FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zhang, JH Dodson, M Liang, QL Benavides, G Darley-Usmar, VM AF Zhang, Jianhua Dodson, Matthew Liang, Qiuli Benavides, Gloria Darley-Usmar, Victor M. TI Autophagy in neuronal bioenergetics and survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Zhang, Jianhua; Dodson, Matthew; Liang, Qiuli; Benavides, Gloria; Darley-Usmar, Victor M.] Univ Alabama Birmingham, Ctr Free Radical Biol & Med, Birmingham, AL USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1086.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504007 ER PT J AU Zou, L Li, Y Feng, Y Zhang, M Chen, C Chao, W AF Zou, Lin Li, Yan Feng, Yan Zhang, Ming Chen, Chan Chao, Wei TI Interplay between complement factor B and Toll-like receptors and its role in septic cardiomyopathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Zou, Lin; Li, Yan; Feng, Yan; Zhang, Ming; Chen, Chan; Chao, Wei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 652.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504441 ER PT J AU Barnes, JA Jacobsen, E Feng, Y Freedman, A Hochberg, EP LaCasce, AS Armand, P Joyce, R Sohani, AR Rodig, SJ Neuberg, D Fisher, DC Abramson, JS AF Barnes, Jeffrey A. Jacobsen, Eric Feng, Yang Freedman, Arnold Hochberg, Ephraim P. LaCasce, Ann S. Armand, Philippe Joyce, Robin Sohani, Aliyah R. Rodig, Scott J. Neuberg, Donna Fisher, David C. Abramson, Jeremy S. TI Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma SO HAEMATOLOGICA LA English DT Article ID RAPAMYCIN INHIBITION; TISSUE MICROARRAY; MAMMALIAN TARGET; PHASE-II; TEMSIROLIMUS AB Diffuse large B-cell lymphoma is an aggressive non-Hodgkin's lymphoma without a standard therapy for patients who relapse after or are not eligible for salvage autologous stem cell transplantation. In vitro analysis of lymphoma cell lines has shown that everolimus can inhibit cell cycle progression in vitro and inhibitors of the mammalian target of rapamycin have already demonstrated single-agent activity in relapsed non-Hodgkin's lymphomas including diffuse large B-cell lymphoma, validating mammalian target of rapamycin as a viable therapeutic target. We performed an open label phase II study of everolimus, an inhibitor of mammalian target of rapamycin, in combination with rituximab to examine efficacy and tolerability in patients with relapsed/refractory diffuse large B-cell lymphoma. Eligible patients were treated with everolimus 10 mg by mouth once daily on days 1-28 of a 28-day cycle with rituximab administered weekly during cycle one and then on day one of subsequent cycles. Patients were treated for a total of 12 cycles or until disease progression. The primary end-point was objective response rate, with secondary end-points being toxicity, progression-free survival, duration of response, and overall survival. Twenty-six patients (24 evaluable) were enrolled and had an overall response rate of 38% [90% CI (21%-56%)] with three complete responses and six partial responses among these 24 patients. The median duration of response among responders was 8.1 months. At a median follow-up of 12 months, the overall survival rate was 37% [90% CI (20%-54%)]. The most common grade 3 to 4 toxicities were neutropenia, anemia, and thrombocytopenia. In conclusion, everolimus in combination with rituximab is well tolerated and demonstrates activity in relapsed diffuse large B-cell lymphoma. Further studies of this combination are warranted. C1 [Barnes, Jeffrey A.; Hochberg, Ephraim P.; Sohani, Aliyah R.; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Jacobsen, Eric; Feng, Yang; Freedman, Arnold; LaCasce, Ann S.; Armand, Philippe; Neuberg, Donna; Fisher, David C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joyce, Robin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Barnes, Jeffrey A.; Jacobsen, Eric; Freedman, Arnold; Hochberg, Ephraim P.; LaCasce, Ann S.; Armand, Philippe; Joyce, Robin; Sohani, Aliyah R.; Rodig, Scott J.; Fisher, David C.; Abramson, Jeremy S.] Harvard Univ, Sch Med, Boston, MA USA. RP Barnes, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM jabarnes@partners.org FU Novartis, Inc. FX This work was funded in part by Novartis, Inc. NR 11 TC 20 Z9 24 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD APR PY 2013 VL 98 IS 4 BP 615 EP 619 DI 10.3324/haematol.2012.075184 PG 5 WC Hematology SC Hematology GA 157LN UT WOS:000319897700030 PM 23144193 ER PT J AU Chen, YH Chauhan, SK Lee, HS Stevenson, W Schaumburg, CS Sadrai, Z Saban, DR Kodati, S Stern, ME Dana, R AF Chen, Yihe Chauhan, Sunil K. Lee, Hyun Soo Stevenson, William Schaumburg, Chris S. Sadrai, Zahra Saban, Daniel R. Kodati, Shilpa Stern, Michael E. Dana, Reza TI Effect of Desiccating Environmental Stress Versus Systemic Muscarinic AChR Blockade on Dry Eye Immunopathogenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE dry eye disease; controlled-environment chamber; scopolamine; CD4+T-cells ID REGULATORY T-CELLS; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC SYSTEM; SJOGRENS-SYNDROME; MOUSE MODEL; IN-VITRO; DISEASE; EXPRESSION; TH17; KERATOCONJUNCTIVITIS AB PURPOSE. A majority of experimental data on dry eye disease (DED) immunopathogenesis have been derived from a murine model of DED that combines desiccating environmental stress with systemic muscarinic acetylcholine receptor (mAChR) inhibition. However, to our knowledge the effects of pharmacologic mAChR blockade on the pathogenesis of experimental DED have not been evaluated systemically. The purpose of our study was to investigate the differential effects of desiccating environmental stress and mAChR inhibition on the pathogenesis of DED. METHODS. DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled-environment chamber or to systemic scopolamine, or by performing extraorbital lacrimal gland excision. Clinical disease was assessed using corneal fluorescein staining (CFS) and the cotton thread test (CTT). Corneal CD11b(+) and conjunctival CD3(+) T-cell infiltration were evaluated by flow cytometry. T-cells from draining cervical lymph nodes (CLN) and distant inguinal lymph nodes (ILN) were analyzed for Th1, Th2, Th17, and Treg responses by flow cytometry and ELISA. RESULTS. Desiccating environmental stress and systemic mAChR blockade induced similar clinical signs of DED. However, desiccating environmental stress imparted higher conjunctival CD3(+) T-cell infiltration, and greater Th17-cell activity and Treg dysfunction than mAChR blockade, while mAChR blockade decreased tear secretion to a greater extent than desiccating environmental stress. Systemic mAChR blockade attenuated Th17 activity and enhanced Th2 and Treg responses without affecting Th1 activity. CONCLUSIONS. In vivo inhibition of mAChRs variably affects CD4(+) T-cell subsets, and desiccating environmental stress and systemic mAChR blockade induce DED through different primary pathogenic mechanisms. C1 [Chen, Yihe; Chauhan, Sunil K.; Lee, Hyun Soo; Stevenson, William; Sadrai, Zahra; Saban, Daniel R.; Kodati, Shilpa; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Schaumburg, Chris S.; Stern, Michael E.] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU NIH [EY20889]; Allergan, Inc. FX Supported by NIH Grant EY20889 and Allergan, Inc. NR 31 TC 13 Z9 15 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2013 VL 54 IS 4 BP 2457 EP 2464 DI 10.1167/iovs.12-11121 PG 8 WC Ophthalmology SC Ophthalmology GA 156KV UT WOS:000319821700007 PM 23482465 ER PT J AU Colby, K AF Colby, Kathryn TI Medical Treatment of Fuchs' Dystrophy in our Lifetime? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Colby, K (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM KAColby@meei.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2013 VL 54 IS 4 BP 2503 EP 2503 DI 10.1167/iovs.13-12034 PG 1 WC Ophthalmology SC Ophthalmology GA 156KV UT WOS:000319821700012 ER PT J AU Kang, MH Oh, DJ Kang, JH Rhee, DJ AF Kang, Min Hyung Oh, Dong-Jin Kang, Ja-heon Rhee, Douglas J. TI Regulation of SPARC by Transforming Growth Factor beta 2 in Human Trabecular Meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE SPARC; matricellular proteins; TGF-beta 2; Smad3; p38 ID PIGMENT EPITHELIAL-CELLS; OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR; INTRAOCULAR-PRESSURE; KINASE PATHWAY; HUMAN EYES; TGF-BETA-2; EXPRESSION; FIBROSIS; COLLAGEN AB PURPOSE. An increased aqueous level of TGF-beta 2 has been found in many primary open-angle glaucoma patients. Secreted Protein, Acidic, and Rich in Cysteine (SPARC)-null mice have a lower intraocular pressure. The mechanistic relationship between SPARC and TGF-beta 2 in trabecular meshwork (TM) is unknown. We hypothesized that TGF-beta 2 upregulates SPARC expression in TM. METHODS. Cultured TM cells were incubated with selective inhibitors for p38 MAP kinase (p38), Smad3, p42, JNK, RhoA, PI3K, or TGF-beta 2 receptor for 2 hours, and then TGF-beta 2 was added for 24 hours in serum-free media. Quantitative polymerase chain reaction (qPCR)and immunoblot analysis were performed. Immunofluorescent microscopy was used to determine nuclear translocation of signaling proteins. Ad5.hSPARC and Lentiviral shRNA for p38 and Smad3 were constructed, and infected human TM cells. RESULTS. SPARC was upregulated by TGF-beta 2 in the human TM cells (3.8 +/- 1.7-fold, n = 6, P = 0.01 for protein and 7.1 +/- 3.7-fold, n = 6, P = 0.01 for mRNA), while upregulation of SPARC had no effect on TGF-beta 2. TGF-beta 2-induced SPARC expression was suppressed by inhibitors against p38 (-40.3 +/- 20.9%, n = 10, P = 0.0001), Smad3 (-56.2 +/- 18.9%, n = 10, P = 0.0001), JNK (-49.1 +/- 24.6%, n = 10, P = 0.0001), and TGF-beta 2 receptor (-83.6 +/- 14.4%, n = 6, P = 0.003). Phosphorylation and translocation of Smad3, p38, and MAPKAPK2 were detected at 30 minutes and 1 hour, respectively, following TGF-beta 2 treatment. Phosphorylation of JNK and c-jun was detected before TGF-beta 2 treatment. SPARC was suppressed 31 +/- 13% (n = 5, P < 0.0001) by shRNA-p38 and 41 +/- 3% (n = 5, P < 0.0001) by shRNA-Smad3. CONCLUSIONS. TGF-beta 2 upregulates SPARC expression in human TM through Smad-dependent (Smad2/3) or -independent (p38) signaling pathways. SPARC may be a downstream regulatory node of TGF-beta 2-mediated IOP elevation. C1 [Kang, Min Hyung; Oh, Dong-Jin; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kang, Ja-heon] Kyung Hee Univ Hosp Gangdong, Dept Ophthalmol, Seoul, South Korea. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU American Glaucoma Society Mid-Career Award, Massachusetts Lions Eye Research Fund, National Eye Institute [EY 019654-01, EY14104] FX Supported by American Glaucoma Society Mid-Career Award, Massachusetts Lions Eye Research Fund, National Eye Institute, EY 019654-01 (DJR) and EY14104 (MEEI Vision-Core Grant). NR 37 TC 14 Z9 14 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2013 VL 54 IS 4 BP 2523 EP 2532 DI 10.1167/iovs.12-11474 PG 10 WC Ophthalmology SC Ophthalmology GA 156KV UT WOS:000319821700015 PM 23513064 ER PT J AU Liu, SH Kam, WR Ding, J Hatton, MP Sullivan, DA AF Liu, Shaohui Kam, Wendy R. Ding, Juan Hatton, Mark P. Sullivan, David A. TI Effect of Growth Factors on the Proliferation and Gene Expression of Human Meibomian Gland Epithelial Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE meibomian gland; growth factors; gene expression ID SERUM-FREE CULTURE; PEROXISOME-PROLIFERATOR; ACTIVATED RECEPTORS; SEBACEOUS GLAND; CLONAL GROWTH; CYCLE REGULATION; MODEL; DIFFERENTIATION; KERATINIZATION; PITUITARY AB PURPOSE. We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. METHODS. Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF + BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. RESULTS. Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. CONCLUSIONS. Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis. C1 [Liu, Shaohui; Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.] Schepens Eye Res Inst, Boston, MA 02114 USA. [Liu, Shaohui; Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA USA. RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu RI Ding, Juan/L-5149-2013 FU NIH [EY05612]; Alcon Research, Ltd. FX Supported by grants from NIH (EY05612) and Alcon Research, Ltd. NR 54 TC 14 Z9 14 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2013 VL 54 IS 4 BP 2541 EP 2550 DI 10.1167/iovs.12-11221 PG 10 WC Ophthalmology SC Ophthalmology GA 156KV UT WOS:000319821700017 PM 23493293 ER PT J AU Li, D Jiao, J Shatos, MA Hodges, RR Dartt, DA AF Li, Dayu Jiao, Jianwei Shatos, Marie A. Hodges, Robin R. Dartt, Darlene A. TI Effect of VIP on Intracellular [Ca2+], Extracellular Regulated Kinase 1/2, and Secretion in Cultured Rat Conjunctival Goblet Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE goblet cells; conjunctiva; ERK; intracellular Ca2+ ID VASOACTIVE INTESTINAL POLYPEPTIDE; DEPENDENT PROTEIN-KINASE; CHOLINERGIC AGONISTS; RECEPTOR SUBTYPES; ACINAR-CELLS; CYCLIC-AMP; CAMP; CALCIUM; PATHWAY; EGF AB PURPOSE. To determine the intracellular signaling pathways that vasoactive intestinal peptide (VIP) uses to stimulate high molecular weight glycoconjugate secretion from cultured rat conjunctival goblet cells. METHODS. Goblet cells from rat bulbar and forniceal conjunctiva were grown in organ culture. Presence and localization of VIP receptors (VPAC1 and 2) were determined by RT-PCR, immunofluorescence microscopy and Western blot analysis. Intracellular [Ca2+] ([Ca2+](i)) was measured using fura-2. Extracellular signal-regulated kinase (ERK)-1/2 activity was determined by Western blot analysis. High molecular weight glycoconjugate secretion was measured with an enzyme-linked lectin assay on cultured goblet cells that were serum-starved for 2 hours before stimulation with VIP, VPAC1-, or VPAC2-specific agonists. Inhibitors were added 30 minutes prior to VIP. Activation of epidermal growth factor receptor (EGFR) was measured by immunoprecipitation using an antibody against pTyr followed by Western blot analysis with an antibody against EGFR. RESULTS. Both VIP receptors were present in rat conjunctiva and cultured goblet cells. VIP- and VPAC-specific agonists increased [Ca2+](i) and secretion in a concentration-dependent manner. VIP also increased ERK1/2 activity, VIP- stimulated increase in [Ca2+](i). Secretion, but not ERK1/2 activity, was inhibited by the protein kinase A inhibitor, H89. VIP-stimulated secretion was inhibited by siRNA for ERK2 but not by siRNA for EGFR. VIP did not increase the phosphorylation of the EGFR. CONCLUSIONS. In conclusion, in cultured rat conjunctival goblet cells, VPAC1 and 2 receptors are functional. VIP stimulates a cAMP-dependent increase in [Ca2+](i) and glycoconjugate secretion, but not ERK1/2 activation. VIP does not activate with EGFR. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dartt, DA (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM darlene.dartt@schepens.harvard.edu RI Jiao, Jianwei/I-1452-2013 OI Jiao, Jianwei/0000-0002-7893-0721 FU NIH [EY019470, EY09570] FX Supported by NIH EY019470 and EY09570. The authors alone are responsible for the content and writing of the paper. NR 32 TC 8 Z9 8 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2013 VL 54 IS 4 BP 2872 EP 2884 DI 10.1167/iovs.12-11264 PG 13 WC Ophthalmology SC Ophthalmology GA 156KV UT WOS:000319821700056 PM 23518767 ER PT J AU Woodward, MJ Patton, SC Olsen, SA Jones, JM Reich, CM Blackwell, N Beck, JG AF Woodward, Matthew J. Patton, Samantha C. Olsen, Shira A. Jones, Judiann M. Reich, Catherine M. Blackwell, Nathali Beck, J. Gayle TI How do attachment style and social support contribute to women's psychopathology following intimate partner violence? Examining clinician ratings versus self-report SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Attachment style; Social support; Psychopathology; Intimate partner violence ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; VEHICLE ACCIDENT SURVIVORS; DEPRESSION-INVENTORY-II; DSM-IV ANXIETY; PSYCHOMETRIC PROPERTIES; ADULT ATTACHMENT; MULTIDIMENSIONAL SCALE; SEXUAL-ABUSE; PSYCHOLOGICAL DISTRESS AB Concurrent associations between attachment style and social support in posttraumatic stress disorder, depression, and generalized anxiety disorder were explored using regression analyses in a sample of 108 victims of intimate partner violence. To examine whether assessment modality influenced findings, self-report and clinician ratings of psychopathology were compared. Both lower perceived social support and higher attachment anxiety were significantly associated with higher self-reported PTSD; however, only lower social support was significantly associated with clinician assessed PTSD. Lower social support, higher attachment anxiety, and lower attachment closeness were related with higher self-reported depression; however, only lower social support was related to clinician assessed depression. Lastly, only higher attachment anxiety was associated with self-reported GAD, whereas lower attachment dependency showed the only significant association in clinician assessed GAD. Possible explanations for discrepancies between assessment modalities are discussed, with emphasis on application to intimate partner violence and suggestions for future research. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Woodward, Matthew J.; Jones, Judiann M.; Reich, Catherine M.; Beck, J. Gayle] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Patton, Samantha C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Olsen, Shira A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Blackwell, Nathali] Univ Memphis, Dept Social Work, Memphis, TN 38152 USA. RP Woodward, MJ (reprint author), Univ Memphis, Dept Psychol, 400 Innovation Dr, Memphis, TN 38152 USA. EM mjwdward@memphis.edu NR 65 TC 5 Z9 5 U1 6 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2013 VL 27 IS 3 BP 312 EP 320 DI 10.1016/j.janxdis.2013.02.007 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 156AQ UT WOS:000319792800007 PM 23602945 ER PT J AU Klann, JG Murphy, SN AF Klann, Jeffrey G. Murphy, Shawn N. TI Computing Health Quality Measures Using Informatics for Integrating Biology and the Bedside SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE medical informatics; healthcare quality assessment; reimbursement; incentive; systems integration; database management systems ID MEANINGFUL USE AB Background: The Health Quality Measures Format (HQMF) is a Health Level 7 (HL7) standard for expressing computable Clinical Quality Measures (CQMs). Creating tools to process HQMF queries in clinical databases will become increasingly important as the United States moves forward with its Health Information Technology Strategic Plan to Stages 2 and 3 of the Meaningful Use incentive program (MU2 and MU3). Informatics for Integrating Biology and the Bedside (i2b2) is one of the analytical databases used as part of the Office of the National Coordinator (ONC)' s Query Health platform to move toward this goal. Objective: Our goal is to integrate i2b2 with the Query Health HQMF architecture, to prepare for other HQMF use-cases (such as MU2 and MU3), and to articulate the functional overlap between i2b2 and HQMF. Therefore, we analyze the structure of HQMF, and then we apply this understanding to HQMF computation on the i2b2 clinical analytical database platform. Specifically, we develop a translator between two query languages, HQMF and i2b2, so that the i2b2 platform can compute HQMF queries. Methods: We use the HQMF structure of queries for aggregate reporting, which define clinical data elements and the temporal and logical relationships between them. We use the i2b2 XML format, which allows flexible querying of a complex clinical data repository in an easy-to-understand domain-specific language. Results: The translator can represent nearly any i2b2-XML query as HQMF and execute in i2b2 nearly any HQMF query expressible in i2b2-XML. This translator is part of the freely available reference implementation of the QueryHealth initiative. We analyze limitations of the conversion and find it covers many, but not all, of the complex temporal and logical operators required by quality measures. Conclusions: HQMF is an expressive language for defining quality measures, and it will be important to understand and implement for CQM computation, in both meaningful use and population health. However, its current form might allow complexity that is intractable for current database systems (both in terms of implementation and computation). Our translator, which supports the subset of HQMF currently expressible in i2b2-XML, may represent the beginnings of a practical compromise. It is being pilot-tested in two Query Health demonstration projects, and it can be further expanded to balance computational tractability with the advanced features needed by measure developers. C1 [Klann, Jeffrey G.; Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02129 USA. [Klann, Jeffrey G.; Murphy, Shawn N.] Partners Healthcare Syst Inc, Research Comp, Boston, MA USA. [Klann, Jeffrey G.; Murphy, Shawn N.] Harvard Univ, Sch Med, Boston, MA USA. RP Klann, JG (reprint author), Massachusetts Gen Hosp, Constitut Ctr 1, Comp Sci Lab, Boston, MA 02129 USA. EM jklann@partners.org FU Office of the National Coordinator for Health Information Technology [ONC 90TR001/01] FX This work was sponsored by the Office of the National Coordinator for Health Information Technology, Grant No. ONC 90TR001/01. NR 23 TC 5 Z9 5 U1 0 U2 13 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD APR PY 2013 VL 15 IS 4 AR UNSP e75 DI 10.2196/jmir.2493 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 151EP UT WOS:000319443800013 PM 23603227 ER PT J AU Dranoff, G Fearon, D AF Dranoff, Glenn Fearon, Douglas TI Tumour immunology SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Fearon, Douglas] Li Ka Shing Ctr, CRUK Cambridge Res Inst, Cambridge CB2 0RE, England. