] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Baar, Joseph] Univ Hosp Cleveland, Seidman Canc Ctr, Case Med Ctr, Cleveland, OH 44106 USA. RP Peereboom, DM (reprint author), Cleveland Clin, Lerner Coll Med, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. EM peerebd@ccf.org FU Novartis Pharmaceuticals FX This work was supported by Novartis Pharmaceuticals. NR 28 TC 7 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2014 VL 16 IS 4 BP 579 EP 583 DI 10.1093/neuonc/not305 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AD5IS UT WOS:000333286400012 PM 24470546 ER PT J AU Ahmed, Z Mai, CL Elder, B Rodriguez, S Yaster, M AF Ahmed, Zulfiqar Mai, Christine L. Elder, Badrea Rodriguez, Samuel Yaster, Myron TI Breaking the glass ceiling: an interview with Dr. Shirley Graves, a pioneering woman in medicine SO PEDIATRIC ANESTHESIA LA English DT Article DE critical care medicine; Shirley Graves; pediatric anesthesia ID VENTILATION AB Shirley Graves M.D., D.Sc. (honorary) (1936), Professor Emeritus of Anesthesiology and Pediatrics at the University of Florida, was one of the most influential women in medicine in the 1960 and 1970s, a time when the medical profession was overwhelmingly male-dominated. In today's society, it is hard to believe that only 50years ago, women were scarce in the field of medicine. Yet Dr. Graves was a pioneer in the fields of pediatric anesthesia and pediatric critical care medicine. She identifies her development of the pediatric intensive care unit and her leadership in the Division of Pediatric Anesthesia at the University of Florida as her defining contributions. Through her journal articles, book chapters, national and international lectures, and leadership in the American Society of Anesthesiology and the Florida Society of Anesthesiology, she inspired a generation of men and women physicians to conquer the unthinkable and break through the glass ceiling. C1 [Ahmed, Zulfiqar] Anesthesia Associates Ann Arbor, Ann Arbor, MI USA. [Ahmed, Zulfiqar] Wayne State Univ, Detroit, MI USA. [Mai, Christine L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Mai, Christine L.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. [Elder, Badrea] Wayne State Univ, Sch Med, Detroit, MI USA. [Rodriguez, Samuel] Boston Childrens Hosp, Dept Anesthesia, Boston, MA USA. [Yaster, Myron] Johns Hopkins Univ, Dept Anesthesiol Crit Care Med, Baltimore, MD USA. [Yaster, Myron] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Yaster, Myron] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org NR 2 TC 0 Z9 0 U1 0 U2 6 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 APR PY 2014 VL 24 IS 4 BP 440 EP 445 DI 10.1111/pan.12363 PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AC8HG UT WOS:000332773500012 PM 24571660 ER PT J AU Efficace, F Baccarani, M Breccia, M Saussele, S Abel, G Caocci, G Guilhot, F Cocks, K Naeem, A Sprangers, M Oerlemans, S Chie, W Castagnetti, F Bombaci, F Sharf, G Cardoni, A Noens, L Pallua, S Salvucci, M Nicolatou-Galitis, O Rosti, G Mandelli, F AF Efficace, Fabio Baccarani, Michele Breccia, Massimo Saussele, Susanne Abel, Gregory Caocci, Giovanni Guilhot, Francois Cocks, Kim Naeem, Adel Sprangers, Mirjam Oerlemans, Simone Chie, Weichu Castagnetti, Fausto Bombaci, Felice Sharf, Giora Cardoni, Annarita Noens, Lucien Pallua, Stephan Salvucci, Marzia Nicolatou-Galitis, Ourania Rosti, Gianantonio Mandelli, Franco TI International development of an EORTC questionnaire for assessing health-related quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24 SO QUALITY OF LIFE RESEARCH LA English DT Article DE Quality of life; Chronic myeloid leukemia; Questionnaire ID DIAGNOSED CHRONIC-PHASE; TYROSINE-KINASE INHIBITORS; REPORTED OUTCOMES; INTERFERON-ALPHA; FOLLOW-UP; IMATINIB; THERAPY; POPULATION; DASATINIB; NILOTINIB AB Background Health-related quality of life (HRQOL) is a key aspect for chronic myeloid leukemia (CML) patients. The aim of this study was to develop a disease-specific HRQOL questionnaire for patients with CML to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30. The process followed a predefined and systematic stepwise iterative process as defined by the EORTC guidelines for questionnaire development. The process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2) operationalization of the HRQOL issues into a set of items, and (3) pretesting the questionnaire for relevance and acceptability. Descriptive statistics and psychometric analyses were also performed. Overall, 655 CML patients were enrolled in 10 countries including the USA and countries in Europe and Asia. Interviews with health-care professionals experienced in CML (n = 59) were also conducted. Results from the interviews, clinical experiences, and statistical analyses were used to develop the EORTC QLQ-CML24. The final module consists of 24 items assessing the following aspects: symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.73 to 0.83 for the proposed scales. The EORTC QLQ-CML24 is an internationally developed HRQOL questionnaire for CML patients, and its implementation in clinical research and practice can provide important information to facilitate clinical decision-making. C1 [Efficace, Fabio; Cardoni, Annarita; Mandelli, Franco] Italian Grp Adult Hematol Dis GIMEMA, Ctr Data, I-00161 Rome, Italy. [Efficace, Fabio; Cardoni, Annarita; Mandelli, Franco] Italian Grp Adult Hematol Dis GIMEMA, Hlth Outcomes Res Unit, I-00161 Rome, Italy. [Baccarani, Michele; Castagnetti, Fausto; Rosti, Gianantonio] Univ Bologna, S Orsola Malpighi Hosp, Dept Hematol Oncol, Bologna, Italy. [Breccia, Massimo] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00185 Rome, Italy. [Saussele, Susanne] Heidelberg Univ, Med Fak Mannheim, Mannheim, Germany. [Abel, Gregory] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. [Caocci, Giovanni] Univ Cagliari, Dept Internist Med Sci, Cagliari, Italy. [Guilhot, Francois] Ctr Hosp Univ Poitiers, Inserm CIC 0802, Poitiers, France. [Cocks, Kim] Univ York, York Trials Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Naeem, Adel] Baghdad Teaching Hosp, Dept Hematol, Baghdad, Iraq. [Sprangers, Mirjam] Univ Amsterdam, Dept Med Psychol, Amsterdam, Netherlands. [Oerlemans, Simone] Comprehens Canc Ctr South, Eindhoven, Netherlands. [Chie, Weichu] Natl Taiwan Univ, Dept Publ Hlth, Grad Inst Prevent Med, Coll Publ Hlth, Taipei 10764, Taiwan. [Bombaci, Felice] Grp AIL Pazienti LMC, Turin, Italy. [Sharf, Giora] CML Advocates Network, Tel Aviv, Israel. [Noens, Lucien] Ghent Univ Hosp, Dept Hematol, Ghent, Belgium. [Pallua, Stephan] Med Univ Innsbruck, Dept Psychiat & Psychotherapy, A-6020 Innsbruck, Austria. [Salvucci, Marzia] Azienda Usl Ravenna, Hematol Unit, Ravenna, Italy. [Nicolatou-Galitis, Ourania] Univ Athens, Clin Hosp Dent, Dent Oncol Unit, Sch Dent, Athens, Greece. RP Efficace, F (reprint author), Italian Grp Adult Hematol Dis GIMEMA, Ctr Data, Via Benevento 6, I-00161 Rome, Italy. EM f.efficace@gimema.it OI Cocks, Kim/0000-0003-2595-708X; Chie, Wei-Chu/0000-0001-5584-6554; Caocci, Giovanni/0000-0002-6585-5187 FU EORTC Quality of Life Group; Italian Group for Adult Hematologic Diseases (GIMEMA); EORTC Quality of Life Department (Brussels); DJCLS [R 10/20] FX This study was supported by a research grant from the EORTC Quality of Life Group. Also, additional support for the conduct of the study was provided by the Italian Group for Adult Hematologic Diseases (GIMEMA). We are grateful to all the patients who participated in this study. We also thank Felice Bombaci and Giora Sharf (from the CML Advocates Network) for their invaluable help in representing the unique patients' perspective throughout the development process. We also thank Dagmara Kulis from the EORTC Quality of Life Department (Brussels) for support in coordinating language translations. Finally, we also express our gratitude to Bernhard Holzner and Marianne Hjermstad for reviewing the module development report on behalf of the EORTC Quality of Life Group. Dr. Susanne Saussele is supported by DJCLS R 10/20. NR 29 TC 8 Z9 8 U1 1 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2014 VL 23 IS 3 BP 825 EP 836 DI 10.1007/s11136-013-0523-5 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AD2PH UT WOS:000333077100008 PM 24026634 ER PT J AU Lee, YT Liu, SI Huang, HC Sun, FJ Huang, CR Yeung, A AF Lee, Yun-Tse Liu, Shen-Ing Huang, Hui-Chun Sun, Fang-Ju Huang, Chiu-Ron Yeung, Albert TI Validity and reliability of the Chinese version of the Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) SO QUALITY OF LIFE RESEARCH LA English DT Article DE Q-LES-Q-SF; Quality of life; Chinese; Validity; Reliability; Questionnaire ID HEALTH SURVEY; CLINICAL-ASSESSMENT; MENTAL-DISORDERS; RATING-SCALE; DEPRESSION; TAIWAN; SF-12; NEUROPSYCHIATRY; SCHIZOPHRENIA; ASSESSMENTS AB Purpose The Short Form version of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) was designed to measure patients' subjective experience of enjoyment and satisfaction. However, it had not yet been validated for Chinese societies. This paper reports on the validation of the Chinese version of the Q-LES-Q-SF among primary care patients in Taiwan. The study included adult patients in primary care clinics. The participants completed the Q-LES-Q-SF, the Patient Health Questionnaire, and the Short Form Health Survey. After that, the trained researchers interviewed the patients using the mood module of the Schedules for Clinical Assessment in Neuropsychiatry and the 17-item Hamilton Rating Scale for Depression. A subsample of participants was reassessed with Q-LES-Q-SF within a 2-week interval. A total of 1,482 patients completed the Q-LES-Q-SF. The content validity was good, with no significant floor/ceiling effect. The internal consistency of the Q-LES-Q-SF proved to be substantial as well as the test-retest reliability. The factor structure was examined by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The EFA yielded a 2-factor structure, which was confirmed by a CFA with acceptable fit indices. Known-group validity of the Q-LES-Q-SF was satisfactory in distinguishing patients with and without depression, according to hierarchical regression analyses. Evidence of concurrent validity was provided for the Q-LES-Q-SF, and its two subscales identified significant correlations with other measures. The Chinese Q-LES-Q-SF was shown to have adequate validity and reliability. It may be a useful tool to measure patients' quality of life in Chinese societies. C1 [Lee, Yun-Tse; Liu, Shen-Ing] Mackay Mem Hosp, Dept Psychiat, Taipei 10449, Taiwan. [Liu, Shen-Ing] Mackay Med Coll, Dept Med, Taipei, Taiwan. [Liu, Shen-Ing; Huang, Hui-Chun; Sun, Fang-Ju] Mackay Jr Coll Med Nursing & Management, Taipei, Taiwan. [Liu, Shen-Ing; Huang, Hui-Chun; Sun, Fang-Ju; Huang, Chiu-Ron] Mackay Mem Hosp, Dept Med Res, Taipei 10449, Taiwan. [Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Liu, SI (reprint author), Mackay Mem Hosp, Dept Psychiat, 92,Sec 2,Chung Shan North Rd, Taipei 10449, Taiwan. EM maryliuyip@gmail.com FU National Health Research Institute, Republic of China [NHRI-EX97-9706PI] FX This study was supported by a grant from the National Health Research Institute, Republic of China (NHRI-EX97-9706PI). We thank all participants for their participation in this study. NR 45 TC 7 Z9 7 U1 5 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2014 VL 23 IS 3 BP 907 EP 916 DI 10.1007/s11136-013-0528-0 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AD2PH UT WOS:000333077100016 PM 24062242 ER PT J AU Chin, JY Pitman, MB Hong, TS AF Chin, Joanna Y. Pitman, Martha B. Hong, Theodore S. TI Intraductal Papillary Mucinous Neoplasm: Clinical Surveillance and Management Decisions SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; PANCREATIC DUCTAL ADENOCARCINOMA; RESECTED CYSTIC TUMORS; K-RAS MUTATION; CLINICOPATHOLOGICAL FEATURES; MALIGNANCY; RISK; SURVIVAL; PROGRESSION; PREDICTORS AB Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare cystic neoplasm. Although most IPMNs appear to be benign and may be managed by surveillance, all IPMNs are considered premalignant lesions with malignant potential. As such, current efforts are focused on identifying those neoplasms that are at high risk for malignancy to optimize treatment strategy and outcome. IPMNs with invasive carcinoma have clinical outcomes that approach those of conventional pancreatic ductal adenocarcinoma. Management guidelines recommend surgical resection for IPMNs with high-risk imaging or cytologic features. The role of adjuvant therapy is unclear, and we review the evidence for chemoradiation here. Some studies suggest adjuvant chemoradiation may have the greatest impact in malignant IPMNs with adverse histologic features, that is, lymph node metastasis at the time of diagnosis or positive surgical margins. As more IPMNs are recognized and treated, more evidence will accumulate to guide clinicians regarding appropriate use of radiotherapy in the management of IPMN. (c) 2014 Elsevier Inc. All rights reserved. C1 [Chin, Joanna Y.; Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox Bldg 3,100 Blossom St, Boston, MA 02114 USA. EM tshong1@partners.org NR 64 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 2014 VL 24 IS 2 BP 77 EP 84 DI 10.1016/j.semradonc.2013.11.005 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AD7HT UT WOS:000333435300003 PM 24635864 ER PT J AU Flaumenhaft, R AF Flaumenhaft, Robert TI Bioengineering in Platelet Biology SO THROMBOSIS RESEARCH LA English DT Editorial Material ID ENDOTHELIAL-CELLS; SHEAR-STRESS; TISSUES; AGGREGATION C1 [Flaumenhaft, Robert] Harvard Univ, Sch Med, Dept Med, Div Hemostasis & Thrombosis,BIDMC, Boston, MA 02130 USA. [Flaumenhaft, Robert] Beth Israel Deaconess Med Ctr, Ctr Life Sci, Boston, MA 02215 USA. RP Flaumenhaft, R (reprint author), Harvard Univ, Sch Med, Dept Med, Div Hemostasis & Thrombosis,BIDMC, Boston, MA 02130 USA. EM rflaumen@bidmc.harvard.edu FU NHLBI NIH HHS [R01 HL112809] NR 17 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR PY 2014 VL 133 IS 4 BP 523 EP 524 DI 10.1016/j.thromres.2013.12.036 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AD2UO UT WOS:000333091200002 PM 24433610 ER PT J AU Somsouk, M To'o, K Ali, M Vittinghoff, E Yeh, BM Yee, J Monto, A Inadomi, JM Aslam, R AF Somsouk, Ma To'o, Katherine Ali, Mujtaba Vittinghoff, Eric Yeh, Benjamin M. Yee, Judy Monto, Alex Inadomi, John M. Aslam, Rizwan TI Esophageal varices on computed tomography and subsequent variceal hemorrhage SO ABDOMINAL IMAGING LA English DT Article DE Portal hypertension; Variceal hemorrhage; CT; Cirrhosis ID UPPER GI ENDOSCOPY; PROSPECTIVE MULTICENTER; PORTAL-HYPERTENSION; CIRRHOTIC-PATIENTS; CAPSULE ENDOSCOPY; LIVER CT; SEDATION AB Endoscopy is recommended to screen for esophageal varices in patients with cirrhosis. The objective of this study was to identify features on abdominal CT imaging associated variceal hemorrhage (VH). A case-control study was performed among patients with cirrhosis who had a CT scan. Consecutive patients who experienced VH were included as cases, and patients without VH served as controls. Two radiologists recorded the maximal esophageal varix diameter in addition to other measures of portal hypertension at CT. The most powerful CT parameter associated with VH was the esophageal varix diameter (5.8 vs. 2.7 mm, p < 0.001; adjusted OR 1.84 per mm, p = 0.009). 63% of individuals with VH had a maximal varix diameter a parts per thousand yen5 mm compared to 7.5% of cirrhotic patients without VH (p < 0.001). In contrast, the proportion of individuals whose largest varix was < 3 mm was 7.4% among VH cases compared to 54.7% among controls (p = 0.001). The varix diameter powerfully discriminated those with and without VH (C-statistic 0.84). A large esophageal varix diameter is strongly associated with subsequent VH. A threshold of < 3 and a parts per thousand yen5 mm appears to identify patients with cirrhosis at low and high risk for hemorrhage. C1 [Somsouk, Ma] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA 94110 USA. [To'o, Katherine; Yeh, Benjamin M.; Yee, Judy; Aslam, Rizwan] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94110 USA. [Ali, Mujtaba] Univ Colorado Hosp, Dept Radiol, Aurora, CO USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Monto, Alex] San Francisco VA Med Ctr, Div Gastroenterol & Hepatol, Dept Med, San Francisco, CA USA. [Inadomi, John M.] Univ Washington, Dept Med, Div Gastroenterol & Hepatol, Seattle, WA USA. RP Somsouk, M (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol, 1001 Potrero Ave, San Francisco, CA 94110 USA. EM ma.somsouk@ucsf.edu FU American Society for Gastrointestinal Endoscopy Endoscopic Research Award; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080941] FX This work was supported by the American Society for Gastrointestinal Endoscopy Endoscopic Research Award (MS) and from the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080941, JI). The funding agencies did not have any role in the design, interpretation, or preparation of the manuscript. NR 16 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2014 VL 39 IS 2 BP 251 EP 256 DI 10.1007/s00261-013-0057-x PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AD2IB UT WOS:000333057000003 PM 24366107 ER PT J AU Singh, AK Gervais, DA Lee, P Westra, S Hahn, PF Novelline, RA Mueller, PR AF Singh, A. K. Gervais, D. A. Lee, P. Westra, S. Hahn, P. F. Novelline, R. A. Mueller, P. R. TI Omental infarct: CT imaging features (vol 31, pg 549, 2006) SO ABDOMINAL IMAGING LA English DT Correction C1 [Singh, A. K.; Gervais, D. A.; Lee, P.; Westra, S.; Hahn, P. F.; Novelline, R. A.; Mueller, P. R.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Emergency Radio, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Emergency Radio, 55 Fruit St, Boston, MA 02114 USA. EM pallaviajay@hotmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2014 VL 39 IS 2 BP 442 EP 442 DI 10.1007/s00261-011-9711-3 PG 1 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AD2IB UT WOS:000333057000026 ER PT J AU Sengupta, S Weeraratne, SD Sun, HY Phallen, J Rallapalli, SK Teider, N Kosaras, B Amani, V Pierre-Francois, J Tang, YJ Nguyen, B Yu, FR Schubert, S Balansay, B Mathios, D Lechpammer, M Archer, TC Tran, P Reimer, RJ Cook, JM Lim, M Jensen, FE Pomeroy, SL Cho, YJ AF Sengupta, Soma Weeraratne, Shyamal Dilhan Sun, Hongyu Phallen, Jillian Rallapalli, Sundari K. Teider, Natalia Kosaras, Bela Amani, Vladimir Pierre-Francois, Jessica Tang, Yujie Brian Nguyen Yu, Furong Schubert, Simone Balansay, Brianna Mathios, Dimitris Lechpammer, Mirna Archer, Tenley C. Phuoc Tran Reimer, Richard J. Cook, James M. Lim, Michael Jensen, Frances E. Pomeroy, Scott L. Cho, Yoon-Jae TI alpha 5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth SO ACTA NEUROPATHOLOGICA LA English DT Article DE Medulloblastoma; GABRA5; QHii066; HOXA5; MYC ID GABA(A) RECEPTORS; C-MYC; CHILDHOOD MEDULLOBLASTOMA; EXPRESSION PROFILES; IONIZING-RADIATION; POOR-PROGNOSIS; HISTONE H2AX; STEM-CELLS; PROLIFERATION; BRAIN AB Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors and, importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABRA5, which encodes the alpha 5-subunit of the GABAA receptor complex, in aggressive MYC-driven, "Group 3" medulloblastomas. We hypothesized that modulation of alpha 5-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABRA5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent alpha 5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABRA5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOXA5 target gene expression. siRNA-mediated knockdown of HOXA5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABRA5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOXA5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of alpha 5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor. C1 [Sengupta, Soma; Weeraratne, Shyamal Dilhan; Sun, Hongyu; Teider, Natalia; Kosaras, Bela; Amani, Vladimir; Pierre-Francois, Jessica; Lechpammer, Mirna; Archer, Tenley C.; Jensen, Frances E.; Pomeroy, Scott L.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Sengupta, Soma] BIDMC, Dept Neurol, Boston, MA USA. [Sun, Hongyu; Jensen, Frances E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Phallen, Jillian; Mathios, Dimitris; Lim, Michael] Johns Hopkins Sch Med, Dept Neurosurg, Baltimore, MD USA. [Rallapalli, Sundari K.; Cook, James M.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53201 USA. [Tang, Yujie; Brian Nguyen; Yu, Furong; Schubert, Simone; Balansay, Brianna; Reimer, Richard J.; Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Lechpammer, Mirna] Univ Calif Davis, Dept Pathol, Sacramento, CA USA. [Phuoc Tran] Johns Hopkins Sch Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA. RP Cho, YJ (reprint author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, 1201 Welch Rd,MSLS Bldg,Room P213, Stanford, CA 94305 USA. EM yjcho1@stanford.edu FU Stanford Cancer Center; Center for Children's Brain Tumors at Stanford University; Child Health Research Institute at Lucile Packard Children's Hospital; St. Baldrick's Foundation Scholar Award; Beirne Faculty Scholar endowment; NIH [U01CA176287, R25NS070682, R01CA109467, P30 HD18655] FX The authors would like to acknowledge core facility support provided by the Boston Children's Hospital, Broad Institute, Stanford Functional Genomics Facility as well as support from the Stanford Cancer Center, Center for Children's Brain Tumors at Stanford University, and the Child Health Research Institute at Lucile Packard Children's Hospital. This work was funded by grants from the St. Baldrick's Foundation Scholar Award and the Beirne Faculty Scholar endowment and (YJC); NIH grants U01CA176287 (YJC), R25NS070682 (SSG), R01CA109467 (SLP), P30 HD18655 (SLP). NR 41 TC 7 Z9 7 U1 0 U2 7 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 APR PY 2014 VL 127 IS 4 BP 593 EP 603 DI 10.1007/s00401-013-1205-7 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AD0XJ UT WOS:000332957400010 PM 24196163 ER PT J AU Harrison, DE Strong, R Allison, DB Ames, BN Astle, CM Atamna, H Fernandez, E Flurkey, K Javors, MA Nadon, NL Nelson, JF Pletcher, S Simpkins, JW Smith, D Wilkinson, JE Miller, RA AF Harrison, David E. Strong, Randy Allison, David B. Ames, Bruce N. Astle, Clinton M. Atamna, Hani Fernandez, Elizabeth Flurkey, Kevin Javors, Martin A. Nadon, Nancy L. Nelson, James F. Pletcher, Scott Simpkins, James W. Smith, Daniel Wilkinson, J. Erby Miller, Richard A. TI Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males SO AGING CELL LA English DT Article DE acarbose; estradiol; heterogeneous mice; lifespan; methylene blue; NDGA ID GENETICALLY HETEROGENEOUS MICE; N-SH CELLS; POSTPRANDIAL HYPERGLYCEMIA; ESTROGEN-RECEPTOR; DIABETES-MELLITUS; ALPHA-GLUCOSIDASE; HORMONE-LEVELS; RAPAMYCIN; 17-BETA-ESTRADIOL; MODULATION AB Four agents acarbose (ACA), 17--estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P<0.0001), but increased female median lifespan by only 5% (P=0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P<0.001) in males and 9% (P=0.001) in females. EST increased male median lifespan by 12% (P=0.002), but did not lead to a significant effect on maximum lifespan. The benefits of EST were much stronger at one test site than at the other two and were not explained by effects on body weight. EST did not alter female lifespan. NDGA increased male median lifespan by 8-10% at three different doses, with P-values ranging from 0.04 to 0.005. Females did not show a lifespan benefit from NDGA, even at a dose that produced blood levels similar to those in males, which did show a strong lifespan benefit. MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P=0.004) increase in female maximum lifespan. These results provide new pharmacological models for exploring processes that regulate the timing of aging and late-life diseases, and in particular for testing hypotheses about sexual dimorphism in aging and health. C1 [Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA. [Strong, Randy; Fernandez, Elizabeth; Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Strong, Randy; Fernandez, Elizabeth] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Ames, Bruce N.; Atamna, Hani] Childrens Hosp Oakland Res Inst, Oakland, CA 94609 USA. [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Pletcher, Scott] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Pletcher, Scott; Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Simpkins, James W.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Smith, Daniel] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Wilkinson, J. Erby] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Harrison, DE (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM david.harrison@jax.org OI Allison, David/0000-0003-3566-9399 FU NIA [AG022308, AG022303, AG022307]; Department of Veterans Affairs Office of Research and Development; [CA034196] FX This work was funded in part by NIA Grants AG022308 (D. E. H.), AG022303 (R. A. M.), and AG022307 (R. S.), with important facilities supported by CA034196 (TJL). RS is supported by a Senior Research Career Scientist Award from the Department of Veterans Affairs Office of Research and Development. We wish to thank P. J. Krason, V. Ingalls, Lisa Burmeister, Sabrina van Roekel, N. Durgin, and Vivian Diaz for reliable technical assistance. NR 36 TC 56 Z9 56 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD APR PY 2014 VL 13 IS 2 BP 273 EP 282 DI 10.1111/acel.12170 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AC4VG UT WOS:000332518600009 PM 24245565 ER PT J AU Zulliger, R Black, S Holtgrave, DR Ciaranello, AL Bekker, LG Myer, L AF Zulliger, Rose Black, Samantha Holtgrave, David R. Ciaranello, Andrea L. Bekker, Linda-Gail Myer, Landon TI Cost-Effectiveness of a Package of Interventions for Expedited Antiretroviral Therapy Initiation During Pregnancy in Cape Town, South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Prevention of mother-to-child transmission (PMTCT); Cost-effectiveness analysis; Costs and cost analysis; Antiretroviral therapy (ART); South Africa ID CHILD HIV TRANSMISSION; PREVENTION; RECOMMENDATIONS; JOHANNESBURG; HEALTH; WOMEN; RISK AB Initiating antiretroviral therapy (ART) early in pregnancy is an important component of effective interventions to prevent the mother-to-child transmission of HIV (PMTCT). The rapid initiation of ART in pregnancy (RAP) program was a package of interventions to expedite ART initiation in pregnant women in Cape Town, South Africa. Retrospective cost-effectiveness, sensitivity and threshold analyses were conducted of the RAP program to determine the cost-utility thresholds for rapid initiation of ART in pregnancy. Costs were drawn from a detailed micro-costing of the program. The overall programmatic cost was US$880 per woman and the base case cost-effectiveness ratio was US$1,160 per quality-adjusted life year (QALY) saved. In threshold analyses, the RAP program remained cost-effective if mother-to-child transmission was reduced by a parts per thousand yen0.33 %; if a parts per thousand yen1.76 QALY were saved with each averted perinatal infection; or if RAP-related costs were under US$4,020 per woman. The package of rapid initiation services was very cost-effective, as compared to standard services in this setting. Threshold analyses demonstrated that the intervention required minimal reductions in perinatal infections in order to be cost-effective. Interventions for the rapid initiation of ART in pregnancy hold considerable potential as a cost-effective use of limited resources for PMTCT in sub-Saharan Africa. C1 [Zulliger, Rose; Holtgrave, David R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21224 USA. [Black, Samantha; Bekker, Linda-Gail; Myer, Landon] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Ciaranello, Andrea L.] Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Myer, Landon] Univ Cape Town, Div Epidemiol & Biostat, Sch Publ Hlth & Family Med, ZA-7925 Cape Town, South Africa. RP Zulliger, R (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, 624 N Broadway, Baltimore, MD 21224 USA. EM rozullig@jhsph.edu FU NIAID NIH HHS [K01 AI078754, K01 AI 078754] NR 34 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2014 VL 18 IS 4 BP 697 EP 705 DI 10.1007/s10461-013-0641-7 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AD4ED UT WOS:000333198900010 PM 24122044 ER PT J AU Baron, JM Lewandrowski, EL Januzzi, JL Bajwa, EK Thompson, BT Lewandrowski, KB AF Baron, Jason M. Lewandrowski, Elizabeth L. Januzzi, James L. Bajwa, Ednan K. Thompson, B. Taylor Lewandrowski, Kent B. TI Measurement of High-Sensitivity Troponin T in Noncardiac Medical Intensive Care Unit Patients Correlation to Mortality and Length of Stay SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Troponin; hsTnT; Medical intensive care unit ID CRITICALLY-ILL PATIENTS; ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROME; CARDIAC TROPONIN; EARLY-DIAGNOSIS; ASSAYS; POPULATION; ELEVATION; RISK AB Objectives: To assess the frequency, magnitude, and prognostic significance of elevations in cardiac troponin T in noncardiac critically ill patients, including elevations at levels below the limit of detection of traditional assays. Methods: Using a high-sensitivity assay, we measured troponin T (high-sensitivity troponin T [hsTnT]) in 451 unique patients within 12 hours of their admission to a noncardiac medical intensive care unit. Outcomes of patients, grouped by hsTnT level, were compared Results: Overall, 98% of the study patients had detectable levels of hsTnT (>3 ng/L), and 33% had levels above the diagnostic cutoff of a traditional fourth-generation cardiac troponin T assay. Patient groups with higher hsTnT levels had markedly higher rates of in-hospital mortality (P < .001) and longer stays in the hospital and intensive care unit (P < .01). Conclusions: In noncardiac critically ill patients, cardiac troponin T elevations are common but often at levels undetectable by traditional assays. hsTnT elevations predict a more complex clinical course and an increased risk of death. C1 [Baron, Jason M.; Lewandrowski, Elizabeth L.; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bajwa, Ednan K.; Thompson, B. Taylor] Massachusetts Gen Hosp, Div Pulm Crit Care, Boston, MA 02114 USA. [Baron, Jason M.; Lewandrowski, Elizabeth L.; Januzzi, James L.; Bajwa, Ednan K.; Thompson, B. Taylor; Lewandrowski, Kent B.] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, KB (reprint author), Bigelow Bldg,Room 504,55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org FU Roche Diagnostics, Indianapolis, IN FX This study was supported by a grant from Roche Diagnostics, Indianapolis, IN. NR 24 TC 5 Z9 5 U1 1 U2 3 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 APR PY 2014 VL 141 IS 4 BP 488 EP 493 DI 10.1309/AJCPLVQQY35XTFVN PG 6 WC Pathology SC Pathology GA AD2MU UT WOS:000333070600008 PM 24619748 ER PT J AU Bentley-Lewis, R Dawson, DL Wenger, JB Thadhani, RI Roberts, DJ AF Bentley-Lewis, Rhonda Dawson, Deanna L. Wenger, Julia B. Thadhani, Ravi I. Roberts, Drucilla J. TI Placental Histomorphometry in Gestational Diabetes Mellitus The Relationship Between Subsequent Type 2 Diabetes Mellitus and Race/Ethnicity SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Placental histomorphometry; Gestational diabetes mellitus; Type 2 diabetes mellitus; Race/ethnicity ID REACTION PATTERNS; REPRODUCIBILITY; PREGNANCIES; NOSOLOGY; LESIONS; RISK AB Objectives: We examined placental histomorphometry in gestational diabetes mellitus (GDM) for factors associated with race/ethnicity and subsequent type 2 diabetes mellitus (T2DM). Methods: We identified 124 placentas from singleton, fullterm live births whose mothers had clinically defined GDM and self-reported race/ethnicity. Clinical and placental diagnoses were abstracted from medical records. Results: Forty-eight white and 76 nonwhite women were followed for 4.1 years (median, range 0.0-8.9 years). White women developed less T2DM (12.5% vs 35.5%; P = .005) but had higher systolic (mean +/- SD, 116 +/- 13 vs 109 +/- 11 mm Hg; P < .001) and diastolic (71 +/- 9 vs 68 +/- 7 mm Hg; P = .02) blood pressure, more smoking (35.4% vs 10.5%; P = .004), and more chorangiosis (52.1% vs 30.3%; P = .02) than nonwhite women. Conclusions: Although more nonwhite women developed T2DM, more white women had chorangiosis, possibly secondary to the higher percentage of smokers among them. Further study is necessary to elucidate the relationship among chorangiosis, subsequent maternal T2DM, and race. C1 [Bentley-Lewis, Rhonda; Dawson, Deanna L.] Massachusetts Gen Hosp, Med Diabet Unit, Boston, MA 02114 USA. [Wenger, Julia B.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Med Div Nephrol, Boston, MA 02114 USA. [Bentley-Lewis, Rhonda; Thadhani, Ravi I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bentley-Lewis, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 4-415, Boston, MA 02114 USA. EM Bentley-Lewis.Rhonda@mgh.harvard.edu FU National Institutes of Health (NIH) [1R03DK096152]; Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program; Harvard Catalyst Summer Clinical and Translational Research Program; NIH [K24 DK094872]; Massachusetts General Hospital (MGH) Pathology Department FX This study was supported by grant 1R03DK096152 from the National Institutes of Health (NIH) and the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program (R.B.-L.); Harvard Catalyst Summer Clinical and Translational Research Program (D.L.D.); K24 DK094872 from the NIH (R.I.T.); and the Massachusetts General Hospital (MGH) Pathology Department (D.J.R.). NR 24 TC 6 Z9 6 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 APR PY 2014 VL 141 IS 4 BP 587 EP 592 DI 10.1309/AJCPX81AUNFPOTLL PG 6 WC Pathology SC Pathology GA AD2MU UT WOS:000333070600021 PM 24619761 ER PT J AU Mayer, KH Skeer, MR O'Cleirigh, C Goshe, BM Safren, SA AF Mayer, Kenneth H. Skeer, Margie R. O'Cleirigh, Conall Goshe, Brett M. Safren, Steven A. TI Factors Associated with Amplified HIV Transmission Behavior Among American Men Who Have Sex with Men Engaged in Care: Implications for Clinical Providers SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE HIV transmission; MSM; Primary care ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; DRUG-USE; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; METHAMPHETAMINE USE; RISK BEHAVIOR; INFECTED MEN; VIRAL LOAD; DISEASE PROGRESSION AB The HIV epidemic continues unabated in the USA, with men who have sex with men (MSM) being most frequently infected. The purpose of this study is to understand the biological and behavioral risk factors associated with increased HIV transmission efficiency, which is HIV transmission risk behavior in the context of uncontrolled HIV replication or intercurrent sexually transmitted infections. Participants were 201 HIV-infected MSM who received their primary care at an HIV ambulatory care center in Boston. Logistic regression models were conducted to determine factors associated with engaging in behavior associated with potentially amplified transmission. In the final model, heavy alcohol use (AOR, 3.27; 95 % CI 1.37-7.79), as well as stimulant drug use (crystal meth, crack, or other cocaine; AOR, 3.00; CI 1.32-6.84), having at least a college degree (OR, 2.74; CI, 1.15-6.54), and decreased duration of HIV infection (OR, 0.91; CI, 0.85-0.97) were each uniquely associated with enhanced HIV transmission behavior. HIV primary care providers should routinely assess patients for potential HIV transmission behaviors, particularly those who are younger and more recently diagnosed with HIV, who drink alcohol heavily, and who use any nonprescription drugs, particularly stimulants, in order to decrease the spread of HIV. C1 [Mayer, Kenneth H.; Skeer, Margie R.; O'Cleirigh, Conall; Goshe, Brett M.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Skeer, Margie R.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St,8th Floor, Boston, MA 02215 USA. EM kmayer@fenwayhealth.org FU NIMH NIH HHS [5R01MH068746-05, K24 MH094214, R01 MH068746]; PHS HHS [H97HA01293] NR 52 TC 15 Z9 15 U1 7 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 IS 2 BP 165 EP 171 DI 10.1007/s12160-013-9527-1 PG 7 WC Psychology, Multidisciplinary SC Psychology GA AD7BO UT WOS:000333416300007 PM 23873338 ER PT J AU Cooper, DC Thayer, JF Waldstein, SR AF Cooper, Denise C. Thayer, Julian F. Waldstein, Shari R. TI Coping with Racism: The Impact of Prayer on Cardiovascular Reactivity and Post-stress Recovery in African American Women SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Prayer; Blood pressure; Heart rate variability; Racism; Coping; Cardiovascular reactivity ID HEART-RATE-VARIABILITY; BLOOD-PRESSURE; STRESS REACTIVITY; PERCEIVED STRESS; ANGER EXPRESSION; HEALTH; DISEASE; HYPERTENSION; RESPONSES; ADULTS AB Prayer is often used to cope with racism-related stress. Little is known about its impact on cardiovascular function. This study examined how prayer coping relates to cardiovascular reactivity (CVR), post-stress recovery, and affective reactivity in response to racism-related stress. African American women (n = 81; mean age=20 years) reported their use of prayer coping on the Perceived Racism Scale and completed anger recall and racism recall tasks while undergoing monitoring of systolic and diastolic blood pressure (DBP), heart rate, heart rate variability (HRV), and hemodynamic measures. Prayer coping was examined for associations with CVR, recovery, and affective change scores using general linear models with repeated measures. Higher prayer coping was associated with decreased state stress and DBP reactivity during racism recall (p's < 0.05) and with decreased DBP and increased HRV during racism recall recovery(p's < 0.05). Coping with racism by utilizing prayer may have cardiovascular benefits for African American women. C1 [Cooper, Denise C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Thayer, Julian F.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. [Cooper, Denise C.] VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Cooper, DC (reprint author), VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM cooped2@uw.edu FU NIGMS NIH HHS [R25-GM55036] NR 55 TC 2 Z9 2 U1 5 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 IS 2 BP 218 EP 230 DI 10.1007/s12160-013-9540-4 PG 13 WC Psychology, Multidisciplinary SC Psychology GA AD7BO UT WOS:000333416300013 PM 24122482 ER PT J AU Bauer, C Sterzik, A Bauernfeind, F Duewell, P Conrad, C Kiefl, R Endres, S Eigler, A Schnurr, M Dauer, M AF Bauer, Christian Sterzik, Alexander Bauernfeind, Franz Duewell, Peter Conrad, Claudius Kiefl, Rosemarie Endres, Stefan Eigler, Andreas Schnurr, Max Dauer, Marc TI Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8(+) T-cell and B-cell responses but improves clinical efficacy in a murine pancreatic carcinoma model SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Vaccination; Dendritic cells; Pancreatic carcinoma; Chemotherapy; Gemcitabine; Survival ID PULSED DENDRITIC CELLS; LOW-DOSE GEMCITABINE; TUMOR-BEARING MICE; SUPPRESSOR-CELLS; POSITIVE SELECTION; ANTITUMOR IMMUNITY; IN-VITRO; CANCER; CHEMOTHERAPY; COMBINATION AB Multiple studies have shown that dendritic cell (DC)-based vaccines can induce antitumor immunity. Previously, we reported that gemcitabine enhances the efficacy of DC vaccination in a mouse model of pancreatic carcinoma. The present study aimed at investigating the influence of gemcitabine on vaccine-induced anti-tumoral immune responses in a syngeneic pancreatic cancer model. Subcutaneous or orthotopic pancreatic tumors were induced in C57BL/6 mice using Panc02 cells expressing the model antigen OVA. Bone marrow-derived DC were loaded with soluble OVA protein (OVA-DC). Animals received gemcitabine twice weekly. OVA-specific CD8(+) T-cells and antibody titers were monitored by FACS analysis and ELISA, respectively. Gemcitabine enhanced clinical efficacy of the OVA-DC vaccine. Interestingly, gemcitabine significantly suppressed the vaccine-induced frequency of antigen-specific CD8(+) T-cells and antibody titers. DC migration to draining lymph nodes and antigen cross-presentation were unaffected. Despite reduced numbers of tumor-reactive T-cells in peripheral blood, in vivo cytotoxicity assays revealed that cytotoxic T-cell (CTL)-mediated killing was preserved. In vitro assays revealed sensitization of tumor cells to CTL-mediated lysis by gemcitabine. In addition, gemcitabine facilitated recruitment of CD8(+) T-cells into tumors in DC-vaccinated mice. T- and B-cell suppression by gemcitabine could be avoided by starting chemotherapy after two cycles of DC vaccination. Gemcitabine enhances therapeutic efficacy of DC vaccination despite its negative influence on vaccine-induced T-cell proliferation. Quantitative analysis of tumor-reactive T-cells in peripheral blood may thus not predict vaccination success in the setting of concomitant chemotherapy. C1 [Bauer, Christian; Sterzik, Alexander; Bauernfeind, Franz; Duewell, Peter; Kiefl, Rosemarie; Schnurr, Max] Univ Munich, Gastroenterol Sect, Med Klin & Poliklin 4, Munich, Germany. [Conrad, Claudius] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Endres, Stefan] Univ Munich, Div Clin Pharmacol, Med Klin & Poliklin 4, Munich, Germany. [Eigler, Andreas] Klinikum Dritter Orden, Dept Internal Med 1, Munich, Germany. [Dauer, Marc] Kliniken St Elisabeth, Dept Med 2, D-86633 Neuburg, Germany. RP Dauer, M (reprint author), Kliniken St Elisabeth, Dept Med 2, Muller Gnadenegg Weg 4, D-86633 Neuburg, Germany. EM marc.dauer@kliniken-st-elisabeth.de OI Duewell, Peter/0000-0003-0836-6448 FU University of Munich [481]; Saarland University (HOMFOR); Deutsche Krebshilfe; Deutsche Forschungsgemeinschaft [SCHN 664/3-1, SCHN 664/3-2, GK 1202] FX Christian Bauer, Franz Bauernfeind and Marc Dauer were supported by grants from the University of Munich (Foe-FoLe No. 481, Promotionsstudium Molekulare Medizin, Gravenhorst-Stiftung) and the Saarland University (HOMFOR). Max Schnurr was supported by the Deutsche Krebshilfe (Max Eder Research Grant) and the Deutsche Forschungsgemeinschaft (SCHN 664/3-1, SCHN 664/3-2 and GK 1202). Transgenic OT-1 animals were kindly provided by Prof. Thomas Brocker (Department of Immunology, University of Munich, Germany). NR 43 TC 15 Z9 15 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2014 VL 63 IS 4 BP 321 EP 333 DI 10.1007/s00262-013-1510-y PG 13 WC Oncology; Immunology SC Oncology; Immunology GA AD1WB UT WOS:000333023300002 PM 24384835 ER PT J AU Kalva, SP Pectasides, M Liu, R Rachamreddy, N Surakanti, S Yeddula, K Ganguli, S Wicky, S Blaszkowsky, LS Zhu, AX AF Kalva, Sanjeeva P. Pectasides, Melina Liu, Raymond Rachamreddy, Niranjan Surakanti, Shravani Yeddula, Kalpana Ganguli, Suvranu Wicky, Stephan Blaszkowsky, Lawrence S. Zhu, Andrew X. TI Safety and Effectiveness of Chemoembolization with Drug-Eluting Beads for Advanced-Stage Hepatocellular Carcinoma SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Interventional oncology; Chemoembolization/chemoembolisation; Liver/hepatic; Cancer; Hepatocellular carcinoma; DEB-TACE ID RANDOMIZED CONTROLLED-TRIALS; TRANSARTERIAL CHEMOEMBOLIZATION; PHASE-II; ARTERIAL EMBOLIZATION; HEPATIC-TUMORS; SOLID TUMORS; DC BEAD; DOXORUBICIN; MANAGEMENT; SORAFENIB AB According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, patients with advanced stage (BCLC-C) hepatocellular carcinoma (HCC) are recommended for systemic treatment or palliative therapy. However, chemoembolization with drug-eluting beads (DEB-TACE) has been shown to be safe in high-risk patients. The purpose of our study was to evaluate the safety and effectiveness of DEB-TACE in patients with an advanced-stage HCC. In this institutional review board-approved, retrospective study, 80 patients with advanced-stage HCC underwent DEB-TACE with doxorubicin. Patients were evaluated for median hospital stay, incidence of Grade 3/4 toxicities, 30-day mortality, progression-free survival (PFS), and overall survival (OS) following DEB-TACE. Univariate and multivariate analysis were performed for predictors of better OS. The median hospital stay following DEB-TACE was 1 day (range: 1-11). The median PFS and OS were 5.1 months [95 % confidence interval (CI): 4.1-7.7] and 13.3 months (95 % CI: 10.1-18.6) respectively. On multivariate analysis ECOG PS a parts per thousand currency sign 1 and > 2 DEB-TACE procedures were associated with better OS. Patients with ECOG PS a parts per thousand currency sign 1 demonstrated a median survival of 17.7 months compared with 5.6 months for patients with ECOG PS > 1 (p = 0.025). Multiple DEB-TACE procedures (> 2 procedures) were associated with improved survival (26.8 months) compared with patients with one or two procedures (11.4 months, p = 0.01). Portal vein thrombosis or extrahepatic disease had no statistically significant association with OS. DEB-TACE is safe and effective in patients with advanced HCC. ECOG PS a parts per thousand currency sign 1 and > 2 DEB-TACE procedures were associated with better OS. C1 [Kalva, Sanjeeva P.] UT Southwestern Med Ctr, Dallas, TX 75390 USA. [Pectasides, Melina; Liu, Raymond; Rachamreddy, Niranjan; Ganguli, Suvranu; Wicky, Stephan] Massachusetts Gen Hosp, Ctr Image Guided Canc Therapy, Boston, MA 02114 USA. [Surakanti, Shravani] Baton Rouge Gen Hosp, Dept Internal Med, Baton Rouge, LA USA. [Yeddula, Kalpana] St Joseph Hosp, Dept Radiol, Chicago, IL USA. [Blaszkowsky, Lawrence S.; Zhu, Andrew X.] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Kalva, SP (reprint author), UT Southwestern Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM sanjeeva.kalva@utsouthwestern.edu; pectasides.melina@mgh.harvard.edu; rliu@partners.org; nrachamreddy@partners.org; docshravani@yahoo.co.in; kalpana.sy@gmail.com; sganguli@partners.org; swicky@partners.org; lblaszkowsky@partners.org; azhu@partners.org NR 41 TC 23 Z9 25 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD APR PY 2014 VL 37 IS 2 BP 381 EP 387 DI 10.1007/s00270-013-0654-7 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD2FI UT WOS:000333048800013 PM 23754191 ER PT J AU Cubeddu, RJ Don, CW Horvath, SA Gupta, PP Cruz-Gonzalez, I Witzke, C Inglessis, I Palacios, IF AF Cubeddu, Roberto J. Don, Creighton W. Horvath, Sofia A. Gupta, Pritha P. Cruz-Gonzalez, Ignacio Witzke, Christian Inglessis, Ignacio Palacios, Igor F. TI VALVULAR AND STRUCTURAL HEART DISEASES SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE balloon aortic valvuloplasty; predictors; outcome LVEDP; TAVI ID BALLOON AORTIC VALVULOPLASTY; END-DIASTOLIC PRESSURE; LONG-TERM SURVIVAL; FOLLOW-UP; EJECTION FRACTION; PREDICTORS; STENOSIS; DETERMINANTS; MORTALITY; FAILURE AB ObjectivesIn this study, we examined the predictive value of the left ventricular end-diastolic pressure (LVEDP) in patients undergoing balloon aortic valvuloplasty (BAV). BackgroundThe LVEDP is a useful indicator of hemodynamic status in patients with severe aortic stenosis. In BAV, decompensated heart failure is associated with worse outcomes. MethodsWe identified all consecutive patients with severe symptomatic aortic stenosis who underwent retrograde BAV at the Massachusetts General Hospital from 2004 to 2008. Patients were stratified and compared according to their baseline LVEDP into 15 mm Hg, 16-20 mm Hg, 21-25 mm Hg, and 26 mm Hg. Procedural and in-hospital outcomes and adverse events were compared. Multivariate logistic regression was used for the adjusted analysis. ResultsA total of 111 patients with a mean age of 8311 years underwent BAV. Of these, the LVEDP was 15 mm Hg in 29 (26%), 16-20 mm Hg in 41 (37%), 21-25 mm Hg in 16 (14%), and 26 mm Hg in 25 (23%) patients. Baseline characteristics were similar among the four groups. Noticeably, patients with high LVEDP levels had significantly higher rates of the combined endpoint of in-hospital death, myocardial infarction (MI), cardiopulmonary arrest, and tamponade was P = 0.02. Periprocedural MI was more common among those with higher LVEDP (16% vs. 2.3%; P = 0.04). Multivariate analysis revealed LVEDP (OR 1.08, for each mm Hg increase in pressure, 95 % CI 1.02-1.14), small LV chamber size, and New York Heart Association class as independent predictors of adverse outcomes. ConclusionsThe LVEDP is an important independent predictor of poor in-hospital outcome during BAV. In these patients, the immediate hemodynamic status may be more important than the baseline left ventricular systolic function. Hemodynamic optimization before or during BAV should be considered and may be beneficial. (c) 2012 Wiley Periodicals, Inc. C1 [Cubeddu, Roberto J.; Horvath, Sofia A.] Aventura Hosp & Med Ctr, Miami, FL 33180 USA. [Cubeddu, Roberto J.; Don, Creighton W.; Gupta, Pritha P.] Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA. [Don, Creighton W.; Cruz-Gonzalez, Ignacio; Witzke, Christian; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Cubeddu, RJ (reprint author), Aventura Hosp & Med Ctr, Struct & Adult Congenital Heart Program, 21097 NE 27th Ct Ste 480, Miami, FL 33180 USA. EM roberto.cubeddu@hcahealthcare.com FU NCRR NIH HHS [KL2 RR025015] NR 26 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR 1 PY 2014 VL 83 IS 5 BP 782 EP 788 DI 10.1002/ccd.24410 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC9WK UT WOS:000332885300023 PM 22511584 ER PT J AU Knoblich, K Wang, HX Sharma, C Fletcher, AL Turley, SJ Hemler, ME AF Knoblich, Konstantin Wang, Hong-Xing Sharma, Chandan Fletcher, Anne L. Turley, Shannon J. Hemler, Martin E. TI Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits beta-catenin degradation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE TSPAN12; Tetraspanin; beta-catenin; Tumor growth; Tumor metastasis ID FAMILIAL EXUDATIVE VITREORETINOPATHY; BREAST-CANCER; CYCLIN A1; CELLS; EXPRESSION; MOTILITY; GENES; TRANSDUCTION; PROGRESSION; MUTATIONS AB Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly decreased primary tumor xenograft growth, while increasing tumor apoptosis. Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells also caused diminished association between FZD4 (a key canonical Wnt pathway receptor) and its co-receptor LRP5. The result likely explains substantially enhanced proteosomal degradation of beta-catenin, a key effecter of canonical Wnt signaling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1, and GSK beta 3 proteins. TSPAN12 ablation also altered expression of several genes regulated by beta-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain altered tumor growth and metastasis. In conclusion, these results provide the first evidence for TSPAN12 playing a role in supporting primary tumor growth and suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4-LRP5 association, in support of canonical Wnt-pathway signaling, leading to enhanced beta-catenin expression and function. C1 [Knoblich, Konstantin; Wang, Hong-Xing; Sharma, Chandan; Fletcher, Anne L.; Turley, Shannon J.; Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Fletcher, Anne L.] Monash Univ, Immunol & Stem Cell Labs, Clayton, Vic, Australia. RP Hemler, ME (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM martin_hemler@dfci.harvard.edu RI Knoblich, Konstantin/B-5980-2009 OI Knoblich, Konstantin/0000-0002-5646-837X FU National Institutes of Health [CA42368] FX This work was supported by National Institutes of Health Grant CA42368 (to M.E.H.). NR 45 TC 13 Z9 13 U1 0 U2 6 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD APR PY 2014 VL 71 IS 7 BP 1305 EP 1314 DI 10.1007/s00018-013-1444-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AD0UG UT WOS:000332949000012 PM 23955570 ER PT J AU Napadow, V Li, A Loggia, ML Kim, J Schalock, PC Lerner, E Tran, TN Ring, J Rosen, BR Kaptchuk, TJ Pfab, F AF Napadow, Vitaly Li, Ang Loggia, Marco L. Kim, Jieun Schalock, Peter C. Lerner, Ethan Thanh-Nga Tran Ring, Johannes Rosen, Bruce R. Kaptchuk, Ted J. Pfab, Florian TI The Brain Circuitry Mediating Antipruritic Effects of Acupuncture SO CEREBRAL CORTEX LA English DT Article DE atopic dermatitis; counter irritation; counter stimulus; insula; itch; pruritus; putamen ID HISTAMINE-INDUCED ITCH; I HYPERSENSITIVITY ITCH; SURFACE-BASED ANALYSIS; ATOPIC-DERMATITIS; CROSSOVER TRIAL; PAIN; COWHAGE; HUMANS; ROBUST; ECZEMA AB Itch is an aversive sensory experience and while systemic therapies, such as acupuncture, have shown promise in alleviating itch in patients suffering from chronic itch, their antipruritic mechanisms are unknown. As several lines of evidence implicate brain-focused mechanisms, we applied functional magnetic resonance imaging and our validated temperature-modulation itch model to evaluate the underlying brain circuitry supporting allergen-induced itch reduction in atopic dermatitis patients by acupuncture, antihistamine, and respective placebo treatments. Brain response to allergen itch demonstrated phase dependency. During an increasing itch phase, activation was localized in anterior insula and striatum, regions associated with salience/interoception and motivation processing. Once itch reached peak plateau, robust activation was noted in prefrontal cognitive and premotor areas. Acupuncture reduced itch and itch-evoked activation in the insula, putamen, and premotor and prefrontal cortical areas. Neither itch sensation nor itch-evoked brain response was altered following antihistamine or placebo acupuncture. Greater itch reduction following acupuncture was associated with greater reduction in putamen response, a region implicated in motivation and habitual behavior underlying the urge to scratch, specifically implicating this region in acupunctures antipruritic effects. Understanding brain circuitry underlying itch reduction following acupuncture and related neuromodulatory therapies will significantly impact the development and applicability of novel therapies to reduce an itch. C1 [Napadow, Vitaly; Li, Ang; Loggia, Marco L.; Kim, Jieun; Rosen, Bruce R.; Pfab, Florian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Loggia, Marco L.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Loggia, Marco L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schalock, Peter C.; Lerner, Ethan; Thanh-Nga Tran] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies, Boston, MA 02215 USA. [Ring, Johannes; Pfab, Florian] Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany. [Pfab, Florian] Tech Univ Munich, Dept Prevent & Sports Med, D-80290 Munich, Germany. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 2301,149 Thirteenth St, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu OI Schalock, Peter/0000-0001-8953-4639 FU NIH [K01-AT002166, R01-AT004714, P01-AT002048, K24-AT004095, R01-AR057744, P41RR14075]; CRC [1 UL1 RR025758]; Harvard Clinical and Translational Science Center; Mental Illness and Neuroscience Discovery (MIND) Institute; International Foundation of Functional Gastrointestinal Disorders; German Research Foundation [pf 690/2-1]; Christine Kuhne Center of Allergy and Education (CK-Care) FX This study was supported by NIH (V.N.: K01-AT002166, R01-AT004714, BRR: P01-AT002048; T. K.: K24-AT004095; E. L.: R01-AR057744, P41RR14075) CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center, Mental Illness and Neuroscience Discovery (MIND) Institute, and the International Foundation of Functional Gastrointestinal Disorders. This study was also partly funded by a grant of the German Research Foundation (pf 690/2-1), and the Christine Kuhne Center of Allergy and Education (CK-Care). The content is solely the responsibility of the authors and does not necessarily represent the official views of our sponsors. NR 47 TC 13 Z9 13 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2014 VL 24 IS 4 BP 873 EP 882 DI 10.1093/cercor/bhs363 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AD2FC UT WOS:000333048200003 PM 23222890 ER PT J AU Okonkwo, OC Xu, GF Oh, JM Dowling, NM Carlsson, CM Gallagher, CL Birdsill, AC Palotti, M Wharton, W Hermann, BP Larue, A Bendlin, BB Rowley, HA Asthana, S Sager, MA Johnson, SC AF Okonkwo, Ozioma C. Xu, Guofan Oh, Jennifer M. Dowling, N. Maritza Carlsson, Cynthia M. Gallagher, Catherine L. Birdsill, Alex C. Palotti, Matthew Wharton, Whitney Hermann, Bruce P. LaRue, Asenath Bendlin, Barbara B. Rowley, Howard A. Asthana, Sanjay Sager, Mark A. Johnson, Sterling C. TI Cerebral Blood Flow is Diminished in Asymptomatic Middle-Aged Adults with Maternal History of Alzheimer's Disease SO CEREBRAL CORTEX LA English DT Article DE Alzheimers disease; cerebral blood flow; maternal family history; preclinical; pseudocontinuous arterial spin labeling ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; FAMILY-HISTORY; NORMAL INDIVIDUALS; OXIDATIVE STRESS; PERFUSION MRI; TEST-BATTERY; LIFE-SPAN; FDG-PET AB Cerebral blood flow (CBF) provides an indication of the metabolic status of the cortex and may have utility in elucidating preclinical brain changes in persons at risk for Alzheimers disease (AD) and related diseases. In this study, we investigated CBF in 327 well-characterized adults including patients with AD (n 28), patients with amnestic mild cognitive impairment (aMCI, n 23), older cognitively normal (OCN, n 24) adults, and asymptomatic middle-aged adults (n 252) with and without a family history (FH) of AD. Compared with the asymptomatic cohort, AD patients displayed significant hypoperfusion in the precuneus, posterior cingulate, lateral parietal cortex, and the hippocampal region. Patients with aMCI exhibited a similar but less marked pattern of hypoperfusion. Perfusion deficits within the OCN adults were primarily localized to the inferior parietal lobules. Asymptomatic participants with a maternal FH of AD showed hypoperfusion in hippocampal and parietofrontal regions compared with those without a FH of AD or those with only a paternal FH of AD. These observations persisted when gray matter volume was included as a voxel-wise covariate. Our findings suggest that having a mother with AD might confer a particular risk for AD-related cerebral hypoperfusion in midlife. In addition, they provide further support for the potential utility of arterial spin labeling for the measurement of AD-related neurometabolic dysfunction, particularly in situations where [18F]fluorodeoxyglucose imaging is infeasible or clinically contraindicated. C1 [Okonkwo, Ozioma C.; Xu, Guofan; Oh, Jennifer M.; Dowling, N. Maritza; Carlsson, Cynthia M.; Gallagher, Catherine L.; Birdsill, Alex C.; Palotti, Matthew; Wharton, Whitney; Bendlin, Barbara B.