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu; dtf1000@cam.ac.uk FU NCI NIH HHS [P01 CA078378, P50 CA100707, P01 CA155258, R01 CA143083]; NIBIB NIH HHS [R01 EB015498] NR 0 TC 4 Z9 4 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2013 VL 25 IS 2 BP 189 EP 191 DI 10.1016/j.coi.2013.02.012 PG 3 WC Immunology SC Immunology GA 150CZ UT WOS:000319369100010 PM 23510648 ER PT J AU Ter-Minassian, M Chan, JA Hooshmand, SM Brais, LK Daskalova, A Heafield, R Buchanan, L Qian, ZR Fuchs, CS Lin, XH Christiani, DC Kulke, MH AF Ter-Minassian, Monica Chan, Jennifer A. Hooshmand, Susanne M. Brais, Lauren K. Daskalova, Anastassia Heafield, Rachel Buchanan, Laurie Qian, Zhi Rong Fuchs, Charles S. Lin, Xihong Christiani, David C. Kulke, Matthew H. TI Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database SO ENDOCRINE-RELATED CANCER LA English DT Article DE neuroendocrine tumors; disease-free survival; overall survival; chromogranin A ID PANCREATIC ENDOCRINE TUMORS; CHROMOGRANIN-A; PROGNOSTIC-FACTORS; SINGLE INSTITUTION; CARCINOID-TUMORS; FOLLOW-UP; MANAGEMENT; DIAGNOSIS; CLASSIFICATION; EPIDEMIOLOGY AB The rarity of neuroendocrine tumors (NET) has contributed to a paucity of large epidemiologic studies of patients with this condition. We characterized presenting symptoms and clinical outcomes in a prospective database of over 900 patients with NET. We used data from patient questionnaires and the medical record to characterize presenting symptoms, disease-free survival (DFS), and overall survival (OS). The majority of patients in this database had gastroenteropancreatic NET. The median duration of patient-reported symptoms before diagnosis was 3.4 months; 19.5% reported durations from 1 to 5 years, 2.5% from 5 to 10 years, and 2% >10 years. The median DFS among patients with resected small bowel NET or pancreatic NET (panNET) was 5.8 and 4.1 years respectively. After correcting for left truncation bias, the median OS was 7.9 years for advanced small bowel NET and 3.9 years for advanced panNET. Chromogranin A (CGA) above twice the upper limit of normal was associated with shorter survival times (hazard ratios 2.8 (1.9, 4.0) P<0.001) in patients with metastatic disease, regardless of tumor subtype. Our data suggest that while most NET patients are diagnosed soon after symptom onset, prolonged symptom duration before diagnosis is a prominent feature of this disease. Though limited to observations from a large referral center, our observations confirm the prognostic value of CGA and suggest that median survival durations may be shorter than that reported in other institutional databases. C1 [Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Buchanan, Laurie; Qian, Zhi Rong; Fuchs, Charles S.; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Ter-Minassian, Monica; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Ter-Minassian, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 1250,450 Brookline Ave, Boston, MA 02215 USA. EM monica_ter-minassian1@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU Raymond and Beverly Sackler American Association of Cancer Research Fellowship for Ileal Carcinoid Research; NIH [R01 CA151532-01A1, 5P50CA127003-05]; Novartis Pharmaceuticals FX Dr M Ter-Minassian is supported by the Raymond and Beverly Sackler American Association of Cancer Research Fellowship for Ileal Carcinoid Research. M H Kulke is supported in part by NIH grants R01 CA151532-01A1 and 5P50CA127003-05 (Gastrointestinal Cancer SPORE). Additional funding for this project was provided by a grant from Novartis Pharmaceuticals. NR 43 TC 23 Z9 24 U1 0 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD APR PY 2013 VL 20 IS 2 BP 187 EP 196 DI 10.1530/ERC-12-0340 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 152TS UT WOS:000319554600008 PM 23319495 ER PT J AU Stone, RM AF Stone, Richard M. TI Highlights in acute myeloid leukemia from the 2012 meeting of the American Society of Hematology SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; ARSENIC TRIOXIDE; THERAPY; MULTICENTER; ADULTS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,M1B-17, Boston, MA 02215 USA. EM rstone@partners.org FU Novartis, Ltd. FX Rill Stone serves as an ad hoc consultant for Teva, Ltd, Celgene, Ltd, Amgen, Inc. and Sunesis Pharmaceuticals, Inc. and has received research support from Novartis, Ltd. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 25 TC 0 Z9 0 U1 0 U2 4 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD APR PY 2013 VL 6 IS 2 BP 127 EP 129 DI 10.1586/EHM.13.14 PG 3 WC Hematology SC Hematology GA 149HC UT WOS:000319308600009 PM 23547861 ER PT J AU Alexander, BM Lee, EQ Reardon, DA Wen, PY AF Alexander, Brian M. Lee, Eudocia Q. Reardon, David A. Wen, Patrick Y. TI Current and future directions for Phase II trials in high-grade glioma SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE angiogenesis; clinical trials; malignant glioma; multitargeted therapy; targeted therapy ID RECURRENT MALIGNANT GLIOMA; NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB PLUS IRINOTECAN; ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; DENDRITIC CELL VACCINATION; TRANS-SODIUM CROCETINATE; STRAND BREAK REPAIR; CANCER STEM-CELLS; T-CELLS AB Despite surgery, radiation and chemotherapy, the prognosis for high-grade glioma (HGG) is poor. Our understanding of the molecular pathways involved in gliomagenesis and progression has increased in recent years, leading to the development of novel agents that specifically target these pathways. Results from most single-agent trials have been modest at best, however. Despite the initial success of antiangiogenesis agents in HGG, the clinical benefit is short-lived and most patients eventually progress. Several novel agents, multi-targeted agents and combination therapies are now in clinical trials for HGG and several more strategies are being pursued. C1 [Alexander, Brian M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Lee, Eudocia Q.; Reardon, David A.; Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div Canc Neurol,Ctr Neurooncol, Boston, MA 02215 USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div Canc Neurol,Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA. EM pwen@partners.org FU Parker Adams Small III and Katherine Currier Small Fund For Brain Tumor Research; Amgen; AstraZeneca; Boehringer Ingelheim; Genentech/Roche; Geron; Medimmune; Merck; Novartis; Sanofi-Aventis; Vascular Biogenics FX The authors gratefully acknowledge the support of the Parker Adams Small III and Katherine Currier Small Fund For Brain Tumor Research. EQ Lee is on the advisory boards for Genentech and Novartis. DA Reardon is a consultant/on the advisory board (receives honoraria) for Roche/Genentech, EMD Serono, Novartis and Abgenix. P Wen receives research support from Amgen, AstraZeneca, Boehringer Ingelheim, Genentech/Roche, Geron, Medimmune, Merck, Novartis, Sanofi-Aventis and Vascular Biogenics; is on the advisory boards for Novartis, NeOnc Technologies, Vascular Biogenics; and is a speaker for Merck, Genentech/Roche and GlaxoSmithKline. BM Alexander has no conflicts to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 177 TC 2 Z9 3 U1 0 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD APR PY 2013 VL 13 IS 4 BP 369 EP 387 DI 10.1586/ERN.12.158 PG 19 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 153ZZ UT WOS:000319642600010 PM 23545053 ER PT J AU Song, FJ Qureshi, AA Giovannucci, EL Fuchs, CS Chen, WY Stampfer, MJ Han, JL AF Song, Fengju Qureshi, Abrar A. Giovannucci, Edward L. Fuchs, Charlie S. Chen, Wendy Y. Stampfer, Meir J. Han, Jiali TI Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study SO PLOS MEDICINE LA English DT Article ID BASAL-CELL CARCINOMA; NUCLEOTIDE EXCISION-REPAIR; ULTRAVIOLET-RADIATION; DNA-REPAIR; INDUCED IMMUNOSUPPRESSION; UNITED-STATES; VITAMIN-D; SUBSEQUENT MALIGNANCY; SUSCEPTIBILITY; MORTALITY AB Background: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC. Methods and Findings: In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05-1.18), and in women (RR = 1.20; 95% CI 1.15-1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years). Conclusion: This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. C1 [Song, Fengju; Han, Jiali] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China. [Song, Fengju; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Qureshi, Abrar A.; Giovannucci, Edward L.; Fuchs, Charlie S.; Chen, Wendy Y.; Stampfer, Meir J.; Han, Jiali] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Qureshi, Abrar A.; Giovannucci, Edward L.; Fuchs, Charlie S.; Chen, Wendy Y.; Stampfer, Meir J.; Han, Jiali] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charlie S.; Chen, Wendy Y.; Stampfer, Meir J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Song, FJ (reprint author), Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China. EM jiali.han@channing.harvard.edu FU US NIH [CA87969, CA055075] FX This work was supported by US NIH CA87969 and CA055075. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 22 Z9 22 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2013 VL 10 IS 4 AR e1001433 DI 10.1371/journal.pmed.1001433 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 154JA UT WOS:000319669600015 PM 23630459 ER PT J AU Werring, DJ Sperling, R AF Werring, David J. Sperling, Reisa TI Inflammatory cerebral amyloid angiopathy and amyloid-modifying therapies: Variations on the Same ARIA? SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE; IMAGING ABNORMALITIES; IMMUNOTHERAPY; BAPINEUZUMAB; SPECTRUM; TRIALS C1 [Werring, David J.] UCL, Inst Neurol, Stroke Res Grp, Dept Brain Repair & Rehabil, London, England. [Werring, David J.] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Boston, MA 02115 USA. RP Werring, DJ (reprint author), UCL, Inst Neurol, Stroke Res Grp, Dept Brain Repair & Rehabil, London, England. FU British Heart Foundation NR 16 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2013 VL 73 IS 4 BP 439 EP 441 DI 10.1002/ana.23891 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 152HY UT WOS:000319523800004 PM 23526685 ER PT J AU Piazza, F Greenberg, SM Savoiardo, M Gardinetti, M Chiapparini, L Raicher, I Nitrini, R Sakaguchi, H Brioschi, M Billo, G Colombo, A Lanzani, F Piscosquito, G Carriero, MR Giaccone, G Tagliavini, F Ferrarese, C DiFrancesco, JC AF Piazza, Fabrizio Greenberg, Steven M. Savoiardo, Mario Gardinetti, Margherita Chiapparini, Luisa Raicher, Irina Nitrini, Ricardo Sakaguchi, Hideya Brioschi, Monica Billo, Giuseppe Colombo, Antonio Lanzani, Francesca Piscosquito, Giuseppe Carriero, Maria Rita Giaccone, Giorgio Tagliavini, Fabrizio Ferrarese, Carlo DiFrancesco, Jacopo C. TI Anti-amyloid beta autoantibodies in cerebral amyloid angiopathy-related inflammation: Implications for amyloid-modifying therapies SO ANNALS OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE PATIENTS; ABETA 1-42 ANTIBODIES; A-BETA; IMAGING ABNORMALITIES; CEREBROSPINAL-FLUID; BOSTON CRITERIA; IMMUNOTHERAPY; HEMORRHAGE; A-BETA-42; ANGIITIS AB Objective Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid (A) autoantibodies in the acute and remission phases of CAA-ri. Methods We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-A autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble A40, A42, tau, P-181 tau, and APOE genotype were also investigated. Results During the acute phase of CAA-ri, anti-A autoantibodies were specifically increased and directly correlated with A mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble A and axonal degeneration markers decreased in parallel. Interpretation Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular A, directly related to autoantibody concentration and soluble A. The CSF dosage of anti-A autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-A autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA. Ann Neurol 2013;73:449-458 C1 [Piazza, Fabrizio; Gardinetti, Margherita; Ferrarese, Carlo; DiFrancesco, Jacopo C.] Univ Milan, Dept Neurosci & Biomed Technol, I-20052 Monza, MI, Italy. [Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program,Dept Neurol, Boston, MA USA. [Savoiardo, Mario; Chiapparini, Luisa] IRCCS, Fdn Neurol Inst Carlo Besta, Dept Neuroradiol, Milan, Italy. [Raicher, Irina; Nitrini, Ricardo] Univ Sao Paulo, Sch Med, Dept Neurol, Sao Paulo, Brazil. [Sakaguchi, Hideya] Kumamoto Univ, Grad Sch Med Sci, Dept Neurol, Kumamoto, Japan. [Brioschi, Monica] Osped Niguarda Ca Granda, Dept Neurosci, Milan, Italy. [Billo, Giuseppe] St Bortolo Hosp, Dept Neurol, Vicenza, Italy. [Colombo, Antonio; Lanzani, Francesca] Desio Hosp, Dept Neurol, Desio, Italy. [Piscosquito, Giuseppe; Carriero, Maria Rita] IRCCS, Fdn Neurol Inst Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Giaccone, Giorgio; Tagliavini, Fabrizio] IRCCS, Fdn Neurol Inst Carlo Besta, Dept Neurodegenerat Dis, Milan, Italy. [Giaccone, Giorgio; Tagliavini, Fabrizio] IRCCS, Fdn Neurol Inst Carlo Besta, Div Neuropathol Neurol, Milan, Italy. RP Piazza, F (reprint author), Univ Milan, Dept Neurosci & Biomed Technol, Via Cadore 48, I-20052 Monza, MI, Italy. EM fabrizio.piazza@unimib.it RI Piazza, Fabrizio/L-2094-2016 OI Piazza, Fabrizio/0000-0002-3385-3224 FU Regione Lombardia and Social European Fund; Human Capital Development Agreement [17AR] FX This work was partially supported by the Regione Lombardia and Social European Fund 2007-2013, Human Capital Development Agreement, grant ID 17AR. NR 38 TC 46 Z9 48 U1 5 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2013 VL 73 IS 4 BP 449 EP 458 DI 10.1002/ana.23857 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 152HY UT WOS:000319523800006 PM 23625526 ER PT J AU Gurol, ME Viswanathan, A Gidicsin, C Hedden, T Martinez-Ramirez, S Dumas, A Vashkevich, A Ayres, AM Auriel, E van Etten, E Becker, A Carmasin, J Schwab, K Rosand, J Johnson, KA Greenberg, SM AF Gurol, M. Edip Viswanathan, Anand Gidicsin, Christopher Hedden, Trey Martinez-Ramirez, Sergi Dumas, Andrew Vashkevich, Anastasia Ayres, Alison M. Auriel, Eitan van Etten, Ellis Becker, Alex Carmasin, Jeremy Schwab, Kristin Rosand, Jonathan Johnson, Keith A. Greenberg, Steven M. TI Cerebral amyloid angiopathy burden associated with leukoaraiosis: A positron emission tomography/magnetic resonance imaging study SO ANNALS OF NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; PITTSBURGH COMPOUND-B; LOBAR INTRACEREBRAL HEMORRHAGE; SMALL VESSEL DISEASE; ALZHEIMERS-DISEASE; HYPERINTENSITY VOLUME; COGNITIVE IMPAIRMENT; CLINICAL-DIAGNOSIS; ELDERLY-PEOPLE; ROTTERDAM SCAN AB Objective We hypothesized that vascular amyloid contributes to chronic brain ischemia, therefore amyloid burden measured by Pittsburgh compound B retention on positron emission tomography (PiB PET) would correlate with the extent of magnetic resonance imaging (MRI) white matter hyperintensities (WMH; or leukoaraiosis) in patients with high vascular amyloid deposition (cerebral amyloid angiopathy [CAA]) but not in patients with high parenchymal amyloid deposition (Alzheimer disease [AD]; mild cognitive impairment [MCI]) or in healthy elderly (HE) subjects. Methods Forty-two nondemented CAA patients, 50 HE subjects, and 43 AD/MCI patients had brain MRI and PiB PET. Multivariate linear regression was used to assess the independent association between PiB retention and white matter disease volume, controlling for age, gender, apolipoprotein E genotype, and vascular risk factors within each group. Results CAA patients were younger than HE and AD subjects (68 +/- 10 vs 73.3 +/- 7 and 74 +/- 7.4, p < 0.01) but had higher amounts of WMH (median = 21 vs 3.2 and 10.8 ml, respectively, p < 0.05 for both comparisons). Global PiB retention and WMH showed strong correlation (rho = 0.52, p < 0.001) in the CAA group but not in HE or AD. These associations did not change in the multivariate models. Lobar microbleed count, another marker of CAA severity, also remained as an independent predictor of WMH volume. Interpretation Our results indicate that amyloid burden in CAA subjects (with primarily vascular amyloid) but not AD subjects (with primarily parenchymal amyloid) independently correlates with WMH volume. These findings support the idea that vascular amyloid burden directly contributes to chronic cerebral ischemia and highlights the possible utility of amyloid imaging as a marker of CAA severity. Ann Neurol 2013;73:529-536 C1 [Gurol, M. Edip; Viswanathan, Anand; Martinez-Ramirez, Sergi; Dumas, Andrew; Vashkevich, Anastasia; Ayres, Alison M.; Auriel, Eitan; van Etten, Ellis; Schwab, Kristin; Rosand, Jonathan; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Ctr, Boston, MA 02114 USA. [Gurol, M. Edip] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gidicsin, Christopher; Hedden, Trey; Becker, Alex; Carmasin, Jeremy; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hedden, Trey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. RP Gurol, ME (reprint author), MGH Stroke Res Ctr, 55 Fruit St CPZ 175 Suite 300, Boston, MA 02114 USA. EM megurol@partners.org RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Ayres, Alison/0000-0002-5492-1695 FU NIH [NINDS-T32NS048005, NIA R01 AG026484]; Fundacion Alfonso Martin Escudero; NIH FX This work was supported by grants from the NIH (NINDS-T32NS048005, NIA R01 AG026484).; A.Vi.: consultancy, Athena Diagnostics. S. R. M.: grants/grants pending, Fundacion Alfonso Martin Escudero. A.Va., A.M.A., J.R., K.A.J.: grants/grants pending, NIH. NR 44 TC 49 Z9 53 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2013 VL 73 IS 4 BP 529 EP 536 DI 10.1002/ana.23830 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 152HY UT WOS:000319523800014 PM 23424091 ER PT J AU Pasquini, M Le-Rademacher, J Kato, K Zhu, X McCarthy, P Ho, V Cooke, K Armstrong, B Smith, A Rizzo, J Burkart, J Brededson, C AF Pasquini, M. Le-Rademacher, J. Kato, K. Zhu, X. McCarthy, P. Ho, V. Cooke, K. Armstrong, B. Smith, A. Rizzo, J. Burkart, J. Brededson, C. TI Comparison of myeloablative intravenous busulfan with cyclophosphamide (BuCy) or fludarabine (BuFlu) prior to haematopoietic cell transplantation (HCT) for myeloid malignancies SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 39th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 07-10, 2013 CL London, ENGLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Pasquini, M.; Zhu, X.; Rizzo, J.; Burkart, J.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Le-Rademacher, J.] Med Coll Wisconsin, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Kato, K.; Armstrong, B.; Smith, A.] Otsuka Pharmaceut Dev & Commercializat, Princeton, NJ USA. [McCarthy, P.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ho, V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cooke, K.] Univ Hosp Case Med Ctr, Ireland Canc Ctr, Cleveland, OH USA. [Brededson, C.] Univ Ottawa, Ottawa, ON, Canada. RI sebastianovitsch, stepan/G-8507-2013 NR 0 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 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2013 VL 48 SU 2 BP S61 EP S62 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 145OB UT WOS:000319025200135 ER PT J AU Ringden, O Brazauskas, R Wang, Z Duncan, C Jacobsohn, D Mattsson, J Sorror, M Majhail, N AF Ringden, O. Brazauskas, R. Wang, Z. Duncan, C. Jacobsohn, D. Mattsson, J. Sorror, M. Majhail, N. TI Second solid cancers in patients treated with allogeneic haematopoietic cell transplantation using reduced intensity/non-myeloablative conditioning regimens: a Center for International Blood and Marrow Transplant Research study SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 39th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 07-10, 2013 CL London, ENGLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Ringden, O.; Mattsson, J.] Karolinska Univ Hosp, Stockholm, Sweden. [Brazauskas, R.; Wang, Z.] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Duncan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobsohn, D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Sorror, M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Majhail, N.] Natl Marrow Donor Program, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2013 VL 48 SU 2 BP S60 EP S60 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 145OB UT WOS:000319025200131 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI BRCA1: A Missing Link in the Fanconi Anemia/BRCA Pathway SO CANCER DISCOVERY LA English DT Editorial Material ID TUMOR SUPPRESSION; BREAST; DNA AB Domchek and colleagues provide a case report of a 28-year-old woman with congenital abnormalities, inherited ovarian cancer, and carboplatin hypersensitivity. Interestingly, the woman had validated germline mutations in both BRCA1 alleles. These findings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and have important implications for BRCA1 genetic testing. (C) 2013 AACR. C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu FU NHLBI NIH HHS [R37 HL052725]; NIDDK NIH HHS [R01 DK043889] NR 12 TC 6 Z9 6 U1 2 U2 10 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 2013 VL 3 IS 4 BP 376 EP 378 DI 10.1158/2159-8290.CD-13-0044 PG 3 WC Oncology SC Oncology GA 147YU UT WOS:000319208900017 PM 23580280 ER PT J AU Ciarlo, CA Zon, LI AF Ciarlo, Christie A. Zon, Leonard I. TI A Model for Primary Melanoma of the CNS Implicates NRAS SO CANCER DISCOVERY LA English DT Editorial Material ID EXPRESSION AB In this issue of Cancer Discovery, Pedersen and colleagues present the first mouse model of primary CNS melanoma, which arises when oncogenic NRAS is expressed from the endogenous Nras promoter in melanocytes during embryogenesis. In support of this model, two pediatric cases of NRAS-mutant primary melanoma of the CNS are identified. (C) 2013 AACR. C1 Harvard Univ, Sch Med, Childrens Hosp, Stem Cell Program, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA USA. RP Zon, LI (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NIH [5 R01 CA103846-10] FX This work was supported by NIH grant 5 R01 CA103846-10. NR 10 TC 1 Z9 1 U1 0 U2 0 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 2013 VL 3 IS 4 BP 382 EP 383 DI 10.1158/2159-8290.CD-13-0076 PG 2 WC Oncology SC Oncology GA 147YU UT WOS:000319208900019 PM 23580282 ER PT J AU Tabernero, J Shapiro, GI LoRusso, PM Cervantes, A Schwartz, GK Weiss, GJ Paz-Ares, L Cho, DC Infante, JR Alsina, M Gounder, MM Falzone, R Harrop, J White, ACS Toudjarska, I Bumcrot, D Meyers, RE Hinkle, G Svrzikapa, N Hutabarat, RM Clausen, VA Cehelsky, J Nochur, SV Gamba-Vitalo, C Vaishnaw, AK Sah, DWY Gollob, JA Burris, HA AF Tabernero, Josep Shapiro, Geoffrey I. LoRusso, Patricia M. Cervantes, Andres Schwartz, Gary K. Weiss, Glen J. Paz-Ares, Luis Cho, Daniel C. Infante, Jeffrey R. Alsina, Maria Gounder, Mrinal M. Falzone, Rick Harrop, Jamie White, Amy C. Seila Toudjarska, Iva Bumcrot, David Meyers, Rachel E. Hinkle, Gregory Svrzikapa, Nenad Hutabarat, Renta M. Clausen, Valerie A. Cehelsky, Jeffrey Nochur, Saraswathy V. Gamba-Vitalo, Christina Vaishnaw, Akshay K. Sah, Dinah W. Y. Gollob, Jared A. Burris, Howard A., III TI First-in-Humans Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement SO CANCER DISCOVERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; IN-VIVO DELIVERY; SOLID TUMORS; NEUROENDOCRINE TUMORS; ENDOMETRIAL CANCER; NONHUMAN-PRIMATES; ANTICANCER AGENTS; PHASE-II; SIRNA AB RNA interference (RNAi) is a potent and specific mechanism for regulating gene expression. Harnessing RNAi to silence genes involved in disease holds promise for the development of a new class of therapeutics. Delivery is key to realizing the potential of RNAi, and lipid nanoparticles (LNP) have proved effective in delivery of siRNAs to the liver and to tumors in animals. To examine the activity and safety of LNP-formulated siRNAs in humans, we initiated a trial of ALN-VSP, an LNP formulation of siRNAs targeting VEGF and kinesin spindle protein (KSP), in patients with cancer. Here, we show detection of drug in tumor biopsies, siRNA-mediated mRNA cleavage in the liver, pharmacodynamics suggestive of target downregulation, and antitumor activity, including complete regression of liver metastases in endometrial cancer. In addition, we show that biweekly intravenous administration of ALN-VSP was safe and well tolerated. These data provide proof-of-concept for RNAi therapeutics in humans and form the basis for further development in cancer. SIGNIFICANCE: The findings in this report show safety, pharmacokinetics, RNAi mechanism of action, and clinical activity with a novel first-in-class LNP-formulated RNAi therapeutic in patients with cancer. The ability to harness RNAi to facilitate specific multitargeting, as well as increase the number of druggable targets, has important implications for future drug development in oncology. (C) 2012 AACR. C1 [Tabernero, Josep; Alsina, Maria] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, P Vall dHebron 119-129, Barcelona 08035, Spain. [Cervantes, Andres] Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain. [Paz-Ares, Luis] Univ Seville, Hosp Virgen del Rocio, Seville, Spain. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cho, Daniel C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Falzone, Rick; Harrop, Jamie; White, Amy C. Seila; Toudjarska, Iva; Bumcrot, David; Meyers, Rachel E.; Hinkle, Gregory; Svrzikapa, Nenad; Hutabarat, Renta M.; Clausen, Valerie A.; Cehelsky, Jeffrey; Nochur, Saraswathy V.; Gamba-Vitalo, Christina; Vaishnaw, Akshay K.; Sah, Dinah W. Y.; Gollob, Jared A.] Alnylam Pharmaceut Inc, Cambridge, MA USA. [LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA. [Schwartz, Gary K.; Gounder, Mrinal M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Weiss, Glen J.] Scottsdale Healthcare, Virginia G Piper Canc Ctr Clin Trials, Scottsdale, AZ USA. [Infante, Jeffrey R.; Burris, Howard A., III] Sarah Cannon Res Inst, Nashville, TN USA. RP Tabernero, J (reprint author), Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, P Vall dHebron 119-129, Barcelona 08035, Spain. EM jtabernero@vhio.net RI Han, ziyi/O-2512-2013; IBIS, NUEVAS TERAPIA/P-3415-2015 FU Alnylam Pharmaceuticals, Inc. FX This study was funded by Alnylam Pharmaceuticals, Inc. NR 44 TC 227 Z9 231 U1 17 U2 85 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 2013 VL 3 IS 4 BP 406 EP 417 DI 10.1158/2159-8290.CD-12-0429 PG 12 WC Oncology SC Oncology GA 147YU UT WOS:000319208900023 PM 23358650 ER PT J AU Sang, J Acquaviva, J Friedland, JC Smith, DL Sequeira, M Zhang, CH Jiang, Q Xue, LQ Lovly, CM Jimenez, JP Shaw, AT Doebele, RC He, SQ Bates, RC Camidge, DR Morris, SW El-Hariry, I Proia, DA AF Sang, Jim Acquaviva, Jaime Friedland, Julie C. Smith, Donald L. Sequeira, Manuel Zhang, Chaohua Jiang, Qin Xue, Liquan Lovly, Christine M. Jimenez, John-Paul Shaw, Alice T. Doebele, Robert C. He, Suqin Bates, Richard C. Camidge, D. Ross Morris, Stephan W. El-Hariry, Iman Proia, David A. TI Targeted Inhibition of the Molecular Chaperone Hsp90 Overcomes ALK Inhibitor Resistance in Non-Small Cell Lung Cancer SO CANCER DISCOVERY LA English DT Article ID RECEPTOR TYROSINE KINASE; ROS1 REARRANGEMENTS; ACQUIRED-RESISTANCE; DOMAIN MUTATIONS; FUSION ONCOGENE; EML4-ALK; GENE; IDENTIFICATION; CRIZOTINIB; PROTEIN AB EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy. Here, we show that the Hsp90 inhibitor ganetespib induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior antitumor efficacy, and prolonged animal survival compared with results obtained with crizotinib. In addition, combinatorial benefit was seen when ganetespib was used with other targeted ALK agents both in vitro and in vivo. Importantly, ganetespib overcame multiple forms of crizotinib resistance, including secondary ALK mutations, consistent with activity seen in a patient with crizotinib-resistant NSCLC. Cancer cells driven by ALK amplification and oncogenic rearrangements of ROS1 and RET kinase genes were also sensitive to ganetespib exposure. Taken together, these results highlight the therapeutic potential of ganetespib for ALK-driven NSCLC. SIGNIFICANCE: In addition to direct kinase inhibition, pharmacologic blockade of the molecular chaperone Hsp90 is emerging as a promising approach for treating tumors driven by oncogenic rearrangements of ALK. The bioactivity profile of ganetespib presented here underscores a new therapeutic opportunity to target ALK and overcome multiple mechanisms of resistance in patients with ALK-positive NSCLC. (C) 2013 AACR. C1 [Sang, Jim; Acquaviva, Jaime; Friedland, Julie C.; Smith, Donald L.; Sequeira, Manuel; Zhang, Chaohua; Jimenez, John-Paul; He, Suqin; Bates, Richard C.; El-Hariry, Iman; Proia, David A.] Synta Pharmaceut Corp, Lexington, MA 02421 USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Jiang, Qin; Xue, Liquan] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Jiang, Qin; Xue, Liquan] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Lovly, Christine M.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37212 USA. [Morris, Stephan W.] Insight Genet, Nashville, TN USA. [Morris, Stephan W.] HealthChart LLC, Morris Labs, Memphis, TN USA. [Doebele, Robert C.; Camidge, D. Ross] Univ Colorado, Ctr Canc, Div Med Oncol, Aurora, CO USA. RP Proia, DA (reprint author), Synta Pharmaceut Corp, 125 Hartwell Ave, Lexington, MA 02421 USA. EM dproia@syntapharma.com RI sebastianovitsch, stepan/G-8507-2013 FU Pfizer; Eli Lilly; ImClone; Synta Pharmaceuticals Corp. FX J. Sang and J. Acquaviva are employed as Scientist II by Synta Pharmaceuticals Corp. C. Zhang is employed as Research Assistant II by Synta Pharmaceuticals Corp. C. M. Lovly is a consultant/advisory board member of Abbott. J.-P. Jimenez is employed as Assoc. Scientist by, and has ownership interest (including patents) in, Synta Pharmaceuticals Corp. A. T. Shaw is a consultant/advisory board member of Daiichi Sankyo and Novartis. R. C. Doebele has commercial research grants from Pfizer, Eli Lilly, and ImClone; has honoraria from Speakers Bureau of Abbott Molecular; and is a consultant/advisory board member of Boehringer Ingelheim and Pfizer. S. He is employed as a Scientist by Synta Pharmaceuticals Corp. R. C. Bates is employed as Senior Science Writer by Synta Pharmaceuticals Corp. S. W. Morris has ownership interest (including patents) in Insight Genetics, Inc. I. El-Hariry is Vice President of Clinical Research and D. A. Proia is Director of Cancer Biology at Synta Pharmaceuticals Corp. No potential conflicts of interest were disclosed by the other authors.; All work was funded by Synta Pharmaceuticals Corp. NR 48 TC 100 Z9 107 U1 4 U2 22 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 2013 VL 3 IS 4 BP 430 EP 443 DI 10.1158/2159-8290.CD-12-0440 PG 14 WC Oncology SC Oncology GA 147YU UT WOS:000319208900025 PM 23533265 ER PT J AU Treon, SP Patterson, CJ Munshi, NC Anderson, KC AF Treon, Steven P. Patterson, Christopher J. Munshi, Nikhil C. Anderson, Kenneth C. TI Proceedings of the Seventh International Workshop on Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Editorial Material C1 [Treon, Steven P.; Patterson, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, M547, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu NR 0 TC 1 Z9 2 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 181 EP 183 DI 10.1016/j.clml.2013.04.001 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400015 PM 23664025 ER PT J AU Poulain, S Herbaux, C Bertrand, E Decambron, A Fouquet, G Boyle, E Gay, J Manier, S Duthilleul, P Roumier, C Leleu, X AF Poulain, Stephanie Herbaux, Charles Bertrand, Elisabeth Decambron, Audrey Fouquet, Guillemette Boyle, Eileen Gay, Julie Manier, Salomon Duthilleul, Patrick Roumier, Christophe Leleu, Xavier TI Genomic Studies Have Identified Multiple Mechanisms of Genetic Changes in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI DE Array-based genomic hybridization; MYD88 mutation; Waldenstrom macroglobulinemia ID MARGINAL ZONE; MICRORNA EXPRESSION; SOMATIC MUTATION; KAPPA-B; LYMPHOMA; CELLS; ABNORMALITIES; DELETIONS; PATHWAYS AB The pathophysiology of Waldenstrom macroglobulinemia (WM), a lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration associated with serum IgM paraprotein, is rather unclear; however, progress has been made in recent years to better determine the genetic profile of WM tumor cells. Studies based on high-throughput genomic analyses-including single-nucleotide polymorphism array (SNPa), array-based comparative genomic hybridization, and, recently, whole-genome sequencing-have improved deciphering some of the key molecular pathways associated with WM. Beyond the discovery of the myeloid differentiation primary response gene 88 (MYD88) L265P mutation, which will help greatly in the differential characterization of WM from other B-cell low-grade lymphomas, several other mechanisms of gene deregulation were identified and mapped that recurrently pointed out nuclear factor-kappa B (NF-kappa B), breakpoint cluster region (BCR), and Toll-like receptor (TLR) signaling pathways as potential targets for a better understanding of the physiopathology of WM and for future drug development. Herein, we summarize the current knowledge of the genomic patterns of WM to highlight its complexity. The clinical and biological presentation of Waldenstrom macroglobulinemia (WM), a rare lymphoproliferative disorder characterized by bone marrow infiltration of lymphoplasmacytic cells associated with serum IgM paraprotein,(1,2) is highly heterogeneous. Although the underlying genetic basis remains to be identified in WM, high-throughput whole-genome techniques such as array-based genomic hybridization, single-nucleotide polymorphism array (SNPa), and whole-genome sequencing have helped improve the comprehensive analysis of WM genetic patterns, including the identification of several genes involved in deregulated pathways.' We seek to summarize the various mechanisms of deregulation at the genomic level currently identified in WM. C1 [Poulain, Stephanie; Decambron, Audrey; Duthilleul, Patrick] Serv Hematol Immunol Cytogenet, Valenciennes, France. [Poulain, Stephanie; Roumier, Christophe] Ctr Biol Pathol, Lab Hematol, Lille, France. [Herbaux, Charles; Bertrand, Elisabeth; Manier, Salomon; Roumier, Christophe; Leleu, Xavier] Inst Rech Canc, INSERM, U837, Lille, France. [Herbaux, Charles; Fouquet, Guillemette; Boyle, Eileen; Gay, Julie; Manier, Salomon; Leleu, Xavier] Ctr Hosp Reg & Univ Lille, Hop Huriez, Serv Malad Sang, F-59037 Lille, France. [Manier, Salomon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Leleu, X (reprint author), CHRU, Hop Huriez, Serv Malad Sang, Lille, France. EM xavier.leleu@chru-lille.fr NR 25 TC 2 Z9 2 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 2013 VL 13 IS 2 BP 202 EP 204 DI 10.1016/j.clml.2013.02.008 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400021 PM 23473949 ER PT J AU Sacco, A Zhang, Y Maiso, P Manier, S Rossi, G Treon, SP Ghobrial, IM Roccaro, AM AF Sacco, Antonio Zhang, Yong Maiso, Patricia Manier, Salomon Rossi, Giuseppe Treon, Steven P. Ghobrial, Irene M. Roccaro, Aldo M. TI microRNA Aberrations in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI DE Locked nucleic acid; micro-RNA; miRNA-155; Waldenstrom macroglobulinemia ID B-CELL LYMPHOMAS; MULTIPLE-MYELOMA; EXPRESSION; PROLIFERATION AB Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the BM (BM) and monoclonal immunoglobulin M in the circulation. Although WM cells showed minimal changes in cytogenetic studies and gene expression analysis, primary WM tumor cells present with a micro-RNA (miRNA) signature that differentiates them from their normal counterparts. This may suggest the importance of miRNAs in supporting WM pathogenesis. Among deregulated miRNAs, miRNA-155 has been shown to play a pivotal role in the biological characteristics of this disease both in vitro and in vivo, thus providing the rationale for testing miRNA-based therapeutic approaches for the treatment of WM. C1 [Sacco, Antonio; Zhang, Yong; Maiso, Patricia; Manier, Salomon; Treon, Steven P.; Ghobrial, Irene M.; Roccaro, Aldo M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rossi, Giuseppe] Spedali Civil Brescia, Dept Hematol, I-25125 Brescia, Italy. RP Roccaro, AM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM aldo_roccaro@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; Rossi, Giuseppe/K-3376-2016; OI Sacco, Antonio/0000-0003-2945-9416; Rossi, Giuseppe/0000-0001-8377-2898; Roccaro, Aldo/0000-0002-1872-5128; Maiso, Patricia/0000-0003-3745-1924 NR 16 TC 3 Z9 3 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 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 205 EP 207 DI 10.1016/j.clml.2013.02.007 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400022 PM 23474146 ER PT J AU Agarwal, A Ghobrial, IM AF Agarwal, Amit Ghobrial, Irene M. TI The Bone Marrow Microenvironment in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI ID TUMOR MICROENVIRONMENT; SOMATIC MUTATION; CELL-GROWTH; ABNORMALITY; CYTOKINES; SUGGESTS; THERAPY; MYELOMA AB Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow (BM). The BM microenvironment serves as not only a site for disease involvement, but it also appears that the interaction of WM cells with the BM is essential for the pathogenesis of WM. The BM microenvironment consists of the cellular and noncellular compartments. The BM has been shown to regulate cell proliferation, cell cycle, and drug resistance as well as cell dissemination and cell trafficking of WM cells. A better understanding of the role of the BM microenvironment in the pathogenesis of WM can help guide better therapeutic strategies that can target the tumor clone and also regulate the BM microenvironment. C1 [Agarwal, Amit] Univ Arizona, Div Hematol Oncol, Tucson, AZ USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Med Oncol Dana Farber Canc Inst, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu FU NCI NIH HHS [R01CA154648, R01CA133799, R01 CA154648, R01 CA133799, R01 CA125690, R01CA125690, R21 CA126119] NR 26 TC 3 Z9 3 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 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 218 EP 221 DI 10.1016/j.clml.2013.02.006 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400026 PM 23490994 ER PT J AU Treon, SP Tripsas, CK Ciccarelli, BT Manning, RJ Patterson, CJ Sheehy, P Hunter, ZR AF Treon, Steven P. Tripsas, Christina K. Ciccarelli, Bryan T. Manning, Robert J. Patterson, Christopher J. Sheehy, Patricia Hunter, Zachary R. TI Patients With Waldenstrom Macroglobulinemia Commonly Present With Iron Deficiency and Those With Severely Depressed Transferrin Saturation Levels Show Response to Parenteral Iron Administration SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; MULTIPLE-MYELOMA; INTRAVENOUS IRON; ANEMIC PATIENTS; HEPCIDIN; FERROPORTIN; INTERNALIZATION; CHEMOTHERAPY; MULTICENTER AB Anemia often prompts therapy in Waldenstrom macroglobulinemia (WM), although is not fully explained by bone marrow disease involvement in many patients. Hepcidin regulates gut absorption and distribution of iron and is elevated and associated with anemia in WM. Since hepcidin evaluation remains experimental, we initiated an American Board of Internal Medicine (ABIM) practice improvement project to determine baseline transferrin saturation (TSAT) levels in untreated anemic patients with WM. Among 108 patients with WM evaluated, 56 (52%) had a TSAT level <= 20%, which included 25 (23%) patients with severely depressed TSAT levels (<= 10%). Sixteen patients with TSAT levels <= 10% received parenteral iron, and 14 of these patients showed improved hematocrit values (28.75% to 32.75%; P < .0001), mean corpuscular volume (MCV) (84.7 to 89.9; P = .006), and TSAT levels (8.1% to 21.2%; P < .0001). Anemia in 8 of these patients was previously refractory to oral iron therapy. Routine screening of iron saturation levels may therefore identify patients with WM and severe iron deficiency who may be candidates for parenteral iron therapy. C1 [Treon, Steven P.; Tripsas, Christina K.; Ciccarelli, Bryan T.; Manning, Robert J.; Patterson, Christopher J.; Sheehy, Patricia; Hunter, Zachary R.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 19 TC 3 Z9 3 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 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 241 EP 243 DI 10.1016/j.clml.2013.02.016 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400032 PM 23523274 ER PT J AU Uljon, SN Treon, SP Tripsas, CK Lindeman, NI AF Uljon, Sacha N. Treon, Steven P. Tripsas, Christina K. Lindeman, Neal I. TI Challenges With Serum Protein Electrophoresis in Assessing Progression and Clinical Response in Patients With Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI ID FREE LIGHT-CHAINS; MYELOMA AB Accurate determination of the immunoglobulin (Ig) M paraprotein concentration is crucial to evaluating response in patients with Waldenstrom macroglobulinemia (WM). In most clinical laboratories, M-spike quantitation is performed by serum protein electrophoresis, which is the same method used to quantitate IgG and IgA paraproteins in patients with multiple myeloma (MM). However, the migration pattern and propensity of IgM paraproteins to form higher-order complexes in serum makes laboratory evaluation of samples from patients with WM especially challenging. We review examples of patients whose IgM paraprotein is particularly ill-suited to M-spike quantitation by serum protein electrophoresis: a case of "sticky M," a case of IgM multimers that cannot be resolved, and a case of an IgM in the beta region. In these and similar cases, a method other than M-spike quantitation, such as IgM heavy chain nephelometry, should be considered in laboratory evaluation of paraprotein concentration. C1 [Uljon, Sacha N.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Uljon, Sacha N.; Treon, Steven P.; Tripsas, Christina K.; Lindeman, Neal I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Treon, Steven P.; Tripsas, Christina K.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Uljon, SN (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM suljon@partners.org NR 11 TC 2 Z9 2 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 247 EP 249 DI 10.1016/j.clml.2013.03.001 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400034 PM 23664026 ER PT J AU Tripsas, CK Patterson, CJ Uljon, SN Lindeman, NI Turnbull, B Treon, SP AF Tripsas, Christina K. Patterson, Christopher J. Uljon, Sacha N. Lindeman, Neal I. Turnbull, Barry Treon, Steven P. TI Comparative Response Assessment by Serum Immunoglobulin M M-Protein and Total Serum Immunoglobulin M After Treatment of Patients With Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 7th International Workshop on Waldenstrom's Macroglobulinemia (IWWM) CY AUG 23-26, 2012 CL Newport, RI ID INTERNATIONAL WORKSHOP; RECOMMENDATIONS; RITUXIMAB; UPDATE AB Serum immunoglobulin (Ig) M monoclonal protein determined by electrophoresis (sIgM-MP) and total serum IgM (sIgM) by nephelometry are widely used for response assessment in Waldenstrom macroglobulinemia (WM), although have not been compared for predicting changes in underlying disease burden. We, therefore, compared these serum markers with changes in bone marrow (BM) and extramedullary disease for 73 patients who were rituximab naive and treated with a rituximab-containing regimen. By linear regression analysis, reductions in sIgM-MP and sIgM showed moderate correlation with BM disease involvement (r = 0.4051 and r = 0.4490, respectively), and did not differ from one another as estimators of BM disease response (P = .3745). Neither sIgM-MP nor sIgM showed a strong correlation with BM disease response in patients with low (<1000 mg/dL) or high (>5000 mg/dL) IgM levels and extramedullary disease response. sIgM-MP and sIgM, therefore, are comparable response markers in WM. Development of newer, more accurate surrogate response markers are needed to better delineate treatment outcomes in patients with WM and with low or high IgM levels, and extramedullary disease. C1 [Tripsas, Christina K.; Patterson, Christopher J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA. [Uljon, Sacha N.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Uljon, Sacha N.; Lindeman, Neal I.; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Turnbull, Barry] BioBridges Inc, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA. EM steven_treon@dfci.harvard.edu NR 14 TC 5 Z9 5 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD APR PY 2013 VL 13 IS 2 BP 250 EP 252 DI 10.1016/j.clml.2013.04.002 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148MJ UT WOS:000319248400035 PM 23664027 ER PT J AU Schlett, CL Truong, QA Ahmed, W Blankstein, R Ferencik, M Uthamalingam, S Bamberg, F Koenig, W Januzzi, JL Hoffmann, U AF Schlett, Christopher L. Truong, Quynh A. Ahmed, Waleed Blankstein, Ron Ferencik, Maros Uthamalingam, Shanmugam Bamberg, Fabian Koenig, Wolfgang Januzzi, James L. Hoffmann, Udo TI High-sensitivity troponin T and C-reactive protein to identify patients without cardiac structural and functional abnormalities as assessed by cardiac CT and SPECT imaging: can biomarkers predict cardiac health? SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Cardiovascular health; High-sensitivity troponin T; High-sensitivity C-reactive protein; Cardiac computed tomography; Single-photon emission computed tomography ID CORONARY-HEART-DISEASE; LEFT-VENTRICULAR FUNCTION; ACUTE CHEST-PAIN; COMPUTED-TOMOGRAPHY; MYOCARDIAL-INFARCTION; CLINICAL-SIGNIFICANCE; CIRCULATING TROPONIN; PROGNOSTIC VALUE; RISK-ASSESSMENT; ARTERY-DISEASE AB While high-sensitivity troponin-T (hsTnT) and C-reactive protein (hsCRP) are associated with structural heart disease, we thought to determine whether biomarkers can predict which heart is healthy based on multimodality imaging. Patients from the emergency department with acute chest pain suggestive of acute coronary syndrome undergoing contrast enhanced cardiac CT and stress single photon emission computed tomography (SPECT) myocardial perfusion imaging were included. HsTnT and hsCRP were assessed at time of CT. Imaging data were assessed for coronary atherosclerosis, left ventricular hypertrophy/dysfunction and myocardial perfusion abnormalities. Patients were stratified into those with or without any cardiac findings, who were considered as cardiac healthy. For biomarkers, low cut-off corresponding to good specificity and high cut-off corresponding to good sensitivity for cardiac health were derived. Among 117 patients (52 years, 55 % male), 42 (36 %) were cardiac healthy based on cardiac CT and SPECT imaging. These patients had significantly lower hsTnT and hsCRP levels as compared to those with functional or structural abnormalities (3.58 vs. 5.63 ng/L, p = 0.002; 0.82 vs. 1.93 mg/L, p = 0.0005; respectively). Patients with both low hsTnT (< 3.00 ng/L) and hsCRP (< 0.45 mg/L) had a probability of 85 % for being cardiac healthy. In contrast, patients with high hsTnT (> 7.00 ng/L) and hsCRP (> 2.00 mg/L) had 8 % probability for being cardiac healthy. Discriminative capacity of a dual-biomarker strategy was significantly improved as compared to hsTnT or hsCRP alone or to Framingham Risk score (AUC: 0.781 vs. 0.691; vs. 0.678; vs. 0.649; all p a parts per thousand currency sign 0.02, respectively). A dual-biomarker strategy of hsTnT and hsCRP is highly discriminative for patients with normal cardiac structure and function and provides incremental value beyond the Framingham risk score. C1 [Schlett, Christopher L.; Truong, Quynh A.; Ahmed, Waleed; Ferencik, Maros; Uthamalingam, Shanmugam; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02114 USA. [Truong, Quynh A.; Ferencik, Maros; Januzzi, James L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Cardiol, Cardiovasc Div, Boston, MA 02115 USA. [Bamberg, Fabian] Univ Munich, Dept Clin Radiol, Munich, Germany. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. RP Schlett, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM cschlett@partners.org; uhoffmann@partners.org FU NIH [R01 HL080053, T32HL076136, K23HL098370, L30HL093896]; Roche Diagnostics; Siemens Diagnostics; BRAHMS FX We thank Mr. Eracleo for his kind support. This work was supported by the NIH (R01 HL080053). Drs. Blankstein, Ahmed, and Truong received support from NIH grant T32HL076136. Dr. Truong also received support from NIH grants K23HL098370 and L30HL093896.; The reagents for high-sensitivity troponin assays were provided free of charge by Roche Diagnostics. Dr. Januzzi has received grant support from Roche Diagnostics, Siemens Diagnostics, and BRAHMS. NR 42 TC 4 Z9 5 U1 0 U2 4 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 2013 VL 29 IS 4 BP 865 EP 873 DI 10.1007/s10554-012-0164-8 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 140YV UT WOS:000318693300016 PM 23274882 ER PT J AU Gao, X Prigerson, HG Diamond, EL Zhang, BH Wright, AA Meyer, F Maciejewski, PK AF Gao, Xin Prigerson, Holly G. Diamond, Eli L. Zhang, Baohui Wright, Alexi A. Meyer, Fremonta Maciejewski, Paul K. TI Minor Cognitive Impairments in Cancer Patients Magnify the Effect of Caregiver Preferences on End-of-Life Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer; terminal illness; end of life; cognitive impairment; treatment preferences; caregiver ID DECISION-MAKING CAPACITY; SUSTAINING TREATMENT; NEAR-DEATH; DEMENTIA; DELIRIUM; OUTCOMES; PEOPLE; IMPACT AB Context. Cognitive impairment commonly affects cancer patients. Objectives. To examine whether minor cognitive impairment in patients with advanced cancer is associated with the intensity of end-of-life (EOL) care or modifies the influence of patient and caregiver preferences on the intensity of EOL care. Methods. Data were derived from structured interviews with 221 advanced cancer patient-caregiver dyads in the Coping with Cancer Study, a multisite, longitudinal cohort study. Deficits in patients' cognitive function were identified using the Short Portable Mental Status Questionnaire (SPMSQ). Patients and caregivers reported preferences regarding life-extending vs. symptom-directed care. Information regarding EOL care was obtained from postmortem interviews with caregivers. Logistic regression analyses modeled main and interactive effects of patients' cognitive impairment and patients' and caregivers' treatment preferences on intensive EOL care. Results. Cognitive impairment was associated with less intensive EOL care (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.34-0.91). Patients and caregivers had poor agreement regarding preferences for life-extending vs. symptom-directed care (Phi = 0.10; chi(2) = 2.32, df = 1, P = 0.13). Patient preference for life-extending care predicted intensive EOL care irrespective of cognitive status (adjusted odds ratio [AOR] = 2.11; 95% CI: 1.04-4.28). For patients with no errors on the SPMSQ, caregiver preference for life-extending care was unrelated to intensive EOL care (AOR = 0.40; 95% CI: 0.09-1.77). However, the association between caregiver preference for life-extending care and intensive EOL care increased by nearly a factor of seven for every error on the SPMSQ (interaction AOR 6.90; 95% CI: 1.40-34.12). Conclusion. Cognitive impairment in patients with advanced cancer is associated with less intensive EOL care. Caregivers' influence on intensive EOL care dramatically increases with minor declines in patients' cognitive function. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Gao, Xin; Prigerson, Holly G.; Zhang, Baohui; Wright, Alexi A.; Maciejewski, Paul K.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Prigerson, Holly G.; Wright, Alexi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gao, Xin; Prigerson, Holly G.; Wright, Alexi A.; Meyer, Fremonta; Maciejewski, Paul K.] Harvard Univ, Sch Med, Boston, MA USA. [Prigerson, Holly G.; Meyer, Fremonta; Maciejewski, Paul K.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Diamond, Eli L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, 1134 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA156732]; Center for Psychosocial Epidemiology and Outcomes Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA106370 and CA156732 from the National Cancer Institute; and the Center for Psychosocial Epidemiology and Outcomes Research, Dana-Farber Cancer Institute. The authors declare no potential conflicts of interest or financial disclosures. All authors have read and approved the article. NR 35 TC 4 Z9 4 U1 2 U2 10 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 2013 VL 45 IS 4 BP 650 EP 659 DI 10.1016/j.jpainsymman.2012.03.003 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 145YP UT WOS:000319056300005 PM 22846621 ER PT J AU Walker, RH AF Walker, Ruth H. TI Commentary for "Delayed onset of progressive chorea after acute basal ganglia injury" SO MOVEMENT DISORDERS LA English DT Editorial Material ID DISORDERS C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, 130 W Kingbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2013 VL 28 IS 5 BP 587 EP 588 DI 10.1002/mds.25481 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 144QG UT WOS:000318953900010 PM 23629806 ER PT J AU Liong, M Hoang, AN Chung, J Gural, N Ford, CB Min, C Shah, RR Ahmad, R Fernandez-Suarez, M Fortune, SM Toner, M Lee, H Weissleder, R AF Liong, Monty Hoang, Anh N. Chung, Jaehoon Gural, Nil Ford, Christopher B. Min, Changwook Shah, Rupal R. Ahmad, Rushdy Fernandez-Suarez, Marta Fortune, Sarah M. Toner, Mehmet Lee, Hakho Weissleder, Ralph TI Magnetic barcode assay for genetic detection of pathogens SO NATURE COMMUNICATIONS LA English DT Article ID REAL-TIME PCR; MYCOBACTERIUM-TUBERCULOSIS; MICROFLUIDIC CHIP; DRUG-RESISTANCE; NANOPARTICLES; DNA; INFECTION; DIAGNOSIS; SYSTEM; HYBRIDIZATION AB The task of rapidly identifying patients infected with Mycobacterium tuberculosis in resource-constrained environments remains a challenge. A sensitive and robust platform that does not require bacterial isolation or culture is critical in making informed diagnostic and therapeutic decisions. Here we introduce a platform for the detection of nucleic acids based on a magnetic barcoding strategy. PCR-amplified mycobacterial genes are sequence-specifically captured on microspheres, labelled by magnetic nanoprobes and detected by nuclear magnetic resonance. All components are integrated into a single, small fluidic cartridge for streamlined on-chip operation. We use this platform to detect M. tuberculosis and identify drug-resistance strains from mechanically processed sputum samples within 2.5 h. The specificity of the assay is confirmed by detecting a panel of clinically relevant non-M. tuberculosis bacteria, and the clinical utility is demonstrated by the measurements in M. tuberculosis-positive patient specimens. Combined with portable systems, the magnetic barcode assay holds promise to become a sensitive, high-throughput and low-cost platform for point-of-care diagnostics. C1 [Liong, Monty; Chung, Jaehoon; Min, Changwook; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Hoang, Anh N.; Gural, Nil; Fernandez-Suarez, Marta; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Surg Serv, Boston, MA 02114 USA. [Ford, Christopher B.; Shah, Rupal R.; Fernandez-Suarez, Marta; Fortune, Sarah M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Ahmad, Rushdy] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Lee, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU NIBIB [R01-EB010011, R01-EB00462605A1, R01-HL113156, P41 EB002503]; NHLBI [HHSN268201000044C]; NIH [T32CA79443, DP2 0D001378]; United States Army Medical Research Acquisition Activity Grant [W81XWH-10-2-0161]; NIAID [U19 AI076217]; Massachusetts General Hospital Executive Committee on Research Fellowship FX We thank I. Bagayev, J. C. Carlson, H. J. Chung, H. Im, M. McKee, N. Sergeyev, H. Shao and J. Song for their assistance with experiments, and W. R. Rodriguez for helpful discussions on point-of-care diagnostic. The patient sputum samples were collected in Dar Es Salaam, Tanzania, under a grant from the Bill and Melinda Gates Foundation as part of Grand Challenge 13. This work was supported in part by NIBIB grants R01-EB010011 (R.W.), R01-EB00462605A1 (R.W.), R01-HL113156 (H.L.), P41 EB002503 (M.T.), NHLBI contract HHSN268201000044C (R.W.), NIH grant T32CA79443 (R.W.), United States Army Medical Research Acquisition Activity Grant W81XWH-10-2-0161 (S.M.F.), NIH grant DP2 0D001378 (S.M.F), NIAID contract U19 AI076217 (S.M.F) and the Massachusetts General Hospital Executive Committee on Research Fellowship (A.N.H and M.F.-S.). NR 41 TC 44 Z9 44 U1 4 U2 100 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 2013 VL 4 AR 1752 DI 10.1038/ncomms2745 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143MR UT WOS:000318872100109 PM 23612293 ER PT J AU Yang, SY O'Cearbhaill, ED Sisk, GC Park, KM Cho, WK Villiger, M Bouma, BE Pomahac, B Karp, JM AF Yang, Seung Yun O'Cearbhaill, Eoin D. Sisk, Geoffroy C. Park, Kyeng Min Cho, Woo Kyung Villiger, Martin Bouma, Brett E. Pomahac, Bohdan Karp, Jeffrey M. TI A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue SO NATURE COMMUNICATIONS LA English DT Article ID AMPHIPHILIC BLOCK-COPOLYMERS; FIBRIN GLUE; SKIN-GRAFTS; BIOCOMPATIBILITY; THICKNESS; SURGERY; CLOSURE; WOUNDS; REPAIR; SITES AB Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host's intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving similar to 3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of similar to 4.5 N cm(-2) from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics. C1 [Yang, Seung Yun; O'Cearbhaill, Eoin D.; Cho, Woo Kyung; Karp, Jeffrey M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Biomed Engn, Boston, MA 02115 USA. [Yang, Seung Yun; O'Cearbhaill, Eoin D.; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Yang, Seung Yun; O'Cearbhaill, Eoin D.; Cho, Woo Kyung; Bouma, Brett E.; Karp, Jeffrey M.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sisk, Geoffroy C.; Pomahac, Bohdan] Brigham & Womens Hosp, Div Plast Surg, Dept Surg, Boston, MA 02115 USA. [Park, Kyeng Min] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [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. RP Karp, JM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Biomed Engn, Boston, MA 02115 USA. EM jkarp@rics.bwh.harvard.edu RI Yang, Seung Yun/B-5974-2016; OI Park, Kyeng Min/0000-0001-6089-6169; Yang, Seung Yun/0000-0002-1233-8960; O'Cearbhaill, Eoin/0000-0002-4666-5863 FU National Institutes of Health (NIH) [GM086433]; NIH [P41EB015903]; Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2012R1A6A3A03039055] FX We would like to thank ADMET for providing an eXpert 760 mechanical tester that was instrumental for this work. Funding for this research was provided by the National Institutes of Health (NIH) grant GM086433 to J.M.K., NIH grant P41EB015903 to B.E.B. and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A6A3A03039055). This work was performed in part through the use of MIT's Microsystems Technology Laboratories and Harvard's Center for Nanoscale Systems. We would like to thank Albert Kwon for providing E. coli and Dr. Bryan Laulicht for helpful discussions. NR 37 TC 51 Z9 51 U1 13 U2 130 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 2013 VL 4 AR 1702 DI 10.1038/ncomms2715 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143MR UT WOS:000318872100059 PM 23591869 ER PT J AU Surawicz, CM Brandt, LJ Binion, DG Ananthakrishnan, AN Curry, SR Gilligan, PH McFarland, LV Mellow, M Zuckerbraun, BS AF Surawicz, Christina M. Brandt, Lawrence J. Binion, David G. Ananthakrishnan, Ashwin N. Curry, Scott R. Gilligan, Peter H. McFarland, Lynne V. Mellow, Mark Zuckerbraun, Brian S. TI Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; PLACEBO-CONTROLLED TRIAL; POLYMERASE-CHAIN-REACTION; FULMINANT PSEUDOMEMBRANOUS COLITIS; FECAL MICROBIOTA TRANSPLANTATION; LACTOBACILLUS-RHAMNOSUS GG; HEALTH-CARE EPIDEMIOLOGY; SERUM ANTIBODY-RESPONSE; PUMP INHIBITOR THERAPY; REAL-TIME PCR AB Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratified depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mild-to-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classification of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI. C1 [Surawicz, Christina M.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98104 USA. [Brandt, Lawrence J.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Brandt, Lawrence J.] Montefiore Med Ctr, Div Gastroenterol, Bronx, NY 10467 USA. [Binion, David G.] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Curry, Scott R.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Gilligan, Peter H.] Univ North Carolina Hosp, Clin Microbiol Immunol Labs, Chapel Hill, NC USA. [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. [McFarland, Lynne V.] Univ Washington, Sch Publ Hlth, Dept Med Chem, Seattle, WA 98104 USA. [Mellow, Mark] INTEGRIS Baptist Med Ctr, Digest Hlth Ctr, Oklahoma City, OK USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Surawicz, CM (reprint author), Univ Washington, Sch Med, Dept Med, Div Gastroenterol, 325 9th Ave, Seattle, WA 98104 USA. EM surawicz@u.washington.edu FU Optimer; Remel Lenexa, KS; Cepheid, Sunnyvale, CA; TechLab, Blacksburg, VA; Meridian Bioscience, Cincinnati, OH FX Dr Ananthakrishnan is on the scientific advisory boards for Prometheus Laboratory and Janssen. Dr Binion has received honoraria and is a consultant for Optimer, Janssen, Abbott, Salix, UCB Pharma, and Given Imaging; Dr Brandt is on the speaker's bureau has received grant funding from Optimer; Dr Gilligan's research was funded by Remel Lenexa, KS, Meridian Bioscience, Cincinnati, OH; Cepheid, Sunnyvale, CA, and TechLab, Blacksburg, VA, and has received honorarium from Alere Scarborough, ME; Dr Mellow is on the speaker's bureau of Optimer; Dr Zuckerbraun is on the speaker's bureau of Pfizer; Dr McFarland is on the advisory board of BioK Canada. Dr McFarland is a Government employee. The remaining authors declare no conflict of interest. NR 254 TC 341 Z9 387 U1 21 U2 118 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2013 VL 108 IS 4 BP 478 EP 498 DI 10.1038/ajg.2013.4 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 141CN UT WOS:000318703300004 PM 23439232 ER PT J AU Ananthakrishnan, AN Gainer, VS Cai, TX Perez, RG Cheng, SC Savova, G Chen, P Szolovits, P Xia, ZQ De Jager, PL Shaw, S Churchill, S Karlson, EW Kohane, I Perlis, RH Plenge, RM Murphy, SN Liao, KP AF Ananthakrishnan, Ashwin N. Gainer, Vivian S. Cai, Tianxi Perez, Raul Guzman Cheng, Su-Chun Savova, Guergana Chen, Pei Szolovits, Peter Xia, Zongqi De Jager, Philip L. Shaw, Stanley Churchill, Susanne Karlson, Elizabeth W. Kohane, Isaac Perlis, Roy H. Plenge, Robert M. Murphy, Shawn N. Liao, Katherine P. TI Similar Risk of Depression and Anxiety Following Surgery or Hospitalization for Crohn's Disease and Ulcerative Colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; POUCH-ANAL ANASTOMOSIS; POPULATION; COHORT; EPIDEMIOLOGY; COLECTOMY; DISORDER; HISTORY; STRESS AB OBJECTIVES: Psychiatric comorbidity is common in Crohn's disease (CD) and ulcerative colitis (UC). Inflammatory bowel disease (IBD)-related surgery or hospitalizations represent major events in the natural history of the disease. The objective of this study is to examine whether there is a difference in the risk of psychiatric comorbidity following surgery in CD and UC. METHODS: We used a multi-institution cohort of IBD patients without a diagnosis code for anxiety or depression preceding their IBD-related surgery or hospitalization. Demographic-, disease-, and treatment-related variables were retrieved. Multivariate logistic regression analysis was performed to individually identify risk factors for depression and anxiety. RESULTS: Our study included a total of 707 CD and 530 UC patients who underwent bowel resection surgery and did not have depression before surgery. The risk of depression 5 years after surgery was 16% and 11% in CD and UC patients, respectively. We found no difference in the risk of depression following surgery in the CD and UC patients (adjusted odds ratio, 1.11; 95% confidence interval, 0.84-1.47). Female gender, comorbidity, immunosuppressant use, perianal disease, stoma surgery, and early surgery within 3 years of care predicted depression after CD surgery; only the female gender and comorbidity predicted depression in UC patients. Only 12% of the CD cohort had >= 4 risk factors for depression, but among them nearly 44% subsequently received a diagnosis code for depression. CONCLUSIONS: IBD-related surgery or hospitalization is associated with a significant risk for depression and anxiety, with a similar magnitude of risk in both diseases. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Xia, Zongqi; De Jager, Philip L.; Shaw, Stanley; Karlson, Elizabeth W.; Kohane, Isaac; Perlis, Roy H.; Plenge, Robert M.; Murphy, Shawn N.; Liao, Katherine P.] Harvard Univ, Sch Med, Boston, MA USA. [Gainer, Vivian S.; Perez, Raul Guzman; Murphy, Shawn N.] Partners HealthCare, Res Comp, Charlestown, MA USA. [Cai, Tianxi; Cheng, Su-Chun] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Savova, Guergana; Chen, Pei; Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA. [Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Xia, Zongqi; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Shaw, Stanley] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Churchill, Susanne; Kohane, Isaac] Brigham & Womens Hosp, I2b2 Natl Ctr Biomed Comp, Boston, MA 02115 USA. [Karlson, Elizabeth W.; Plenge, Robert M.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880]; American Gastroenterological Association; US National Institutes of Health [K23 DK097142]; Katherine Swan Ginsburg Fund; US National Institutes of Health (NIH) [R01-AR056768, U01-GM092691, R01-AR059648]; Burroughs Wellcome Fund FX This study was supported by NIH U54-LM008748. A.N.A is supported by funding from the American Gastroenterological Association and from the US National Institutes of Health (K23 DK097142). K.P.L. is supported by the NIH K08 AR060257 and the Katherine Swan Ginsburg Fund. R.M.P. is supported by grants from the US National Institutes of Health (NIH; R01-AR056768, U01-GM092691, and R01-AR059648) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. E.W.K is supported by grants from the NIH (K24 AR052403, P60 AR047782, and R01 AR049880). NR 44 TC 24 Z9 24 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2013 VL 108 IS 4 BP 594 EP 601 DI 10.1038/ajg.2012.471 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 141CN UT WOS:000318703300016 PM 23337479 ER PT J AU Shah, D Sah, S Wanchu, A Wu, MX Bhatnagar, A AF Shah, Dilip Sah, Sangita Wanchu, Ajay Wu, Mei X. Bhatnagar, Archana TI Altered redox state and apoptosis in the pathogenesis of systemic lupus erythematosus SO IMMUNOBIOLOGY LA English DT Article DE Glutathione; Altered redox state; Apoptosis; Systemic lupus erythematosus (SLE) ID OXIDATIVE STRESS; DISEASE-ACTIVITY; MITOCHONDRIAL HYPERPOLARIZATION; RHEUMATOID-ARTHRITIS; GLUTATHIONE; BLOOD; ANTIOXIDANT; DAMAGE; CELLS; DEPLETION AB An altered redox status and increased lymphocyte apoptosis have been implicated in the development of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between glutathione (GSH) depletion, reactive oxygen species (ROS) and, the progression of apoptosis and their association with SLE severity. Significant low levels of intracellular glutathione, total thiol and altered redox state (GSH/GSSG) were found in SLE patients, in which lymphocyte apoptosis and activated caspase-3 expression in the lymphocytes were remarkably increased. The severity of disease was positively allied with the increased levels of lymphocyte apoptosis and caspase-3, but negatively with the decreased levels of total thiol, depleted intracellular glutathione and altered redox state (GSH/GSSG). The lymphocyte apoptosis and activated caspase-3 expression were negatively associated with intracellular levels of GSH and redox state and positively associated with the elevated levels of multiple oxidative stress markers: ROS and lipid peroxidation measured as malondialdehyde (MDA). These results suggest that GSH depletion and elevated oxidative stress trigger apoptosis and may be coupled with the severity of the disease. (C) 2012 Elsevier GmbH. All rights reserved. C1 [Shah, Dilip; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Shah, Dilip; Bhatnagar, Archana] Panjab Univ, Dept Biochem, Chandigarh 160014, India. [Sah, Sangita] KIE Univ, Jawaharlal Nehru Med Coll, Dept Biochem, Belgaum, India. [Wanchu, Ajay] Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis OP09, Portland, OR 97239 USA. [Wu, Mei X.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Bhatnagar, A (reprint author), Panjab Univ, Dept Biochem, Basic Med Sci Bldg, Chandigarh 160014, India. EM bhatnagar.archana@gmail.com FU Council of Scientific and Industrial Research, New Delhi, India FX This work was supported by grant received from Council of Scientific and Industrial Research, New Delhi, India. The authors would like to acknowledge Dr. Aman Sharma for analyzing the clinical data, Dr. Narendra Kumar for cutesy help in statistics analysis, Mrs Bhupinder and Mrs Sandhya for flow cytometry analysis of the samples. NR 46 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD APR PY 2013 VL 218 IS 4 BP 620 EP 627 DI 10.1016/j.imbio.2012.07.030 PG 8 WC Immunology SC Immunology GA 145NQ UT WOS:000319024100022 PM 22940256 ER PT J AU Maughan-Brown, B Venkataramani, AS AF Maughan-Brown, Brendan Venkataramani, Atheendar S. TI Incorrect Beliefs About Male Circumcision and Male-to-Female HIV Transmission Risk in South Africa: Implications for Prevention SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Maughan-Brown, Brendan] Univ Cape Town, Southern Africa Labour & Dev Res Unit, ZA-7925 Cape Town, South Africa. [Venkataramani, Atheendar S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Venkataramani, AS (reprint author), Massachusetts Gen Hosp, Dept Med, Charlestown HealthCare Ctr, 73 High St, Charlestown, MA 02129 USA. EM avenkataramani@partners.org NR 8 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2013 VL 62 IS 4 BP E121 EP E123 DI 10.1097/QAI.0b013e3182826343 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 145SM UT WOS:000319037700005 PM 24135737 ER PT J AU Ebert, MH Findling, RL Gelenberg, AJ Kane, JM Nierenberg, AA Tariot, PN AF Ebert, Michael H. Findling, Robert L. Gelenberg, Alan J. Kane, John M. Nierenberg, Andrew A. Tariot, Pierre N. TI The Effects of the Affordable Care Act on the Practice of Psychiatry SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 [Ebert, Michael H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Ebert, Michael H.] VA Connecticut Healthcare Syst, New Haven, CT USA. [Findling, Robert L.] Johns Hopkins Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Findling, Robert L.] Kennedy Krieger Inst, Baltimore, MD USA. [Gelenberg, Alan J.] Penn State Hershey Milton S Hershey Med Ctr, Dept Psychiat, Hershey, PA USA. [Kane, John M.