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Okonkwo, Ozioma C.; Xu, Guofan; Oh, Jennifer M.; Dowling, N. Maritza; Carlsson, Cynthia M.; Birdsill, Alex C.; Palotti, Matthew; Wharton, Whitney; Hermann, Bruce P.; LaRue, Asenath; Bendlin, Barbara B.; Rowley, Howard A.; Asthana, Sanjay; Sager, Mark A.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53705 USA. [Okonkwo, Ozioma C.; Hermann, Bruce P.; LaRue, Asenath; Bendlin, Barbara B.; Sager, Mark A.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53705 USA. [Xu, Guofan; Rowley, Howard A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI 53705 USA. [Dowling, N. Maritza] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Gallagher, Catherine L.; Hermann, Bruce P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53705 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU Veterans Administration Merit Review grant [I01CX000165]; National Institute on Aging [AG021155, AG027161, P50 AG033514, P50 AG033514-S1]; Clinical and Translational Science Award [UL1RR025011] FX This work was supported by a Veterans Administration Merit Review grant I01CX000165 (S.C.J.); by National Institute on Aging grants AG021155 (to S.C.J.), AG027161 (to M. A. S.), P50 AG033514 (to S. A.), and P50 AG033514-S1 (to O.C.O.); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Additionally, portions of this research were supported by facilities and resources at the Geriatric Research Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. This is GRECC manuscript #2012-03. NR 58 TC 14 Z9 15 U1 2 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2014 VL 24 IS 4 BP 978 EP 988 DI 10.1093/cercor/bhs381 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AD2FC UT WOS:000333048200012 PM 23236200 ER PT J AU Agarwal, N Bellmunt, J Maughan, BL Boucher, KM Choueiri, TK Qu, AQ Vogelzang, NJ Fougeray, R Niegisch, G Albers, P Wong, YN Ko, YJ Sridhar, SS Tantravahi, SK Galsky, MD Petrylak, DP Vaishampayan, UN Mehta, AN Beer, TM Sternberg, CN Rosenberg, JE Sonpavde, G AF Agarwal, Neeraj Bellmunt, Joaquim Maughan, Benjamin L. Boucher, Kenneth M. Choueiri, Toni K. Qu, Angela Q. Vogelzang, Nicholas J. Fougeray, Ronan Niegisch, Guenter Albers, Peter Wong, Yu-Ning Ko, Yoo-Joung Sridhar, Srikala S. Tantravahi, Srinivas K. Galsky, Matthew D. Petrylak, Daniel P. Vaishampayan, Ulka N. Mehta, Amitkumar N. Beer, Tomasz M. Sternberg, Cora. N. Rosenberg, Jonathan E. Sonpavde, Guru TI Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Advanced urothelial carcinoma; Intermediate endpoint; Overall survival; Progression-free survival at 6 months; Second-line treatment ID TRANSITIONAL-CELL CARCINOMA; PHASE-III TRIAL; PLATINUM-CONTAINING REGIMEN; BLADDER-CANCER; TRACT; CHEMOTHERAPY; PACLITAXEL; GEMCITABINE; VINFLUNINE; CISPLATIN AB This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective: Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods: Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results: In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R-2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, K = 0.45). Response correlated with OS12 at the individual level less robustly (78%,. = 0.36), and the trial level association was not statistically significant (R-2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%,K = 0.44) appeared stronger than the correlation of response (76%, K = 0.17) with OS12 in the external validation dataset. Conclusions: PFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Agarwal, Neeraj; Maughan, Benjamin L.; Tantravahi, Srinivas K.] Univ Utah, Huntsman Canc Inst, Dept Internal Med Med Oncol, Salt Lake City, UT USA. [Bellmunt, Joaquim] Univ Hosp del Mar IMIM, Barcelona, Spain. [Boucher, Kenneth M.] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Choueiri, Toni K.; Qu, Angela Q.] Dana Farber Canc Inst, Dept Med Solid Tumor Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Qu, Angela Q.] Harvard Univ, Sch Med, Boston, MA USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Fougeray, Ronan] Inst Rech Pierre Fabre, Boulogne, France. [Niegisch, Guenter; Albers, Peter] Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Ko, Yoo-Joung] Sunnybrook Odette Canc Ctr, Dept Med, Toronto, ON, Canada. [Sridhar, Srikala S.] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada. [Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, Dept Med Hematol & Med Oncol, New York, NY USA. [Petrylak, Daniel P.] Yale Univ, Ctr Canc, Dept Internal Med Med Oncol, New Haven, CT USA. [Vaishampayan, Ulka N.] Wayne State Univ, Dept Oncol, Detroit, MI USA. [Mehta, Amitkumar N.; Sonpavde, Guru] UAB Comprehens Canc Ctr, Dept Med Hematol Oncol, Birmingham, AL 35294 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Med Hematol Oncol, Portland, OR 97201 USA. [Sternberg, Cora. N.] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med Hematol Oncol, New York, NY 10021 USA. RP Sonpavde, G (reprint author), UAB Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, 1824 6th Ave S,WTI 520A, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu OI Niegisch, Gunter/0000-0001-6929-8691; Rosenberg, Jonathan/0000-0003-2637-4249; Boucher, Kenneth/0000-0003-2833-0127 FU Boehringer-Ingelheim; AstraZeneca; Pierre-Fabre; BMS; Celgene; GSK; Eli-Lilly FX G. Sonpavde, N. J. Vogelzang: research support to institution from Boehringer-Ingelheim. R. Fougeray: employee of Pierre-Fabre. T. K. Choueiri, A. Q. Qu, J. E. Rosenberg, G. Sonpavde: research support to institution from AstraZeneca. J. Bellmunt: research support to institution from Pierre-Fabre. Y.-N. Wong: research support to institution from BMS. Y.-J. Ko, S. S. Sridhar, G. Sonpavde: research support to institution from Celgene. U. N. Vaishampayan: research support to institution from GSK. M. D. Galsky: research support to institution from Eli-Lilly. G. Niegisch and P. Albers: research support to institution from Eli Lilly and BMS. N. Agarwal, K. M. Boucher, B. L. Maughan, A. M. Mehta, D. P. Petrylak, T. M. Beer, C. N. Sternberg: no relevant conflicts. N. Agarwal, J. Bellmunt, and B. L. Maughan contributed equally as first authors. Presented in part at: the poster discussion session, American Society of Clinical Oncology conference, June 1-5, 2012, Chicago, Illinois, and as an oral presentation at: the European Society for Medical Oncology Congress, September 28 to October 2, 2012, Vienna, Austria. NR 20 TC 14 Z9 14 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD APR PY 2014 VL 12 IS 2 BP 130 EP 137 DI 10.1016/j.clgc.2013.09.002 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AC8HV UT WOS:000332775000021 PM 24220220 ER PT J AU Melia, MT Brau, N Poordad, F Lawitz, EJ Shiffman, ML McHutchison, JG Muir, AJ Galler, GW Nyberg, LM Lee, WM Schiff, E Long, JM Noviello, S Brass, CA Pedicone, LD Sulkowski, MS AF Melia, Michael T. Braeu, Norbert Poordad, Fred Lawitz, Eric J. Shiffman, Mitchell L. McHutchison, John G. Muir, Andrew J. Galler, Greg W. Nyberg, Lisa M. Lee, William M. Schiff, Eugene Long, Jianmin Noviello, Stephanie Brass, Clifford A. Pedicone, Lisa D. Sulkowski, Mark S. TI Infections During Peginterferon/Ribavirin Therapy Are Associated With the Magnitude of Decline in Absolute Lymphocyte Count: Results of the IDEAL Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE hepatitis C virus; lymphopenia; infections; neutropenia; interferon ID CHRONIC HEPATITIS-C; COMBINATION THERAPY; PLUS RIBAVIRIN; CLINICAL-PRACTICE; INTERFERON-ALPHA; NEUTROPENIA; DISEASES; UPDATE AB Background. Myelosuppression due to pegylated interferon (peg-IFN) is common during treatment for hepatitis C virus. The relationship between infection risk and decreases in leukocyte lines, however, is not well established. The objective of this analysis was to determine the incidence of and risk factors for infections during peg-IFN/ribavirin (RBV) therapy. Methods. A total of 3070 treatment-naive, chronic hepatitis C genotype 1-infected patients were treated for up to 48 weeks with peg-IFN alfa-2b 1.5 mu g/kg/week or 1 mu g/kg/week, or peg-IFN alfa-2a 180 mu g/week plus RBV. On-treatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 x 10(9) cells/L, and treatment discontinuation was required for a neutrophil count <0.5 x 10(9) cells/L. Granulocyte colony-stimulating factor was prohibited. Data on infections were captured at each study visit and categorized according to MedDRA version 13.0. Results. A total of 581 (19%) patients experienced moderate, severe, or life-threatening infections as assessed by the investigator; 648 (21%) patients had at least 1 neutrophil count <0.75 x 10(9) cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 x 10(9) cells/L at any time while on treatment. Twelve patients had severe or life-threatening infection and grade 3/4 neutropenia, but only 4 had temporally related infections. In a multivariate logistic regression model, nadir lymphocyte count, history of depression, and female sex, but not nadir neutrophil count, were associated with moderate, severe, or life-threatening infection. Conclusions. Nadir lymphocyte count, not nadir neutrophil count, was independently associated with moderate, severe, or life-threatening infections in the IDEAL study. Clinicians should be aware of their patients' absolute lymphocyte counts during peg-IFN/RBV therapy; peg-IFN dose reductions may be a consideration in patients with significant lymphocytopenia (<0.5 x 10(9) cells/L). C1 [Melia, Michael T.; Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Braeu, Norbert] Bronx Vet Affairs Med Ctr, New York, NY USA. [Poordad, Fred; Lawitz, Eric J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Richmond, VA USA. [McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Muir, Andrew J.] Duke Univ, Med Ctr, Durham, NC USA. [Galler, Greg W.] Kelsey Res Fdn, Houston, TX USA. [Nyberg, Lisa M.] Kaiser Permanente, San Diego Med Ctr, San Diego, CA USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Clin Ctr Liver Dis, Dallas, TX 75390 USA. [Schiff, Eugene] Univ Miami, Ctr Liver Dis, Coral Gables, FL 33124 USA. [Long, Jianmin; Noviello, Stephanie; Brass, Clifford A.; Pedicone, Lisa D.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. RP Melia, MT (reprint author), Johns Hopkins Univ, Sch Med, 1830 E Monument St,448, Baltimore, MD 21287 USA. EM mmelia4@jhmi.edu FU Schering-Plough Research Institute FX Financial support. This work was supported by grants from Schering-Plough Research Institute, now Merck Research Laboratories. NR 20 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2014 VL 58 IS 7 BP 960 EP 969 DI 10.1093/cid/ciu009 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2HM UT WOS:000333055400009 PM 24399086 ER PT J AU Micco, JA Henin, A Hirshfeld-Becker, DR AF Micco, Jamie A. Henin, Aude Hirshfeld-Becker, Dina R. TI Efficacy of Interpretation Bias Modification in Depressed Adolescents and Young Adults SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Interpretation bias; Cognitive bias modification; Adolescents; Depression ID AMBIGUOUS INFORMATION; EXPERIMENTAL MANIPULATION; MODIFYING INTERPRETATION; CLINICAL DEPRESSION; AUTOMATIC THOUGHTS; ANXIETY DISORDER; COGNITIVE BIASES; ANIMAL FEAR; CHILDREN; SYMPTOMS AB This study evaluated the efficacy of a four-session Cognitive Bias Modification-Interpretation program for 45 depressed adolescents and young adults (14-21 years old; 12 males, 33 females; Beck Depressive Inventory, Second Edition a parts per thousand yen14) randomized to an active intervention condition (repeated exposure to positive outcomes of depression-relevant ambiguous scenarios; n = 23) or a control condition (n = 22). Both conditions experienced reductions on a Test of Interpretation Bias at post-treatment, with no significant between-group differences. When limited to those with negative bias at baseline, the intervention group showed greater improvement in interpretation bias at mid- and post-treatment. In addition, the intervention group overall had greater improvements in self-reported negative cognitions than the control group at post-intervention and two-week follow-up. However, there were no differences between groups in depression or anxiety symptom change. Potential factors contributing to mixed findings are discussed. C1 [Micco, Jamie A.; Henin, Aude; Hirshfeld-Becker, Dina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Child Cognit Behav Therapy Program, Boston, MA 02114 USA. RP Micco, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Child Cognit Behav Therapy Program, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. EM jmicco@partners.org FU NIMH NIH HHS [F32 MH088165] NR 66 TC 14 Z9 16 U1 9 U2 28 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2014 VL 38 IS 2 SI SI BP 89 EP 102 DI 10.1007/s10608-013-9578-4 PG 14 WC Psychology, Clinical SC Psychology GA AD0YR UT WOS:000332961200002 PM 24729643 ER PT J AU Swenson, ER AF Swenson, Erik R. TI Safety of carbonic anhydrase inhibitors SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE acetazolamide; carbonic anhydrase; side effects; sulfamate; sulfonamide ID CEREBRAL-BLOOD-FLOW; CROSS-REACTIVITY; RENAL-FUNCTION; ACETAZOLAMIDE TERATOGENESIS; OCULAR HYPERTENSION; SMOOTH-MUSCLE; IN-VIVO; METHAZOLAMIDE; ACIDOSIS; GLAUCOMA AB Introduction: Carbonic anhydrase (CA) inhibitors have an impressive safety record despite the multiple functions that CA isozymes serve because they are not fully inhibited with most dosing. While reducing the targeted CA-dependent process sufficiently for disease control, residual activity and uncatalyzed rates in combination with compensations are adequate to avoid lethal consequences. Some drugs have in vitro selectivity differences against the 13 active isozymes, but none are convincingly selective in vivo or clinically. Efforts to synthesize selective inhibitors should result in safer drugs with fewer side effects. Areas covered: This review will focus on approved drugs with CA-inhibiting activity, whether used directly for this purpose or others. Side effects are discussed in relation to various organ systems and the disease being treated. Causes of side effects are considered, and strategies for symptom reduction are given. Expert opinion: Common side effects of paresthesias, dyspepsia, lassitude and fatigue in 30-40% of patients are generally tolerable or abate, but if not can be partially relieved by bicarbonate supplementation. The most important safety concerns are severe acidosis, respiratory failure and encephalopathy in patients with renal, pulmonary and hepatic disease where caution is critical, as is also the case in persons with sulfa drug allergies. C1 Univ Washington, Med Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Med Serv, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111 PLUM, Seattle, WA 98108 USA. EM Erik.Swenson@va.gov NR 128 TC 11 Z9 11 U1 2 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD APR PY 2014 VL 13 IS 4 BP 459 EP 472 DI 10.1517/14740338.2014.897328 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD2ET UT WOS:000333047200006 PM 24611470 ER PT J AU Laubach, JP Tai, YT Richardson, PG Anderson, KC AF Laubach, Jacob P. Tai, Yu-Tzu Richardson, Paul G. Anderson, Kenneth C. TI Daratumumab granted breakthrough drug status SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE antibody-dependent cellular cytotoxicity; complement-dependent cytotoxicity; daratumumab; multiple myeloma ID CHRONIC LYMPHOCYTIC-LEUKEMIA; REFRACTORY MULTIPLE-MYELOMA; HUMAN CD38; DOSE DEXAMETHASONE; CHIMERIC RECEPTOR; CELLS; IMMUNOTHERAPY; COMBINATION; LENALIDOMIDE; IMMUNOTOXIN AB Multiple myeloma (MM) remains incurable despite important recent advances in treatment due to its inherent resistance, characterized by highly complex and heterogeneous molecular abnormalities, as well as the support from myeloma bone marrow (BM) microenvironment. A novel therapeutic strategy that effectively targets specific molecules on myeloma cells and also potentially overcomes tumor microenvironment-mediated drug resistance and the downstream effects of genetic instability is thus urgently needed. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM. Early-stage clinical trials have found DARA to be safe and to have encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) as well as stem cell transplant has already failed. DARA may, therefore, be the first mAb with significant anti-MM activity both as a monotherapy and in combination. It is currently being further evaluated both alone and in combination with conventional and novel anti-MM agents as part of prospective clinical trials. This review discusses the preclinical and clinical development of DARA, its pathophysiological basis, and its prospects for future use in MM. C1 [Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Je Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Tai, Yu-Tzu] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 50 Brookline Ave,Mayer 556, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu NR 56 TC 30 Z9 30 U1 1 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD APR PY 2014 VL 23 IS 4 BP 445 EP 452 DI 10.1517/13543784.2014.889681 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC9OS UT WOS:000332864600001 PM 24555809 ER PT J AU Zhang, HL Wu, LM Wu, XJ Zhu, J AF Zhang, Hong-Liang Wu, Limin Wu, Xiujuan Zhu, Jie TI Can IFN-gamma be a therapeutic target in Guillain-Barre syndrome? SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE cytokine; experimental autoimmune neuritis; Guillain-Barre syndrome; IFN-gamma; T helper cell ID EXPERIMENTAL AUTOIMMUNE NEURITIS; EXPERIMENTAL ALLERGIC NEURITIS; PERIPHERAL NERVOUS-SYSTEM; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; MESSENGER-RNA EXPRESSION; GROWTH-FACTOR-BETA; RAT SCHWANN-CELLS; CD4+ T-CELLS; INTERFERON-GAMMA; MYELIN PROTEINS AB Introduction: Guillain-Barre syndrome (GBS) is an immune-mediated acute inflammatory disorder of the PNS in humans characterized by inflammatory infiltration and damage to myelin and axon. Experimental autoimmune neuritis (EAN) is a useful animal model for studying the pathogenesis and treatment of GBS. Immunocompetent cells together with cytokines produced by various cells contribute to the inflammatory process of GBS and EAN by acting as mediators or effectors. Areas covered: Both GBS and EAN have long been attributed to T helper (Th) 1 cell-mediated autoimmune disorders. IFN-gamma acts as a central mediator of Th1-mediated autoimmune disorders by deflecting the immune response toward a Th1 phenotype by inducing the differentiation of T cells to a Th1 phenotype and inhibiting the development of Th2 cells in autoimmune disorders such as GBS. In this review, we present an overview of current knowledge on the inflammatory and immunoregulatory role of IFN-gamma in GBS and EAN, which is important for evaluating whether IFN-gamma can become a potential therapeutic target in GBS. Expert opinion: Analysis of immunopathogenesis of GBS and EAN revealed the significance of IFN-gamma in both diseases, even though the complex mechanism of the delicate modulation of the cytokine is still under debate. More work needs to be done to rule out its potential in immunoregulatory function and pave the way for new therapeutic strategies for GBS. C1 [Zhang, Hong-Liang; Wu, Limin; Wu, Xiujuan; Zhu, Jie] Jilin Univ, Dept Neurol, Hosp 1, Changchun 130023, Peoples R China. [Zhang, Hong-Liang; Zhu, Jie] Karolinska Inst, Dept Neurobiol Care Sci & Soc, SE-14186 Stockholm, Sweden. [Wu, Limin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Zhu, Jie] Karolinska Inst, Karolinska Univ Hosp, Div Neurodegenerat, Dept Neurobiol Care Sci & Soc, SE-14186 Stockholm, Sweden. RP Zhu, J (reprint author), Karolinska Inst, Karolinska Univ Hosp, Div Neurodegenerat, Dept Neurobiol Care Sci & Soc, Plan 5, SE-14186 Stockholm, Sweden. EM Jie.Zhu@ki.se NR 77 TC 3 Z9 3 U1 1 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD APR PY 2014 VL 18 IS 4 BP 355 EP 363 DI 10.1517/14728222.2014.882899 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD2AM UT WOS:000333034800002 PM 24479493 ER PT J AU McBride, SM Parambi, RJ Jang, JW Goldsmith, T Busse, PM Chan, AW AF McBride, Sean M. Parambi, Ron J. Jang, Joanne W. Goldsmith, Tessa Busse, Paul M. Chan, Annie W. TI Intensity- modulated versus conventional radiation therapy for oropharyngeal carcinoma: Long- term dysphagia and tumor control outcomes SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE oropharynx; intensity-modulated radiation therapy; survival; toxicity; xerostomia; stricture ID NECK-CANCER; CONCURRENT CHEMOTHERAPY; COMPETING RISK; RADIOTHERAPY; HEAD; CHEMORADIATION AB BackgroundThe purpose of this study was to determine the relative clinical benefits of intensity-modulated radiation therapy (IMRT) versus conventional radiotherapy (CRT) in the treatment of patients with oropharyngeal carcinoma. MethodsWe compared tumor control and toxicity outcomes in 132 patients with stage III to IVA/B oropharyngeal carcinoma treated with definitive chemoradiation in the human papillomavirus (HPV) era. ResultsPatients treated with IMRT had lower rates of xerostomia (p = .01) and shorter duration of gastrostomy-tube dependence (p < .0001), but increased risk of cervical esophageal stricture (p = .03). The overall rates of late dysphagia were not different between the 2 groups (p = .40). In multivariate analysis, IMRT was a significant predictor of decreased disease-specific mortality (hazard ratio [HR] = 0.24; p = .03) after adjustment for T-category and active smoking. After adjustment for T classification, IMRT use was associated with a trend toward a significant decrease in locoregional failure (HR = 0.17; p = .08). ConclusionThe incidence of late dysphagia is similar in IMRT and CRT, but the mechanism of dysphagia is different. (c) 2013 Wiley Periodicals, Inc. Head Neck36: 492-498, 2014 C1 [McBride, Sean M.; Parambi, Ron J.; Jang, Joanne W.; Busse, Paul M.; Chan, Annie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [McBride, Sean M.; Jang, Joanne W.] Harvard Radiat Oncol Program, Boston, MA USA. [Goldsmith, Tessa] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. RP Chan, AW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox Bldg 337, Boston, MA 02114 USA. EM awchan@partners.org NR 20 TC 17 Z9 17 U1 0 U2 13 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 APR PY 2014 VL 36 IS 4 BP 492 EP 498 DI 10.1002/hed.23319 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AC7IE UT WOS:000332700600009 PM 23729221 ER PT J AU Prerau, MJ Lipton, PA Eichenbaum, HB Eden, UT AF Prerau, Michael J. Lipton, Paul A. Eichenbaum, Howard B. Eden, Uri T. TI Characterizing Context- Dependent Differential Firing Activity in the Hippocampus and Entorhinal Cortex SO HIPPOCAMPUS LA English DT Article DE hippocampus; entorhinal cortex; memory; grid cells; place cells ID RECEPTIVE-FIELD PLASTICITY; PLACE CELLS; NEURONS; DISCHARGE; DYNAMICS; MAPS; INFORMATION; VARIABILITY; FRAMEWORK; PATTERNS AB The rat hippocampus and entorhinal cortex have been shown to possess neurons with place fields that modulate their firing properties under different behavioral contexts. Such context-dependent changes in neural activity are commonly studied through electrophysiological experiments in which a rat performs a continuous spatial alternation task on a T-maze. Previous research has analyzed context-based differential firing during this task by describing differences in the mean firing activity between left-turn and right-turn experimental trials. In this article, we develop qualitative and quantitative methods to characterize and compare changes in trial-to-trial firing rate variability for sets of experimental contexts. We apply these methods to cells in the CA1 region of hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC), characterizing the context-dependent differences in spiking activity during spatial alternation. We identify a subset of cells with context-dependent changes in firing rate variability. Additionally, we show that dcMEC populations encode turn direction uniformly throughout the T-maze stem, whereas CA1 populations encode context at major waypoints in the spatial trajectory. Our results suggest scenarios in which individual cells that sparsely provide information on turn direction might combine in the aggregate to produce a robust population encoding. (c) 2014 Wiley Periodicals, Inc. C1 [Prerau, Michael J.; Lipton, Paul A.; Eichenbaum, Howard B.; Eden, Uri T.] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA. [Prerau, Michael J.; Lipton, Paul A.; Eichenbaum, Howard B.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Eichenbaum, Howard B.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Prerau, Michael J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Prerau, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM prerau@nmr.mgh.harvard.edu FU NIMH [MH51570, MH71702]; National Science Foundation [IIS-0643995] FX Grant sponsor: NIMH; Grant numbers: MH51570, MH71702; Grant sponsor: the National Science Foundation under; Grant number: IIS-0643995. NR 44 TC 2 Z9 2 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD APR PY 2014 VL 24 IS 4 BP 476 EP 492 DI 10.1002/hipo.22243 PG 17 WC Neurosciences SC Neurosciences & Neurology GA AC8FH UT WOS:000332768400012 PM 24436108 ER PT J AU Kim, SS Okechukwu, CA Dennerlein, JT Boden, LI Hopcia, K Hashimoto, DM Sorensen, G AF Kim, Seung-Sup Okechukwu, Cassandra A. Dennerlein, Jack T. Boden, Leslie I. Hopcia, Karen Hashimoto, Dean M. Sorensen, Glorian TI Association between perceived inadequate staffing and musculoskeletal pain among hospital patient care workers SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE Inadequate staffing; Musculoskeletal pain; Back pain; Hospital worker ID PSYCHOSOCIAL RISK-FACTORS; LOW-BACK-PAIN; FAMILY CONFLICT; SAFETY CLIMATE; NURSE BURNOUT; INJURIES; OUTCOMES; QUESTIONNAIRE; PREVENTION; MORTALITY AB To examine association between perceived inadequate staffing and musculoskeletal pain and to evaluate the role of work-related psychosocial and physical work factors in the association among hospital patient care workers. A cross-sectional study was conducted among 1,572 patient care workers in two academic hospitals. Perceived inadequate staffing was measured using the "staffing adequacy subscale" of Nursing Work Index, which is a continuous scale that averages estimates of staffing adequacy by workers in the same units. Musculoskeletal pain (i.e., neck/shoulder, arm, low back, lower extremity, any musculoskeletal pain, and the number of area in pain) in the past 3 months was assessed using a self-reported Nordic questionnaire. Multilevel logistic regression was applied to examine associations between perceived inadequate staffing and musculoskeletal pain, considering clustering among the workers in the same units. We found significant associations of perceived inadequate staffing with back pain (OR 1.50, 95 % CI 1.06, 2.14) and the number of body area in pain (OR 1.42, 95 % CI 1.01, 2.00) after adjusting for confounders including work characteristics (job title, having a second job or not, day shift or not, and worked hours per week). When we additionally adjusted for physical work factors (i.e., use of a lifting device, and the amount of the time for each of five physical activities on the job), only the association between perceived inadequate staffing and back pain remained significant (OR 1.50, 95 % CI 1.03, 2.19), whereas none of the associations was significant for all of musculoskeletal pains including back pain (OR 0.96, 95 % CI 0.66, 1.41) when we additionally adjusted for work-related psychosocial factors (i.e., job demands, job control, supervisor support, and co-worker support) instead of physical work factors. Perceived inadequate staffing may be associated with higher prevalence of back pain, and work-related psychosocial factor may play an important role in the potential pathway linking staffing level to back pain among hospital workers. C1 [Kim, Seung-Sup] Korea Univ, Dept Healthcare Management, Seoul, South Korea. [Okechukwu, Cassandra A.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.; Hashimoto, Dean M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.] Northeastern Univ, Dept Phys Therapy, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Boden, Leslie I.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Hopcia, Karen] Univ Illinois, Coll Nursing, Chicago, IL USA. [Hashimoto, Dean M.] Partners HealthCare Syst, Occupat Hlth Serv, Boston, MA USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Kim, SS (reprint author), Korea Univ, Dept Healthcare Management, Seoul, South Korea. EM ssk3@korea.ac.kr OI Dennerlein, Jack/0000-0001-7703-643X; Boden, Leslie/0000-0002-9779-207X FU National Institute for Occupational Safety and Health [U19 OH008861] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard School of Public Health Center for Work, Health and Wellbeing. This study would not have been accomplished without the participation of Partners HealthCare System and leadership from Dennis Colling, Sree Chaguturu, and Kurt Westerman. The authors would like to thank Partners Occupational Health Services including Marlene Freeley for her guidance, as well as Elizabeth Taylor, Elizabeth Tucker O'Day, and Terry Orechia. We also thank individuals at each of the hospitals including Jeanette Ives Erickson and Jacqueline Somerville in Patient Care Services leadership, and Jeff Davis and Julie Celano in Human Resources. Additionally, we wish to thank Charlene Feilteau, Mimi O'Connor, Margaret Shaw, Eddie Tan and Shari Weingarten for assistance with supporting databases. We also thank Chris Kenwood of NERI for his statistical and programming support, Evan McEwing, Project Director, and Linnea Benson-Whelan for her assistance with the production of this manuscript. Our thanks also go to Anne M. Stoddard for her comments about data analyses. NR 42 TC 6 Z9 6 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-0131 EI 1432-1246 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD APR PY 2014 VL 87 IS 3 BP 323 EP 330 DI 10.1007/s00420-013-0864-y PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD0VW UT WOS:000332953300011 PM 23475312 ER PT J AU Saunders, GH Dann, SM Griest, SE Frederick, MT AF Saunders, Gabrielle H. Dann, Serena M. Griest, Susan E. Frederick, Melissa T. TI Development and evaluation of a questionnaire to assess knowledge, attitudes, and behaviors towards hearing loss prevention SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Hearing conservation; health behaviors; health belief model; questionnaires ID MENTAL-STATE-EXAMINATION; HEALTH-PROMOTION MODEL; PRIMARY-CARE; NOISE; MUSIC; INTERVENTIONS; CONSERVATION; PREVALENCE; PROTECTION; EXPOSURE AB Objective: To develop and evaluate a questionnaire assessing knowledge, attitudes, and behaviors (KAB) as they pertain to hearing conservation, using the constructs of the health belief model (HBM). Design: The KAB was completed by 235 participants. Relationships between knowledge and attitudes about hearing and hearing conservation, participation in noisy activities, and use of hearing protection were examined. Study sample: 117 males and 118 females aged between 18 and 80 years (mean = 42.3, SD = 4.1) recruited from the Portland VA Medical Center, local universities, and a community college. Results: Knowledge scores ranged from 15.6% to 93.8%. Factor analyses revealed six attitude factors, interpreted as measuring perceived susceptibility, perceived severity, perceived benefits, perceived barriers, perceived self-efficacy, and cues to action. Over 95% of participants routinely participated in at least one noisy activity but few used hearing protection while doing so. The attitude scores of individuals who used hearing protection differed significantly from the scores of those who did not. Conclusions: Significant relationships between use of hearing protection and scores on the KAB provide validation that the HBM is a valuable framework for understanding hearing health behaviors, and evidence that the KAB is a valid tool for assessing these attitudes and behaviors. C1 [Saunders, Gabrielle H.; Dann, Serena M.; Griest, Susan E.; Frederick, Melissa T.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Saunders, Gabrielle H.; Griest, Susan E.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Saunders, GH (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM gabrielle.saunders@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Grant [C7214R] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Grant # #C7214R. Aspects of these data were presented at the National Hearing Conservation Association (NHCA), Mesa, USA, February 24-26, 2011, at the Academy of Rehabilitative Audiology Institute, San Francisco, USA, September 12 - 14, 2010. NR 46 TC 5 Z9 5 U1 1 U2 19 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1499-2027 EI 1708-8186 J9 INT J AUDIOL JI Int. J. Audiol. PD APR PY 2014 VL 53 IS 4 BP 209 EP 218 DI 10.3109/14992027.2013.860487 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AC9PR UT WOS:000332867100001 PM 24467444 ER PT J AU Sumino, K O'Brian, K Bartle, B Au, DH Castro, M Lee, TA AF Sumino, Kaharu O'Brian, Katiuscia Bartle, Brian Au, David H. Castro, Mario Lee, Todd A. TI Coexisting chronic conditions associated with mortality and morbidity in adult patients with asthma SO JOURNAL OF ASTHMA LA English DT Article DE Comorbidities; mental disorders; observational study; outcome research; veterans ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; POORLY CONTROLLED ASTHMA; SLEEP-APNEA SYNDROME; HEALTH-CARE; MULTIMORBIDITY; PREVALENCE; RHINITIS; RISK; DEPRESSION AB Objective: Many asthma patients suffer from chronic conditions other than asthma. We investigated the specific contribution of common comorbidities on mortality and morbidity in adult asthma. Methods: In an observational study of adults with incident asthma identified between 1999 and 2003 using National Veterans Affairs and Centers for Medicare and Medicaid Services encounter databases (n = 25 975, follow-up 3.0 +/- 1.7 years), association between 13 most prevalent comorbidities (hypertension, ischemic heart disease (IHD), osteoarthritis, rheumatoid arthritis, diabetes, mental disorders, substance/drug abuse, enlarged prostate, depression, cancer, alcoholism, HIV and heart failure) and four conditions previously associated with asthma (sleep apnea, gastroesophageal reflux disease (GERD), rhinitis and sinusitis) and mortality, hospitalizations and asthma exacerbations were assessed using multivariate regression analyses adjusted for other clinically important covariates. Results: HIV followed by alcoholism and mental disorders among 18-45-years old, and heart failure, diabetes, IHD and cancer among those >= 65 years old were associated with an increased risk of all-cause mortality. Many conditions were associated with increased risk for all-cause hospitalizations, but the increased risk was consistent across all ages for mental disorders. For asthma exacerbations, mental disorder followed by substance abuse and IHD were associated with increased risk among those 18-45 years old, and chronic sinusitis, mental disorder and IHD among those >= 65-years old. GERD was associated with decreased risk for asthma exacerbation in all ages. Conclusions: Many comorbidities are associated with poor outcome in adult asthmatics and their effect differs by age. Mental disorders are associated with increased risk of mortality and morbidity across ages. C1 [Sumino, Kaharu; O'Brian, Katiuscia; Castro, Mario] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Sumino, Kaharu; O'Brian, Katiuscia] St Louis VA Med Ctr, St Louis, MO USA. [Bartle, Brian] Hines VA Hosp, Hines, IL USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Practice, Chicago, IL USA. RP Sumino, K (reprint author), Washington Univ, Sch Med, Dept Med, 660 Euclid Ave,Campus Box 8052, St Louis, MO 63110 USA. EM ksumino@dom.wustl.edu FU NIH, American Lung Association and Veterans administration; Department of Veterans Affairs, Health Services Research and Development; NIH [1KM1CA156708-1]; American Lung Association; U.S. Department of Veterans Affairs Health Services Research and Development FX KS received Institutional grant monies from NIH, American Lung Association and Veterans administration. No potential conflicts exist with companies/organizations whose product or services pertinent to this article.; AU is funded by the Department of Veterans Affairs, Health Services Research and Development. AU is an unpaid research consultant for Bosch LLC.; MC receives University Grant monies from NIH and American Lung Association. No potential conflicts exist with other companies/organizations whose product or services pertinent to this article.; This research was funded by the U.S. Department of Veterans Affairs Health Services Research and Development. The funding agency did not play any role in the design, conduct, data analysis, or interpretation of the study. KS was supported by NIH 1KM1CA156708-1. NR 39 TC 15 Z9 15 U1 2 U2 12 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 EI 1532-4303 J9 J ASTHMA JI J. Asthma PD APR PY 2014 VL 51 IS 3 BP 306 EP 314 DI 10.3109/02770903.2013.879881 PG 9 WC Allergy; Respiratory System SC Allergy; Respiratory System GA AD2VO UT WOS:000333094100013 PM 24432868 ER PT J AU Shenoy, ES Noubary, F Kim, J Rosenberg, ES Cotter, JA Lee, H Walensky, RP Hooper, DC AF Shenoy, Erica S. Noubary, Farzad Kim, JiYeon Rosenberg, Eric S. Cotter, Jessica A. Lee, Hang Walensky, Rochelle P. Hooper, David C. TI Concordance of PCR and Culture from Nasal Swabs for Detection of Methicillin-Resistant Staphylococcus aureus in a Setting of Concurrent Antistaphylococcal Antibiotics SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SOFT-TISSUE INFECTIONS; HEALTH-CARE SETTINGS; CONTACT PRECAUTIONS; DISCONTINUATION; COLONIZATION; SKIN; MRSA AB The effect of concurrent administration of antibiotics on the detection of methicillin-resistant Staphylococcus aureus (MRSA) remains unresolved. Here, we assessed the concordance of paired nasal swabs processed using commercial PCR and culture and found high concordance in both the absence and presence of antibiotics with activity against MRSA (93.7% [95% confidence interval [CI], 88.1%, 96.8%] and 90.9% [95% CI, 84.8%, 94.7%], respectively), although PCR was more likely to be positive in the presence of antibiotics. (This study has been registered at ClinicalTrials.gov under registration no. NCT01234831.) C1 [Shenoy, Erica S.; Rosenberg, Eric S.; Walensky, Rochelle P.; Hooper, David C.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Shenoy, Erica S.; Cotter, Jessica A.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Shenoy, Erica S.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Kim, JiYeon; Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Shenoy, Erica S.; Noubary, Farzad; Kim, JiYeon; Rosenberg, Eric S.; Lee, Hang; Walensky, Rochelle P.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. EM eshenoy@partners.org FU Harvard Catalyst; National Center for Research Resources; National Center for Advanced Translational Sciences [8UL1TR000170-05, 1UL1RR025758]; Harvard University; MGH; National Institutes of Health [T32A107061]; MGH Departmental Funds; Harvard Center for AIDS Research [P30A1060354]; Pfizer, Inc.; LeClair Ryan FX This work was conducted with support from the Harvard Catalyst, National Center for Research Resources, and the National Center for Advanced Translational Sciences (grants 8UL1TR000170-05 and 1UL1RR025758) and financial contributions from Harvard University and its affiliated academic health centers, by the MGH 2010-2011 Clinical Innovation Award, the National Institutes of Health (grant T32A107061), MGH Departmental Funds, and the Harvard Center for AIDS Research (grant P30A1060354). The PCR reagents and testing equipment were provided without charge by Cepheid.; E.S.R. reports consultancy with T2 Biosystems, Microphage, and royalties from Up to Date, all outside the scope of the work herein. J.A.C. reports receiving grant support from Pfizer, Inc., unrelated to the scope of work herein. R. P. W. reports receiving consultancy fees from LeClair Ryan, unrelated to the scope of work herein. D. C. H. reports receiving grant support from Pfizer, Inc., unrelated to the scope of work herein. The other authors report no potential conflicts of interest. NR 12 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 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2014 VL 52 IS 4 BP 1235 EP 1237 DI 10.1128/JCM.02972-13 PG 3 WC Microbiology SC Microbiology GA AC9CS UT WOS:000332832300036 PM 24452168 ER PT J AU Redmond, RW Rajadurai, A Udayakumar, D Sviderskaya, EV Tsao, H AF Redmond, Robert W. Rajadurai, Anpuchchelvi Udayakumar, Durga Sviderskaya, Elena V. Tsao, Hensin TI Melanocytes Are Selectively Vulnerable to UVA-Mediated Bystander Oxidative Signaling SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ULTRAVIOLET-RADIATION; XERODERMA-PIGMENTOSUM; MALIGNANT-MELANOMA; DNA-DAMAGE; RISK; COMPLEMENTATION; PHOTOPRODUCTS; MUTATIONS; SUNLAMPS; EXPOSURE AB Long-wave UVA is the major component of terrestrial UV radiation and is also the predominant constituent of indoor sunlamps, both of which have been shown to increase cutaneous melanoma risk. Using a two-chamber model, we show that UVA-exposed target cells induce intercellular oxidative signaling to non-irradiated bystander cells. This UVA-mediated bystander stress is observed between all three cutaneous cell types (i.e., keratinocytes, melanocytes, and fibroblasts). Significantly, melanocytes appear to be more resistant to direct UVA effects compared with keratinocytes and fibroblasts, although melanocytes are also more susceptible to bystander oxidative signaling. The extensive intercellular flux of oxidative species has not been previously appreciated and could possibly contribute to the observed cancer risk associated with prolonged UVA exposure. C1 [Redmond, Robert W.; Rajadurai, Anpuchchelvi; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02466 USA. [Udayakumar, Durga] UT Southwestern Med Ctr, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX USA. [Sviderskaya, Elena V.] Univ London, Cell Signalling Res Ctr, Div Biomed Sci, London, England. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Edwards 211,48 Blossom St, Boston, MA 02466 USA. EM htsao@partners.org FU CDMRP grant from the US Department of Defense [CA093588]; MGH Millennium Melanoma Fund; National Institutes of Health [K24 CA149202] FX This work was supported in part by a CDMRP grant (CA093588) from the US Department of Defense and the generous philanthropic donors to the MGH Millennium Melanoma Fund. Mentorship and supervision for DU was supported in part by a grant from the National Institutes of Health (K24 CA149202 to HT). NR 30 TC 2 Z9 2 U1 4 U2 11 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 APR PY 2014 VL 134 IS 4 BP 1083 EP 1090 DI 10.1038/jid.2013.479 PG 8 WC Dermatology SC Dermatology GA AD4DQ UT WOS:000333197500028 PM 24335898 ER PT J AU Jahshan, C Wynn, JK McCleery, A Glahn, DC Altshuler, LL Green, MF AF Jahshan, Carol Wynn, Jonathan K. McCleery, Amanda Glahn, David C. Altshuler, Lori L. Green, Michael F. TI Cross-diagnostic comparison of visual processing in bipolar disorder and schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Schizophrenia; Visual processing; Perception; Masking; Attentional blink ID BACKWARD-MASKING PERFORMANCE; PSYCHIATRIC RATING-SCALE; ATTENTIONAL BLINK; OBJECT SUBSTITUTION; QUALITY-ASSURANCE; PERCEPTION; DEPRESSION; COGNITION; DEFICITS; MANIA AB Patients with Schizophrenia (SZ) show deficits across various stages of visual information processing. Whether patients with Bipolar Disorder (BD) exhibit these deficits is unclear. In this study, we conducted a detailed comparison of specific stages of early visual perception in BD and SZ. Forty-three BD patients, 43 SZ patients, and 51 matched healthy control subjects (HC) were administered three visual processing paradigms emphasizing: 1) an early stage of object formation (location backward masking), 2) a middle stage of object substitution (four-dot backward masking), and 3) a later stage at the perception-attention interface (rapid serial visual processing (RSVP) task eliciting the attentional blink). SZ performed significantly worse than BD and HC on location and four-dot masking. BD did not significantly differ from HC on either masking task. Both patient groups performed significantly worse than HC on the RSVP task; unlike SZ, BD did not show a significant attentional blink effect compared to HC. Our results indicate that BD patients were intact at the early and middle stages of visual processing (object formation and substitution) but intermediate between the SZ and HC groups at a later processing stage involving perceptual and attentional processes (RSVP task). These findings suggest that SZ is characterized by a diffuse pathophysiology affecting all stages of visual processing whereas in BD disruption is only at the latest stage involving higher order attentional functions. Published by Elsevier Ltd. C1 [Jahshan, Carol; Wynn, Jonathan K.; Altshuler, Lori L.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Los Angeles, CA 90073 USA. [Jahshan, Carol; Wynn, Jonathan K.; McCleery, Amanda; Altshuler, Lori L.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Glahn, David C.] Olin Neuropsychiat Res Ctr, Inst Living, New Haven, CT USA. [Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM carol.jahshan@ucla.edu RI Wynn, Jonathan/H-3749-2014; McCleery, Amanda/D-5471-2016 OI Wynn, Jonathan/0000-0002-1763-8540; McCleery, Amanda/0000-0003-2714-6897 FU NIH [MH089634, MH43292] FX Funding for this study was provided by NIH Grants MH089634 and MH43292 (MFG). The NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 42 TC 6 Z9 7 U1 0 U2 3 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 APR PY 2014 VL 51 BP 42 EP 48 DI 10.1016/j.jpsychires.2013.12.014 PG 7 WC Psychiatry SC Psychiatry GA AD0FI UT WOS:000332909500006 PM 24433849 ER PT J AU Bot, AGJ Menendez, ME Neuhaus, V Ring, D AF Bot, Arjan G. J. Menendez, Mariano E. Neuhaus, Valentin Ring, David TI The influence of psychiatric comorbidity on perioperative outcomes after shoulder arthroplasty SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Psychiatric illness; shoulder arthroplasty; comorbidities ID TOTAL KNEE ARTHROPLASTY; QUALITY-OF-LIFE; MEDICARE BENEFICIARIES; CARDIOVASCULAR-DISEASE; DEPRESSIVE SYMPTOMS; OLDER-ADULTS; RISK-FACTORS; HEALTH; PREVALENCE; SURGERY AB Background: Psychiatric comorbidity has been associated with increased health risks and poor long-term treatment outcomes in numerous medical disciplines, but its effect in short-term perioperative settings is incompletely understood. The purpose of this study was to evaluate the influence of a preoperative diagnosis of depressive disorder, anxiety disorder, schizophrenia, or dementia on in-hospital (1) adverse events, (2) blood transfusion, and (3) nonroutine discharge in patients undergoing shoulder arthroplasty. Methods: Using the National Hospital Discharge Survey (NHDS) database, we identified 348,824 discharges having undergone partial or total shoulder arthroplasty from 1990 to 2007. Multivariable regression analysis was performed for each of the outcome variables. Results: The prevalence of diagnosed depressive disorder was 4.4%, anxiety disorder, 1.6%; schizophrenia, 0.6%; and dementia, 1.5%. Preoperative psychiatric disorders, with the exception of schizophrenia, were associated with higher rates of adverse events. Depression and schizophrenia were associated with higher perioperative rates of blood transfusion. Any preoperative psychiatric illness was associated with higher rates of nonroutine discharge. Conclusions: Patients with preoperative psychiatric illness undergoing shoulder arthroplasty are at increased risk for perioperative morbidity and posthospitalization care. Preoperative screening of psychiatric illness might help with planning of shoulder arthroplasty. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Bot, Arjan G. J.; Menendez, Mariano E.; Neuhaus, Valentin; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU Prins Bernhard Cultuurfonds/Banning-de Jong Fonds; VSB Fonds; Anna Fonds, the Netherlands; "Gottfried und Julia Bangerter-Rhyner-Stiftung,'' Switzerland, for Scientific Research; Skeletal Dynamics LLC (Miami, FL, USA); Wright Medical Technology, Inc (Arlington, TN, USA) FX Dr Bot was supported by the Prins Bernhard Cultuurfonds/Banning-de Jong Fonds, VSB Fonds, and the Anna Fonds, the Netherlands. Dr Neuhaus was supported by the "Gottfried und Julia Bangerter-Rhyner-Stiftung,'' Switzerland, for Scientific Research.; Dr Ring certifies that he has or may receive payments or benefits, during the study period, of less than $10,000 from Skeletal Dynamics LLC (Miami, FL, USA) and Wright Medical Technology, Inc (Arlington, TN, USA). NR 42 TC 15 Z9 15 U1 1 U2 8 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 APR PY 2014 VL 23 IS 4 BP 519 EP 527 DI 10.1016/j.jse.2013.12.006 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AD2IN UT WOS:000333058300018 PM 24630546 ER PT J AU Goel, DP Romanowski, JR Shi, LL Warner, JJP AF Goel, Danny P. Romanowski, James R. Shi, Lewis L. Warner, Jon J. P. TI Scapulothoracic fusion: outcomes and complications SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Scapulothoracic fusion; complications; scapular winging; facioscapulohumeral dystrophy ID FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; ABNORMAL MOTION; SHOULDER; ARTHRODESIS AB Background: Scapulothoracic fusion (STF) may be an option to alleviate pain and restore function. The purpose of this study is to report the clinical outcome of patients who underwent STF for the treatment of painful scapular winging. Materials and methods: From 1999 through 2008, 10 patients (12 shoulders) underwent an STF for painful winging of the scapula. The mean follow-up period was 41 months (range, 8-72 months). Indications for STF included winging in association with excessive medial and/or lateral clavicular resection and facio-scapulohumeral dystrophy, as well as scapular winging related to combined long thoracic and spinal accessory nerve palsy. A retrospective review was performed to evaluate the subjective shoulder value, visual analog scale score, range of motion, unions, and complications. Results: There was a statistically significant improvement in the subjective shoulder value, visual analog scale score, range of motion, and satisfaction postoperatively. The overall complication rate was 50% (6 of 12). There were 2 persistent nonunions (2 of 12, 17%), and 50% (6 of 12) of all fusions required subsequent hardware removal because of discomfort. Complications included pleural effusion (3 of 12, 25%), hemop-neumothorax (1 of 12, 8%) pulmonary embolus (1 of 12, 8%), and infection (1 of 12, 8%). With the exception of the revision nonunion, all complications resolved with no negative sequelae. Conclusion: STF results in improved function and pain relief. STF is associated with a high short-term complication rate with limited long-term sequelae. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Goel, Danny P.] Univ British Columbia, Dept Orthoped, Div Arthroscop Reconstruct Surg & Joint Preservat, Burnaby, BC, Canada. [Romanowski, James R.] Gill Orthopaed, Charlotte Shoulder Inst, Charlotte, NC USA. [Shi, Lewis L.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Harvard Shoulder Serv, Ste 3G,55 Fruit St, Boston, MA 02114 USA. EM jwarner@partners.org NR 14 TC 3 Z9 3 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD APR PY 2014 VL 23 IS 4 BP 542 EP 547 DI 10.1016/j.jse.2013.08.009 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AD2IN UT WOS:000333058300021 PM 24280353 ER PT J AU Cohen, MS Jupiter, JB AF Cohen, Mark S. Jupiter, Jesse B. TI Intra-articular osteotomy for malunited articular fractures of the distal end of the humerus SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Distal humeral fracture; malunion; outcomes; fracture fixation; elbow; intra-articular fracture; shear fracture ID CORRECTIVE OSTEOTOMY; NONUNION; ELBOW; RECONSTRUCTION; RADIUS; HEAD; PART AB Background: The precarious anatomy of the articular surface of the distal humerus, as well as its meager subchondral bony support and limited soft-tissue attachments, presents enormous challenges for the operative correction of post-traumatic intra-articular deformities. This study presents 8 patients who underwent articular osteotomy with a mean follow-up period of 10.6 years, with an emphasis on functional, patient-rated, and radiographic outcomes. Methods: Eight patients (mean age, 39 years; range, 17-60 years) were followed up for a mean period of 10.6 years. The original fracture was a type C variant in 4 patients, a type B unicondylar fracture in 2, and a type B articular shearing fracture in 2. The initial injury was treated operatively in 5 patients and non-operatively in 3. The osteotomy and reconstruction were performed on average 8 months after injury (range, 6-11 months). The mean preoperative elbow arc of motion was 37 degrees. Two patients had ulnar nerve dysfunction. Results: All the osteotomies healed after the index procedure without evidence of avascular necrosis. Two patients required a second procedure for stiffness. At follow-up, the mean arc of elbow motion improved to 104 degrees (P = .001), with a mean flexion contracture of 26 degrees. The mean Disabilities of the Arm, Shoulder and Hand score at follow-up was 13 (range, 1-37); the mean patient satisfaction rating on a Likert scale (from 0 to 10) was 9.1; and the mean Mayo Elbow Performance Index score was 83 points (range, 70-100 points). Grade II osteoarthritic changes were seen in 3 patients, grade I in 3, and grade 0 in 2. Conclusions: In selected patients with a defined intra-articular malunion, the results of our experience support corrective osteotomy. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Cohen, Mark S.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Div Hand & Elbow Surg, Chicago, IL 60612 USA. [Jupiter, Jesse B.] Harvard Univ, Sch Med, Boston, MA USA. [Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Cohen, MS (reprint author), Rush Univ, Med Ctr, Dept Orthopaed Surg, Div Hand & Elbow Surg, 1611 W Harrison St,Third Floor, Chicago, IL 60612 USA. EM mark_s_cohen@rush.edu NR 21 TC 5 Z9 5 U1 0 U2 4 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 APR PY 2014 VL 23 IS 4 BP 579 EP 585 DI 10.1016/j.jse.2013.12.020 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AD2IN UT WOS:000333058300027 PM 24630550 ER PT J AU Ficarro, SB Biagi, JM Wang, JH Scotcher, J Koleva, RI Card, JD Adelmant, G He, H Askenazi, M Marshall, AG Young, NL Gray, NS Marto, JA AF Ficarro, Scott B. Biagi, Jessica M. Wang, Jinhua Scotcher, Jenna Koleva, Rositsa I. Card, Joseph D. Adelmant, Guillaume He, Huan Askenazi, Manor Marshall, Alan G. Young, Nicolas L. Gray, Nathanael S. Marto, Jarrod A. TI Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Mass spectrometry; LC-MS; MS/MS; FTMS; Fourier transform mass spectrometry; Ion cyclotron resonance; Time-of-flight mass spectrometry; Isotopologue; Nuclear binding energy ID COMPLEX PROTEIN MIXTURES; ION-CYCLOTRON RESONANCE; CYTOKINE RECEPTORS; SPECTROMETRY; QUANTIFICATION; PEPTIDE; RESOLUTION; DISEASE; GRANULOPOIESIS; PROLIFERATION AB We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (1) robust targeting of peptide N-termini and lysyl side chains, (2) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (3) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (4) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da, are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition, we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally, we provide exemplar data that extend the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers. C1 [Ficarro, Scott B.; Biagi, Jessica M.; Wang, Jinhua; Koleva, Rositsa I.; Card, Joseph D.; Adelmant, Guillaume; Askenazi, Manor; Gray, Nathanael S.