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Kane, John M.] Hofstra North Shore Long Isl Jewish Sch Med, Dept Psychiat, Uniondale, NY USA. [Kane, John M.] North Shore Long Isl Jewish Hlth Syst, Behav Hlth Serv, New Hyde Pk, NY USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Bipolar Clin, Boston, MA USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Res Program, Depress Clin & Res Program, Boston, MA USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tariot, Pierre N.] Univ Arizona, Coll Med, Alzheimers Prevent Initiat, Banner Alzheimers Inst, Phoenix, AZ USA. [Tariot, Pierre N.] Univ Arizona, Coll Med, Dept Psychiat, Phoenix, AZ USA. RP Ebert, MH (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. NR 15 TC 4 Z9 4 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2013 VL 74 IS 4 BP 357 EP 361 DI 10.4088/JCP.12128co1c PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 146KS UT WOS:000319090600003 PM 23656840 ER PT J AU Goss, PE Lee, BL Badovinac-Crnjevic, T Strasser-Weippl, K Chavarri-Guerra, Y St Louis, J Villarreal-Garza, C Unger-Saldana, K Ferreyra, M Debiasi, M Liedke, PER Touya, D Werutsky, G Higgins, M Fan, L Vasconcelos, C Cazap, E Vallejos, C Mohar, A Knaul, F Arreola, H Batura, R Luciani, S Sullivan, R Finkelstein, D Simon, S Barrios, C Kightlinger, R Gelrud, A Bychkovsky, V Lopes, G Stefani, S Blaya, M Souza, FH Santos, FS Kaemmerer, A de Azambuja, E Zorilla, AFC Murillo, R Jeronimo, J Tsu, V Carvalho, A Gil, CF Sternberg, C Duenas-Gonzalez, A Sgroi, D Cuello, M Fresco, R Reis, RM Masera, G Gabus, R Ribeiro, R Knust, R Ismael, G Rosenblatt, E Roth, B Villa, L Solares, AL Leon, MX Torres-Vigil, I Covarrubias-Gomez, A Hernandez, A Bertolino, M Schwartsmann, G Santillana, S Esteva, F Fein, L Mano, M Gomez, H Hurlbert, M Durstine, A Azenha, G AF Goss, Paul E. Lee, Brittany L. Badovinac-Crnjevic, Tanja Strasser-Weippl, Kathrin Chavarri-Guerra, Yanin St Louis, Jessica Villarreal-Garza, Cynthia Unger-Saldana, Karla Ferreyra, Mayra Debiasi, Marcio Liedke, Pedro E. R. Touya, Diego Werutsky, Gustavo Higgins, Michaela Fan, Lei Vasconcelos, Claudia Cazap, Eduardo Vallejos, Carlos Mohar, Alejandro Knaul, Felicia Arreola, Hector Batura, Rekha Luciani, Silvana Sullivan, Richard Finkelstein, Dianne Simon, Sergio Barrios, Carlos Kightlinger, Rebecca Gelrud, Andres Bychkovsky, Vladimir Lopes, Gilberto Stefani, Stephen Blaya, Marcelo Souza, Fabiano Hahn Santos, Franklin Santana Kaemmerer, Alberto de Azambuja, Evandro Cardona Zorilla, Andres Felipe Murillo, Raul Jeronimo, Jose Tsu, Vivien Carvalho, Andre Gil, Carlos Ferreira Sternberg, Cinthya Duenas-Gonzalez, Alfonso Sgroi, Dennis Cuello, Mauricio Fresco, Rodrigo Reis, Rui Manuel Masera, Guiseppe Gabus, Raul Ribeiro, Raul Knust, Renata Ismael, Gustavo Rosenblatt, Eduardo Roth, Berta Villa, Luisa Lara Solares, Argelia Ximena Leon, Marta Torres-Vigil, Isabel Covarrubias-Gomez, Alfredo Hernandez, Andres Bertolino, Mariela Schwartsmann, Gilberto Santillana, Sergio Esteva, Francisco Fein, Luis Mano, Max Gomez, Henry Hurlbert, Marc Durstine, Alessandra Azenha, Gustavo TI Planning cancer control in Latin America and the Caribbean SO LANCET ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; UNIVERSAL HEALTH COVERAGE; WOOD-SMOKE EXPOSURE; NEPHRECTOMY INITIAL-EXPERIENCE; HER2-POSITIVE BREAST-CANCER; FACTOR RECEPTOR MUTATIONS; MIDDLE-INCOME COUNTRIES; LONG-TERM SURVIVAL; OF-THE-LITERATURE AB Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies. C1 [Goss, Paul E.; Lee, Brittany L.; Badovinac-Crnjevic, Tanja; St Louis, Jessica; Higgins, Michaela; Fan, Lei; Finkelstein, Dianne] Massachusetts Gen Hosp, Avon Int Breast Canc Res Program, Boston, MA 02114 USA. [Lee, Brittany L.; Knaul, Felicia; Sgroi, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Brittany L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol & Hematol, Vienna, Austria. [Chavarri-Guerra, Yanin] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol Oncol, Salvador Zubiran, Mexico. [Villarreal-Garza, Cynthia] Inst Nacl Cancerol, Med Oncol & Breast Canc Dept, Mexico City, DF, Mexico. [Ferreyra, Mayra] Maria Curie Hosp, Dept Oncol, Buenos Aires, DF, Argentina. [Debiasi, Marcio; Liedke, Pedro E. R.; Kaemmerer, Alberto] Hosp Mae Deus, Inst Canc, Hosp Clin Porto Alegre, Serv Oncol, Porto Alegre, RS, Brazil. [Debiasi, Marcio] Pontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Dept Med Oncol, Porto Alegre, RS, Brazil. [Liedke, Pedro E. R.; Schwartsmann, Gilberto] Univ Fed Rio Grande do Sul, Dept Med Oncol, Hosp Clin, Porto Alegre, RS, Brazil. [Touya, Diego; Cuello, Mauricio; Fresco, Rodrigo] Univ Republica, Hosp Clin, Dept Oncol, Montevideo, Uruguay. [Werutsky, Gustavo] Hosp Sao Lucas PUCRS, Latin Amer Cooperat Oncol Grp, Porto Alegre, RS, Brazil. [Werutsky, Gustavo] Hosp Sao Lucas PUCRS, Dept Med Oncol, Porto Alegre, RS, Brazil. [Vasconcelos, Claudia] Grp Brasileiro Estudios Canc Mama, Sao Paulo, Brazil. [Cazap, Eduardo] UICC, Geneva, Switzerland. [Cazap, Eduardo] Minist Hlth, Natl Canc Inst, Buenos Aires, DF, Argentina. [Vallejos, Carlos] Inst Nacl Enfermedades Neoplas, Dept Med Oncol, Lima, Peru. [Mohar, Alejandro] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Mohar, Alejandro; Duenas-Gonzalez, Alfonso] Inst Nacl Cancerol, Mexico City, DF, Mexico. [Knaul, Felicia] Harvard Global Equity Initiat, Boston, MA USA. [Knaul, Felicia] Mexican Hlth Fdn, Mexico City, DF, Mexico. [Knaul, Felicia] Tomatelo Pecho, Mexico City, DF, Mexico. [Arreola, Hector] Fdn Mexicana Salud, Tlalpan, Mexico. [Batura, Rekha] Kings Coll London, Kings Hlth Partners, Inst Oncopolicy, London WC2R 2LS, England. [Sullivan, Richard] Kings Coll London, Kings Hlth Partners, Guys Hosp, Integrated Canc Ctr, London WC2R 2LS, England. [Luciani, Silvana] Pan Amer Hlth Org, Area Hlth Surveillance Dis Prevent & Control, Washington, DC USA. [Finkelstein, Dianne] Massachusetts Gen Hosp, Dept Biostat, Ctr Biostat, Boston, MA 02114 USA. [Unger-Saldana, Karla] CIDE, Mexico City, DF, Mexico. [Simon, Sergio] Fed Univ Sao Paulo UNIFESP, Dept Clin Oncol, Sao Paulo, Brazil. [Simon, Sergio] Brazilian Breast Canc Study Grp GBECAM, Sao Paulo, Brazil. [Barrios, Carlos] Hosp Mae Deus, Inst Canc, PUCRS Sch Med, Dept Med, Porto Alegre, RS, Brazil. [Barrios, Carlos] LACOG, Porto Alegre, RS, Brazil. [Kightlinger, Rebecca] Univ Virginia, Dept Obstet & Gynecol, Charlottesville, VA USA. [Gelrud, Andres] Univ Chicago, Med Ctr, Ctr Pancreat Dis, Chicago, IL 60637 USA. [Bychkovsky, Vladimir] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Lopes, Gilberto] Johns Hopkins Singapore Int Med Ctr, Dept Med Oncol, Singapore, Singapore. [Lopes, Gilberto] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Stefani, Stephen] ICMD, Porto Alegre, RS, Brazil. [Stefani, Stephen] Fundacao Unimed, Porto Alegre, RS, Brazil. [Blaya, Marcelo] East Jefferson Gen Hosp, Dept Med, Metairie, LA USA. [Souza, Fabiano Hahn] Roche Diagnost Latin Amer, Med & Sci Affairs, Sao Paulo, Brazil. [Santos, Franklin Santana] Arnaldo Vieira de Carvalho Inst Canc, Palliat Care Unit, Sao Paulo, Brazil. [de Azambuja, Evandro] Inst Jules Bordet, Breast European Adjuvant Studies Team BREAST, Ctr Data, B-1000 Brussels, Belgium. [Cardona Zorilla, Andres Felipe] Fdn Santa Fe, Inst Oncol, Clin & Translat Oncol Grp, Bogota, Colombia. [Murillo, Raul] Inst Nacl Cancerol, Bogota, Colombia. [Jeronimo, Jose; Tsu, Vivien] PATH, Seattle, WA USA. [Carvalho, Andre; Reis, Rui Manuel] Barretos Canc Hosp, Teaching & Res Inst, Mol Oncol Res Ctr, Barretos, Brazil. [Gil, Carlos Ferreira] Inst Nacl Canc Jose Alencar Gomes da Silva, Dept Clin Res, Rio De Janeiro, Brazil. [Sternberg, Cinthya] Insitituto Nacl Canc INCA, Chief Translat Program, Rio De Janeiro, Brazil. [Knust, Renata] Insitituto Nacl Canc INCA, Coordenacao Pesquisa Clin & Inc Tecnol, Rio De Janeiro, Brazil. [Duenas-Gonzalez, Alfonso] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unit Biomed Res Canc, Mexico City, DF, Mexico. [Sgroi, Dennis] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Masera, Guiseppe] Univ Milano Bicocca, Fdn MBBM AOS Gerardo, Dept Pediat, Monza, Italy. [Gabus, Raul] Hosp Maciel, Serv Hematol & Bone Marrow Transplantat, Montevideo, Uruguay. [Ribeiro, Raul] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Ribeiro, Raul] St Jude Childrens Res Hosp, Int Outreach Program, Memphis, TN 38105 USA. [Ribeiro, Raul] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pediat, Memphis, TN 38163 USA. [Ismael, Gustavo] Hosp Amaral Carvalho, Clin Oncol & Hematol Dept, Jau, Brazil. [Rosenblatt, Eduardo] IAEA, Div Human Hlth, Appl Radiat Biol & Radiotherapy Sect, A-1400 Vienna, Austria. [Roth, Berta] Univ Buenos Aires, Inst Oncol Angel H Roffo, Area Terapia Radiante & Diagnost Imagenes, Buenos Aires, DF, Argentina. [Villa, Luisa] Santa Casa, Sch Med, Sao Paulo, Brazil. [Villa, Luisa] Univ Sao Paulo, Sao Paulo, Brazil. [Lara Solares, Argelia; Covarrubias-Gomez, Alfredo; Hernandez, Andres] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Pain & Palliat Med, Mexico City, DF, Mexico. [Ximena Leon, Marta] Univ La Sabana, Bogota, Colombia. [Torres-Vigil, Isabel] Univ Houston, Dorothy I Height Ctr Hlth Equ & Evaluat Res, Houston, TX USA. [Torres-Vigil, Isabel] Univ Texas MD Anderson Canc Ctr, Dept Palliat Canc Med, Houston, TX 77030 USA. [Bertolino, Mariela] Hosp Tornu FEMEBA Fdn, Palliat Care Unit, Buenos Aires, DF, Argentina. [Bertolino, Mariela] Icalma Fdn, Buenos Aires, DF, Argentina. [Santillana, Sergio] GlaxoSmithKline Oncol, Clin Dev Oncol, Collegeville, PA USA. [Esteva, Francisco] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Smithville, TX USA. [Fein, Luis] IOR, Rosario, Argentina. [Mano, Max] Hosp Sirio Libanes, Ctr Oncol, Sao Paulo, Brazil. [Gomez, Henry] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Hurlbert, Marc] Avon Fdn Breast Canc Crusade, New York, NY USA. [Durstine, Alessandra; Azenha, Gustavo] Amer Canc Soc, New York, NY USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Avon Breast Canc Ctr Excellence, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org RI Sternberg, Cinthya/K-4038-2012; Reis, Rui/C-2859-2009; Debiasi, Marcio/G-7780-2014; Ferreira, Carlos Gil/G-4957-2013; Barrios, Carlos/G-8525-2015; Schwartsmann, Gilberto/G-4256-2016; Stefani, Stefania/K-8075-2016; OI Sternberg, Cinthya/0000-0002-4760-6339; Reis, Rui/0000-0002-9639-7940; Schwartsmann, Gilberto/0000-0002-7850-1644; Stefani, Stefania/0000-0003-1594-7427; Fresco, Rodrigo/0000-0001-5342-3486; Gomez, Henry/0000-0003-2660-1843; Hurlbert, Marc/0000-0003-3301-3572; Sullivan, Richard/0000-0002-6435-1825 FU Avon Foundation, New York FX PEG thanks Julio Frenk for his support in the preparation of part 2. PEG, JS, TBC, and LF are supported by the Avon Foundation, New York. NR 371 TC 102 Z9 118 U1 9 U2 59 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 2013 VL 14 IS 5 BP 391 EP 436 PG 46 WC Oncology SC Oncology GA 140TY UT WOS:000318679700008 PM 23628188 ER PT J AU Rhee, SJ Cantelmo, NL Conrad, MF Stoughton, J AF Rhee, Soo J. Cantelmo, Nancy L. Conrad, Mark F. Stoughton, Julianne TI Factors Influencing the Incidence of Endovenous Heat-Induced Thrombosis (EHIT) SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE varicose veins; venous thrombosis; venous insuffiency; endothermal ablation ID GREATER SAPHENOUS-VEIN; RADIOFREQUENCY ABLATION; VENOUS THROMBOEMBOLISM; RISK-ASSESSMENT; LASER THERAPY; SINGLE-CENTER; COMPLICATIONS; EXPERIENCE; EFFICACY; REFLUX AB Introduction: Extension of thrombus from the great saphenous vein into the common femoral vein can be an early post-procedural complication of endothermal ablation (ETA). Methods: A retrospective review was performed over a 3-year period. Intraprocedural ultrasound images demonstrating the distance of the catheter tip to the saphenofemoral junction (SFJ) were available for 519 procedures, and this distance was measured. Results: Twenty-one (4.0%) cases of endovenous heat-induced thrombus (EHIT) were diagnosed. In all, 15 (6.4%) EHITs occurred following endovenous laser ablation and 6 (2.1%) after radio-frequency (P=.02). Distance from catheter tip to SFJ, vein diameter, concomitant treatments, and perioperative anticoagulation were not significant risk factors for EHIT. Of the clinical factors assessed, gender (P=.002), Clinical, Etiologic, Anatomic and Pathophysiologic classification 3 to 6 (P=.003), history of prior thrombosis (P=.04), and Caprini thrombosis risk factor assessment score (P=.004) were significant. On multivariate analysis, Caprini score (P=.0002) and male gender (P=.0003) remained significant. Conclusions: Male gender and increased Caprini score are predictive factors for EHIT following ETA. C1 [Rhee, Soo J.; Cantelmo, Nancy L.; Stoughton, Julianne] VeinSolut North Suburban Boston, Stoneham, MA USA. [Cantelmo, Nancy L.; Conrad, Mark F.; Stoughton, Julianne] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Cantelmo, Nancy L.; Conrad, Mark F.; Stoughton, Julianne] Harvard Univ, Sch Med, Boston, MA USA. RP Stoughton, J (reprint author), Massachusetts Gen Hosp, 15 Parkman St WAC 440, Boston, MA 02114 USA. EM jstoughton@partners.org NR 19 TC 11 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD APR PY 2013 VL 47 IS 3 BP 207 EP 212 DI 10.1177/1538574413478494 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 145GY UT WOS:000319004400006 PM 23427285 ER PT J AU Karia, P Azzi, J Heher, E Schmults, C AF Karia, P. Azzi, J. Heher, E. Schmults, C. TI A Cohort Study of Solid Organ Transplant Recipients Who Develop Malignancy: Risk of Subsequent Malignancy on mTOR vs. Non-mTOR Regimens. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Karia, P.; Azzi, J.; Schmults, C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Heher, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 97 EP 97 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300219 ER PT J AU Yamada, Y Boskovic, S Lee, S Nadazdin, O Smith, R Colvin, R Madsen, J Sachs, D Cosimi, A Kawai, T Benichou, G AF Yamada, Y. Boskovic, S. Lee, S. Nadazdin, O. Smith, R. Colvin, R. Madsen, J. Sachs, D. Cosimi, A. Kawai, T. Benichou, G. TI In Vivo IL-2 Administration Can Abrogate Tolerance to Kidney Allografts Induced Via Mixed Chimerism in Non-Human Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Yamada, Y.; Boskovic, S.; Lee, S.; Nadazdin, O.; Smith, R.; Colvin, R.; Madsen, J.; Sachs, D.; Cosimi, A.; Kawai, T.; Benichou, G.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 103 EP 103 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300241 ER PT J AU Yamada, Y Lee, S Boskovic, S Nadazdin, O Smith, R Colvin, R Madsen, J Sachs, D Benichou, G Cosimi, B Kawai, T AF Yamada, Y. Lee, S. Boskovic, S. Nadazdin, O. Smith, R. Colvin, R. Madsen, J. Sachs, D. Benichou, G. Cosimi, B. Kawai, T. TI Development of a Clinically Relevant Conditioning Regimen Using Available Costimulatory Blockade Reagents for Induction of Renal Allograft Tolerance Via Mixed Hematopoietic Chimerism SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Yamada, Y.; Lee, S.; Boskovic, S.; Nadazdin, O.; Smith, R.; Colvin, R.; Madsen, J.; Sachs, D.; Benichou, G.; Cosimi, B.; Kawai, T.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 104 EP 104 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300242 ER PT J AU Gilstrap, L Niehaus, E Maurer, M Feltrin, G Estep, J Witteles, R Zucker, M Baran, D Kushwaha, S Seldin, D Semigran, M AF Gilstrap, L. Niehaus, E. Maurer, M. Feltrin, G. Estep, J. Witteles, R. Zucker, M. Baran, D. Kushwaha, S. Seldin, D. Semigran, M. TI A Multi-Center, International Registry of Cardiac Transplantation for Light Chain (AL) and Transthyreitin (TTR) Amyloidosis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Gilstrap, L.; Niehaus, E.; Semigran, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maurer, M.] Columbia Univ, Med Ctr, New York, NY USA. [Feltrin, G.] Univ Padua, Padua, Italy. [Estep, J.] Methodist Hosp, Houston, TX 77030 USA. [Zucker, M.; Baran, D.] Newark Beth Israel, Newark, NJ USA. [Kushwaha, S.] Mayo Clin, Rochester, MN USA. [Seldin, D.] Boston Univ, Boston, MA 02215 USA. NR 0 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 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 130 EP 130 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300321 ER PT J AU Bergstrom, B Louis, S Peterson, F Aguiar, H Friedman, M Malinoski, D AF Bergstrom, B. Louis, S. Peterson, F. Aguiar, H. Friedman, M. Malinoski, D. TI The Use of the Flotrac System To Guide Donor Management Is Associated with Increased Organs Transplanted Per Donor. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Bergstrom, B.] Donor Network Arizona, Phoenix, AZ USA. [Louis, S.; Malinoski, D.] Portland VA Med Ctr, Portland, OR USA. [Peterson, F.; Aguiar, H.; Friedman, M.] OneLegacy, Los Angeles, CA 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 138 EP 138 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300346 ER PT J AU Lee, S Yamada, Y Boskovic, S Atif, M Tonsho, M Nadazdin, O Smith, R Colvin, R Allan, J Madsen, J Cosimi, A Benichou, G Kawai, T AF Lee, S. Yamada, Y. Boskovic, S. Atif, M. Tonsho, M. Nadazdin, O. Smith, R. Colvin, R. Allan, J. Madsen, J. Cosimi, A. Benichou, G. Kawai, T. TI Renal Allograft Tolerance Can Be Achieved in Non-Human Primates Via Delayed Mixed-Hematopoietic Chimerism and Alefacept Treatment. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Lee, S.; Yamada, Y.; Boskovic, S.; Atif, M.; Tonsho, M.; Nadazdin, O.; Smith, R.; Colvin, R.; Allan, J.; Madsen, J.; Cosimi, A.; Benichou, G.; Kawai, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 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 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 149 EP 149 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300381 ER PT J AU Lee, S Aoyama, A Tonsho, M Boskovic, S Yamada, Y Nadazdin, O Smith, R Colvin, R Cosimi, A Madsen, J Kawai, T Benichou, G Allan, J AF Lee, S. Aoyama, A. Tonsho, M. Boskovic, S. Yamada, Y. Nadazdin, O. Smith, R. Colvin, R. Cosimi, A. Madsen, J. Kawai, T. Benichou, G. Allan, J. TI Lung Allograft Tolerance in Non-Human Primates Via Establishment of Stable Mixed Hematopoietic Chimerism. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Lee, S.; Aoyama, A.; Tonsho, M.; Boskovic, S.; Yamada, Y.; Nadazdin, O.; Smith, R.; Colvin, R.; Cosimi, A.; Madsen, J.; Kawai, T.; Benichou, G.; Allan, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 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 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 150 EP 150 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300382 ER PT J AU Ferdman, J Porcheray, F Moore, C Gao, B DeVito, J Tullius, S Kawai, T Wong, W Zorn, E AF Ferdman, J. Porcheray, F. Moore, C. Gao, B. DeVito, J. Tullius, S. Kawai, T. Wong, W. Zorn, E. TI Expansion and Differentiation of B Cell Clones in Rejected Kidney Grafts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Ferdman, J.; Porcheray, F.; Moore, C.; Gao, B.; DeVito, J.; Kawai, T.; Wong, W.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tullius, S.] Brigham & Womens Hosp, Boston, MA 02115 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 178 EP 178 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300477 ER PT J AU Tonsho, M Benichou, G Boskovic, S Nadazdin, O Smith, N Colvin, R Sachs, D Cosimi, A Kawai, T Madsen, J AF Tonsho, M. Benichou, G. Boskovic, S. Nadazdin, O. Smith, N. Colvin, R. Sachs, D. Cosimi, A. Kawai, T. Madsen, J. TI Successful Tolerance Induction of Cardiac Allografts in Nonhuman Primates through Donor Kidney Co-Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Tonsho, M.; Benichou, G.; Boskovic, S.; Nadazdin, O.; Smith, N.; Colvin, R.; Cosimi, A.; Kawai, T.; Madsen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, D.; Madsen, J.] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 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 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 181 EP 182 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300491 ER PT J AU Fan, Z Jung, K Yun, S Strom, T Koulmanda, M AF Fan, Z. Jung, K. Yun, S. Strom, T. Koulmanda, M. TI Critical Role of Allograft Infiltrating ROR Gamma t Positive Innate Immune Cells and Hematopoietic Progenitor Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Fan, Z.; Strom, T.; Koulmanda, M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst, Boston, MA 02215 USA. [Jung, K.; Yun, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 189 EP 189 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300516 ER PT J AU Porcheray, F Fraser, J Gao, B McColl, A DeVito, J Dargon, I Helou, Y Wong, W Girouard, T Saidman, S Colvin, R Palmisano, A Maggiore, U Vaglio, A Smith, R Zorn, E AF Porcheray, F. Fraser, J. Gao, B. McColl, A. DeVito, J. Dargon, I. Helou, Y. Wong, W. Girouard, T. Saidman, S. Colvin, R. Palmisano, A. Maggiore, U. Vaglio, A. Smith, R. Zorn, E. TI Humoral Rejection of Human Kidney Grafts Associates with Polyreactive Antibodies That Bind Apoptotic Cells and Activate Complement SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Porcheray, F.; Fraser, J.; Gao, B.; McColl, A.; DeVito, J.; Dargon, I.; Helou, Y.; Wong, W.; Girouard, T.; Saidman, S.; Colvin, R.; Smith, R.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palmisano, A.; Maggiore, U.; Vaglio, A.] Univ Hosp Parma, Parma, Italy. RI sebastianovitsch, stepan/G-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 232 EP 233 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300659 ER PT J AU Zhao, G Yang, M Wei, L Huang, X Lei, J Markmann, J Deng, S AF Zhao, G. Yang, M. Wei, L. Huang, X. Lei, J. Markmann, J. Deng, S. TI A Prevascularized Tissue-Engineered Construct Serves as an Alternative Site for Pancreatic Islet Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Zhao, G.; Yang, M.; Wei, L.; Huang, X.; Deng, S.] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, G.; Yang, M.; Wei, L.; Lei, J.; Markmann, J.; Deng, S.] Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 238 EP 238 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300676 ER PT J AU Grijalva, J Camargo, F Sadri-Vakili, G Vakili, K AF Grijalva, J. Camargo, F. Sadri-Vakili, G. Vakili, K. TI YAP Phosphorylation Is Altered during Liver Regeneration in a Rat Hepatectomy Model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Grijalva, J.; Vakili, K.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Camargo, F.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Sadri-Vakili, G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 256 EP 257 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300746 ER PT J AU Heaphy, E Mandelbrot, D Rodriquez, J Schold, J Poggio, E AF Heaphy, E. Mandelbrot, D. Rodriquez, J. Schold, J. Poggio, E. TI First-Year Renal Function Changes among Living Kidney Donors (LKD) in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Poggio, E.] Cleveland Clin, Nephrol & HTN, Cleveland, OH 44106 USA. [Heaphy, E.; Schold, J.] Cleveland Clin, Cleveland, OH 44106 USA. [Mandelbrot, D.; Rodriquez, J.