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Ficarro, Scott B.; Biagi, Jessica M.; Card, Joseph D.; Adelmant, Guillaume; Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Ficarro, Scott B.; Wang, Jinhua; Koleva, Rositsa I.; Adelmant, Guillaume; Askenazi, Manor; Gray, Nathanael S.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Scotcher, Jenna; He, Huan; Marshall, Alan G.; Young, Nicolas L.] Natl High Magnet Field Lab, Ion Cyclotron Resonance Program, Tallahassee, FL 32310 USA. [He, Huan; Marshall, Alan G.] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM jarrod_marto@dfci.harvard.edu OI Young, Nicolas/0000-0002-3323-2815 FU Susan Smith Center for Women's Cancers; Strategic Research Initiative at the Dana-Farber Cancer Institute; National Institutes of Health [P01NS047572, HG006097-03]; National Science Foundation Division of Materials Research [DMR-11-57490]; State of Florida FX The authors thank Dr. Michael Senko at ThermoFisher Scientific for providing modified ITCL code and guidance to enable acquisition of extended length time domain transients with the Orbitrap XL instrument. Generous financial support for this work was provided by the Susan Smith Center for Women's Cancers and the Strategic Research Initiative at the Dana-Farber Cancer Institute, in addition to the National Institutes of Health, P01NS047572 (to J.A.M.) and HG006097-03 (to N.S.G). This work was also supported by the National Science Foundation Division of Materials Research through DMR-11-57490 (to A. G. M) and the State of Florida. NR 59 TC 1 Z9 1 U1 1 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 EI 1879-1123 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD APR PY 2014 VL 25 IS 4 BP 636 EP 650 DI 10.1007/s13361-013-0811-x PG 15 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA AD2IL UT WOS:000333058100015 PM 24496597 ER PT J AU Lorenzini, A Salmon, AB Lerner, C Torres, C Ikeno, Y Motch, S McCarter, R Sell, C AF Lorenzini, Antonello Salmon, Adam B. Lerner, Chad Torres, Claudio Ikeno, Yuji Motch, Susan McCarter, Roger Sell, Christian TI Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE IGF-1; Insulin; Metabolism; Obesity; Gluconeogenesis ID LONGITUDINAL BONE-GROWTH; I RECEPTOR GENE; IGF-I; CAENORHABDITIS-ELEGANS; MOLECULAR EVOLUTION; POSTNATAL-GROWTH; CELL-PROLIFERATION; LIT MUTATION; MUTANT MICE; HORMONE AB Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice. C1 [Lorenzini, Antonello] Univ Bologna, Dept Biomed & Neuromotor Sci, I-40126 Bologna, Italy. [Lorenzini, Antonello; Lerner, Chad; Torres, Claudio; Sell, Christian] Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19104 USA. [Salmon, Adam B.; Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Res, San Antonio, TX 78229 USA. [Salmon, Adam B.; Ikeno, Yuji] Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Helathcare Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Motch, Susan] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. [McCarter, Roger] Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. RP Sell, C (reprint author), Drexel Univ COM, Dept Pathol, 245 N 15th St, Philadelphia, PA 19102 USA. EM Christian.sell@dexelmed.edu RI Lorenzini, Antonello/G-4463-2012; LORENZINI, ANTONELLO/E-6582-2016 OI LORENZINI, ANTONELLO/0000-0001-9615-9697 FU National Institutes of Health from the National Institute on Aging [T32 AG021890-05, AG223343]; Drexel University Aging Initiative FX This work was supported by National Institutes of Health training grants (T32 AG021890-05, AG223343) from the National Institute on Aging and by funds from the Drexel University Aging Initiative. NR 63 TC 10 Z9 10 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2014 VL 69 IS 4 BP 410 EP 419 DI 10.1093/gerona/glt108 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6QI UT WOS:000333385500005 PM 23873963 ER PT J AU Koyama, A Steinman, M Ensrud, K Hillier, TA Yaffe, K AF Koyama, Alain Steinman, Michael Ensrud, Kristine Hillier, Teresa A. Yaffe, Kristine TI Long-term Cognitive and Functional Effects of Potentially Inappropriate Medications in Older Women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Dementia; Cognitive aging; Medication; Epidemiology; Physical function ID ELDERLY-PATIENTS; CONTROLLED-TRIAL; ALZHEIMERS TYPE; SEX-DIFFERENCES; ADULTS; IMPAIRMENT; DEMENTIA; RISK; ANTICHOLINERGICS; METAANALYSIS AB Background. The use of potentially inappropriate medications in older adults can lead to known adverse drug events, but long-term effects are less clear. We therefore conducted a prospective cohort study of older women to determine whether PIM use is associated with risk of functional impairment or low cognitive performance. Methods. We followed up 1,429 community-dwelling women (>= 75 years) for a period of 5 years at four clinical sites in the United States. The primary predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes included scores on a battery of six cognitive tests at follow-up and having one or more incident impairments in instrumental activities of daily living. Regression models were adjusted for baseline age, race, education, smoking, physical activity, a modified Charlson Comorbidity Index, and cognitive score. Results. The mean +/- SD age of women at baseline was 83.2 +/- 3.3. In multivariate models, baseline PIM use and higher ACB scores were significantly associated with poorer performance in category fluency (PIM: p = .01; ACB: p = .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p = .04). Both PIM use (odds ratio [OR]: 1.36 [1.05-1.75]) and higher ACB scores (OR: 1.11 [1.04-1.19]) were also strongly associated with incident functional impairment. Conclusions. The results provide suggestive evidence that PIM use and increased anticholinergic load may be associated with risk of functional impairment and low cognitive performance. More cautious selection of medications in older adults may reduce these potential risks. C1 [Koyama, Alain] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Koyama, Alain; Steinman, Michael; Yaffe, Kristine] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Steinman, Michael] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ensrud, Kristine] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Hillier, Teresa A.] Kaiser Permanente Northwest Hawaii, Ctr Hlth Res, Portland, OR USA. [Hillier, Teresa A.] Kaiser Permanente Northwest Hawaii, Ctr Hlth Res, Honolulu, HI USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Koyama, A (reprint author), 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA. EM akk412@mail.harvard.edu FU National Institute of Aging at the National Institutes of Health [K24 AG 031155, R01 AG 026720]; Alzheimer's Association [IIRG-08-88872]; National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576] FX This work was supported by the National Institute of Aging at the National Institutes of Health (grants K24 AG 031155, R01 AG 026720) and the Alzheimer's Association (grant IIRG-08-88872). The Study of Osteoporotic Fractures is supported by the National Institutes of Health. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. NR 41 TC 19 Z9 19 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2014 VL 69 IS 4 BP 423 EP 429 DI 10.1093/gerona/glt192 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6QI UT WOS:000333385500006 PM 24293516 ER PT J AU Hohman, MH Kim, SW Heller, ES Frigerio, A Heaton, JT Hadlock, TA AF Hohman, Marc H. Kim, Sang W. Heller, Elizabeth S. Frigerio, Alice Heaton, James T. Hadlock, Tessa A. TI Determining the threshold for asymmetry detection in facial expressions SO LARYNGOSCOPE LA English DT Article DE Facial paralysis; facial asymmetry ID PARALYSIS; ATTRACTIVENESS; BEAUTY; STIMULATION; PERCEPTION; SYMMETRY; FACE; EYE AB Objectives/Hypothesis To quantify the threshold for human perception of asymmetry for eyebrow elevation, eye closure, and smile, and to ascertain whether asymmetry detection thresholds and perceived severity of asymmetry differ in distinct facial zones. Study Design Online survey. Methods Photographs of a female volunteer performing eyebrow elevation, eye closure, and smile were digitally manipulated to introduce left-to-right asymmetry in 1-mm increments from 0 mm to 6 mm. One hundred and forty-five participants viewed these photographs using an online survey, measuring accuracy of asymmetry detection and perceived expression unnaturalness (on a scale of 1-5). Results Photographs of facial asymmetries were correctly judged as asymmetrical over 90% of the time for 2 mm or more of asymmetry in eyelid closure, and 3 mm or more of asymmetry during smiling. Identification of eyebrow elevation asymmetry gradually rose from 23% correct to 97% correct across the range of 1 mm to 6 mm of asymmetry. Greater degrees of asymmetry were ranked as significantly more unnatural across all expressions (3 tests; X-2 (6, N = 145) = 405.52 to 656.27, all P <0.001). Conclusion Thresholds for asymmetry detection vary across different zones of the face; once detected, asymmetry in eyelid position is perceived as more unnatural than asymmetries in either brow elevation or smile. These data will inform counseling of patients with segmental facial weakness and may provide more objective goals for facial reanimation procedures. Level of Evidence 4. Laryngoscope, 124:860-865, 2014 C1 [Hohman, Marc H.; Kim, Sang W.; Frigerio, Alice; Hadlock, Tessa A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Hohman, Marc H.; Kim, Sang W.; Frigerio, Alice; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA 02114 USA. [Heller, Elizabeth S.; Heaton, James T.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hohman, MH (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM marc_hohman@meei.harvard.edu OI Frigerio, Alice/0000-0001-9202-9553 FU NINDS NIH HHS [R01 NS071067] NR 14 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2014 VL 124 IS 4 BP 860 EP 865 DI 10.1002/lary.24331 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AD1AB UT WOS:000332965100019 PM 23900726 ER PT J AU Kozin, ED Remenschneider, AK Cunnane, ME Deschler, DG AF Kozin, Elliott D. Remenschneider, Aaron K. Cunnane, Mary Elizabeth Deschler, Daniel G. TI Otolaryngologist-assisted fluoroscopic-guided nasogastric tube placement in the postoperative laryngectomy patient SO LARYNGOSCOPE LA English DT Article DE laryngectomy; fluoroscopy; Nasogastric tube; head and neck anatomy ID NUTRITION; HEAD; NECK AB Laryngoscope, 124:916-920, 2014 C1 [Kozin, Elliott D.; Remenschneider, Aaron K.; Cunnane, Mary Elizabeth; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kozin, ED (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM elliott_kozin@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 11 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2014 VL 124 IS 4 BP 916 EP 920 DI 10.1002/lary.24560 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AD1AB UT WOS:000332965100029 PM 24347385 ER PT J AU Darr, EA Tufano, RP Ozdemir, S Kamani, D Hurwitz, S Randolph, G AF Darr, E. Ashlie Tufano, Ralph P. Ozdemir, Suleyman Kamani, Dipti Hurwitz, Shelley Randolph, Gregory TI Superior laryngeal nerve quantitative intraoperative monitoring is possible in all thyroid surgeries SO LARYNGOSCOPE LA English DT Article DE external branch of superior laryngeal nerve identification (EBSLN); electromyography (EMG); recurrent laryngeal nerve; cricothyroid muscle (CTM) twitch; NIM TriVantage EMG Tube; Intraoperative nerve monitoring (IONM); monopolar and bipolar probe ID IN-VIVO MODEL; EXTERNAL-BRANCH; PARALYSIS; IDENTIFICATION; MUSCLE; PRESERVATION; RECOGNITION; ANATOMY AB Objectives/Hypothesis To report normative electromyography (EMG) data on the external branch of the superior laryngeal nerve (EBSLN) and to compare this to analogous data of the recurrent laryngeal nerve (RLN) and vagus nerve (VN) during intraoperative neural monitoring (IONM) using both the standard monopolar stimulator probe and a novel bipolar stimulator probe. Study Design Prospective multiple tertiary care center study. Method A prospective study of EBSLN, RLN and VN EMG data in 22 thyroid surgeries was performed. Subjects with preoperative vocal fold paralysis were excluded. Postoperative laryngoscopy was normal in all subjects. Normative EMG data were acquired using both a standard monopolar and a novel bipolar stimulator probe, as well as a novel endotracheal tube. Cricothyroid muscle (CTM) twitch response during EBSLN stimulation was analyzed. Results In 100% of cases, EBSLN was identified and quantifiable EMG response was observed. EMG amplitude did not change despite extensive nerve dissection and multiple nerve stimulations. EBSLN amplitude was similar for left and right sides for patients under age 50 and aged 50 or older, for both genders, and with monopolar and bipolar stimulators. Conclusions Intraoperative neural monitoring may be used to safely assist in EBSLN identification during thyroid surgery in 100% of patients. A novel endotracheal tube allows for quantifiable EBSLN EMG activity in 100% of cases. Monopolar and bipolar stimulator probes produce similar EMG data. Level of Evidence 4. Laryngoscope, 124:1035-1041, 2014 C1 [Darr, E. Ashlie; Kamani, Dipti; Randolph, Gregory] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Surg,Dept Laryngol & Ot, Boston, MA USA. [Hurwitz, Shelley] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02115 USA. [Randolph, Gregory] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ozdemir, Suleyman] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Endocrine Surg, Baltimore, MD 21205 USA. RP Randolph, G (reprint author), Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Surg, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu NR 27 TC 13 Z9 13 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2014 VL 124 IS 4 BP 1035 EP 1041 DI 10.1002/lary.24446 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AD1AB UT WOS:000332965100049 PM 24115215 ER PT J AU Tarhini, AA Shin, D Lee, SJ Stuckert, J Sander, CA Kirkwood, JM AF Tarhini, Ahmad A. Shin, Donghoon Lee, Sandra J. Stuckert, Joseph Sander, Cindy A. Kirkwood, John M. TI Serologic evidence of autoimmunity in E2696 and E1694 patients with high-risk melanoma treated with adjuvant interferon alfa SO MELANOMA RESEARCH LA English DT Article DE interferon; autoimmunity; melanoma; adjuvant ID COOPERATIVE-ONCOLOGY-GROUP; HIGH-DOSE INTERFERON-ALPHA-2B; CHRONIC HEPATITIS-C; RESECTED STAGE-III; METASTATIC MELANOMA; CUTANEOUS MELANOMA; PROGNOSTIC-SIGNIFICANCE; RENAL-CARCINOMA; POOLED ANALYSIS; IV MELANOMA AB We evaluated Eastern Cooperative Group phase II and III trials E2696 and E1694 to assess the incidence and prognostic significance of autoimmunity induced by adjuvant high-dose interferon-alpha 2b (HDI). In E2696, patients with resectable high-risk melanoma were randomized to receive vaccination with GM2-KLH/QS-1 (GMK) plus concurrent HDI, GMK plus sequential HDI, or GMK alone. E1694 randomized patients to either HDI or GMK. Sera from 103 patients in E2696 and 691 patients in E1694 banked at baseline and up to three subsequent time points were tested by ELISA for the development of five autoantibodies. In E2696, autoantibodies were induced in 16 patients (23.2%; n=69) receiving HDI and GMK and two patients (5.9%; n=34) receiving GMK alone (P=0.031). Of 691 patients in E1694, 67 (19.1%) who received HDI (n=350) developed autoantibodies, but only 16 patients (4.7%) developed autoantibodies in the vaccine group (n=341; P < 0.001). Almost all induced autoantibodies were detected at >= 12 weeks after the initiation of therapy. A 1-year landmark analysis among resected stage III patients treated with HDI in E1694 showed a trend toward a survival advantage associated with HDI-induced autoimmunity (hazard ratio=0.80; 95% confidence interval: 0.50-1.98; P=0.33). Therefore, adjuvant HDI therapy is associated with the induction of autoimmunity that should be further investigated prospectively as a surrogate marker of adjuvant therapeutic benefit. This potential biomarker develops over the course of up to 1 year, and cannot be used to alter the course of therapy. Studies of the genetic determinants of this response may better discriminate patients more likely to benefit from HDI immunomodulatory therapy. C1 [Tarhini, Ahmad A.; Kirkwood, John M.] Univ Pittsburgh, Dept Med, Clin & Translat Sci Inst, Pittsburgh, PA 15232 USA. [Tarhini, Ahmad A.; Stuckert, Joseph; Sander, Cindy A.; Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. [Shin, Donghoon; Lee, Sandra J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tarhini, AA (reprint author), Univ Pittsburgh, Inst Canc, UPMC Canc Pavilion,5150 Ctr Ave 555, Pittsburgh, PA 15232 USA. EM tarhiniaa@upmc.edu FU ECOG; NIH [P50CA121973]; DiaSorin Inc.; NIH/NCI award [P30CA047904] FX This investigator-initiated study was supported by the ECOG and by NIH award P50CA121973 and in part by DiaSorin Inc. UPCI shared resources that are supported in part by NIH/NCI award P30CA047904 were used for this project. NR 46 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0960-8931 EI 1473-5636 J9 MELANOMA RES JI Melanoma Res. PD APR PY 2014 VL 24 IS 2 BP 150 EP 157 DI 10.1097/CMR.0000000000000050 PG 8 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA AC6AD UT WOS:000332601400008 PM 24509407 ER PT J AU Kimberly, WT Battey, TWK Pham, L Wu, O Yoo, AJ Furie, KL Singhal, AB Elm, JJ Stern, BJ Sheth, KN AF Kimberly, W. Taylor Battey, Thomas W. K. Ly Pham Wu, Ona Yoo, Albert J. Furie, Karen L. Singhal, Aneesh B. Elm, Jordan J. Stern, Barney J. Sheth, Kevin N. TI Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients SO NEUROCRITICAL CARE LA English DT Article DE Stroke; Cerebral edema; Glyburide; Biomarker ID MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC-STROKE; MATRIX-METALLOPROTEINASE EXPRESSION; NONSELECTIVE CATION CHANNEL; ADULT-RAT BRAIN; HEMORRHAGIC TRANSFORMATION; PLASMINOGEN-ACTIVATOR; CARDIOEMBOLIC STROKE; REACTIVE ASTROCYTES; FOCAL ISCHEMIA AB Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Using a case-control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial. C1 [Kimberly, W. Taylor; Battey, Thomas W. K.; Ly Pham] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Kimberly, W. Taylor; Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoulo A Martinos Ctr Biomed Imaging, Boston, MA USA. [Kimberly, W. Taylor; Singhal, Aneesh B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA. [Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA USA. [Furie, Karen L.] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Elm, Jordan J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, NC USA. [Stern, Barney J.] Univ Maryland, Sch Med, Dept Neurol & Emergency Med, Baltimore, MD 21201 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA. [Sheth, Kevin N.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. RP Kimberly, WT (reprint author), Lunder 644,55 Fruit St, Boston, MA 02114 USA. EM wtkimberly@partners.org FU National Institutes of Health/National Institute of Neurological Diseases and Stroke [K23 NS076597]; NIH [P50 NS051343, R01 NS051412]; Remedy Pharmaceuticals, Inc FX This work was supported by the National Institutes of Health/National Institute of Neurological Diseases and Stroke (K23 NS076597, W. T. K.). Some of the samples and data used in this research were originally collected with funding through the NIH (P50 NS051343, K. L. F. and R01 NS051412, A. B. S.) or through Remedy Pharmaceuticals, Inc (GAMES-Pilot study). NR 41 TC 21 Z9 21 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD APR PY 2014 VL 20 IS 2 BP 193 EP 201 DI 10.1007/s12028-013-9917-z PG 9 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA AD0XA UT WOS:000332956400004 PM 24072459 ER PT J AU Simard, JM Sheth, KN Kimberly, WT Stern, BJ del Zoppo, GJ Jacobson, S Gerzanich, V AF Simard, J. Marc Sheth, Kevin N. Kimberly, W. Taylor Stern, Barney J. del Zoppo, Gregory J. Jacobson, Sven Gerzanich, Volodymyr TI Glibenclamide in Cerebral Ischemia and Stroke SO NEUROCRITICAL CARE LA English DT Review DE Cerebral ischemia; Stroke; Sur1; Sur1-Trpm4 channel; Glibenclamide; RP-1127; Stroke Therapy Academic Industry Roundtable (STAIR) ID K-ATP CHANNELS; SENSITIVE POTASSIUM CHANNELS; SULFONYLUREA RECEPTOR 1; PLASMINOGEN-ACTIVATOR USE; POTENTIAL MELASTATIN 4; SPINAL-CORD-INJURY; MALIGNANT INFARCTION; HYPOXIA-ISCHEMIA; ARTERY OCCLUSION; NONHUMAN PRIMATE AB The sulfonylurea receptor 1 (Sur1)-transient receptor potential 4 (Trpm4) channel is an important molecular element in focal cerebral ischemia. The channel is upregulated in all cells of the neurovascular unit following ischemia, and is linked to microvascular dysfunction that manifests as edema formation and secondary hemorrhage, which cause brain swelling. Activation of the channel is a major molecular mechanism of cytotoxic edema and "accidental necrotic cell death." Blockade of Sur1 using glibenclamide has been studied in different types of rat models of stroke: (i) in conventional non-lethal models (thromboembolic, 1-2 h temporary, or permanent middle cerebral artery occlusion), glibenclamide reduces brain swelling and infarct volume and improves neurological function; (ii) in lethal models of malignant cerebral edema, glibenclamide reduces edema, brain swelling, and mortality; (iii) in models with rtPA, glibenclamide reduces swelling, hemorrhagic transformation, and death. Retrospective studies of diabetic patients who present with stroke have shown that those whose diabetes is managed with a sulfonylurea drug and who are maintained on the sulfonylurea drug during hospitalization for stroke have better outcomes at discharge and are less likely to suffer hemorrhagic transformation. Here, we provide a comprehensive review of the basic science, preclinical experiments, and retrospective clinical studies on glibenclamide in focal cerebral ischemia and stroke. We also compare the preclinical work in stroke models to the updated recommendations of the Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here provide a strong foundation for a translational research program to study glibenclamide in patients with ischemic stroke. C1 [Simard, J. Marc; Gerzanich, Volodymyr] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care, New Haven, CT 06510 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Kimberly, W. Taylor] Harvard Univ, Sch Med, Boston, MA USA. [Stern, Barney J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [del Zoppo, Gregory J.] Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98195 USA. [del Zoppo, Gregory J.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Jacobson, Sven] Remedy Pharmaceut Inc, New York, NY USA. RP Simard, JM (reprint author), Univ Maryland, Sch Med, Dept Neurosurg, 22 S Greene St,Suite S12D, Baltimore, MD 21201 USA. EM msimard@smail.umaryland.edu FU National Institute of Neurological Disorders and Stroke [NS061808]; National Heart, Lung and Blood Institute [HL082517] FX This work was supported by Grants to JMS from the National Institute of Neurological Disorders and Stroke (NS061808) and the National Heart, Lung and Blood Institute (HL082517). NR 84 TC 10 Z9 10 U1 2 U2 12 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD APR PY 2014 VL 20 IS 2 BP 319 EP 333 DI 10.1007/s12028-013-9923-1 PG 15 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA AD0XA UT WOS:000332956400020 PM 24132564 ER PT J AU Wetherill, RR Childress, AR Jagannathan, K Bender, J Young, KA Suh, JJ O'Brien, CP Franklin, TR AF Wetherill, Reagan R. Childress, Anna Rose Jagannathan, Kanchana Bender, Julian Young, Kimberly A. Suh, Jesse J. O'Brien, Charles P. Franklin, Teresa R. TI Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals SO PSYCHOPHARMACOLOGY LA English DT Article DE Addiction; Cannabis cues; Neuroimaging; Cannabis craving; Subliminal; Marijuana cues; Marijuana craving; Reward ID LIKELIHOOD ESTIMATION METAANALYSIS; ORBITOFRONTAL CORTEX; LIMBIC ACTIVATION; QUANTITATIVE METAANALYSIS; CONDITIONED-RESPONSES; ANTERIOR CINGULATE; INHIBITORY CONTROL; DECISION-MAKING; HUMAN AWARENESS; PERFUSION FMRI AB Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug-seeking behaviors. Using an equivalent paradigm, we tested whether cannabis cues activate reward neurocircuitry in treatment-seeking, cannabis-dependent individuals and whether activation was associated with relevant behavioral anchors: baseline cannabis craving (drug-seeking behavior) and duration of use (degree of conditioning). Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, sexual, and aversive cues presented in a backward-masking paradigm. Drug use history and cannabis craving were assessed prior to imaging. Participants showed increased activity to backward-masked cannabis cues in regions supporting reward detection and interoception, including the left anterior insula, left ventral striatum/amygdala, and right ventral striatum. Cannabis cue-related activity in the bilateral insula and perigenual anterior cingulate cortex was positively associated with baseline cannabis craving, and cannabis cue-related activity in the medial orbitofrontal cortex was positively correlated with years of cannabis use. Neural responses to backward-masked sexual cues were similar to those observed during cannabis cue exposure, while activation to aversive cues was observed only in the left anterior insula and perigenual anterior cingulate cortex. These data highlight the sensitivity of the brain to subliminal reward signals and support hypotheses promoting a common pathway of appetitive motivation. C1 [Wetherill, Reagan R.; Childress, Anna Rose; Jagannathan, Kanchana; Bender, Julian; Young, Kimberly A.; Suh, Jesse J.; O'Brien, Charles P.; Franklin, Teresa R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Childress, Anna Rose; Suh, Jesse J.; O'Brien, Charles P.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Wetherill, RR (reprint author), Univ Penn, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM rweth@mail.med.upenn.edu FU Pennsylvania Department of Health Commonwealth Universal Research Enhancement (CURE) FX This research was made possible by the Pennsylvania Department of Health Commonwealth Universal Research Enhancement (CURE) funding. NR 80 TC 14 Z9 15 U1 6 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2014 VL 231 IS 7 BP 1397 EP 1407 DI 10.1007/s00213-013-3342-z PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AD0WI UT WOS:000332954600012 PM 24186078 ER PT J AU Siler, DA Gonzalez, JA Wang, RK Cetas, JS Alkayed, NJ AF Siler, Dominic A. Gonzalez, Jorge A. Wang, Ruikang K. Cetas, Justin S. Alkayed, Nabil J. TI Intracisternal Administration of Tissue Plasminogen Activator Improves Cerebrospinal Fluid Flow and Cortical Perfusion After Subarachnoid Hemorrhage in Mice SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Early brain injury; Global ischemia; Intracranial pressure; Subarachnoid hemorrhage; Tissue plasminogen activator; Cerebral blood flow ID ANEURYSMAL INTRAVENTRICULAR HEMORRHAGE; EARLY BRAIN-INJURY; PRIMATE MODEL; INTRATHECAL FIBRINOLYSIS; THROMBOLYTIC THERAPY; CEREBRAL-ISCHEMIA; ACUTE-PHASE; VASOSPASM; PREVENTION; CLOT AB Early brain injury (EBI) during the first 72 h after subarachnoid hemorrhage (SAH) is an important determinant of clinical outcome. A hallmark of EBI, global cerebral ischemia, occurs within seconds of SAH and is thought to be related to increased intracranial pressure (ICP). We tested the hypothesis that ICP elevation and cortical hypoperfusion are the result of physical blockade of cerebrospinal fluid (CSF) flow pathways by cisternal microthrombi. In mice subjected to SAH, we measured cortical blood volume (CBV) using optical imaging, ICP using pressure transducers, and patency of CSF flow pathways using intracisternally injected tracer dye. We then assessed the effects of intracisternal injection of recombinant tissue plasminogen activator (tPA). ICP rose immediately after SAH and remained elevated for 24 h. This was accompanied by a decrease in CBV and impaired dye movement. Intracisternal administration of tPA immediately after SAH lowered ICP, increased CBV, and partially restored CSF flow at 24 h after SAH. Lowering ICP without tPA, by draining CSF, improved CBV at 1 h, but not 24 h after SAH. These findings suggest that blockade of CSF flow by microthrombi contributes to the early decline in cortical perfusion in an ICP-dependent and ICP-independent manner and that intracisternal tPA may reduce EBI and improve outcome after SAH. C1 [Siler, Dominic A.; Gonzalez, Jorge A.