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 305 EP 305 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301127 ER PT J AU Faustman, D AF Faustman, D. TI Modification of Donor Tissue Antigens with Papain To Inhibit Transplant Rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA USA. Harvard Med, Charlestown, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 318 EP 318 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301169 ER PT J AU Baddley, J Klausing, B Brizendine, K Kumar, V Julian, B Eckhoff, D Tallaj, J Wille, K Moser, S Pappas, P AF Baddley, J. Klausing, B. Brizendine, K. Kumar, V. Julian, B. Eckhoff, D. Tallaj, J. Wille, K. Moser, S. Pappas, P. TI Treatment of Cryptococcosis in Solid-OrganTransplant Recipients: Relapse Is Rare after Discontinuation of Therapy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Baddley, J.; Klausing, B.; Kumar, V.; Julian, B.; Eckhoff, D.; Tallaj, J.; Wille, K.; Moser, S.; Pappas, P.] Univ Alabama Birmingham, Birmingham, AL USA. [Baddley, J.] Birmingham VAMC, Birmingham, AL USA. [Brizendine, K.] Cleveland Clin, Cleveland, OH 44106 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 344 EP 344 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301266 ER PT J AU Martins, P Almusa, A Markmann, J Hertl, M Elias, N AF Martins, P. Almusa, A. Markmann, J. Hertl, M. Elias, N. TI Acute Diverticulitis Incidence, Management, and Outcomes in Solid Organ Transplant Patients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Martins, P.; Almusa, A.; Markmann, J.; Hertl, M.; Elias, N.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Transplant Div, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 346 EP 346 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301271 ER PT J AU Lee, K Lian, M Stott, R Yeh, H Deng, S Kim, J Markmann, J AF Lee, K. Lian, M. Stott, R. Yeh, H. Deng, S. Kim, J. Markmann, J. TI Spontaneous Acceptance of Mouse Islet Allografts in B Cell-Deficient Donor and Recipient Is Associated with Donor-Derived Plasmacytoid Dendritic Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Lee, K.; Lian, M.; Stott, R.; Yeh, H.; Deng, S.; Kim, J.; Markmann, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 360 EP 361 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301319 ER PT J AU Kim, J Lee, K Zhao, G Stott, R Soohoo, J Lian, M Fitzgerald, L Yeh, H Deng, S Markmann, J AF Kim, J. Lee, K. Zhao, G. Stott, R. Soohoo, J. Lian, M. Fitzgerald, L. Yeh, H. Deng, S. Markmann, J. TI Transplantation Tolerance That Depends on Regulatory T Cells Induced by TGF-beta-Producing Regulatory B Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Kim, J.; Lee, K.; Zhao, G.; Stott, R.; Soohoo, J.; Lian, M.; Fitzgerald, L.; Yeh, H.; Deng, S.; Markmann, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhao, G.; Markmann, J.] Sichual Prov Peoples Hosp, Chengdu, Sichuan Provinc, Peoples R China. [Fitzgerald, L.] Tufts Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 361 EP 361 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301321 ER PT J AU Shinoda, K Akiyoshi, T Chase, C Farkash, E Russell, P Madsen, J Colvin, R AF Shinoda, K. Akiyoshi, T. Chase, C. Farkash, E. Russell, P. Madsen, J. Colvin, R. TI Depletion of Both Recipient and Donor Foxp3+Cells Can Break Tolerance of Skin or Heart Allografts Induced by Mixed Chimerism in Mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Shinoda, K.; Akiyoshi, T.; Chase, C.; Farkash, E.; Russell, P.; Madsen, J.; Colvin, R.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Akiyoshi, T.; Farkash, E.; Colvin, R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 362 EP 362 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301325 ER PT J AU Madariaga, M Michel, S Tasaki, M Villani, V Farkash, E La Muraglia, G Allan, J Sachs, D Yamada, K Madsen, J AF Madariaga, M. Michel, S. Tasaki, M. Villani, V. Farkash, E. La Muraglia, G., II Allan, J. Sachs, D. Yamada, K. Madsen, J. TI Kidney-Induced Cardiac Allograft Tolerance across a Full MHC-Barrier in Miniature Swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Madariaga, M.; Michel, S.; Tasaki, M.; Villani, V.; La Muraglia, G., II; Allan, J.; Sachs, D.; Yamada, K.; Madsen, J.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cardiothorac Transplantat Lab, Boston, MA 02114 USA. [Madariaga, M.; Michel, S.; Tasaki, M.; Villani, V.; Farkash, E.; La Muraglia, G., II; Allan, J.; Sachs, D.; Yamada, K.; Madsen, J.] Harvard Univ, Sch Med, Boston, MA USA. [Farkash, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 365 EP 365 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301337 ER PT J AU Gao, B Porcheray, F Moore, C McColl, A Ferdman, J Abidoglu, C Girouard, T DeVito, J Paine, R Saidman, S Wong, W Zorn, E AF Gao, B. Porcheray, F. Moore, C. McColl, A. Ferdman, J. Abidoglu, C. Girouard, T. DeVito, J. Paine, R. Saidman, S. Wong, W. Zorn, E. TI Pre-Transplant Serum IgG Reactivity to Apoptotic Cells Correlates with HLA Reactivity and Kidney Graft Loss. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Gao, B.; Porcheray, F.; Moore, C.; McColl, A.; Ferdman, J.; Abidoglu, C.; Girouard, T.; DeVito, J.; Paine, R.; Saidman, S.; Wong, W.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gao, B.] Jilin Univ, Hosp 1, Changchun 130023, Jilin, Peoples R China. 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 366 EP 367 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301343 ER PT J AU Tena, A Leonard, D Tasaki, M Mallard, C Germana, S Terlouw, S Dobrinsky, J Mtango, N Verstegen, J Sachs, D Hawley, R AF Tena, A. Leonard, D. Tasaki, M. Mallard, C. Germana, S. Terlouw, S. Dobrinsky, J. Mtango, N. Verstegen, J. Sachs, D. Hawley, R. TI GalKO-hCD47 Transgenic Hematopoietic Stem and Progenitor Cells for Induction of Mixed Xenogeneic Chimerism in Primates: Initial Results. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Tena, A.; Leonard, D.; Tasaki, M.; Mallard, C.; Germana, S.; Sachs, D.; Hawley, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Terlouw, S.; Dobrinsky, J.; Mtango, N.; Verstegen, J.] Minitube Amer, Verona, WI 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 371 EP 371 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301361 ER PT J AU Ueno, T Yeung, M Jun, K McGrath, M Da Silva, N Ikeda, T Najafian, N Sylvie, B Brown, D Yun, A Weissleder, R Sayegh, M AF Ueno, T. Yeung, M. Jun, K. McGrath, M. Da Silva, N. Ikeda, T. Najafian, N. Sylvie, B. Brown, D. Yun, A. Weissleder, R. Sayegh, M. TI Potential Contributions to the Direct Pathway by Donor Dendritic Cells at Vascularized Graft. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Ueno, T.; Da Silva, N.; Sylvie, B.; Brown, D.; Weissleder, R.] Massachusetts Gen Hosp, CSB, Boston, MA 02114 USA. [Ueno, T.; Yeung, M.; McGrath, M.; Najafian, N.; Sayegh, M.] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Jun, K.; Yun, A.] Massachusetts Gen Hosp, Wellman Ctr, Boston, MA 02114 USA. [Ueno, T.; Ikeda, T.] Tokyo Med Univ Hosp, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 376 EP 376 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301378 ER PT J AU Madariaga, M Sihag, S Gottschall, J Farkash, E Haas, M Carroll, M Allan, J AF Madariaga, M. Sihag, S. Gottschall, J. Farkash, E. Haas, M. Carroll, M. Allan, J. TI Mitigating Lung Ischemia-Reperfusion Injury in Miniature Swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Madariaga, M.; Sihag, S.; Gottschall, J.; Haas, M.; Allan, J.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cardiothorac Transplantat Lab, Boston, MA 02114 USA. [Farkash, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carroll, M.] Harvard Univ, Sch Med, Boston, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 410 EP 410 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301499 ER PT J AU Jain, N Wong, I Wong, E Boneschansker, L Aranyosi, A Briscoe, D Irimia, D AF Jain, N. Wong, I. Wong, E. Boneschansker, L. Aranyosi, A. Briscoe, D. Irimia, D. TI Live-Time Imaging of Chemotactic Responses in Activated T Cells Demonstrate Novel Exploratory Patterns of Migration towards Chemokines. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Jain, N.; Boneschansker, L.; Briscoe, D.] Boston Childrens Hosp, Div Nephrol, Boston, MA USA. [Jain, N.; Wong, I.; Wong, E.; Aranyosi, A.; Irimia, D.] Massachusetts Gen Hosp, Dept Surg, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Jain, N.; Wong, I.; Wong, E.; Boneschansker, L.; Aranyosi, A.; Briscoe, D.; Irimia, D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 412 EP 412 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301506 ER PT J AU Farris, A Chan, S Climenhaga, J Colvin, R Mengel, M AF Farris, A. Chan, S. Climenhaga, J. Colvin, R. Mengel, M. TI The Multicenter Banff Fibrosis Trial: Comparing Visual Assessment of Interstitial Fibrosis in Kidney Biopsies to Computer-Based Image Analysis and Organ Function. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Farris, A.] Emory Univ, Atlanta, GA 30322 USA. [Chan, S.; Climenhaga, J.; Mengel, M.] Univ Alberta, Edmonton, AB, Canada. [Colvin, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 420 EP 420 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301530 ER PT J AU Chen, G Ko, D Wang, C Qiu, J Han, M He, X Chen, L AF Chen, G. Ko, D. Wang, C. Qiu, J. Han, M. He, X. Chen, L. TI Utilization of Kidneys from Donors after Circulatory Death in China: An Initial Report from a Single Center. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Chen, G.; Wang, C.; Qiu, J.; Han, M.; He, X.; Chen, L.] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Ko, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Ko, D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 481 EP 482 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301741 ER PT J AU Martins, P Berendsen, T Yeh, H Bruinsma, B Izamis, M Uygun, K McDaid, J Yarmush, M Markmann, J AF Martins, P. Berendsen, T. Yeh, H. Bruinsma, B. Izamis, M. Uygun, K. McDaid, J. Yarmush, M. Markmann, J. TI Perfluorocarbon Added to the University of Winsconsin Solution Reduces Ischemia Reperfusion Injury and Prolongs Survival of DCD Liver Grafts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Martins, P.; Yeh, H.; McDaid, J.; Markmann, J.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. [Berendsen, T.; Bruinsma, B.; Izamis, M.; Uygun, K.; Yarmush, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Berendsen, T.; Bruinsma, B.; Izamis, M.; Uygun, K.; Yarmush, M.] Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 490 EP 490 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301770 ER PT J AU Da Silva, C Studer, P Csizmadia, E Minussi, D Daniels, K Ferran, C AF Da Silva, C. Studer, P. Csizmadia, E. Minussi, D. Daniels, K. Ferran, C. TI Fish Oil Diet Overcomes Genetic Predisposition Restoring Hepatocyte Proliferation in Livers of A20 Heterozygous Mice Following Partial Hepatectomy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Da Silva, C.; Studer, P.; Csizmadia, E.; Minussi, D.; Daniels, K.; Ferran, C.] Beth Israel Deaconess Med Ctr HMS, Boston, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 492 EP 492 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301778 ER PT J AU Irwin, L Cetrulo, C Winograd, J Marquez, A Noska, S Israelian, A Parker, H Norman, A Fishman, J AF Irwin, L. Cetrulo, C. Winograd, J. Marquez, A. Noska, S. Israelian, A. Parker, H. Norman, A. Fishman, J. TI Incorporating a Vascularized Composite Allograft Transplant Program into a Transplant Center. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Irwin, L.; Cetrulo, C.; Winograd, J.; Marquez, A.; Noska, S.; Israelian, A.; Parker, H.; Norman, A.; Fishman, J.] Massachusetts Gen Hosp, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 538 EP 539 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301932 ER PT J AU Myaskovsky, L Pleis, J Ramkumar, M Mittalhenkle, A Langone, A Thomas, C AF Myaskovsky, L. Pleis, J. Ramkumar, M. Mittalhenkle, A. Langone, A. Thomas, C. TI Has the VA Found a Way To Reduce Racial Disparities in Kidney Transplant Evaluation? Preliminary Results from the National VA Kidney Transplant Study. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] U Pittsburgh, Pittsburgh, PA USA. [Mittalhenkle, A.] Portland VA Med Ctr, Portland, Dorset, England. [Langone, A.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Thomas, C.] Iowa City VA Healthcare, Iowa City, IA 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 541 EP 541 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301941 ER PT J AU Lowalekar, S Cao, H Lu, X Treanor, P Thatte, H AF Lowalekar, S. Cao, H. Lu, X. Treanor, P. Thatte, H. TI Somah - A Novel Modality for Subnormothermic Preservation of Donor Hearts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Lowalekar, S.; Cao, H.; Lu, X.; Treanor, P.; Thatte, H.] VA Boston Healthcare Syst, Cardiac Surg Div, Boston, MA USA. [Lowalekar, S.; Cao, H.; Lu, X.; Thatte, H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lowalekar, S.; Cao, H.; Lu, X.; Thatte, H.] Harvard Univ, Sch Med, Boston, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 550 EP 550 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301972 ER PT J AU Morris, H Shen, Y Kawai, T Robins, H Sykes, M AF Morris, H. Shen, Y. Kawai, T. Robins, H. Sykes, M. TI Role of Deletion of Donor-Reactive T Cells in Maintaining Human Allograft Tolerance Achieved via Combined Kidney and Bone Marrow Transplantation (CKBMT). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Morris, H.; Shen, Y.; Sykes, M.] Columbia Univ, Med Ctr, New York, NY USA. [Robins, H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kawai, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 550 EP 550 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301973 ER PT J AU Ndishabandi, D Shinoda, K Colvin, R Alessandrini, A AF Ndishabandi, D. Shinoda, K. Colvin, R. Alessandrini, A. TI Strain Specific Induction of Regulatory T Cells by Plasmacytoid Dendritic Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Ndishabandi, D.; Shinoda, K.; Colvin, R.; Alessandrini, A.] Massachusetts Gen Hosp, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 550 EP 551 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301975 ER PT J AU Zhang, LT Zhang, LJ Zhang, JJ Ye, XX Xie, AM Chen, LY Kang, JX Cai, C AF Zhang, Liang-Tao Zhang, Li-Jian Zhang, Jun-Jie Ye, Xiao-Xia Xie, Ai-Mei Chen, Li-Yu Kang, Jing X. Cai, Chun TI Quantification of the sixth DNA base 5-hydroxymethylcytosine in colorectal cancer tissue and C-26 cell line SO BIOANALYSIS LA English DT Article ID ONCOMETABOLITE 2-HYDROXYGLUTARATE; GENOMIC DNA; 5-METHYLCYTOSINE; SPECTROMETRY; METHYLATION; EPIGENETICS; TET1 AB Background: DNA methylation at the five position of cytosine is well recognized as an important epigenetic modification in human health and disease. Recent evidences demonstrated that 5-methylcytosine (5-mC) by the TET family of enzymes can be converted to 5-hydroxymethylcytosine (5-hmC). Here, we use an ultrasensitive and accurate isotope-based LC-MS/MS method to precisely determine the levels of 5-hmC and 5-mC in colorectal cancer and the C-26 colon adenocarcinoma cell line. Results: Our data showed that 5-hmC content is significantly reduced (approximately sixfold) in colorectal cancer as compared with adjacent normal tissue. Similarly, the ratio of 5-hmC to 5-mC dropped from 0.054 +/- 0.005 in normal tissues, to 0.011 +/- 0.002 in cancer. Conclusion: The analysis of 5-hmC levels and the ratio of 5-hmC:5-mC during tumor progression might provide insight into the role of this modification in cellular immortalization and transformation. C1 [Zhang, Liang-Tao; Zhang, Li-Jian; Zhang, Jun-Jie; Ye, Xiao-Xia; Xie, Ai-Mei; Chen, Li-Yu; Cai, Chun] Guangdong Med Coll, Zhanjiang 524023, Guangdong, Peoples R China. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Cai, C (reprint author), Guangdong Med Coll, Zhanjiang 524023, Guangdong, Peoples R China. EM caichun2006@tom.com FU Science & Technology Innovation Fun of Guangdong Medical College [STIF201125] FX This work was supported by Science & Technology Innovation Fun of Guangdong Medical College, STIF201125. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 25 TC 11 Z9 12 U1 0 U2 25 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD APR PY 2013 VL 5 IS 7 BP 839 EP 845 DI 10.4155/BIO.13.28 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 139LW UT WOS:000318585200014 PM 23534428 ER PT J AU Kassab, GS Bhatt, DL Lefevre, T Louvard, Y AF Kassab, Ghassan S. Bhatt, Deepak L. Lefevre, Thierry Louvard, Yves TI Relation of angiographic side branch calibre to myocardial mass: a proof of concept myocardial infarct index SO EUROINTERVENTION LA English DT Editorial Material DE allometric scaling; biomarkers; design; ischaemia; scaling laws ID PERCUTANEOUS CORONARY INTERVENTION; SCALING LAWS; DESIGN; ARTERIES; VOLUME; TREES AB Elevation of biomarkers and ischaemia after coronary stenting of a bifurcation is not uncommon due to side branch (SB) occlusion. Hence, it is important to understand the relation between the lumen calibre of the SB and the myocardial mass affected. The objective of this proof of concept perspective is to provide a formulation for the relation between the SB calibre and perfused myocardial mass based on experimentally-validated scaling laws. A lumen calibre-mass scaling law provides a nearly linear relation between cross-sectional area of SB and the myocardial mass at risk. It is clinically known that the larger the diameter of the SB the more myocardial mass is at risk. The present analysis formulates this notion quantitatively and provides a simple relation where the %infarct can be determined directly from the angiographic cross-sectional area of SB. This relation can help guide the decision for bifurcation stenting where the SB may be at risk for occlusion. This brief proof of concept perspective provides a basis for future human studies that may demarcate the calibre (and hence myocardial mass) in relation to cardiac biomarkers as a cut-off for treatment of SB. C1 [Kassab, Ghassan S.] Indiana Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA. [Kassab, Ghassan S.] Indiana Purdue Univ, Dept Surg, Indianapolis, IN 46202 USA. [Kassab, Ghassan S.] Indiana Purdue Univ, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Lefevre, Thierry; Louvard, Yves] Inst Cardiovasc Paris Sud, Massy, France. RP Kassab, GS (reprint author), Indiana Purdue Univ, 635 Barnhill Dr,MS 2069, Indianapolis, IN 46202 USA. EM gkassab@iupui.edu FU NHLBI NIH HHS [HL092048-5] NR 14 TC 4 Z9 4 U1 0 U2 1 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD APR PY 2013 VL 8 IS 12 BP 1461 EP 1463 DI 10.4244/EIJV8I12A220 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141UJ UT WOS:000318751700017 PM 23680961 ER PT J AU Kumbhani, DJ Steg, PG Cannon, CP Eagle, KA Smith, SC Crowley, K Goto, S Ohman, EM Bakris, GL Perlstein, TS Kinlay, S Bhatt, DL AF Kumbhani, Dharam J. Steg, P. Gabriel Cannon, Christopher P. Eagle, Kim A. Smith, Sidney C., Jr. Crowley, Kevin Goto, Shinya Ohman, E. Magnus Bakris, George L. Perlstein, Todd S. Kinlay, Scott Bhatt, Deepak L. CA REACH Registry Investigators TI Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis SO EUROPEAN HEART JOURNAL LA English DT Article DE Resistant hypertension; Atherosclerosis; Mortality; Stroke; Heart failure ID AMBULATORY BLOOD-PRESSURE; PRESERVED EJECTION FRACTION; CARDIOVASCULAR EVENT RATES; UNITED-STATES; EUROPEAN-SOCIETY; HEART-FAILURE; RISK-FACTORS; DOUBLE-BLIND; TASK-FORCE; OUTPATIENTS AB The effect of resistant hypertension on outcomes in patients with atherothrombotic disease is currently unknown. Accordingly, we sought to determine the prevalence and outcomes of resistant hypertension in stable hypertensive outpatients with subclinical or established atherothombotic disease enrolled in the international Reduction of Atherothrombosis for Continued Health (REACH) registry. Resistant hypertension was defined as a blood pressure 140/90 mmHg at baseline (130/80 mmHg if diabetes/renal insufficiency) with the use of 3 antihypertensive medications, including a diuretic. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 4 years. A total of 53 530 hypertensive patients were included. The prevalence of resistant hypertension was 12.7; 6.2 on 3 antihypertensive agents, 4.6 on 4 agents, and 1.9 on 5 agents (mean: 4.7 0.8). In addition to a diuretic, these patients were being treated mostly with ACE-inhibitors/angiotensin receptor blockers (90.1), beta-blockers (67.0), and calcium channel blockers (50.8). Patients with resistant hypertension had a higher risk of the primary endpoint on multivariable analysis [hazard ratio (HR) 1.11, 95 confidence interval (CI) 1.021.20; P 0.017], including an increased non-fatal stroke risk (HR: 1.26; 95 CI: 1.101.45; P 0.0008). Hospitalizations due to congestive heart failure were higher (P 0.0001). Patients on 5 agents had a higher adjusted risk for the primary endpoint when compared with those on 3 agents (P 0.03). The presence of resistant hypertension identifies a subgroup of patients with hypertension and atherothrombosis who are at heightened risk for adverse long-term outcomes. C1 [Kumbhani, Dharam J.; Cannon, Christopher P.; Perlstein, Todd S.; Kinlay, Scott; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kumbhani, Dharam J.; Cannon, Christopher P.; Perlstein, Todd S.; Kinlay, Scott; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Steg, P. Gabriel] INSERM, U698, Paris, France. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Steg, P. Gabriel] AP HP, Paris, France. [Cannon, Christopher P.; Crowley, Kevin] TIMI Study Grp, Boston, MA USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. Univ Chicago Med, Chicago, IL USA. [Kinlay, Scott; Bhatt, Deepak L.] VA Boston Healthcare Syst, Div Cardiol, Boston, MA 02132 USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu RI sebastianovitsch, stepan/G-8507-2013 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Servier; Intekrin Therapeutics; Accumetrics; AstraZeneca; GlaxoSmithKline; Merck; Takeda; Blue Cross Blue Shield of Michigan; National Institutes of Health (NIH); Mardigian Foundation Varbedian Fund; GORE; Hewlett Foundation; Eisai; Berlinger-Ingelheim; CV Therapeutics; Daiichi-Sankyo; Datascope; Eli Lilly; Marquet; Schering-Plough; Medicines Company; Forest Labs; Relapsya; WebMD; Amarin; Ethicon; Medtronic (co-PI of SYMPLICITY HTN-3) FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. No funding was received for this manuscript. No sponsors reviewed this manuscript.; D.J.K.: Honoraria: American College of Cardiology, SomahLutions. Ph.G.S.: Research grant from Servier; participated in consultancy or advisory board for Eisai, Amgen, Astellas, Bayer, Boehringer Ingelheim, BMS, Daiichi-Sankyo-Lilly, GSK, Merck, Pfizer, Roche, The Medicines Company, AstraZeneca, Sanofi-Aventis, Servier; and being a stockholder in Aterovax. C. P. C.: Research grants from Intekrin Therapeutics, Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Takeda; honoraria from Pfizer, AstraZeneca; participated in consultancy or advisory board for Bristol-Myers Squibb/Sanofi, Novartis, Alnylam; and having ownership interest in Automedics Medical Systems. K. A. E.: Grant/research support from Bristol-Myers Squibb, Blue Cross Blue Shield of Michigan, the National Institutes of Health (NIH), Sanofi-Aventis, the Mardigian Foundation Varbedian Fund, GORE, and the Hewlett Foundation and being a consultant for the NIH National Heart, Lung, and Blood Institute, Sanofi-Aventis, and the Robert Wood Johnson. Foundation: S. C. S.: None. K. C.: None. S. G.: Research grants from Sanofi-Aventis, Eisai, Berlinger-Ingelheim; participated in consultancy or advisory board for Eisai, Sanofi-Aventis, Otsuka. E.M.O.: Research grants from Bristol-Myers Squibb, CV Therapeutics, Daiichi-Sankyo, Datascope, Eli Lilly, Marquet, Sanofi-Aventis, Schering-Plough, and The Medicines Company, and providing consulting or other services for Abiomed, AstraZeneca, CV Therapeutics, Datascope, Gilead Sciences, Liposcience, Marquet, Northpoint Domain, Pozen, Response Biomedical, Sanofi-Aventis, The Medicines Company, and WebMD (theheart.org). G. L. B.: Research Grants from Forest Labs, Relapsya, WebMD and Consultant to: Abbott, Takeda, Johnson & Johnson, Daichi-Sankyo, Medtronic. T. S. P.: None. S. K.: None. D. L. B.: Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Other: Senior Associate Editor, Journal of Invasive Cardiology; Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic (co-PI of SYMPLICITY HTN-3), Sanofi-Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. NR 37 TC 67 Z9 69 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR PY 2013 VL 34 IS 16 BP 1204 EP 1214 DI 10.1093/eurheartj/ehs368 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139AN UT WOS:000318553800010 PM 23144048 ER PT J AU Massimini, DF Singh, A Wells, JH Li, GA Warner, JJP AF Massimini, Daniel F. Singh, Anshu Wells, Jessica H. Li, Guoan Warner, Jon J. P. TI Suprascapular nerve anatomy during shoulder motion: a cadaveric proof of concept study with implications for neurogenic shoulder pain SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE In-vivo biomechanics; neuropathy; rotator cuff tear; nerve tracking ID ROTATOR-CUFF TEARS; GEOMETRIC IMAGE DISTORTION; ARTHROSCOPIC RELEASE; VOLLEYBALL PLAYERS; GANGLION CYSTS; NEUROPATHY; SUPRASPINATUS; ENTRAPMENT; MUSCLE; NOTCH AB Background: The suprascapular nerve (SSN) carries sensory fibers which may contribute to shoulder pain. Prior anatomic study demonstrated that alteration in SSN course with simulated rotator cuff tendon (RCT) tears cause tethering and potential traction injury to the nerve at the suprascapular notch. Because the SSN has been implicated as a major source of pain with RCT tearing, it is critical to understand nerve anatomy during shoulder motion. We hypothesized that we could evaluate the SSN course with a novel technique to evaluate effects of simulated RCT tears, repair, and/or release of the nerve. Methods: The course of the SSN was tracked with a dual fluoroscopic imaging system in a cadaveric model with simulated rotator cuff muscle forces during dynamic shoulder motion. Results: After a simulated full-thickness supraspinatus/infraspinatus tendon tear, the SSN translated medially 3.5 mm at the spinoglenoid notch compared to the anatomic SSN course. Anatomic footprint repair of these tendons restored the SSN course to normal. Open release of the transverse scapular ligament caused the SSN to move 2.5 mm superior-posterior out of the suprascapular notch. Conclusion: This pilot study demonstrated that the dynamic SSN course can be evaluated and may be altered by a RCT tear. Preliminary results suggest release of the transverse scapular ligament allowed the SSN to move upward out of the notch. This provides a biomechanical proof of concept that SSN traction neuropathy may occur with RCT tears and that release of the transverse scapular ligament may alleviate this by altering the course of the nerve. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Massimini, Daniel F.; Singh, Anshu; Wells, Jessica H.; Li, Guoan; Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA USA. [Massimini, Daniel F.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 3200, Boston, MA 02114 USA. EM jwarner@partners.org FU Harvard Shoulder Service FX This work was supported by unrestricted funds of the Harvard Shoulder Service. NR 30 TC 10 Z9 10 U1 1 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 2013 VL 22 IS 4 BP 463 EP 470 DI 10.1016/j.jse.2012.04.018 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 140UB UT WOS:000318680100010 PM 22819576 ER PT J AU Neuhaus, V Ring, D AF Neuhaus, Valentin Ring, David TI Effect of different statistical methods on union or time to union in a published study about clavicular fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Clavicle; fracture; intention-to-treat; time to union; union ID CLINICAL-TRIALS; TREAT AB Background: Time to union is a suspect measure for comparing treatments given the absence of a consensus definition of union, the limited reliability of diagnostic tests, and inconsistency in evaluation times. The purpose of this study was to quantify the variations in union and time to union according to different statistical methods and different approaches to missing data. Materials and methods: Data from a published multicenter, randomized trial comparing operative and nonoperative treatment of clavicular fractures were reanalyzed. Two main types of missing data were encountered: (1) lost to follow-up or died before union and (2) missed appointment. We studied the effect of four statistical methods-comparison of means, comparison of medians, x(2), and Kaplan-Meier curves-for comparing union or time to union between cohorts for the following scenarios: strict intention-to-treat, intention-to-treat with exclusion of patients with less than 12 months of follow-up, as-treated analysis, and four different imputation methods for missing data. Results: Mean and median time to union varied up to 17%, but comparative statistics consistently demonstrated shorter time to union among operatively treated patients. There were significant differences in the odds ratio, x(2) values, and the number needed to treat (8%-62%) of union vs nonunion for the three principal analyses. Conclusion: Different strategies for handling missed evaluations seem to influence categoric results (eg, union or nonunion) more than continuous measures such as time to union. C1 [Neuhaus, Valentin; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 9 TC 1 Z9 1 U1 0 U2 3 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 2013 VL 22 IS 4 BP 471 EP 477 DI 10.1016/j.jse.2012.03.015 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 140UB UT WOS:000318680100011 PM 22525939 ER PT J AU Ravicz, ME Rosowski, JJ AF Ravicz, Michael E. Rosowski, John J. TI Inner-ear sound pressures near the base of the cochlea in chinchilla: Further investigation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID FREQUENCY-POSITION MAP; MIDDLE-EAR; INPUT IMPEDANCE; INTRACOCHLEAR PRESSURE; GERBIL; CAT; ADMITTANCE; TRANSMISSION; MECHANICS; VELOCITY AB The middle-ear pressure gain G(MEP), the ratio of sound pressure in the cochlear vestibule P-V to sound pressure at the tympanic membrane P-TM, is a descriptor of middle-ear sound transfer and the cochlear input for a given stimulus in the ear canal. G(MEP) and the cochlear partition differential pressure near the cochlear base Delta P-CP, which determines the stimulus for cochlear partition motion and has been linked to hearing ability, were computed from simultaneous measurements of P-V, P-TM, and the sound pressure in scala tympani near the round window P-ST in chinchilla. G(MEP) magnitude was approximately 30 dB between 0.1 and 10 kHz and decreased sharply above 20 kHz, which is not consistent with an ideal transformer or a lossless transmission line. The G(MEP) phase was consistent with a roughly 50-mu s delay between P-V and P-TM. G(MEP) was little affected by the inner-ear modifications necessary to measure P-ST. G(MEP) is a good predictor of Delta P-CP at low and moderate frequencies where P-V >> P-ST but overestimates Delta P-CP above a few kilohertz where P-V approximate to P-ST. The ratio of P-ST to P-V provides insight into the distribution of sound pressure within the cochlear scalae. (C) 2013 Acoustical Society of America. C1 [Ravicz, Michael E.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol & Hlth Sci & Technol, Boston, MA 02115 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mike_ravicz@meei.harvard.edu FU National Science Foundation under NSF Award [ECS-0335765]; NIDCD FX We thank Elizabeth Olson and Wei Dong for much help in learning to fabricate and use the pressure sensors, Elizabeth Olson for many helpful discussions, Melissa McKinnon for animal surgery and assistance with experiments, and the staff of the Eaton-Peabody Laboratory for technical support. The reviewers offered helpful comments. This work was carried out in part through the use of MIT's Microsystems Technology Laboratories and the help of Kurt Broderick and in part at the Center for Nanoscale Systems (CNS) with the help of Ed Macomber. CNS is a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the National Science Foundation under NSF Award No. ECS-0335765, and a part of the Faculty of Arts and Sciences at Harvard University. Supported by NIDCD. NR 51 TC 8 Z9 8 U1 0 U2 6 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2013 VL 133 IS 4 BP 2208 EP 2223 DI 10.1121/1.4792139 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 139BB UT WOS:000318555300055 PM 23556590 ER PT J AU Shera, CA Cooper, NP AF Shera, Christopher A. Cooper, Nigel P. TI Basilar-membrane interference patterns from multiple internal reflection of cochlear traveling waves SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EVOKED OTOACOUSTIC EMISSIONS; AUDITORY-NERVE-FIBER; COHERENT REFLECTION; MIDDLE-EAR; DISTORTION PRODUCTS; ACOUSTIC EMISSIONS; CHINCHILLA COCHLEA; CLICK RESPONSES; GROUP DELAY; MECHANICS AB At low stimulus levels, basilar-membrane (BM) mechanical transfer functions in sensitive cochleae manifest a quasiperiodic rippling pattern in both amplitude and phase. Analysis of the responses of active cochlear models suggests that the rippling is a mechanical interference pattern created by multiple internal reflection within the cochlea. In models, the interference arises when reverse-traveling waves responsible for stimulus-frequency otoacoustic emissions (SFOAEs) reflect off the stapes on their way to the ear canal, launching a secondary forward-traveling wave that combines with the primary wave produced by the stimulus. Frequency-dependent phase differences between the two waves then create the rippling pattern measurable on the BM. Measurements of BM ripples and SFOAEs in individual chinchilla ears demonstrate that the ripples are strongly correlated with the acoustic interference pattern measured in ear-canal pressure, consistent with a common origin involving the generation of SFOAEs. In BM responses to clicks, the ripples appear as temporal fine structure in the response envelope (multiple lobes, waxing and waning). Analysis of the ripple spacing and response phase gradients provides a test for the role of fast-and slow-wave modes of reverse energy propagation within the cochlea. The data indicate that SFOAE delays are consistent with reverse slow-wave propagation but much too long to be explained by fast waves. (C) 2013 Acoustical Society of America. C1 [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Cooper, Nigel P.] Keele Univ, Sch Life Sci, Keele ST5 5BG, Staffs, England. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM christopher.shera@gmail.com FU NIDCD, National Institutes of Health [R01 DC003687]; Royal Society; MRC (UK) FX We thank Bill Rhode for generously sharing his data and Christopher Bergevin, John Guinan, and the anonymous reviewers for helpful comments on the manuscript. Supported by the NIDCD, National Institutes of Health (Grant No. R01 DC003687), the Royal Society, and the MRC (UK). NR 52 TC 10 Z9 10 U1 0 U2 7 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2013 VL 133 IS 4 BP 2224 EP 2239 DI 10.1121/1.4792129 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 139BB UT WOS:000318555300056 PM 23556591 ER PT J AU Noel, VA Eddington, DK AF Noel, Victor A. Eddington, Donald K. TI Sensitivity of bilateral cochlear implant users to fine-structure and envelope interaural time differences SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MINIMUM AUDIBLE ANGLE; SPEECH-INTELLIGIBILITY; SOUND LOCALIZATION; ELECTRIC HEARING; BINAURAL SENSITIVITY; INFERIOR COLLICULUS; DELAY SENSITIVITY; LATERALIZATION; LEVEL; NOISE AB Bilateral cochlear implant users have poor sensitivity to interaural time differences (ITDs) of high-rate pulse trains, which precludes use of these stimuli to convey fine-structure ITD cues. However, previous reports of single-neuron recordings in cats demonstrated good ITD sensitivity to 1000 pulses-per-second (pps) pulses when the pulses were sinusoidally amplitude modulated. The ability of modulation to restore ITD sensitivity to high-rate pulses in humans was tested by measuring ITD thresholds for three conditions: ITD encoded in the modulated carrier pulses alone, in the envelope alone, and in the whole waveform. Five of six subjects were not sensitive to ITD in the 1000-pps carrier, even with modulation. One subject's 1000-pps carrier ITD sensitivity did significantly improve due to modulation. Sensitivity to ITD encoded in the envelope was also measured as a function of modulation frequency, including at frequencies from 4 to 16 Hz where much of the speech envelope's energy and information resides. Sensitivity was best at the modulation frequency of 100 Hz and degraded rapidly outside of a narrow range. These results provide little evidence to support encoding ITD in the carrier of current bilateral processors, and suggest envelope ITD sensitivity is poor for an important segment of the speech modulation spectrum. (C) 2013 Acoustical Society of America. C1 [Noel, Victor A.; Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Noel, VA (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, 243 Charles St, Boston, MA 02114 USA. EM victor_noel@meei.harvard.edu FU NIH [R01-DC005775, R01-DC007528] FX This work was supported by NIH Grant Nos. R01-DC005775 and R01-DC007528. Advanced Bionics provided the binaural-research-interface hardware. NR 50 TC 3 Z9 3 U1 0 U2 9 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2013 VL 133 IS 4 BP 2314 EP 2328 DI 10.1121/1.4794372 PG 15 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 139BB UT WOS:000318555300063 PM 23556598 ER PT J AU Singer, SJ Friedberg, MW Kiang, MV Dunn, T Kuhn, DM AF Singer, Sara J. Friedberg, Mark W. Kiang, Mathew V. Dunn, Toby Kuhn, Diane M. TI Development and Preliminary Validation of the Patient Perceptions of Integrated Care Survey SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE integration; coordination; patient-centeredness; survey; psychometric analysis ID CLINICIAN AB Valid measures of the integration of patient care could provide rapid and accurate feedback on the successfulness of current efforts to improve health care delivery systems. This article describes the development and pilot testing of a new survey, based on a novel conceptual model, which measures the integration of patient care as experienced by patients. We administered the survey to 1,289 patients with multiple chronic conditions from one health system and received responses from 527 patients (43%). Psychometric analysis of responses supported a six-dimension model of integration with satisfactory internal consistency, discriminant validity, and goodness of fit. The Patient Perceptions of Integrated Care survey can be used to measure the integration of care received by chronically ill patients for two main purposes: as a research tool to compare interventions intended to improve the integration of care and as a quality improvement tool intended to guide the refinement of delivery system innovations. C1 [Singer, Sara J.; Kiang, Mathew V.] Harvard Univ, Boston, MA 02115 USA. [Singer, Sara J.; Friedberg, Mark W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Friedberg, Mark W.] RAND Corp, Boston, MA USA. [Friedberg, Mark W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kuhn, Diane M.] Harvard Univ, Cambridge, MA 02138 USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Sch Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, 677 Huntington Ave,Kresge Bldg 3,Room 317, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu FU Kaiser Permanente Institute for Health Policy for the Integrated Patient Care Roundtable FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support was provided by Kaiser Permanente Institute for Health Policy for the Integrated Patient Care Roundtable, the Lucian Leape Institute for cognitive testing, and the Harvard School of Public Health for the pilot survey and research. NR 20 TC 6 Z9 6 U1 0 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD APR PY 2013 VL 70 IS 2 BP 143 EP 164 DI 10.1177/1077558712465654 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 138QK UT WOS:000318523300002 PM 23161612 ER PT J AU Penuelas, O Frutos-Vivar, F Gordo, F Apezteguia, C Restrepo, MI Gonzalez, M Arabi, Y Santos, C Alhashemi, JA Perez, F Esteban, A Anzueto, A AF Penuelas, O. Frutos-Vivar, F. Gordo, F. Apezteguia, C. Restrepo, M. I. Gonzalez, M. Arabi, Y. Santos, C. Alhashemi, J. A. Perez, F. Esteban, A. Anzueto, A. TI Outcome of tracheotomized patients following reintubation SO MEDICINA INTENSIVA LA Spanish DT Article DE Reintubation; Tracheotomy; Mechanical ventilation; Mortality ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; ICU PATIENTS; TRACHEOSTOMY; DURATION AB Objective: To evaluate the outcome of tracheotomized patients after reintubation. Method: Secondary analysis from a prospective, multicenter and observational study including 36 Intensive Care Units (ICUs) from 8 countries. Patients: A total of 180 patients under mechanical ventilation for more than 48 hours, extubated and reintubated within 48 hours. Interventions: None. Outcomes: ICU mortality, length of ICU stay, organ failure. Results: Fifty-two patients (29%) underwent tracheotomy after reintubation. The median time from reintubation to tracheotomy was 2.5 days (interquartile range (IQR) 1-8 days). The length of ICU stay was significantly longer in the tracheotomy group compared with the group without tracheotomy (median time 25 days, IQR 17-43 versus 16.5 days (IQR 11-25); p < 0.001). ICU mortality in the tracheotomy group was not significantly different (31% versus 27%; p 0.57). Conclusions: In our cohort of reintubated patients, tracheotomy is a common procedure in the ICU. Patients with tracheotomy had an outcome similar to those without tracheotomy. (C) 2012 Elsevier Espana, S.L. and SEMICYUC. All rights reserved. C1 [Penuelas, O.; Frutos-Vivar, F.; Esteban, A.] Hosp Univ Getafe, Madrid, Spain. [Penuelas, O.; Frutos-Vivar, F.; Esteban, A.] CIBER Enfermedades Resp, Madrid, Spain. [Gordo, F.] Hosp Henares, Madrid, Spain. [Apezteguia, C.] Hosp Prof A Posadas, Buenos Aires, DF, Argentina. [Restrepo, M. I.; Anzueto, A.] South Texas Vet Hlth Care Syst, VERDICT, Audie L Murphy Div, San Antonio, TX USA. [Restrepo, M. I.; Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gonzalez, M.] Clin Medellin, Medellin, Colombia. [Gonzalez, M.] Univ Pontificia Bolivariana, Medellin, Colombia. [Arabi, Y.] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Santos, C.] Hosp Clin Montevideo, Montevideo, Uruguay. [Alhashemi, J. A.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Perez, F.] Hosp Clin Caracas, Caracas, Venezuela. RP Penuelas, O (reprint author), Hosp Univ Getafe, Madrid, Spain. EM openuelas@gmail.com RI Restrepo, Marcos/H-4442-2014; OI Frutos-Vivar, Fernando/0000-0002-4648-9636 FU NHLBI NIH HHS [K23 HL096054] NR 19 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0210-5691 J9 MED INTENSIVA JI Med. Intensiv. PD APR PY 2013 VL 37 IS 3 BP 142 EP 148 DI 10.1016/j.medin.2012.03.013 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 139LE UT WOS:000318583400003 PM 22608302 ER PT J AU Sacanell, J Rey, T Lopez, E Vicente, R Ballesteros, MA Iranzo, R Robles, JC Restrepo, MI Rello, J AF Sacanell, J. Rey, T. Lopez, E. Vicente, R. Ballesteros, M. A. Iranzo, R. Robles, J. C. Restrepo, M. I. Rello, J. CA Network PLUTO Postoperative Lung TI Antifungal prophylaxis in the postoperative period of lung transplant surgery in Spain SO MEDICINA INTENSIVA LA Spanish DT Article DE Prophylaxis; Postoperative period; Lung transplant ID LIPOSOMAL AMPHOTERICIN-B; ASPERGILLUS INFECTION; PHARMACOKINETICS; PREVENTION; RECIPIENTS; SAFETY AB Objectives: To examine the type and duration of antifungal prophylaxis provided during the postoperative period of lung transplant recipients, together with the most frequent complications during admission to Intensive Care Units in Spain. Patients and methods: A questionnaire was developed including demographic data on each transplant center, the type of antifungal prophylaxis used, its duration, and the most frequent complications. The questionnaire was distributed among the 7 Spanish national lung transplant centers, followed by analysis of the results obtained. Results: All 7 centers completed the questionnaire. All of them provided universal prophylaxis in lung transplant patients. Monotherapy was the most widely used protocol (5/7; 71.4%), with ambhotericin B in liposomal or conventional form being the most frequent drug, administered via the inhalatory route. In the case of combination therapy, a great diversity of drugs was observed. The most frequently administered second choice drug was anidulafungin (3/7; 43%), followed by voriconazole (2/7; 28.5%). Antifungal therapy was maintained on an indefinite basis by 43% of the centers. Invasive fungal infection (IFI) in the postoperative period of transplantation during admission to the Intensive Care Unit was suspected in 5-10% of the cases but was confirmed in less than 5%. Among other complications registered in these patients in the Intensive Care Unit, the most frequent problems were respiratory infections (5/7; 71.5%). Conclusions: Antifungal prophylaxis during the postoperative period of lung transplantation is provided on a universal basis, though consensus is lacking as to the drug of choice, the administration route and the duration of such treatment. (C) 2012 Elsevier Espana, S.L. and SEMICYUC. All rights reserved. C1 [Sacanell, J.; Rello, J.] Hosp Univ Vall dHebron, Serv Med Intens, Barcelona, Spain. [Rey, T.] Hosp Univ A Coruna, Serv Anestesiol & Reanimac, La Coruna, Spain. [Lopez, E.] Hosp Univ Doce Octubre, Serv Anestesiol & Reanimac, Madrid, Spain. [Vicente, R.] Hosp Univ La Fe, Serv Anestesiol & Reanimac, Valencia, Spain. [Ballesteros, M. A.] Hosp Univ Marques de Valdecilla, Serv Med Intens, Santander, Spain. [Iranzo, R.] Hosp Univ Puerta de Hierro, Serv Anestesiol & Reanimac, Madrid, Spain. [Robles, J. C.] Hosp Univ Reina Sofia, Serv Med Intens, Cordoba, Spain. [Restrepo, M. I.