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Siler, Dominic A.; Cetas, Justin S.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Cetas, Justin S.] Portland VA Med Ctr, Portland, OR 97239 USA. [Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd,UHN 2, Portland, OR 97239 USA. EM alkayedn@ohsu.edu FU NHLBI [F30 HL108624, R01 HL093140]; Oregon Brain Institute; NINDS [R01 NS044313, NS070837]; NIBIB [R01 EB009682] FX Dominic A. Siler-NHLBI F30 HL108624, Oregon Brain Institute.; Nabil J. Alkayed-NINDS R01 NS044313 and NS070837; Ruikang K. Wang-NHLBI R01 HL093140 and NIBIB R01 EB009682 NR 42 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD APR PY 2014 VL 5 IS 2 BP 227 EP 237 DI 10.1007/s12975-014-0329-y PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD2FT UT WOS:000333050000007 PM 24526376 ER PT J AU Hiramoto, JS Katz, R Ix, JH Wassel, C Rodondi, N Windham, BG Harris, T Koster, A Satterfield, S Newman, A Shlipak, MG AF Hiramoto, Jade S. Katz, Ronit Ix, Joachim H. Wassel, Christina Rodondi, Nicolas Windham, B. Gwen Harris, Tamara Koster, Annemarie Satterfield, Suzanne Newman, Anne Shlipak, Michael G. CA Hlth ABC Study TI Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study SO VASCULAR LA English DT Article DE women; peripheral artery disease; epidemiology; sex-specific ID ANKLE-BRACHIAL INDEX; CRITICAL LIMB ISCHEMIA; PREDICT CARDIOVASCULAR EVENTS; NUTRITION EXAMINATION SURVEY; AMERICAN-HEART-ASSOCIATION; MIDDLE-AGED POPULATION; BLOOD-PRESSURE INDEX; LOWER-EXTREMITY; ARM INDEX; NATIONAL-HEALTH AB The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD. C1 [Hiramoto, Jade S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Wassel, Christina] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, La Jolla, CA 92093 USA. [Rodondi, Nicolas] Univ Bern, Inselspital, Dept Gen Internal Med, CH-3012 Bern, Switzerland. [Windham, B. Gwen] Univ Mississippi, Med Ctr, Dept Internal Med, Jackson, MS 39216 USA. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, Maastricht, Netherlands. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Hiramoto, JS (reprint author), UCSF Vasc Surg, 400 Parnassus Ave,A-581,Box 0222, San Francisco, CA 94143 USA. EM jade.hiramoto@ucsfmedctr.org RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIH/NCRR/OD UCSF-CTSI [KL2 RR024130, IH R01DK087961-01A1, R01AG027002-05A1, R01AG034853]; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01-NR012459]; Intramural Research Program of the NIH, National Institute on Aging FX This publication was supported by NIH/NCRR/OD UCSF-CTSI grant Number KL2 RR024130 (Dr Hiramoto), NIH R01DK087961-01A1, R01AG027002-05A1 and R01AG034853 (Dr Shlipak). Its contents are the responsibility of the authors and do not necessarily represent the official views of the NIH. This research was also supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050 and NINR grant R01-NR012459, and in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 36 TC 9 Z9 10 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1708-5381 EI 1708-539X J9 VASCULAR JI Vascular PD APR PY 2014 VL 22 IS 2 BP 142 EP 148 DI 10.1177/1708538113476023 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC9HY UT WOS:000332846400011 PM 23512905 ER PT J AU Murphy, AC Weyhenmeyer, B Noonan, J Kilbride, SM Schimansky, S Loh, KP Kogel, D Letai, AG Prehn, JHM Murphy, BM AF Murphy, A. C. Weyhenmeyer, B. Noonan, J. Kilbride, S. M. Schimansky, S. Loh, K. P. Koegel, D. Letai, A. G. Prehn, J. H. M. Murphy, B. M. TI Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis SO APOPTOSIS LA English DT Article DE Glioblastoma; TRAIL; R-roscovitine; Mcl-1 ID BCL-2 FAMILY-MEMBERS; INHIBITOR R-ROSCOVITINE; DOWN-REGULATION; GLIOMA-CELLS; STEM-CELLS; MITOCHONDRIAL APOPTOSIS; SIGNALING PATHWAY; MALIGNANT GLIOMA; UP-REGULATION; MEDIATED APOPTOSIS AB Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma. C1 [Murphy, A. C.; Weyhenmeyer, B.; Noonan, J.; Kilbride, S. M.; Schimansky, S.; Loh, K. P.; Prehn, J. H. M.; Murphy, B. M.] Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Ctr Syst Med, Dublin 2, Ireland. [Koegel, D.] Johann Wolfgang Goethe Univ Hosp, Ctr Neurol & Neurosurg, D-60590 Frankfurt, Germany. [Letai, A. G.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. [Letai, A. G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Murphy, BM (reprint author), Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Ctr Syst Med, York House, Dublin 2, Ireland. EM bronamurphy@rcsi.ie RI Murphy, Brona/D-4873-2012; Loh, Kian Ping/M-3122-2016; Prehn, Jochen/A-3928-2010 OI Murphy, Brona/0000-0002-6740-8858; Loh, Kian Ping/0000-0002-1491-743X; Prehn, Jochen/0000-0003-3479-7794 FU Health Research Board [RP/2008/69, HRA_POR/2012/88]; RCSI Research Committee [GR 08-0155]; Science Foundation Ireland Stokes Lecturer [07/SK/B1243a]; Deutsche Krebshilfe [108795]; Science Foundation Ireland Short Term Travel Fellowship [08/IN. 1/B1949-STTF 11] FX This research was generously supported by two grants from the Health Research Board (RP/2008/69 and HRA_POR/2012/88) and the RCSI Research Committee (GR 08-0155) to BMM. BMM is a Science Foundation Ireland Stokes Lecturer (07/SK/B1243a). This research was also supported by a grant from Deutsche Krebshilfe (grant 108795) to DK. SK was supported by a Science Foundation Ireland Short Term Travel Fellowship (08/IN. 1/B1949-STTF 11). NR 58 TC 19 Z9 21 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 EI 1573-675X J9 APOPTOSIS JI Apoptosis PD APR PY 2014 VL 19 IS 4 BP 629 EP 642 DI 10.1007/s10495-013-0935-2 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AC4IX UT WOS:000332485700007 PM 24213561 ER PT J AU Briet, JP Hageman, MG Blok, R Ring, D AF Briet, Jan Paul Hageman, Michiel G. Blok, Robin Ring, David TI When Do Patients With Hand Illness Seek Online Health Consultations and What Do They Ask? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID DOCTOR SERVICE; WEB SURVEY; ARM PAIN; INTERNET; SATISFACTION; DISABILITY; DISTRESS AB Several websites allow people to post health questions and get answers from doctors. Knowing more about what patients seek from these websites might help in-office educational efforts, but little is known about what occurs on these sites. This study addressed whether patients seeking advice online already have seen a physician, the type of questions asked, if they are dissatisfied with their doctor, the characteristics of the physicians who respond, and the content of their answers. This study documents the circumstances and content of questions asked about hand illness, the characteristics of the physician responders, and their responses. One hundred thirty-one hand surgery-related questions from an online health consultation website were reviewed retrospectively. The timing of and reason for the consultation, the content of the questions, the specialty of physician responder, and the content of the responses were recorded. Sixty patients (46%) were seeking information before seeing a doctor, 21 (16%) after a medical encounter, and 19 (15%) after hand surgery. With increasing contact with providers, patient queries transitioned from diagnosis, to treatment, to prognosis, and potential complications. Patients who had seen a doctor often expressed dissatisfaction (16 of 37 patients [43%]) as did those who had hand surgery (seven of 26 patients [27%]). Between one and eight doctors (average, two) answered each query. Most of the answering physicians were hand surgeons. The information they provided predominantly addressed diagnosis. Online consultations are most common among patients who have not seen a doctor, but also reflect uncertainty and dissatisfaction after seeing a doctor. Although online health consultations might support patients' quest for information and understanding, and the potential for multiple answers from different doctors creates the possibility for increased balance and breadth of opinions, the quality of the information and cost-effectiveness of this approach are uncertain and need to be evaluated carefully in future studies. C1 [Briet, Jan Paul; Hageman, Michiel G.; Blok, Robin; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr,Sch Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr,Sch Med, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM Dring@partners.org OI Blok, Robin/0000-0002-5291-546X FU Marti-Keuning Eckhardt fonds (Lunteren, The Netherlands); Spinoza fonds (Amsterdam, The Netherlands); AnnaFonds Travel grant (Oegstgeest, The Netherlands); Spinoza fonds (Oegstgeest, The Netherlands); Skeletal Dynamics (Miami, FL, USA); Wright Medical (Memphis, TN, USA); Biomet (Warsaw, IN, USA); AO North America (Philadelphia, PA, USA); AO International (Dubendorf, Switzerland) FX One of the authors (MGH) certifies that he has received funding from Marti-Keuning Eckhardt fonds (Lunteren, The Netherlands) an amount less than USD 10,000), Spinoza fonds (Amsterdam, The Netherlands) an amount less than USD 10,000), and AnnaFonds Travel grant (Oegstgeest, The Netherlands) an amount less than USD 10,000; one of the authors (RB) certifies that he has received funding from Spinoza fonds (Oegstgeest, The Netherlands) an amount less than USD 10,000; one of the authors (DR) certifies that he has received funding from Skeletal Dynamics (Miami, FL, USA) an amount from USD 10,000 to 100,000, Wright Medical (Memphis, TN, USA), Biomet (Warsaw, IN, USA), AO North America (Philadelphia, PA, USA), and AO International (Dubendorf, Switzerland), all amounts less than USD 10,000. NR 26 TC 3 Z9 3 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 APR PY 2014 VL 472 IS 4 BP 1246 EP 1250 DI 10.1007/s11999-014-3461-9 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AC5QU UT WOS:000332576400031 PM 24442841 ER PT J AU Zhang, DF Hess, K Nielsen, GP Schwab, JH AF Zhang, Dafang Hess, Kathryn Nielsen, G. Petur Schwab, Joseph H. TI A 33-year-old Man With Low Back Pain SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MONOSTOTIC FIBROUS DYSPLASIA; GIANT-CELL TUMOR; CERVICAL-SPINE; THORACIC SPINE; VERTEBRAL HEMANGIOMAS; SURGICAL-TREATMENT; NATURAL-HISTORY; BONE; CHILDREN; MRI C1 [Zhang, Dafang; Hess, Kathryn; Schwab, Joseph H.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhang, DF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM dzhang9@partners.org NR 39 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2014 VL 472 IS 4 BP 1345 EP 1350 DI 10.1007/s11999-014-3502-4 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AC5QU UT WOS:000332576400047 PM 24522387 ER PT J AU Wong, JYY De Vivo, I Lin, XH Grashow, R Cavallari, J Christiani, DC AF Wong, Jason Y. Y. De Vivo, Immaculata Lin, Xihong Grashow, Rachel Cavallari, Jennifer Christiani, David C. TI The Association Between Global DNA Methylation and Telomere Length in a Longitudinal Study of Boilermakers SO GENETIC EPIDEMIOLOGY LA English DT Article DE telomere; longitudinal; DNA methylation; Alu; LINE-1 ID STRUCTURAL EQUATION MODELS; PARTICULATE MATTER; CARDIOVASCULAR-DISEASE; OCCUPATIONAL-EXPOSURE; QUANTITATIVE PCR; WELDING EXPOSURE; AIR-POLLUTION; TERM EXPOSURE; SAMPLE-SIZE; CANCER AB The objectives of this study were to determine if global DNA methylation, as reflected in LINE-1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated-measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow-up period was 29 months. LINE-1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real-time qPCR. Linear-mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE-1 and Alu methylation levels, and telomere length. For every incremental increase in LINE-1 methylation, there was a statistically significant 1.0 x 10(-1) (95% CI: 4.6 x 10(-2), 1.5 x 10(-1), P < 0.01) unit increase in relative telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m(2)) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 x 10(-2) (95% CI: 1.0 x 10(-2), 1.1 x 10(-1), P = 0.02) unit increase in relative telomere length. The interaction between LINE-1 methylation and follow-up time was statistically significant with an estimate -9.8 x 10(-3) (95% CI: -1.8 x 10(-2), -1.9 x 10(-3), P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE-1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline. C1 [Wong, Jason Y. Y.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wong, Jason Y. Y.; Grashow, Rachel; Cavallari, Jennifer; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Wong, Jason Y. Y.; De Vivo, Immaculata] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [De Vivo, Immaculata; Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cavallari, Jennifer] Univ Connecticut, Ctr Hlth, Div Occupat & Environm Med, Farmington, CT USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wong, JYY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jyw285@mail.harvard.edu OI Wong, Jason/0000-0002-8167-540X FU National Institute of Environmental Health Sciences (NIEHS) [R01ES009860, P50ES00002]; CPWR: The Center for Construction Research and Training through NIOSH [OH009762] FX This project was made possible by funding from the National Institute of Environmental Health Sciences (NIEHS) grants R01ES009860 and P50ES00002, in addition to the CPWR: The Center for Construction Research and Training through NIOSH cooperative agreement OH009762. We would like to thank Jinming Zhang, Hyang-Min Byun, Shona Fang, Li Su, Zhonghua Liu, Joel Schwartz, and Donna Spiegelman for their support. NR 63 TC 4 Z9 4 U1 2 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2014 VL 38 IS 3 BP 254 EP 264 DI 10.1002/gepi.21796 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA AC7IB UT WOS:000332700300008 PM 24616077 ER PT J AU Evers, K Panis, S Torfs, K Steyaert, J Noens, I Wagemans, J AF Evers, Kris Panis, Sven Torfs, Katrien Steyaert, Jean Noens, Ilse Wagemans, Johan TI Disturbed Interplay Between Mid- and High-Level Vision in ASD? Evidence from a Contour Identification Task with Everyday Objects SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Visual perception; Object identification; Weak central coherence theory; Enhanced perceptual functioning hypothesis; Bottom-up versus top-down; Gabor; Local versus global processing ID AUTISM SPECTRUM DISORDERS; TOP-DOWN FACILITATION; VISUAL-PERCEPTION; CATEGORY-SPECIFICITY; OUTLINE VERSIONS; WEAK COHERENCE; CHILDREN; RECOGNITION; INTEGRATION; CONNECTIVITY AB Atypical visual processing in children with autism spectrum disorder (ASD) does not seem to reside in an isolated processing component, such as global or local processing. We therefore developed a paradigm that requires the interaction between different processes-an identification task with Gaborized object outlines-and applied this to two age groups of 6-to-10 and 10-to-14 year old children with and without ASD. Event history analyses demonstrated an identification disadvantage in the ASD group, which remained quite stable during the temporal unfolding of the outline. The typically developing group particularly outperformed the ASD group when more complex contours were shown. Together, our results suggest that the interplay between local and global processes and between bottom-up and top-down processes is disturbed in ASD. C1 [Evers, Kris; Panis, Sven; Torfs, Katrien; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Louvain, Belgium. [Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Louvain, Belgium. [Evers, Kris; Steyaert, Jean; Noens, Ilse; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Louvain, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, B-3000 Louvain, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Evers, K (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, Tiensestr 102,Box 3711, B-3000 Louvain, Belgium. EM kris.evers@psy.kuleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 NR 58 TC 5 Z9 5 U1 4 U2 17 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 APR PY 2014 VL 44 IS 4 BP 801 EP 815 DI 10.1007/s10803-013-1931-7 PG 15 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900007 PM 24037639 ER PT J AU Baurer, D Yonek, JC Cohen, AB Restuccia, JD Hasnain-Wynia, R AF Baurer, Danielle Yonek, Julie C. Cohen, Alan B. Restuccia, Joseph D. Hasnain-Wynia, Romana TI System-Level Factors Affecting Clinicians' Perceptions and Use of Interpreter Services in California Public Hospitals SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Language services; Hospitals; Clinicians ID LIMITED ENGLISH PROFICIENCY; LANGUAGE ACCESS SERVICES; HEALTH-CARE; RESIDENT PHYSICIANS; AD-HOC; BARRIERS; QUALITY; LESSONS; IMPACT AB Professional language interpreters are skilled in the nuances of interpretation and are less likely to make errors of clinical significance but clinicians infrequently use them. We examine system-level factors that may shape clinicians' perceptions and use of professional interpreters. Exploratory qualitative study in 12 California public hospitals. We conducted in-person key informant interviews with hospital leadership, clinical staff, and administrative staff. Five emergent themes highlight system-level factors that may influence clinicians' perceptions and use of professional interpreters in hospitals: (1) organization-wide commitment to improving language access for LEP patients; (2) organizational investment in remote interpreter technologies to increase language access; (3)training clinicians on how to access and work with interpreters; (4) hospital supports the training and certification of bilingual staff to serve as interpreters to expand in-person, on-site, interpreter capacity; and (5)organizational investment in readily accessible telephonic interpretation. Multiple system-level factors underlie clinicians' use of professional interpreters. Interventions that target these factors could improve language services for patients with limited English proficiency. C1 [Baurer, Danielle; Yonek, Julie C.; Hasnain-Wynia, Romana] Northwestern Univ, Inst Healthcare Studies, Ctr Healthcare Equ, Chicago, IL 60611 USA. [Cohen, Alan B.] Boston Univ, Hlth Policy Inst, Boston, MA 02215 USA. [Restuccia, Joseph D.] Boston Univ, Sch Management, Boston, MA 02215 USA. [Restuccia, Joseph D.] Boston VA Healthcare Syst, COLMR, Boston, MA USA. RP Hasnain-Wynia, R (reprint author), Northwestern Univ, Inst Healthcare Studies, Ctr Healthcare Equ, Chicago, IL 60611 USA. EM r-hasnainwynia@northwestern.edu NR 27 TC 2 Z9 2 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 EI 1557-1920 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD APR PY 2014 VL 16 IS 2 BP 211 EP 217 DI 10.1007/s10903-012-9722-3 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC6RR UT WOS:000332652800005 PM 23054539 ER PT J AU Kuten-Shorrer, M Kelley, JM Sonis, ST Treister, NS AF Kuten-Shorrer, M. Kelley, J. M. Sonis, S. T. Treister, N. S. TI Placebo effect in burning mouth syndrome: a systematic review SO ORAL DISEASES LA English DT Review DE randomized control trials; burning mouth syndrome; BMS; placebo; treatment; oral dysesthesia ID ALPHA-LIPOIC ACID; IRRITABLE-BOWEL-SYNDROME; DOUBLE-BLIND; CONTROLLED TRIAL; PAIN; METAANALYSIS; CLONAZEPAM; DEPRESSION; CAPSAICIN; EFFICACY AB Placebo controls play a critical role in the evaluation of any pharmacotherapy. This review surveys the placebo arm in 12 randomized controlled trials (RCTs) investigating burning mouth syndrome (BMS) and documents a positive placebo response in 6 of them. On average, treatment with placebos produced a response that was 72% as large as the response to active drugs. The lack of homogeneity in the use of placebos adds to the difficulty in comparing results and aggregating data. Future RCTs investigating BMS would benefit from larger sample sizes, adequate follow-up periods, and use of a standard placebo. C1 [Kuten-Shorrer, M.; Sonis, S. T.; Treister, N. S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kelley, J. M.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Kelley, J. M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kelley, J. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kelley, J. M.] Endicott Coll, Beverly, MA USA. [Sonis, S. T.; Treister, N. S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. RP Kuten-Shorrer, M (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM michal@hsdm.harvard.edu NR 35 TC 8 Z9 8 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD APR PY 2014 VL 20 IS 3 BP e1 EP e6 DI 10.1111/odi.12192 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AC8BE UT WOS:000332757200001 PM 24164777 ER PT J AU Barake, M Evins, AE Stoeckel, L Pachas, GN Nachtigall, LB Miller, KK Biller, BMK Tritos, NA Klibanski, A AF Barake, Maya Evins, A. Eden Stoeckel, Luke Pachas, Gladys N. Nachtigall, Lisa B. Miller, Karen K. Biller, Beverly M. K. Tritos, Nicholas A. Klibanski, Anne TI Investigation of impulsivity in patients on dopamine agonist therapy for hyperprolactinemia: a pilot study SO PITUITARY LA English DT Article DE Cabergoline; Dopamine agonist; Hyperprolactinemia; Impulsivity; Pituitary adenoma ID CONTROL DISORDERS; PARKINSONS-DISEASE; CABERGOLINE; PROLACTINOMAS; ACTIVATION; RISK; TASK AB The use of dopamine agonists (DAs) has been associated with increased impulsivity and impulse control disorders in several diseases, including Parkinson's disease. Such an effect of DAs on impulsivity has not been clearly characterized in hyperprolactinemic patients, where DAs are the mainstay of therapy. We studied the effects of DAs on impulsivity in hyperprolactinemic patients treated at a tertiary pituitary center, using validated psychometric tests. Cross-sectional study. Impulsivity was evaluated in 30 subjects, 10 hyperprolactinemic patients on DAs compared to two control groups; one comprising untreated hyperprolactinemic patients (n = 10) and a second group consisting of normoprolactinemic controls with pituitary lesions (n = 10). Measures of impulsivity included both self-report questionnaires as well as laboratory-based tasks. Hyperprolactinemic patients on DAs had a higher score (mean +/- A SD) in one self-report measure of impulsivity, the attention subscale of the Barratt Impulsiveness Scale (16.2 +/- A 2.7), as compared to the hyperprolactinemic control group (12.3 +/- A 2.5) and the normoprolactinemic group (14.7 +/- A 4.4) (p = 0.04). No statistically significant difference was found between groups with regards to the other impulsivity scales. In the DA-treated group, a correlation was observed between increased impulsivity (as assessed in the Experiential Discounting Task) and higher weekly cabergoline dose (r(2) = 0.49, p = 0.04). The use of DAs in hyperprolactinemic patients is associated with an increase in one aspect of impulsivity. This effect should be further characterized in larger, longitudinal studies. C1 [Barake, Maya; Nachtigall, Lisa B.; Miller, Karen K.; Biller, Beverly M. K.; Tritos, Nicholas A.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Barake, Maya; Evins, A. Eden; Stoeckel, Luke; Pachas, Gladys N.; Nachtigall, Lisa B.; Miller, Karen K.; Biller, Beverly M. K.; Tritos, Nicholas A.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Evins, A. Eden; Stoeckel, Luke; Pachas, Gladys N.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org FU NIDA NIH HHS [K24 DA030443] NR 21 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X EI 1573-7403 J9 PITUITARY JI Pituitary PD APR PY 2014 VL 17 IS 2 BP 150 EP 156 DI 10.1007/s11102-013-0480-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AC6VC UT WOS:000332662300008 PM 23504371 ER PT J AU Jones, R Capen, DE AF Jones, Rosemary Capen, Diane E. TI Imaging Circulating Monocytic Cells Fusing to Endothelial Cells in Acutely Injured and Regenerating Capillaries SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE Blood-borne cells; fusion to endothelium; immunopositive cells ID LUNG NEOVASCULARIZATION MODEL; PULMONARY-HYPERTENSION; SMOOTH-MUSCLE; GROWTH-FACTOR; T-CELLS; PROGENITOR CELLS; HYPEROXIC INJURY; PRECURSOR CELLS; ANGIOGENESIS; WALL AB The present studies focus on monocytic circulating cells (CCs) interacting with the endothelial cells of pulmonary capillaries in acute lung injury. The CCs are further defined into sub-sets based on their structural profiles, i.e. CC1-3. They are shown to move into close apposition to adjacent capillary endothelium and to fuse to endothelial plasmalemmal membranes. Similarly, CCs are seen to fuse to the endothelial cells of regenerating capillaries after injury. Immunogold labeling studies demonstrate that CCs express a mediator promoting endothelial cell migration, proliferation and stability, i.e. VEGF, further supporting the potential of a paracrine interaction between the fusing cells, while the expression of CXCR4 by CCs, and of SDF-1 alpha by adjacent endothelial cells, demonstrates a mechanism for retention of these cells at the capillary surface. Myeloid VEGF-R2(+)CD11b(+) precursors and PDGF-R beta(+) expressing cells are identified within the CC population. The findings establish that, by fusing to endothelial cells, the monocytic CC population studied has the potential to promote capillary surface stability/integrity through a paracrine mechanism. C1 [Jones, Rosemary; Capen, Diane E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Jones, Rosemary] Harvard Univ, Sch Med, Boston, MA USA. RP Jones, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,MGH EAST CNY, 149 13th St, Boston, MA 02115 USA. EM rcjones@partners.org FU NIH HL [R01 089252] FX The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by NIH HL R01 089252. NR 22 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD APR PY 2014 VL 38 IS 2 BP 93 EP 103 DI 10.3109/01913123.2013.846450 PG 11 WC Microscopy; Pathology SC Microscopy; Pathology GA AC7TX UT WOS:000332735900005 PM 24605767 ER PT J AU Mai, XM Chen, Y Camargo, CA Langhammer, A AF Mai, X. -M. Chen, Y. Camargo, C. A., Jr. Langhammer, A. TI Serum 25-hydroxyvitamin D levels and self-reported allergic rhinitis in Norwegian adults - The HUNT Study SO ALLERGY LA English DT Article DE allergy; vitamin D; serum 25-hydroxyvitamin D; allergic rhinitis; prospective study ID VITAMIN-D DEFICIENCY; INCIDENT ASTHMA; BIRTH COHORT; CHILDREN; FOOD; SENSITIZATION; PREGNANCY; DISEASE; INFANCY; OBESITY AB Background The role of low vitamin D status in the development of allergic rhinitis is unclear. We aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] and incidence of allergic rhinitis in adults. Methods The study included a random sample from an adult population who participated in the second and third surveys of the Nord-Trondelag Health Study (HUNT) in Norway (HUNT2, 1995-1997 and HUNT3, 2006-2008). Serum 25(OH)D levels were measured in blood samples collected at baseline. Among 1351 adults who did not report allergic rhinitis at baseline, incident allergic rhinitis was identified by participant report of having or having had allergic rhinitis or hay fever at follow-up. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated after adjustment for age, smoking, physical activity, socioeconomic status, family history of allergy, body mass index, and season. The analyses were stratified by sex due to its significant interaction with 25(OH)D levels (P<0.02). Results Over an average of 11years, 9% of men and 15% of women developed allergic rhinitis. Among men, serum 25(OH)D level <50nM was associated with an increased risk of incident allergic rhinitis (AOR 2.55; 95% CI 1.01-6.49); each 25nM reduction in 25(OH)D level was associated with an AOR of 1.84 (95% CI 1.18-2.87). In women, however, the association was opposite, with AOR being 0.83 (95% CI 0.66-1.05) for each 25nM reduction in serum 25(OH)D level. Conclusions Vitamin D appears to play different roles in the development of allergic rhinitis among men and women. C1 [Mai, X. -M.; Langhammer, A.] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. [Chen, Y.] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mai, XM (reprint author), Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. EM xiao-mei.mai@ntnu.no FU Research Council of Norway [201895/V50] FX This study was supported by the Research Council of Norway (project no. 201895/V50). NR 36 TC 11 Z9 11 U1 1 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD APR PY 2014 VL 69 IS 4 BP 488 EP 493 DI 10.1111/all.12365 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AC0LM UT WOS:000332186200009 PM 24467227 ER PT J AU Hsu, SM Mathew, R Taylor, AW Stein-Streilein, J AF Hsu, S. -M. Mathew, R. Taylor, A. W. Stein-Streilein, J. TI Ex-vivo tolerogenic F4/80(+) antigen-presenting cells (APC) induce efferent CD8(+) regulatory T cell-dependent suppression of experimental autoimmune uveitis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE ACAID; EAU; autoimmunity; tolerogenic APC; CD8+ Treg ID IMMUNE DEVIATION ACAID; EYE-DERIVED TOLERANCE; ANTERIOR-CHAMBER; DENDRITIC CELLS; IN-VITRO; PERIPHERAL TOLERANCE; PRIVILEGED EYE; RD8 MUTATION; CRB1 GENE; B-CELLS AB It is known that inoculation of antigen into the anterior chamber (a.c.) of a mouse eye induces a.c.-associated immune deviation (ACAID), which is mediated in part by antigen-specific local and peripheral tolerance to the inciting antigen. ACAID can also be induced in vivo by intravenous (i.v.) inoculation of ex-vivo-generated tolerogenic antigen-presenting cells (TolAPC). The purpose of this study was to test if in-vitro-generated retinal antigen-pulsed TolAPC suppressed established experimental autoimmune uveitis (EAU). Retinal antigen-pulsed TolAPC were injected i.v. into mice 7 days post-induction of EAU. We observed that retinal antigen-pulsed TolAPC suppressed the incidence and severity of the clinical expression of EAU and reduced the expression of associated inflammatory cytokines. Moreover, extract of whole retina efficiently replaced interphotoreceptor retinoid-binding protein (IRBP) in the preparation of TolAPC used to induce tolerance in EAU mice. Finally, the suppression of EAU could be transferred to a new set of EAU mice with CD8(+) but not with CD4(+)regulatory T cells (T-reg). Retinal antigen-pulsed TolAPC suppressed ongoing EAU by inducing CD8(+) T-reg cells that, in turn, suppressed the effector activity of the IRBP-specific T cells and altered the clinical symptoms of autoimmune inflammation in the eye. The ability to use retinal extract for the antigen raises the possibility that retinal extract could be used to produce autologous TolAPC and then used as therapy in human uveitis. C1 [Hsu, S. -M.; Mathew, R.; Stein-Streilein, J.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Taylor, A. W.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Hsu, S. -M.] Natl Cheng Kung Univ Hosp, Dept Ophthalmol, Tainan 70428, Taiwan. RP Stein-Streilein, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM joan_stein@meei.harvard.edu FU NIH [EY023659, EY11983] FX S.- M. H. and R. M. performed the experiments and wrote parts of the manuscript. A. W. T. contributed intellectually to the project by participating in experimental discussions, and by providing reagents and protocols. J. S.- S. designed the study, interpreted the data and wrote the paper. The research was supported in part by NIH grants: EY023659; EY11983. NR 63 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2014 VL 176 IS 1 BP 37 EP 48 DI 10.1111/cei.12243 PG 12 WC Immunology SC Immunology GA AC2DG UT WOS:000332307300004 PM 24266626 ER PT J AU Colombo, E Tentorio, P Musio, S Rajewsky, K Pedotti, R Casola, S Farina, C AF Colombo, E. Tentorio, P. Musio, S. Rajewsky, K. Pedotti, R. Casola, S. Farina, C. TI Skewed B cell differentiation affects lymphoid organogenesis but not T cell-mediated autoimmunity SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE B cell receptor; EAE; B cells; LMP2A ID BALB/C MICE; PROTEIN; ENCEPHALOMYELITIS; ACTIVATION; DISEASE; ANTIGEN AB B cell receptor (BCR) signalling determines B cell differentiation and may potentially alter T cell-mediated immune responses. In this study we used two transgenic strains of BCR-deficient mice expressing Epstein-Barr virus latent membrane protein (LMP)2A in B cells, where either follicular and marginal zone differentiation (D(H)LMP2A mice) or B-1 cell development (V(H)LMP2A mice) were supported, and evaluated the effects of skewed B lymphocyte differentiation on lymphoid organogenesis and T cell responses in vivo. Compared to wild-type animals, both transgenic strains displayed alterations in the composition of lymphoid organs and in the dynamics of distinct immune cell subsets following immunization with the self-antigen PLP185-206. However, ex-vivo T cell proliferation to PLP185-206 peptide measured in immunized D(H)LMP2A and V(H)LMP2A mice was similar to that detected in immunized control mice. Further, clinical expression of experimental autoimmune encephalitis in both LMP2A strains was identical to that of wild-type mice. In conclusion, mice with skewed B cell differentiation driven by LMP2A expression in BCR-negative B cells do not show changes in the development of a T cell mediated disease model of autoimmunity, suggesting that compensatory mechanisms support the generation of T cell responses. C1 [Colombo, E.; Tentorio, P.; Farina, C.] Ist Sci San Raffaele, INSpe Inst Expt Neurol, Div Neurosci, I-20132 Milan, Italy. [Colombo, E.; Tentorio, P.; Musio, S.; Pedotti, R.; Farina, C.] Fdn IRCCS Neurol Inst Carlo Besta, Neuroimmunol & Neuromuscular Disorders Unit, Milan, Italy. [Casola, S.] FIRC Inst Mol Oncol Fdn, IFOM, Milan, Italy. [Rajewsky, K.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Rajewsky, K.] Immune Dis Inst, Boston, MA USA. RP Farina, C (reprint author), Ist Sci San Raffaele, INSpe Inst Expt Neurol, Div Neurosci, Via Olgettina 58, I-20132 Milan, Italy. EM farina.cinthia@hsr.it RI Farina, Cinthia/G-8911-2014; Colombo, Emanuela/J-7315-2016; Musio, Silvia/K-3072-2016 OI Farina, Cinthia/0000-0002-4466-9676; Colombo, Emanuela/0000-0001-8754-1739; Musio, Silvia/0000-0002-8051-7389 FU Ministero Italiano Salute (Ricerca Corrente and Progetto Giovani Ricercatori) [2009-1607206] FX This study was supported by Ministero Italiano Salute (Ricerca Corrente and Progetto Giovani Ricercatori 2009-1607206 to R. P. and C. F.). NR 22 TC 0 Z9 0 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2014 VL 176 IS 1 BP 58 EP 65 DI 10.1111/cei.12250 PG 8 WC Immunology SC Immunology GA AC2DG UT WOS:000332307300006 PM 24325711 ER PT J AU Duboc, H Tache, Y Hofmann, AF AF Duboc, Henri Tache, Yvette Hofmann, Alan F. TI The bile acid TGR5 membrane receptor: From basic research to clinical application SO DIGESTIVE AND LIVER DISEASE LA English DT Review DE Bile acids; Diabetes; Inflammation; Motility; TGR5 receptor ID IRRITABLE-BOWEL-SYNDROME; PRIMARY SCLEROSING CHOLANGITIS; ENTERIC NERVOUS-SYSTEM; FUNCTIONAL GASTROINTESTINAL DISORDERS; GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; BENIGN ULCER DISEASE; FARNESOID X RECEPTOR; TARGETED DISRUPTION; CULTURED ASTROCYTES AB The TGR5 receptor (or GP-BAR1, or M-BAR) was characterized ten years ago as the first identified G-coupled protein receptor specific for bile acids. TGR5 gene expression is widely distributed, including endocrine glands, adipocytes, muscles, immune organs, spinal cord, and the enteric nervous system. The effect of TGR5 activation depends on the tissue where it is expressed and the signalling cascade that it induces. Animal studies suggest that TGR5 activation influences energy production and thereby may be involved in obesity and diabetes. TGR5 activation also influences intestinal motility. This review provides an overview of TGR5-bile acid interactions in health as well as the possible involvement of TGR5 in human disease. (c) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. C1 [Duboc, Henri; Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Ctr, Los Angeles, CA 90024 USA. [Duboc, Henri; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA USA. [Duboc, Henri; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Duboc, Henri] Univ Paris Diderot, Louis Mourier Hosp, AP HP, Sorbonne Paris Cite,Dept Gastroenterol & Hepatol, Paris, France. [Duboc, Henri] Univ Paris 06, Hop St Antoine, AP HP, ERL,INSERM,U1057,UMR 7203, Paris, France. [Hofmann, Alan F.] Univ Calif San Diego, Dept Med, Div Gastroenterol, San Diego, CA 92103 USA. RP Duboc, H (reprint author), Hop Louis Mourier, Serv Gastroenterol, F-92700 Colombes, France. EM henri.duboc@gmail.com; AFHofmann@gmail.com FU Robert Tournut Grant from the Societe Nationale Francaise de Gastroenterologie; Philippe Foundation; Assistance-Publique Hopitaux de Paris; Research Career Scientist Award; NIHDDK [R01 57238, DK-41301] FX H.D. was supported by a Robert Tournut Grant from the Societe Nationale Francaise de Gastroenterologie, a research grant from the Philippe Foundation, a Mobility Grant from Assistance-Publique Hopitaux de Paris. Y.T is a recipient of a Research Career Scientist Award, and NIHDDK R01 57238 and DK-41301 (Animal Core). NR 93 TC 58 Z9 60 U1 3 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1590-8658 EI 1878-3562 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD APR PY 2014 VL 46 IS 4 BP 302 EP 312 DI 10.1016/j.dld.2013.10.021 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AC3LL UT WOS:000332420200004 PM 24411485 ER PT J AU Dunne, RM Shyn, PB Sung, JC Tatli, S Morrison, PR Catalano, PJ Silverman, SG AF Dunne, Ruth M. Shyn, Paul B. Sung, Jeffrey C. Tatli, Servet Morrison, Paul R. Catalano, Paul J. Silverman, Stuart G. TI Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: A comparison of the safety of cryoablation and radiofrequency ablation SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Ablation techniques; Carcinoma, Hepatocellular; Liver cirrhosis ID TUMOR ABLATION; LIVER-TUMORS; HEPATIC MALIGNANCIES; INITIAL-EXPERIENCE; CRYOTHERAPY; COMPLICATIONS; CRYOSURGERY; CT AB Purpose: To compare the safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis. Materials and methods: This retrospective HIPAA-compliant study received institutional review board approval. Forty-two adult patients with cirrhosis underwent image-guided percutaneous ablation of hepatocellular carcinoma from 2003 to 2011. Twenty-five patients underwent 33 cryoablation procedures to treat 39 tumors, and 22 underwent 30 radiofrequency ablation procedures to treat 39 tumors. Five patients underwent both cryoablation and radiofrequency ablation procedures. Complication rates and severity per procedure were compared between the ablation groups. Potential confounding patient, procedure, and tumor-related variables were also compared. Statistical analyses included Kruskal-Wallis, Wilcoxon rank sum, and Fisher's exact tests. Two-sided P-values <0.05 were considered significant. Results: The overall complication rates, 13 (39.4%) of 33 cryoablation procedures versus eight (26.7%) of 30 radiofrequency ablation procedures and severe/fatal complication rates, two (6.1%) of 33 cryoablation procedures versus one (3.3%) of 30 radiofrequency ablation procedures, were not significantly different between the ablation groups (both P = 0.26). Severe complications included pneumothoraces requiring chest tube insertion during two cryoablation procedures. One death occurred within 90 days of a radiofrequency ablation procedure; all other complications were managed successfully. Conclusion: No significant difference was seen in the overall safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Dunne, Ruth M.; Shyn, Paul B.; Sung, Jeffrey C.; Tatli, Servet; Morrison, Paul R.; Silverman, Stuart G.] Brigham & Womens Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Shyn, PB (reprint author), Brigham & Womens Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM rmdunne@partners.org; pshyn@partners.org; jcsung@gmail.com; statli@partners.org; pcata@jimmy.harvard.edu; sgsilverman@partners.org NR 30 TC 14 Z9 16 U1 0 U2 6 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 APR PY 2014 VL 83 IS 4 BP 632 EP 638 DI 10.1016/j.ejrad.2014.01.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC3GR UT WOS:000332405200005 PM 24529593 ER PT J AU Biederman, J Petty, CR Fried, R Woodworth, KY Faraone, SV AF Biederman, Joseph Petty, Carter R. Fried, Ronna Woodworth, K. Yvonne Faraone, Stephen V. TI Is the Diagnosis of ADHD Influenced by Time of Entry to School? An Examination of Clinical, Familial, and Functional Correlates in Children at Early and Late Entry Points SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE developmental; educational AB Objective: The authors examined the proposed immaturity hypothesis, which suggests that younger children may have developmental immaturity and not ADHD, using data from a large, clinically referred population of individuals with and without ADHD. Method: The sample consisted of individuals with and without an ADHD diagnosis, ascertained from ongoing studies in our laboratory, born in August (Younger Cohort N = 562) and born in September (Older Cohort N = 529). The authors compared studywide diagnosis rates of ADHD, ADHD familiality patterns, ADHD symptoms, psychiatric comorbidity, and functional impairments between the two cohorts. Results: Studywide rates of ADHD diagnosis, ADHD-associated symptoms, ADHD-associated impairments, ADHD-associated comorbid disorders, and familiality were similar in the two age cohorts. Conclusion: Results showed that ADHD-associated familial, clinical, and functional correlates are similar irrespective of age at entry to school, indicating that when ADHD symptoms are present, a diagnosis of ADHD should be considered rather than attributing these symptoms to developmental immaturity. C1 [Biederman, Joseph; Fried, Ronna] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Petty, Carter R.] Massachusetts Gen Hosp, Dept Psychopharmacol, Boston, MA 02114 USA. [Woodworth, K. Yvonne] Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02114 USA. [Woodworth, K. Yvonne] Massachusetts Gen Hosp, Adult ADHD Program, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU MGH Pediatric Psychopharmacology Council Fund FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the MGH Pediatric Psychopharmacology Council Fund. NR 17 TC 3 Z9 3 U1 0 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 EI 1557-1246 J9 J ATTEN DISORD JI J. Atten. Disord. PD APR PY 2014 VL 18 IS 3 BP 179 EP 185 DI 10.1177/1087054712445061 PG 7 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA AC0WE UT WOS:000332215400001 PM 22628145 ER PT J AU Soares, GMS Mendes, JAV Silva, MP Faveri, M Teles, R Socransky, SS Wang, X Figueiredo, LC Feres, M AF Soares, Geisla M. S. Mendes, Juliana A. V. Silva, Maike P. Faveri, Marcelo Teles, Ricardo Socransky, Sigmund S. Wang, Xiaoshan Figueiredo, Luciene C. Feres, Magda TI Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a secondary analysis of microbiological results from a randomized clinical trial SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontitis; amoxicillin; microbiology; chronic periodontitis; periodontal disease; metronidazole ID SYSTEMIC AMOXICILLIN/METRONIDAZOLE; AGGRESSIVE PERIODONTITIS; MICROBIAL COMPLEXES; THERAPY; DISEASE; BENEFITS; METAANALYSIS; PLAQUE AB Aim To evaluate the changes occurring in the subgingival microbial profile of subjects with generalized chronic periodontitis (ChP) treated by scaling and root planing (SRP) alone or with metronidazole (MTZ) or MTZ+amoxicillin (AMX). A secondary aim was to examine a possible added effect of chlorhexidine (CHX) to these therapies. Methods One hundred and eighteen subjects were randomly assigned to receive SRP-only or with MTZ [400mg/thrice a day (TID)] or MTZ+AMX (500mg/TID) for 14days. Half of the subjects in each group rinsed with 0.12% CHX twice a day (BID) for 2months. Nine subgingival plaque samples/subject were analysed by checkerboard DNA-DNA hybridization for 40 bacterial species at baseline, 3, 6 and 12months post-therapy. Results At 12months, the antibiotic-treated groups harboured lower mean counts and proportions of key periodontal pathogens than the SRP group (p<0.05). These benefits were observed at initially deep and shallow sites. Initial reductions in periodontal pathogens obtained with SRP partially rebound after 12months. CHX rinsing enhanced the microbiological effects of the MTZ+AMX treatment in shallow sites. Conclusion The adjunctive use of MTZ and MTZ+AMX results in a greater reduction in the levels of periodontal pathogens in generalized ChP subjects compared to SRP alone. C1 [Soares, Geisla M. S.; Mendes, Juliana A. V.; Silva, Maike P.; Faveri, Marcelo; Figueiredo, Luciene C.; Feres, Magda] Univ Guarulhos, Dept Periodontol, Dent Res Div, Sao Paulo, Brazil. [Teles, Ricardo; Socransky, Sigmund S.; Wang, Xiaoshan] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Teles, Ricardo] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Feres, M (reprint author), Univ Guarulhos, Ctr Posgrad & Pesquisa CEPPE, Praca Tereza Cristina,229 Ctr, BR-07023070 Guarulhos, SP, Brazil. EM mferes@ung.br RI Soares, Geisla/D-9778-2014; Feres, Magda/H-7964-2012 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil) [07/55291-9] FX The authors declare that they have no conflict of interests. This study was supported by Research Grant #07/55291-9 from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil). NR 31 TC 14 Z9 15 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 2014 VL 41 IS 4 BP 366 EP 376 DI 10.1111/jcpe.12217 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AC0II UT WOS:000332177600006 PM 24834504 ER PT J AU Hwang, DY Yagoda, D Perrey, HM Tehan, TM Guanci, M Ananian, L Currier, PF Cobb, JP Rosand, J AF Hwang, David Y. Yagoda, Daniel Perrey, Hilary M. Tehan, Tara M. Guanci, Mary Ananian, Lillian Currier, Paul F. Cobb, J. Perren Rosand, Jonathan TI Assessment of Satisfaction With Care Among Family Members of Survivors in a Neuroscience Intensive Care Unit SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article DE communication; consumer satisfaction; intensive care units; professional-family relations ID ICU; QUALITY; NEEDS; QUESTIONNAIRE; SUPPORT AB Many prior nursing studies regarding family members specifically of neuroscience intensive care unit (neuro-ICU) patients have focused on identifying their primary needs. A concept related to identifying these needs and assessing whether they have been met is determining whether families explicitly report satisfaction with the care that both they and their loved ones have received. The objective of this study was to explore family satisfaction with care in an academic neuro-ICU and compare results with concurrent data from the same hospital's medical ICU (MICU). Over 38 days, we administered the Family Satisfaction-ICU instrument to neuro-ICU and MICU patients' families at the time of ICU discharge. Those whose loved ones passed away during ICU admission were excluded. When asked about the respect and compassion that they received from staff, 76.3% (95% CI [66.5, 86.1]) of neuro-ICU families were completely satisfied, as opposed to 92.7% in the MICU (95% CI [84.4, 101.0], p = .04). Respondents were less likely to be completely satisfied with the courtesy of staff if they reported participation in zero formal family meeting. Less than 60% of neuro-ICU families were completely satisfied by (1) frequency of physician communication, (2) inclusion and (3) support during decision making, and (4) control over the care of their loved ones. Parents of patients were more likely than other relatives to feel very included and supported in the decision-making process. Future studies may focus on evaluating strategies for neuro-ICU nurses and physicians to provide better decision-making support and to implement more frequent family meetings even for those patients who may not seem medically or socially complicated to the team. Determining satisfaction with care for those families whose loved ones passed away during their neuro-ICU admission is another potential avenue for future investigation. C1 [Hwang, David Y.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Hwang, David Y.] Yale New Haven Med Ctr, Neurosci Intens Care Unit, New Haven, CT 06504 USA. [Yagoda, Daniel] Massachusetts Gen Hosp, Crit Care Ctr, Boston, MA 02114 USA. [Perrey, Hilary M.; Cobb, J. Perren] MGH, Crit Care Ctr, Boston, MA USA. [Tehan, Tara M.; Guanci, Mary; Rosand, Jonathan] MGH, Neurosci Intens Care Unit, Boston, MA USA. [Ananian, Lillian] MGH, Med Intens Care Unit, Boston, MA USA. [Currier, Paul F.; Cobb, J. Perren; Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Currier, Paul F.] MGH, Div Pulmonol & Crit Care, Boston, MA USA. [Currier, Paul F.] MGH, Resp Acute Care Unit, Boston, MA USA. [Currier, Paul F.] MGH, Dept Med, Boston, MA USA. [Rosand, Jonathan] MGH, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. RP Hwang, DY (reprint author), Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. EM david.hwang@yale.edu FU MGH Critical Care Center; MGH Neurosciences Intensive Care Research Fund; 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 Science, National Institutes of Health) [UL1 RR 025758]; Harvard University and its affiliated academic healthcare centers FX Conflicts of interest and sources of funding: This study was primarily supported by the MGH Critical Care Center and the MGH Neurosciences Intensive Care Research Fund. The authors have no relevant conflicts of interest to declare. Statistical analysis was also 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 Science, National Institutes of Health Award #UL1 RR 025758, 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 view of Harvard Catalyst, Harvard University, and its affiliated academic healthcare centers or the National Institutes of Health. NR 26 TC 7 Z9 7 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0888-0395 EI 1945-2810 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD APR PY 2014 VL 46 IS 2 BP 106 EP 116 DI 10.1097/JNN.0000000000000038 PG 11 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA AB9DM UT WOS:000332090000008 PM 24556658 ER PT J AU Bergman, BG Greene, MC Slaymaker, V Hoeppner, BB Kelly, JF AF Bergman, Brandon G. Greene, M. Claire Slaymaker, Valerie Hoeppner, Bettina B. Kelly, John F. TI Young adults with co-occurring disorders: substance use disorder treatment response and outcomes SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Co-occurring disorders; Dual diagnosis; Young adults; Emerging adults; Addiction; Substance use disorder treatment ID LEEDS-DEPENDENCE-QUESTIONNAIRE; DRUG-TREATMENT OUTCOMES; ABUSE TREATMENT; PSYCHOMETRIC VALIDATION; RESIDENTIAL-TREATMENT; SELF-EFFICACY; ALCOHOL; DEPRESSION; PSYCHOPATHOLOGY; ADOLESCENTS AB Compared to other life stages, young adulthood (ages 18-24) is characterized by qualitative differences including the highest rates of co-occurring substance use and psychiatric disorders (COD). Little is known, however, regarding young adults' response to substance use disorder (SUD) treatment, especially those with COD. Greater knowledge in this area could inform and enhance the effectiveness and efficiency of SUD care for this patient population. The current study investigated differences between 141 COD and 159 SUD-only young adults attending psychiatrically-integrated residential SUD treatment on intake characteristics, during-treatment changes on clinical targets (e.g., coping skills; abstinence self-efficacy), and outcomes during the year post-discharge. Contrary to expectations, despite more severe clinical profiles at intake, COD patients showed similar during-treatment improvements on clinical target variables, and comparable post-treatment abstinence rates and psychiatric symptoms. Clinicians referring young adults with COD to specialized care may wish to consider residential SUD treatment programs that integrate evidence-based psychiatric services. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bergman, Brandon G.; Greene, M. Claire; Hoeppner, Bettina B.; Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Bergman, Brandon G.; Hoeppner, Bettina B.; Kelly, John F.] Harvard Univ, Sch Med, Ctr Addict Med, Boston, MA USA. [Slaymaker, Valerie] Hazelden Fdn, Ctr City, MN USA. RP Bergman, BG (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM bgbergman@mgh.harvard.edu FU NIAAA NIH HHS [1R21AA018185-01A2, R21 AA018185]; NIDA NIH HHS [K01 DA027097, K01DA027097] NR 57 TC 4 Z9 4 U1 1 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2014 VL 46 IS 4 BP 420 EP 428 DI 10.1016/j.jsat.2013.11.005 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AC3OD UT WOS:000332430200003 PM 24484710 ER PT J AU Hafkin, JS Osborn, MK Localio, AR Amorosa, VK Kostman, JR Stern, JJ De LaTorre, P Mounzer, K Frank, I Gross, R Chang, KM Lo Re, V AF Hafkin, J. S. Osborn, M. K. Localio, A. R. Amorosa, V. K. Kostman, J. R. Stern, J. J. De LaTorre, P. Mounzer, K. Frank, I. Gross, R. Chang, K. -M. Lo Re, V., III TI Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE HIV; hepatitis B virus; lamivudine; HIV/hepatitis B virus co-infection; tenofovir ID CHRONIC HEPATITIS-B; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; NATURAL-HISTORY; INTERNATIONAL PANEL; DISOPROXIL-FUMARATE; COINFECTED PATIENTS; TREATMENT RESPONSE; HIV COINFECTION; 2008 UPDATE AB Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA >= 2.6 log IU/mL) at 1year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression. C1 [Hafkin, J. S.; Amorosa, V. K.; Kostman, J. R.; Stern, J. J.; Mounzer, K.; Frank, I.; Gross, R.; Lo Re, V., III] Univ Penn, Perelman Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Hafkin, J. S.; Localio, A. R.; Gross, R.; Lo Re, V., III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Hafkin, J. S.; Amorosa, V. K.; Gross, R.; Chang, K. -M.; Lo Re, V., III] Philadelphia Vet Affairs Med Ctr, Med Serv, Philadelphia, PA USA. [Osborn, M. K.] Emory Sch Med, Div Infect Dis, Dept Med, Atlanta, GA USA. [Kostman, J. R.; Lo Re, V., III] Penn Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA. [Stern, J. J.] Penn Hosp, Dept Med, Philadelphia, PA 19107 USA. [De LaTorre, P.] Cooper Univ Hosp, Dept Med, Div Infect Dis, Camden, NJ USA. [Mounzer, K.] Philadelphia Field Initiating Grp HIV Trials, Jonathan Lax Treatment Ctr, Philadelphia, PA USA. [Chang, K. -M.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU National Institutes of Health [K01 AI070001]; Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics [HS10399]; Penn Center for AIDS Research [P30 AI 045008] FX This work was supported by National Institutes of Health research grant K01 AI070001 [to V.L.R.], an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement (grant #HS10399) [to J.S.H., V.L.R., A.R.L. and R.G.] and the Penn Center for AIDS Research (P30 AI 045008). The funding sources played no role in study design or conduct, data collection, management, analysis or interpretation or in manuscript development. NR 47 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1352-0504 EI 1365-2893 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD APR PY 2014 VL 21 IS 4 BP 288 EP 296 DI 10.1111/jvh.12142 PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA AC1EU UT WOS:000332237800008 PM 24597697 ER PT J AU Andronesi, OC Bhat, H Reuter, M Mukherjee, S Caravan, P Rosen, BR AF Andronesi, Ovidiu C. Bhat, Himanshu Reuter, Martin Mukherjee, Shreya Caravan, Peter Rosen, Bruce R. TI Whole brain mapping of water pools and molecular dynamics with rotating frame MR relaxation using gradient modulated low-power adiabatic pulses SO NEUROIMAGE LA English DT Article DE Rotating frame relaxation (Tip; T2p); Macromolecular content; Correlation time; Exchange time; Bound water fraction; Neurodegeneration ID GENE-THERAPY; IN-VIVO; SELECTIVE EXCITATION; CHEMICAL-EXCHANGE; CEREBRAL-ISCHEMIA; T-1-RHO; CONTRAST; FIELD; GLIOMA; RAT AB Nuclear magnetic resonance (NMR) relaxation in the rotating frame is sensitive to molecular dynamics on the time scale of water molecules interacting with macromolecules or supramolecular complexes, such as proteins, myelin and cell membranes. Hence, longitudinal (Tip) and transverse (T2p) relaxation in the rotating frame may have a great potential to probe the macromolecular fraction of tissues. This stimulated a large interest in using this MR contrast to image brain under healthy and disease conditions. However, experimental challenges related to the use of intense radiofrequency irradiation have limited the widespread use of Tip and T2p imaging. Here, we present methodological development to acquire 3D high-resolution or 2D (multi-)slice selective Tip and T2p maps of the entire human brain within short acquisition times. These improvements are based on a class of gradient modulated adiabatic pulses that reduce the power deposition, provide slice selection, and mitigate artifacts resulting from inhomogeneities of B7 and Bo magnetic fields. Based on an analytical model of the Tlp and T2p relaxation we compute the maps of macromolecular bound water fraction, correlation and exchange time constants as quantitative biomarkers informative of tissue macromolecular content. Results obtained from simulations, phantoms and five healthy subjects are included. (C) 2013 Elsevier Inc. All rights reserved. C1 [Andronesi, Ovidiu C.; Mukherjee, Shreya; Caravan, Peter; Rosen, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. [Bhat, Himanshu] Siemens Med Solut USA Inc, Charlestown, MA 02129 USA. [Reuter, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Neur, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Andronesi, OC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM ovidiu@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU Harvard Clinical and Translational Science Center [8KL2TR000168-05]; National Cancer Institute of the National Institutes of Health [1K22 CA178269-01]; National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health; NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program [SlORR021110] FX Funding provided to O.C.A. by the KL2 MeRIT award from the Harvard Clinical and Translational Science Center (8KL2TR000168-05) and the K22 Career Development Award from the National Cancer Institute of the National Institutes of Health (1K22 CA178269-01) is acknowledged. Resources provided to Martinos Center by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health are also thanked. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program, specifically grant SlORR021110. Discussions with Dr. Michael Garwood, Dr. Shalom Michaeli, Dr. Silvia Mangia and Dr. Wolfgang Bogner are gratefully acknowledged. NR 51 TC 6 Z9 6 U1 0 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 APR 1 PY 2014 VL 89 BP 92 EP 109 DI 10.1016/j.neuroimage.2013.12.007 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AB8RJ UT WOS:000332057400009 PM 24345390 ER PT J AU Ruffini, G Fox, MD Ripolles, O Miranda, PC Pascual-Leone, A AF Ruffini, Giulio Fox, Michael D. Ripolles, Oscar Miranda, Pedro Cavaleiro Pascual-Leone, Alvaro TI Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields SO NEUROIMAGE LA English DT Article DE tCS; tDCS; tACS; Transcranial direct current stimulation; Transcranial alternating current stimulation; Electric fields; Targeted stimulation; Multifocal stimulation; Human head model; TES; NIBS; fMRI; PET; rs-fcMRI ID HUMAN MOTOR CORTEX; TREATMENT-RESISTANT DEPRESSION; BRAIN-STIMULATION; MAGNETIC STIMULATION; CONTROLLED-TRIAL; EXCITABILITY; CONNECTIVITY; HUMANS; MODULATION; EXCITATION AB Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). (c) 2013 Elsevier Inc. All rights reserved. C1 [Ruffini, Giulio] Starlab Barcelona, Barcelona 08022, Spain. [Ruffini, Giulio; Ripolles, Oscar; Miranda, Pedro Cavaleiro] Neuroelect Barcelona, Barcelona 08022, Spain. [Fox, Michael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp,Med Sch, Boston, MA USA. [Fox, Michael D.; Pascual-Leone, Alvaro] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Sch Med, Boston, MA 02215 USA. [Miranda, Pedro Cavaleiro] Univ Lisbon, Fac Ciencias, Inst Biofis & Engn Biomed, P-1749016 Lisbon, Portugal. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Univ Adscrit, Inst Guttmann, Hosp Neurorehabil, E-08193 Barcelona, Spain. RP Ruffini, G (reprint author), Starlab Barcelona, C Teodor Roviralta 45, Barcelona 08022, Spain. EM giulio.ruffini@starlab.es RI Miranda, Pedro/A-5643-2013; OI Miranda, Pedro/0000-0002-6793-8111; Ruffini, Giulio/0000-0003-3084-0177 FU EU FP7 FET Open HIVE project [FET-Open grant 222079] FX We are very grateful to Helen S. Mayberg for providing the PET data used in this paper. This work was partly supported by the EU FP7 FET Open HIVE project (FET-Open grant 222079) and by the Portuguese Foundation for Science and Technology (FCT). Work on this project was supported in part by Grant Number 8 UL1 TR000170, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science. NR 53 TC 49 Z9 49 U1 3 U2 25 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 APR 1 PY 2014 VL 89 BP 216 EP 225 DI 10.1016/j.neuroimage.2013.12.002 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AB8RJ UT WOS:000332057400019 PM 24345389 ER PT J AU Everett, CM Thorpe, CT Palta, M Carayon, P Gilchrist, VJ Smith, MA AF Everett, Christine M. Thorpe, Carolyn T. Palta, Mari Carayon, Pascale Gilchrist, Valerie J. Smith, Maureen A. TI The roles of primary care PAs and NPs caring for older adults with diabetes SO JAAPA-JOURNAL OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS LA English DT Article DE physician assistant; nurse practitioner; diabetes; primary care; patient-centered medical home; teams ID PHYSICIAN ASSISTANTS; NURSE-PRACTITIONERS; AMBULATORY CARE; UNITED-STATES; CHRONIC ILLNESS; ROLE-CONFLICT; MANAGEMENT; PERFORMANCE; FUTURE; TEAMS AB Electronic health record data linked with Medicare data from an academic physician group were used to propose a multidimensional characterization of PA and NP roles on panels of primary care patients with diabetes. Seven PA and NP roles were defined based on level of involvement, visits with complex patients, and delivery of chronic care. Findings suggest that PAs and NPs in primary care perform a variety of roles and frequently perform multiple roles within a clinic. C1 [Everett, Christine M.] Duke Univ, Sch Med, PA Program, Durham, NC 27708 USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Palta, Mari; Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Carayon, Pascale] Univ Wisconsin, Dept Ind & Syst Engn, Ctr Qual & Prod Improvement, Madison, WI 53706 USA. [Gilchrist, Valerie J.; Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Madison, WI 53706 USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. RP Everett, CM (reprint author), Duke Univ, Sch Med, PA Program, Durham, NC 27708 USA. FU Agency for Healthcare Research and Quality [R21 HS017646, R01 HS018368]; Health Innovation Program; Community-Academic Partnerships core of the University of Wisconsin Institute for [1UL1RR025011]; UW School of Medicine and Public Health from the Wisconsin Partnership Program; AHRQ/National Research Service [5-T32-HS00083]; American Academy of Physician Assistants' Breitman-Dorn Fellowship FX The authors disclose that funding for this project was provided by the Agency for Healthcare Research and Quality, grant numbers R21 HS017646 and R01 HS018368. Additional support was provided by the Health Innovation Program, which assisted with institutional review board application, Medicare data management, variable creation, and manuscript formatting; the 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; and the UW School of Medicine and Public Health from the Wisconsin Partnership Program. One author was supported by the AHRQ/National Research Service Award T-32 Institutional Training Program Grant Number: 5-T32-HS00083 and the American Academy of Physician Assistants' Breitman-Dorn Fellowship. No other funding source had a role in the design or conduct; data collection, management, analysis or interpretation; or preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. NR 43 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1547-1896 EI 0893-7400 J9 JAAPA-J AM ACAD PHYS JI JAAPA-J. Am. Acad. Physician Assist. PD APR PY 2014 VL 27 IS 4 BP 45 EP 49 DI 10.1097/01.JAA.0000444736.16669.76 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CM3GG UT WOS:000357569400013 PM 24662258 ER PT J AU Butler, J Fonarow, GC Zile, MR Lam, CS Roessig, L Schelbert, EB Shah, SJ Ahmed, A Bonow, RO Cleland, JGF Cody, RJ Chioncel, O Collins, SP Dunnmon, P Filippatos, G Lefkowitz, MP Marti, CN McMurray, JJ Misselwitz, F Nodari, S O'Connor, C Pfeffer, MA Pieske, B Pitt, B Rosano, G Sabbah, HN Senni, M Solomon, SD Stockbridge, N Teerlink, JR Georgiopoulou, VV Gheorghiade, M AF Butler, Javed Fonarow, Gregg C. Zile, Michael R. Lam, Carolyn S. Roessig, Lothar Schelbert, Erik B. Shah, Sanjiv J. Ahmed, Ali Bonow, Robert O. Cleland, John G. F. Cody, Robert J. Chioncel, Ovidiu Collins, Sean P. Dunnmon, Preston Filippatos, Gerasimos Lefkowitz, Martin P. Marti, Catherine N. McMurray, John J. Misselwitz, Frank Nodari, Savina O'Connor, Christopher Pfeffer, Marc A. Pieske, Burkert Pitt, Bertram Rosano, Giuseppe Sabbah, Hani N. Senni, Michele Solomon, Scott D. Stockbridge, Norman Teerlink, John R. Georgiopoulou, Vasiliki V. Gheorghiade, Mihai TI Developing Therapies for Heart Failure With Preserved Ejection Fraction Current State and Future Directions SO JACC-HEART FAILURE LA English DT Article DE epidemiology; heart failure; preserved ejection fraction; prognosis; treatment ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; VENTRICULAR DIASTOLIC DYSFUNCTION; CONVERTING ENZYME-INHIBITORS; PRIOR MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE LEVELS; SINGLE-BLIND TRIAL; EXERCISE CAPACITY; SYSTOLIC FUNCTION; ELDERLY-PATIENTS AB The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting. (C) 2014 by the American College of Cardiology Foundation C1 [Butler, Javed; Marti, Catherine N.; Georgiopoulou, Vasiliki V.] Emory Univ, Dept Med, Emory Cardiovasc Clin Res Inst, Atlanta, GA 30322 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Zile, Michael R.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Lam, Carolyn S.] Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore, Singapore. [Roessig, Lothar; Misselwitz, Frank] Bayer HealthCare, Global Clin Dev, Wuppertal, Germany. [Schelbert, Erik B.] Univ Pittsburgh, Dept Med, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Shah, Sanjiv J.; Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Dept Med, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Ahmed, Ali] Univ Alabama Birmingham, Div Gerontol, Birmingham, AL USA. [Cleland, John G. F.] Castle Hill Hosp, Hull York Med Sch, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Cody, Robert J.] Janssen Pharmaceut, Cardiovasc & Metab Div, Raritan, NJ USA. [Chioncel, Ovidiu] Inst Emergency Cardiovasc Dis, Cardiol, Bucharest, Romania. [Collins, Sean P.] Vanderbilt Univ, Dept Emergency Med, Nashville, TN 37235 USA. [Dunnmon, Preston; Stockbridge, Norman] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Filippatos, Gerasimos] Athens Univ Hosp, Dept Cardiol, Athens, Greece. [Lefkowitz, Martin P.] Novartis Pharmaceut Inc, E Hanover, NJ USA. [McMurray, John J.] Univ Glasgow, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland. [Nodari, Savina] Univ Brescia, Div Cardiol, Brescia, Italy. [O'Connor, Christopher] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Pieske, Burkert] Med Univ Graz, Dept Cardiol, Graz, Austria. [Pitt, Bertram] Univ Michigan, Sch Med, Dept Med, Div Cardiol, Ann Arbor, MI 48104 USA. [Rosano, Giuseppe] Ctr Clin & Basic Sci, Rome, Italy. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Senni, Michele] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Butler, J (reprint author), Emory Clin, Cardiovasc Res Inst, 1462 Clifton Rd Northeast,Suite AT 504, Atlanta, GA 30322 USA. EM javed.butler@emory.edu OI chioncel, ovidiu/0000-0002-3197-3628; Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975 FU NHLBI NIH HHS [U10 HL110302] NR 93 TC 66 Z9 67 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD APR PY 2014 VL 2 IS 2 BP 97 EP 112 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4CX UT WOS:000365647100002 PM 24720916 ER PT J AU Aytaman, A Fox, RK Nunez, M Jain, M Vispo, E Kikuchi, L Page, E Taylor, L Minguez, B Ventura, M Merchante, N Kaplan, DE Harris, M Klinker, H Hernandez, MD Hunt, KK Pineda, JA Nelson, M Barreiro, P Brau, N AF Aytaman, A. Fox, R. K. Nunez, M. Jain, M. Vispo, E. Kikuchi, L. Page, E. Taylor, L. Minguez, B. Ventura, M. Merchante, N. Kaplan, D. E. Harris, M. Klinker, H. Hernandez, M. D. Hunt, K. K. Pineda, J. A. Nelson, M. Barreiro, P. Braeu, N. CA Liver Canc HIV Study Grp TI IMPACT OF SCREENING ON SURVIVAL OF HEPATOCELLULAR CARCINOMA (HCC) IN HIV/HBV-COINFECTED PATIENTS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Aytaman, A.] VA New York Harbor HCS, Brooklyn, NY USA. [Aytaman, A.] SUNY Downstate Hlth Sci Ctr, Brooklyn, NY USA. [Fox, R. K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nunez, M.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Jain, M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Vispo, E.; Barreiro, P.] Hosp Carlos III, Madrid, Spain. [Kikuchi, L.] Univ Sao Paulo, Sao Paulo, Brazil. [Page, E.; Nelson, M.] Chelsea & Westminster Hosp, London, England. [Page, E.; Nelson, M.] Univ London Imperial Coll Sci Technol & Med, London, England. [Taylor, L.] Miriam Hosp, Providence, RI 02906 USA. [Taylor, L.] Brown Univ, Providence, RI 02912 USA. [Minguez, B.; Ventura, M.] Hosp Univ Vall dHebron, Barcelona, Spain. [Minguez, B.] CIBERehd, Barcelona, Spain. [Merchante, N.; Pineda, J. A.] Hosp Univ Valme, Seville, Spain. [Kaplan, D. E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kaplan, D. E.] Univ Penn, Philadelphia, PA 19104 USA. [Harris, M.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Harris, M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Klinker, H.] Univ Klinikum Wurzburg, Wurzburg, Germany. [Hernandez, M. D.] Univ Cincinnati, Cincinnati, OH USA. [Hunt, K. K.; Braeu, N.] JJP Vet Affairs Med Ctr, Bronx, NY USA. [Hunt, K. K.; Braeu, N.] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA. [Braeu, N.] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA. EM ayse.aytaman@va.gov NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P558 BP S255 EP S255 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700719 ER PT J AU Basu, PP Aloysius, M Shah, NJ AF Basu, P. P. Aloysius, M. Shah, N. J. TI RESTLESS LEG SYNDROME (RLS) IS ASSOCIATED WITH HEPATIC ENCEPHALOPATHY (HE) IN DECOMPENSATED CIRRHOSIS. A CLINICAL PILOT STUDY SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Basu, P. P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Basu, P. P.; Aloysius, M.] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, N. J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Bronx, NY USA. EM basu.patrick@gmail.com NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P528 BP S246 EP S246 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700689 ER PT J AU Basu, PP Aloysius, M Shah, NJ Brown, RS AF Basu, P. P. Aloysius, M. Shah, N. J. Brown, R. S., Jr. TI ROLE OF MYCOPHENOLATE MOFETIL (MMF) IN STEROID NON RESPONSIVE SEVERE ACUTE ALCOHOLIC HEPATITIS: A RANDOMIZED OPEN LABEL PLACEBO CONTROL PROSPECTIVE CLINICAL PILOT TRIAL - MASH TRIAL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Basu, P. P.; Brown, R. S., Jr.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Basu, P. P.; Aloysius, M.] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, N. J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Bronx, NY USA. EM basu.patrick@gmail.com NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P328 BP S175 EP S176 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700489 ER PT J AU Basu, PP Shah, NJ Aloysius, M Brown, RS AF Basu, P. P. Shah, N. J. Aloysius, M. Brown, R. S., Jr. TI BERBERINE WITH ALFA LIPOIC ACID (ALA) IN NON ALCOHOLIC STEATO-HEPATITIS (NASH). A RANDOMIZED DOUBLE BLINDED PLACEBO CONTROL TRIAL. A CLINICAL PILOT - THE BANISH TRIAL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Basu, P. P.; Brown, R. S., Jr.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Basu, P. P.; Aloysius, M.] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, N. J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Bronx, NY USA. EM basu.patrick@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2014 VL 60 IS 1 SU S MA P853 BP S356 EP S356 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5DT UT WOS:000362828600270 ER PT J AU Curry, MP Smith, L Chung, RT Schiano, TD Chapman, WC Mantry, PS Brown, KA Molrine, DC AF Curry, M. P. Smith, L. Chung, R. T. Schiano, T. D. Chapman, W. C. Mantry, P. S. Brown, K. A. Molrine, D. C. TI PERI-TRANSPLANT TREATMENT WITH ANTI-HCV E2 HUMAN MONOCLONAL ANTIBODY MBL-HCV1 IN COMBINATION WITH A PROTEASE INHIBITOR RESULTS IN UNDETECTABLE HCV RNA IN THE EARLY POST-TRANSPLANT PERIOD SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Curry, M. P.] Univ Massachusetts, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02125 USA. [Smith, L.; Molrine, D. C.] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02125 USA. [Chung, R. T.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Schiano, T. D.] Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA. [Chapman, W. C.] Washington Univ, Div Gen Surg, St Louis, MO USA. [Mantry, P. S.] Methodist Dallas Med Ctr, Liver Inst, Dallas, TX USA. [Brown, K. A.] Henry Ford Hlth Syst, Div Gastroenterol & Hepatol, Detroit, MI USA. EM mcurry@bidmc.harvard.edu NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P1161 BP S471 EP S471 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5DT UT WOS:000362828600577 ER PT J AU Dumontet, E Danger, R Vagefi, P Londono, MC Pallier, A Lozano, JJ Giral, M Degauque, N Martinez-Llordella, M Latournerie, M Boudjema, K Dulong, J Tarte, K Soulillou, JP Sanchez-Fueyo, A Feng, S Brouard, S Conchon, S AF Dumontet, E. Danger, R. Vagefi, P. Londono, M. -C. Pallier, A. Lozano, J. J. Giral, M. Degauque, N. Martinez-Llordella, M. Latournerie, M. Boudjema, K. Dulong, J. Tarte, K. Soulillou, J. -P. Sanchez-Fueyo, A. Feng, S. Brouard, S. Conchon, S. TI SPECIFIC PHENOTYPE AND GENE EXPRESSION PROFILES OF COMBINED LIVER AND KIDNEY TRANSPLANTED PATIENTS IN PERIPHERAL BLOOD MONONUCLEAR CELLS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Dumontet, E.; Danger, R.; Pallier, A.; Giral, M.; Degauque, N.; Soulillou, J. -P.; Brouard, S.; Conchon, S.] INSERM, U1064, Nantes, France. [Dumontet, E.; Giral, M.; Soulillou, J. -P.] Hop Hotel Dieu, Ctr Hosp Univ, Nantes, France. [Dumontet, E.; Giral, M.; Degauque, N.; Soulillou, J. -P.; Brouard, S.; Conchon, S.] Univ Nantes, Nantes, France. [Danger, R.; Martinez-Llordella, M.; Sanchez-Fueyo, A.] Kings Coll Hosp London, Inst Liver Studies, Kings Coll London, London SE5 8RX, England. [Vagefi, P.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Vagefi, P.] Harvard Univ, Sch Med, Boston, MA USA. [Londono, M. -C.; Lozano, J. J.; Martinez-Llordella, M.; Sanchez-Fueyo, A.] Hosp Clin Barcelona, Liver Unit, Barcelona, Spain. [Londono, M. -C.; Lozano, J. J.; Martinez-Llordella, M.; Sanchez-Fueyo, A.] Hosp Clin Barcelona, Bioinformat Platform, Barcelona, Spain. [Latournerie, M.; Boudjema, K.; Dulong, J.; Tarte, K.] Ctr Hosp Univ Pontchaillou, Rennes, France. [Dulong, J.; Tarte, K.] EFS Bretagne, Rennes, France. [Dulong, J.; Tarte, K.] INSERM, U917, Rennes, France. [Feng, S.] Univ Calif San Francisco, Dept Surg, Div Transplantat, San Francisco, CA USA. EM erwan.dumontet@etu.univ-nantes.fr NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P890 BP S371 EP S371 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5DT UT WOS:000362828600307 ER PT J AU Everson, GT Tran, TT Towner, WJ Davis, MN Wyles, D Nahass, R McNally, J Brainard, DM Han, L Doehle, B Mogalian, E Symonds, WT McHutchison, JG Morgan, T Chung, RT AF Everson, G. T. Tran, T. T. Towner, W. J. Davis, M. N. Wyles, D. Nahass, R. McNally, J. Brainard, D. M. Han, L. Doehle, B. Mogalian, E. Symonds, W. T. McHutchison, J. G. Morgan, T. Chung, R. T. TI SAFETY AND EFFICACY OF TREATMENT WITH THE INTERFERON-FREE, RIBAVIRIN-FREE COMBINATION OF SOFOSBUVIR + GS-5816 FOR 12 WEEKS IN TREATMENT NAIVE PATIENTS WITH GENOTYPE 1-6 HCV INFECTION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Everson, G. T.] Univ Colorado Denver, Aurora, CO USA. [Tran, T. T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Towner, W. J.] Kaiser Permanente, Los Angeles, CA USA. [Davis, M. N.] South Florida Ctr Gastroenterol LLC, Digest CARE, Wellington, FL USA. [Wyles, D.] Univ Calif San Diego, San Diego, CA 92103 USA. [Nahass, R.] ID CARE, Hillsborough, NJ USA. [McNally, J.; Brainard, D. M.; Han, L.; Doehle, B.; Mogalian, E.; Symonds, W. T.; McHutchison, J. G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Morgan, T.] VA Long Beach, Long Beach, CA USA. [Chung, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM greg.everson@ucdenver.edu NR 0 TC 19 Z9 19 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 APR PY 2014 VL 60 IS 1 SU S MA O111 BP S46 EP S46 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700112 ER PT J AU Mangia, A Marcellin, P Kwo, P Foster, GR Buti, M Brau, N Muir, A Yang, JC Mo, H Ding, X Pang, PS Symonds, WT McHutchison, JG Zeuzem, S Afdhal, N AF Mangia, A. Marcellin, P. Kwo, P. Foster, G. R. Buti, M. Braeu, N. Muir, A. Yang, J. C. Mo, H. Ding, X. Pang, P. S. Symonds, W. T. McHutchison, J. G. Zeuzem, S. Afdhal, N. TI ALL ORAL FIXED-DOSE COMBINATION SOFOSBUVIR/LEDIPASVIR WITH OR WITHOUT RIBAVIRIN FOR 12 OR 24 WEEKS IN TREATMENT-NAIVE GENOTYPE 1 HCV-INFECTED PATIENTS: THE PHASE 3 ION-1 STUDY SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Mangia, A.] Osped Casa Sollievo Sofferenza, Unita Epatol, Foggia, Italy. [Marcellin, P.] Hop Beaujon, Serv Hepatol, Ile De France, France. [Kwo, P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Foster, G. R.] Barts Hlth NHS Trust, Royal London Hosp, London, England. [Foster, G. R.] Ambrose King Cent, Grahame Hayton Unit, London, England. [Buti, M.] Hosp Univ Vall dHebron, Barcelona, Spain. [Braeu, N.] Bronx Vet Affairs Med Ctr, Bronx, NY USA. [Muir, A.] Duke Univ, Durham, NC USA. [Yang, J. C.; Mo, H.; Ding, X.; Pang, P. S.; Symonds, W. T.; McHutchison, J. G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Zeuzem, S.] Klinikum Johann Wolfgang Goethe Univ, Med Klin 1, Frankfurt, Germany. [Afdhal, N.] Beth Israel Deaconess Med Ctr, Boston, MA USA. EM a.mangia@tin.it NR 0 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 APR PY 2014 VL 60 IS 1 SU S MA O164 BP S523 EP S524 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5DT UT WOS:000362828600715 ER PT J AU Merchante, N Minguez, B Tural, C Kikuchi, L Rodriguez-Arrondo, F Chen, TY Ventura, M Harris, M Daruich, J Kaplan, DE Merino, E Silva, MF Rockstroh, J Munoz, J Jover, F Klinker, H Delgado-Fernandez, M Marcus, S Aberg, J Pineda, JA Sherman, M Hoshida, Y Marrero, J Brau, N AF Merchante, N. Minguez, B. Tural, C. Kikuchi, L. Rodriguez-Arrondo, F. Chen, T-Y. Ventura, M. Harris, M. Daruich, J. Kaplan, D. E. Merino, E. Silva, M. F. Rockstroh, J. Munoz, J. Jover, F. Klinker, H. Delgado-Fernandez, M. Marcus, S. Aberg, J. Pineda, J. A. Sherman, M. Hoshida, Y. Marrero, J. Braeu, N. CA Liver Canc HIV Study Grp TI PREDICTING SURVIVAL OF HIV-INFECTED PATIENTS WITH LIVER CANCER - THE SHILCA SCORE AND STAGING MODEL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Merchante, N.; Pineda, J. A.] Hosp Univ Valme, Seville, Spain. [Merchante, N.; Delgado-Fernandez, M.; Pineda, J. A.] SAEI, Grp Andaluz Estudio Hepatitis Vir HEPAVIR, Seville, Spain. [Minguez, B.; Ventura, M.] Hosp Univ Vall dHebron, Barcelona, Spain. [Minguez, B.] CIBERehd, Barcelona, Spain. [Tural, C.] Hosp Badalona Germans Trias & Pujol, Badalona, Spain. [Kikuchi, L.] Univ Sao Paulo, Sao Paulo, Brazil. [Rodriguez-Arrondo, F.] Hosp Univ Donostia, San Sebastian, Spain. [Rodriguez-Arrondo, F.; Munoz, J.] Soc Enfermedades Infecciosas Norte SEINORTE, Pamplona, Spain. [Chen, T-Y.; Marrero, J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Harris, M.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Harris, M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Daruich, J.] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Kaplan, D. E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kaplan, D. E.] Univ Penn, Philadelphia, PA 19104 USA. [Merino, E.] Hosp Gen Univ Alicante, Alicante, Spain. [Merino, E.; Jover, F.] SEICV, Valencia, Spain. [Silva, M. F.] Univ Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, Brazil. [Rockstroh, J.] Univ Bonn, Bonn, Germany. [Munoz, J.] Hosp Basurto, Bilbao, Spain. [Jover, F.] Hosp Clin Univ San Juan, Alicante, Spain. [Klinker, H.] Univ Klinikum Wurzburg, Wurzburg, Germany. [Delgado-Fernandez, M.] Hosp Reg Carlos Haya, Malaga, Spain. [Marcus, S.; Braeu, N.] JJP Vet Affairs Med Ctr, Bronx, NY USA. [Aberg, J.] Bellevue Hosp Ctr, New York, NY 10016 USA. [Aberg, J.] NYU, Sch Med, New York, NY USA. [Sherman, M.] Toronto Gen Hosp, Toronto, ON, Canada. [Sherman, M.] Univ Toronto, Toronto, ON, Canada. [Hoshida, Y.; Braeu, N.] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA. [Braeu, N.] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA. EM norbert.brau@va.gov NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR PY 2014 VL 60 IS 1 SU S MA O35 BP S15 EP S15 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700036 ER PT J AU Park, JJ Wong, DK Wahed, AS Lee, WM Feld, JJ Terrault, N Khalili, M Kowdley, KV Lau, DT Sterling, RK Kim, WR Smith, C Carithers, R Levine, DL Keith, J Valiga, ME Lok, ASF Chang, KM AF Park, J. -J. Wong, D. K. Wahed, A. S. Lee, W. M. Feld, J. J. Terrault, N. Khalili, M. Kowdley, K. V. Lau, D. T. Sterling, R. K. Kim, W. R. Smith, C. Carithers, R. Levine, D. L. Keith, J. Valiga, M. E. Lok, A. S. F. Chang, K. -M. TI IMMUNE CORRELATES OF VACCINE-MEDIATED PROTECTIVE IMMUNITY VERSUS VIRAL PERSISTENCE IN HEPATITIS B VIRUS INFECTION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Park, J. -J.; Levine, D. L.; Keith, J.; Valiga, M. E.; Chang, K. -M.] Univ Penn, Philadelphia, PA 19104 USA. [Park, J. -J.; Levine, D. L.; Keith, J.; Valiga, M. E.; Chang, K. -M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Wong, D. K.; Feld, J. J.] Univ Toronto, Toronto, ON, Canada. [Wahed, A. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Lee, W. M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Terrault, N.] Div Gastroenterol, San Francisco, CA USA. [Khalili, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kowdley, K. V.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Lau, D. T.] Harvard Univ, Div Gastroenterol, Boston, MA 02115 USA. [Sterling, R. K.] Virginia Commonwealth Univ, Richmond, VA USA. [Kim, W. R.] Mayo Clin Rochester, Rochester, MN USA. [Smith, C.] Mayo Clin, Rochester, MN USA. [Smith, C.] Univ Minnesota, Plymouth, MN USA. [Carithers, R.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Lok, A. S. F.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA. EM kmchang@mail.med.upenn.edu NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P163 BP S120 EP S120 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700324 ER PT J AU Tarantino, L Sabbatino, F Ambrosino, P Iovino, V Cuccorese, G Giordano, R AF Tarantino, L. Sabbatino, F. Ambrosino, P. Iovino, V. Cuccorese, G. Giordano, R. TI REPEATED LOCO-REGIONAL TREATMENTS IN CASE OF RECURRENCES FROM HEPATOCELLULAR CARCINOMA: 10 YEARS EXPERIENCE IN A LARGE SERIES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Tarantino, L.] A Tortora Hosp ASL Salerno, Dept Surg, Intervent Hepatol Unit, Torre Del Greco, Italy. [Sabbatino, F.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Ambrosino, P.] Dept Clin & Expt Med, Naples, Italy. [Iovino, V.] A Tortora Hosp ASL SalernoTortora, Oncol, Pagani, Italy. [Cuccorese, G.] Di Miccoli Hosp, Med, Barletta, Italy. [Giordano, R.] A Tortora Hosp ASL Salerno, DPT Surg, Pagani, Italy. EM luciano_tarantino@fastwebnet.it NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P987 BP S404 EP S404 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5DT UT WOS:000362828600403 ER PT J AU Walker, A Skibbe, K Megger, DA Kuntzen, T Groten, S Lauer, GM Kim, AY Sitek, B Allen, TM Timm, J AF Walker, A. Skibbe, K. Megger, D. A. Kuntzen, T. Groten, S. Lauer, G. M. Kim, A. Y. Sitek, B. Allen, T. M. Timm, J. TI DISTINCT ESCAPE PATHWAY BY HCV GENOTYPE 1A FROM A DOMINANT CD8(+) T CELL RESPONSE BY SELECTION OF ALTERED EPITOPE PROCESSING SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 09-13, 2014 CL London, ENGLAND SP European Assoc Study Liver C1 [Walker, A.; Skibbe, K.; Groten, S.; Timm, J.] Univ Duisburg Essen, Inst Virol, Univ Hosp Essen, Essen, Germany. [Megger, D. A.; Sitek, B.] Ruhr Univ Bochum, Med Proteom Ctr, Bochum, Germany. [Kuntzen, T.] Univ Hosp Zurich USZ, Dept Gastroenterol & Hepatol, Zurich, Switzerland. [Lauer, G. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Kim, A. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dieases Unit, Boston, MA USA. [Allen, T. M.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. EM andreas.walker@uk-essen.de NR 0 TC 0 Z9 0 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 APR PY 2014 VL 60 IS 1 SU S MA P222 BP S140 EP S140 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3HB UT WOS:000361961700383 ER PT J AU Hage, FG AlJaroudi, W AF Hage, Fadi G. AlJaroudi, Wael TI Review of Cardiovascular Literature SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material C1 [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. [AlJaroudi, Wael] Amer Univ Beirut, Med Ctr, Div Cardiovasc Med Cardiovasc Imaging, Beirut, Lebanon. RP AlJaroudi, W (reprint author), Amer Univ Beirut, Med Ctr, Div Cardiovasc Med Cardiovasc Imaging, Beirut, Lebanon. EM wjaroudi@hotmail.com OI Hage, Fadi/0000-0002-1397-4942 NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2014 VL 21 IS 2 BP 229 EP 232 DI 10.1007/s12350-013-9839-3 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V42GV UT WOS:000209603200002 ER EF