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Evidence Res Implementat & Disseminat Ctr, San Antonio, TX 78229 USA. [Rello, J.] Univ Automona Barcelona, Serv Med Intens, Hosp Univ Vall dHebron, Ctr Invest Biomed Red Enfermedades Resp, Barcelona, Spain. RP Sacanell, J (reprint author), Hosp Univ Vall dHebron, Serv Med Intens, Barcelona, Spain. EM jsacanell@vhebron.net RI Restrepo, Marcos/H-4442-2014; OI Masclans, Joan R/0000-0002-0809-6823; Rello, Jordi/0000-0003-0676-6210 FU NHLBI NIH HHS [K23 HL096054] NR 20 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0210-5691 J9 MED INTENSIVA JI Med. Intensiv. PD APR PY 2013 VL 37 IS 3 BP 201 EP 205 DI 10.1016/j.medin.2012.10.003 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 139LE UT WOS:000318583400009 PM 23260267 ER PT J AU Xin, XF Gfeller, D Cheng, J Tonikian, R Sun, L Guo, AL Lopez, L Pavlenco, A Akintobi, A Zhang, YN Rual, JF Currell, B Seshagiri, S Hao, T Yang, XP Shen, YA Salehi-Ashtiani, K Li, JJ Cheng, AT Bouamalay, D Lugari, A Hill, DE Grimes, ML Drubin, DG Grant, BD Vidal, M Boone, C Sidhu, SS Bader, GD AF Xin, Xiaofeng Gfeller, David Cheng, Jackie Tonikian, Raffi Sun, Lin Guo, Ailan Lopez, Lianet Pavlenco, Alevtina Akintobi, Adenrele Zhang, Yingnan Rual, Jean-Francois Currell, Bridget Seshagiri, Somasekar Hao, Tong Yang, Xinping Shen, Yun A. Salehi-Ashtiani, Kourosh Li, Jingjing Cheng, Aaron T. Bouamalay, Dryden Lugari, Adrien Hill, David E. Grimes, Mark L. Drubin, David G. Grant, Barth D. Vidal, Marc Boone, Charles Sidhu, Sachdev S. Bader, Gary D. TI SH3 interactome conserves general function over specific form SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE network evolution; phage display; protein interaction conservation; SH3 domains; yeast two-hybrid ID PROTEIN-PROTEIN INTERACTIONS; SEMANTIC SIMILARITY MEASURES; PEPTIDE RECOGNITION MODULES; CAENORHABDITIS-ELEGANS; C-ELEGANS; INTERACTION NETWORKS; INTERACTION DATABASE; REGULATORY NETWORKS; EVOLUTION; DOMAINS AB Src homology 3 (SH3) domains bind peptides to mediate protein-protein interactions that assemble and regulate dynamic biological processes. We surveyed the repertoire of SH3 binding specificity using peptide phage display in a metazoan, the worm Caenorhabditis elegans, and discovered that it structurally mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the worm SH3 interactome using stringent yeast two-hybrid and compared it with the equivalent map for yeast. We found that the worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired. Our results suggest a model of network evolution where general function of the SH3 domain network is conserved over its specific form. C1 [Xin, Xiaofeng; Gfeller, David; Tonikian, Raffi; Lopez, Lianet; Pavlenco, Alevtina; Li, Jingjing; Boone, Charles; Sidhu, Sachdev S.; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Xin, Xiaofeng; Tonikian, Raffi; Li, Jingjing; Boone, Charles; Sidhu, Sachdev S.; Bader, Gary D.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Cheng, Jackie; Cheng, Aaron T.; Bouamalay, Dryden; Drubin, David G.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Sun, Lin; Akintobi, Adenrele; Grant, Barth D.] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08855 USA. [Guo, Ailan] Cell Signaling Technol, Danvers, MA USA. [Zhang, Yingnan] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA. [Rual, Jean-Francois; Hao, Tong; Yang, Xinping; Shen, Yun A.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Rual, Jean-Francois; Hao, Tong; Yang, Xinping; Shen, Yun A.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Rual, Jean-Francois; Hao, Tong; Yang, Xinping; Shen, Yun A.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Currell, Bridget; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. [Lugari, Adrien] CNRS, IMR Lab, UPR 3243, Inst Microbiol Mediterannee, Marseille 20, France. [Lugari, Adrien] Aix Marseille Univ, Marseille 20, France. [Grimes, Mark L.] Univ Montana, Div Biol Sci, Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. [Bader, Gary D.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. RP Boone, C (reprint author), Univ Toronto, Donnelly Ctr, 160 Coll St,602, Toronto, ON M5S 3E1, Canada. EM charlie.boone@utoronto.ca; sachdev.sidhu@utoronto.ca; gary.bader@utoronto.ca RI Li, Jingjing/B-5136-2016; Xin, Xiaofeng/G-7736-2016; gfeller, david/D-3395-2009; OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Li, Jingjing/0000-0001-6025-9522; Xin, Xiaofeng/0000-0002-2439-7183; gfeller, david/0000-0002-3952-0930; Rual, Jean-Francois/0000-0003-4465-8819; Lugari, Adrien/0000-0001-8337-6043; Grant, Barth/0000-0002-5943-8336 FU Canadian Institutes of Health Research [MOP-84324, MOP-93725]; US National Institutes of Health [R01 GM067237, R01 GM65462, NHGRI R01 HG001715]; EMBO [EMBO-ALTF 241-2010]; SNSF [PBELA33-120936] FX We thank Q Li, H Huang, J Gu, R Isserlin, H Fares, A Audhya, A Shi, S Pant, and D Carranza for experimental and computational support. This work was supported by the Canadian Institutes of Health Research (Grants MOP-84324 to GDB and MOP-93725 to SSS) and the US National Institutes of Health (Grants R01 GM067237 to BDG, R01 GM65462 to DGD and NHGRI R01 HG001715 awarded to MV and DEH). DG acknowledges the financial support of EMBO (EMBO-ALTF 241-2010) and SNSF (PBELA33-120936). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 88 TC 21 Z9 21 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD APR PY 2013 VL 9 AR 652 DI 10.1038/msb.2013.9 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140YS UT WOS:000318693000013 PM 23549480 ER PT J AU Vitte, J Chareyre, F Stemmer-Rachamimov, A Giovannini, M AF Vitte, Jeremie Chareyre, Fabrice Stemmer-Rachamimov, Anat Giovannini, Marco TI CONDITIONAL INACTIVATION OF SMARCB1 IN P0 PERMISSIVE MOUSE CELLS RECAPITULATES THE TUMOR SPECTRUM OF BOTH HUMAN SMARCB1-RELATED SCHWANNOMATOSIS AND RHABDOID TUMOR PREDISPOSITION SYNDROMES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Vitte, Jeremie; Chareyre, Fabrice; Giovannini, Marco] Univ So Calif, House Res Inst, Ctr Neural Tumor Res, Los Angeles, CA USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Mol Neurooncol & Pathol Dept, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Boston, MA USA. RI Vitte, Jeremie/B-9874-2017 OI Vitte, Jeremie/0000-0002-2567-7988 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0058 BP 15 EP 15 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500055 ER PT J AU Bergthold, G Rich, B Bandopadhayay, P Chan, J Santaga, S Hoshida, Y Golub, T Tabak, B Ferrer-Luna, R Grill, J Wen, PY Stiles, C Kieran, M Ligon, K Beroukhim, R AF Bergthold, Guillaume Rich, Benjamin Bandopadhayay, Pratiti Chan, Jennifer Santaga, Sandro Hoshida, Yujin Golub, Todd Tabak, Barbara Ferrer-Luna, Ruben Grill, Jacques Wen, Patrick Yung Stiles, Charles Kieran, Mark Ligon, Keith Beroukhim, Rameen TI GENE EXPRESSION ANALYSIS OF 163 PEDIATRIC LOW-GRADE GLIOMA ACROSS DIFFERENT AGES, LOCATIONS, HISTOLOGICAL SUBTYPES AND BRAF GENOMIC STATUS REVEALS ASSOCIATED MOLECULAR CHARACTERISTICS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Bergthold, Guillaume; Rich, Benjamin; Bandopadhayay, Pratiti; Ferrer-Luna, Ruben; Stiles, Charles; Kieran, Mark; Ligon, Keith; Beroukhim, Rameen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, Jennifer; Santaga, Sandro; Wen, Patrick Yung] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hoshida, Yujin; Golub, Todd; Tabak, Barbara] Broad Inst MIT & Harvard, Boston, MA USA. [Grill, Jacques] Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0064 BP 16 EP 16 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500061 ER PT J AU Snuderl, M Batista, A Kirkpatrick, N de Almodovar, CR Riedemann, L Knevels, E Schmidt, T Peterson, T Roberge, S Bais, C Yip, S Hasselblatt, M Rossig, C Ferrara, N Klagsbrun, M Duda, D Fukumura, D Xu, L Carmeliet, P Jain, R AF Snuderl, Matija Batista, Ana Kirkpatrick, Nathaniel de Almodovar, Carmen Ruiz Riedemann, Lars Knevels, Ellen Schmidt, Thomas Peterson, Teresa Roberge, Sylvie Bais, Carlos Yip, Stephen Hasselblatt, Martin Rossig, Claudia Ferrara, Napoleone Klagsbrun, Michael Duda, Dan Fukumura, Dai Xu, Lei Carmeliet, Peter Jain, Rakesh TI PLACENTAL GROWTH FACTOR/NEUROPILIN 1 SIGNALING IS A THERAPEUTIC TARGET IN PEDIATRIC MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Batista, Ana; Kirkpatrick, Nathaniel; Riedemann, Lars; Peterson, Teresa; Roberge, Sylvie; Duda, Dan; Fukumura, Dai; Xu, Lei; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [de Almodovar, Carmen Ruiz; Knevels, Ellen; Schmidt, Thomas; Carmeliet, Peter] Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, Louvain, Belgium. [Bais, Carlos; Ferrara, Napoleone] Genentech Inc, San Francisco, CA USA. [Yip, Stephen] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Hasselblatt, Martin; Rossig, Claudia] Univ Hosp Munster, Inst Neuropathol, Munster, Germany. [Hasselblatt, Martin; Rossig, Claudia] Univ Hosp Munster, Dept Pediat Hematol & Oncol, Munster, Germany. [Klagsbrun, Michael] Childrens Hosp Boston, Dept Surg, Vasc Biol Program, Boston, MA USA. RI Riedemann, Lars/J-5725-2014 OI Riedemann, Lars/0000-0002-9510-1845 NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0074 BP 19 EP 20 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500071 ER PT J AU Pak, E Zhao, XS Ponomaryov, T Segal, R AF Pak, Ekaterina Zhao, Xuesong Ponomaryov, Tatyana Segal, Rosalind TI IDENTIFICATION OF RESISTANCE MECHANISMS TO SMO INHIBITION IN MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Pak, Ekaterina; Zhao, Xuesong; Ponomaryov, Tatyana; Segal, Rosalind] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pak, Ekaterina; Zhao, Xuesong; Ponomaryov, Tatyana; Segal, Rosalind] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pak, Ekaterina; Zhao, Xuesong; Ponomaryov, Tatyana; Segal, Rosalind] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Pak, Ekaterina; Zhao, Xuesong; Ponomaryov, Tatyana; Segal, Rosalind] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0131 BP 35 EP 35 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500126 ER PT J AU Bandopadhayay, P Nguyen, B Masoud, S Vue, N Gholamin, S Yu, FR Schubert, S Bergthold, G Mitra, S Qi, J Bradner, J Kieran, M Beroukhim, R Cho, YJ AF Bandopadhayay, Pratiti Nguyen, Brian Masoud, Sabran Vue, Nujsaubnusi Gholamin, Sharareh Yu, Furong Schubert, Simone Bergthold, Guillaume Mitra, Siddhartha Qi, Jun Bradner, James Kieran, Mark Beroukhim, Rameen Cho, Yoon-Jae TI BET BROMODOMAIN INHIBITION OF MYC-AMPLIFIED MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Bandopadhayay, Pratiti; Bergthold, Guillaume; Qi, Jun; Bradner, James; Kieran, Mark; Beroukhim, Rameen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bandopadhayay, Pratiti; Bergthold, Guillaume; Qi, Jun; Bradner, James; Kieran, Mark; Beroukhim, Rameen] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, Brian; Masoud, Sabran; Vue, Nujsaubnusi; Gholamin, Sharareh; Yu, Furong; Schubert, Simone; Mitra, Siddhartha; Cho, Yoon-Jae] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nguyen, Brian; Masoud, Sabran; Vue, Nujsaubnusi; Gholamin, Sharareh; Yu, Furong; Schubert, Simone; Mitra, Siddhartha; Cho, Yoon-Jae] Lucile Packard Childrens Hosp, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0135 BP 36 EP 36 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500130 ER PT J AU Chi, SS Cohen, K Fisher, M Biegel, J Bowers, D Fangusaro, J Manley, P Janss, A Zimmerman, MA Kieran, M AF Chi, Susan Cohen, Kenneth Fisher, Michael Biegel, Jaclyn Bowers, Daniel Fangusaro, Jason Manley, Peter Janss, Anna Zimmerman, Mary Ann Kieran, Mark TI LONG-TERM OUTCOMES FROM A PROSPECTIVE PHASE II STUDY OF MULTI-AGENT SYSTEMIC AND INTRATHECAL CHEMOTHERAPY WITH AGE- AND RISK-ADAPTED RADIATION THERAPY FOR CHILDREN WITH NEWLY DIAGNOSED CNS ATYPICAL TERATOID/RHABDOID TUMOR (DFCI #02-294) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Chi, Susan; Manley, Peter; Zimmerman, Mary Ann; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Kenneth] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Fisher, Michael; Biegel, Jaclyn] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Bowers, Daniel] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Fangusaro, Jason] Lurie Childrens Hosp Chicago, Chicago, IL USA. [Janss, Anna] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0133 BP 36 EP 36 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500128 ER PT J AU Calligaris, D Liu, XH Feldman, D Thompson, C Ide, J Buhrlage, S Gray, N Kieran, M Stiles, C Agar, N AF Calligaris, David Liu, Xiaohui Feldman, Daniel Thompson, Christopher Ide, Jennifer Buhrlage, Sara Gray, Nathanael Kieran, Mark Stiles, Charles Agar, Nathalie TI DEVELOPMENT OF COMBINED PK/PD STUDIES OF RAF/MEK/mTOR INHIBITORS FOR THE TREATMENT OF PEDIATRIC LOW-GRADE ASTROCYTOMAS BY MALDI MASS SPECTROMETRY IMAGING SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Calligaris, David; Liu, Xiaohui; Feldman, Daniel; Ide, Jennifer; Agar, Nathalie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kieran, Mark] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Buhrlage, Sara; Gray, Nathanael; Stiles, Charles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thompson, Christopher] Bruker Daltonics Inc, Billerica, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0139 BP 37 EP 37 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500134 ER PT J AU Liu, XH Ebling, M Ide, J Wang, L Davis, E Marchionni, M Stuart, D Alberta, J Kieran, M Stiles, C Agar, N AF Liu, Xiaohui Ebling, Maritza Ide, Jennifer Wang, Lan Davis, Erin Marchionni, Mark Stuart, Darrin Alberta, John Kieran, Mark Stiles, Charles Agar, Nathalie TI VALIDATION OF HEME AS A MARKER OF THE VASCULATURE FOR MALDI IMAGING OF THE BLOOD-BRAIN BARRIERS IN DRUG DEVELOPMENT SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Liu, Xiaohui; Ide, Jennifer; Agar, Nathalie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ebling, Maritza; Wang, Lan; Davis, Erin; Marchionni, Mark; Alberta, John; Stiles, Charles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kieran, Mark] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Stuart, Darrin] Novartis Inst Biomed Res, Emeryville, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0143 BP 38 EP 39 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500138 ER PT J AU Ramkissoon, L Horowitz, P Craig, J Ramkissoon, S Rich, B Bergthold, G Tabori, U Taha, H Bowers, D Hawkins, C Packer, R Eberhart, C Goumnerova, L Chan, J Santagata, S Pomcroy, S Ligon, A Kieran, M Beroukhim, R Ligon, K AF Ramkissoon, Lori Horowitz, Peleg Craig, Justin Ramkissoon, Shakti Rich, Benjamin Bergthold, Guillaume Tabori, Uri Taha, Hala Bowers, Daniel Hawkins, Cynthia Packer, Roger Eberhart, Charles Goumnerova, Liliana Chan, Jennifer Santagata, Sandro Pomcroy, Scott Ligon, Azra Kieran, Mark Beroukhim, Rameen Ligon, Keith TI GENOMIC ANALYSIS OF DIFFUSE PEDIATRIC LOW-GRADE GLIOMAS IDENTIFIES RECURRENT, ONCOGENIC MYBL1-TRUNCATING REARRANGEMENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 [Ramkissoon, Lori; Craig, Justin; Rich, Benjamin; Bergthold, Guillaume; Ligon, Keith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horowitz, Peleg; Ramkissoon, Shakti; Santagata, Sandro; Ligon, Azra] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Goumnerova, Liliana; Pomcroy, Scott; Kieran, Mark] Boston Childrens Hosp, Boston, MA USA. [Eberhart, Charles] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Taha, Hala] Childrens Canc Hosp, Cairo, Egypt. [Tabori, Uri; Hawkins, Cynthia] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bowers, Daniel] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Chan, Jennifer] Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0146 BP 39 EP 39 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500141 ER PT J AU Sun, YG Stiles, C AF Sun, Yu Grace Stiles, Charles TI GENETIC ABLATION OF THE bHLH TRANSCRIPTION FACTOR OLIG2 IS SYNTHETIC LETHAL TO BRAF ONCOGENES IN A MURINE MODEL OF PEDIATRIC LOW-GRADE ASTROCYTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Annual Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 16-17, 2013 CL Fort Lauderdale, FL C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 SU 1 MA 0172 BP 46 EP 46 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 139GR UT WOS:000318570500166 ER PT J AU Westover, MB Bianchi, MT Yang, CH Schneider, JA Greenberg, SM AF Westover, M. Brandon Bianchi, Matt T. Yang, Chunhui Schneider, Julie A. Greenberg, Steven M. TI Estimating cerebral microinfarct burden from autopsy samples SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; OLDER PERSONS; RELIGIOUS ORDERS; AGING PROJECT; RUSH MEMORY; INFARCTS; DEMENTIA; LESIONS AB Objective: To estimate whole-brain microinfarct burden from microinfarct counts in routine postmortem examination. Methods: We developed a simple mathematical method to estimate the total number of cerebral microinfarcts from counts obtained in the small amount of tissue routinely examined in brain autopsies. We derived estimates of total microinfarct burden from autopsy brain specimens from 648 older participants in 2 community-based clinical-pathologic cohort studies of aging and dementia. Results: Our results indicate that observing 1 or 2 microinfarcts in 9 routine neuropathologic specimens implies a maximum-likelihood estimate of 552 or 1,104 microinfarcts throughout the brain. Similar estimates were obtained when validating in larger sampled brain volumes. Conclusions: The substantial whole-brain burden of cerebral microinfarcts suggested by even a few microinfarcts on routine pathologic sampling suggests a potential mechanism by which these lesions could cause neurologic dysfunction in individuals with small-vessel disease. The estimation framework developed here may generalize to clinicopathologic correlations of other imaging-negative micropathologies. C1 [Westover, M. Brandon; Bianchi, Matt T.; Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Westover, M. Brandon; Bianchi, Matt T.; Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Chunhui; Schneider, Julie A.] Rush Univ, Rush Alzheimers Dis Ctr, Dept Pathol, Med Ctr, Chicago, IL 60612 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. EM sgreenberg@partners.org FU NIH [R01 AG026484]; National Institute on Aging [R01 AG15819, R01 AG17917, P30 AG10161, K08 AG00849] FX M.B. Westover, M.T. Bianchi, and C. Yang report no disclosures. J.A. Schneider contributed data used in this work from the Funding for the Religious Orders Study and the Rush Memory and Aging Project, which were supported by grants from the National Institute on Aging (R01 AG15819, R01 AG17917, P30 AG10161, and K08 AG00849). S.M. Greenberg is funded by R01AG026484 from the NIH. Go to Neurology.org for full disclosures. NR 24 TC 38 Z9 38 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2013 VL 80 IS 15 BP 1365 EP 1369 DI 10.1212/WNL.0b013e31828c2f52 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 139RM UT WOS:000318601600008 PM 23486880 ER PT J AU Sharma, N AF Sharma, Nutan TI Lysosomal enzyme defects and Parkinson disease SO NEUROLOGY LA English DT Editorial Material ID MUTATIONS C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sharma, N (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM nsharma@partners.org NR 6 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2013 VL 80 IS 17 BP 1544 EP 1545 DI 10.1212/WNL.0b013e31828f1958 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 140ZC UT WOS:000318694000005 PM 23535496 ER PT J AU Martinez-Ramirez, S Pontes-Neto, OM Dumas, AP Auriel, E Halpin, A Quimby, M Gurol, ME Greenberg, SM Viswanathan, A AF Martinez-Ramirez, Sergi Pontes-Neto, Octavio Marques Dumas, Andrew P. Auriel, Eitan Halpin, Amy Quimby, Megan Gurol, Mahmut Edip Greenberg, Steven M. Viswanathan, Anand TI Topography of dilated perivascular spaces in subjects from a memory clinic cohort SO NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; VIRCHOW-ROBIN SPACES; SMALL VESSEL DISEASE; ALZHEIMERS-DISEASE; WHITE-MATTER; ROTTERDAM-SCAN; BLOOD-PRESSURE; MICROBLEEDS; MRI; DEMENTIA AB Objective: To investigate whether the topography of dilated perivascular spaces (DPVS) corresponds with markers of particular small-vessel diseases such as cerebral amyloid angiopathy and hypertensive vasculopathy. Methods: Patients were recruited from an ongoing single-center prospective longitudinal cohort study of patients evaluated in a memory clinic. All patients underwent structural, high-resolution MRI, and had a clinical assessment performed within 1 year of scan. DPVS were rated in basal ganglia (BG-DPVS) and white matter (WM-DPVS) on T1 sequences, using an established 4-point semiquantitative score. DPVS degree was classified as high (score > 2) or low (score <= 2). Independent risk factors for high degree of BG-DPVS and WM-DPVS were investigated. Results: Eighty-nine patients were included (mean age 72.7 +/- 9.9 years, 57% female). High degree of WM-DPVS was more frequent than low degree in patients with presence of strictly lobar microbleeds (45.5% vs 28.4% of subjects). High BG-DPVS degree was associated with older age, hypertension, and higher white matter hyperintensity volumes. In multivariate analysis, increased lobar microbleed count was an independent predictor of high degree of WM-DPVS (odds ratio [OR] 1.53 [95% confidence interval (CI) 1.06-2.21], p = 0.02). By contrast, hypertension was an independent predictor of high degree of BG-DPVS (OR 9.4 [95% CI 1-85.2], p = 0.04). Conclusions: The associations of WM-DPVS with lobar microbleeds and BG-DPVS with hypertension raise the possibility that the distribution of DPVS may indicate the presence of underlying small-vessel diseases such as cerebral amyloid angiopathy and hypertensive vasculopathy in patients with cognitive impairment. C1 [Martinez-Ramirez, Sergi; Pontes-Neto, Octavio Marques; Dumas, Andrew P.; Auriel, Eitan; Halpin, Amy; Quimby, Megan; Gurol, Mahmut Edip; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. [Martinez-Ramirez, Sergi] Univ Autonoma Barcelona, Escola Postgrau, Bellaterra, Cerdanyola Del, Spain. RP Martinez-Ramirez, S (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. EM srmartinez@partners.org RI Pontes-Neto, Octavio/G-4294-2012; Gurol, Edip/J-2279-2014 OI Pontes-Neto, Octavio/0000-0003-0317-843X; Gurol, Edip/0000-0002-2169-4457 FU National Institute on Aging [5P50AG005134-28]; Fundacion Alfonso Martin Escudero, Madrid (Spain) FX Supported by grant 5P50AG005134-28 from the National Institute on Aging. Dr. Martinez-Ramirez is a recipient of the research grant "Becas de Investigacion en Universidades y Centros del Extranjero" from Fundacion Alfonso Martin Escudero, Madrid (Spain). Funding entities had no involvement in study design, data collection, analysis and interpretation, writing of the manuscript, or the decision to submit for publication. NR 30 TC 42 Z9 45 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2013 VL 80 IS 17 BP 1551 EP 1556 DI 10.1212/WNL.0b013e31828f1876 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 140ZC UT WOS:000318694000007 PM 23553482 ER PT J AU Suzuki, R Ferris, HA Chee, MJ Maratos-Flier, E Kahn, CR AF Suzuki, Ryo Ferris, Heather A. Chee, Melissa J. Maratos-Flier, Eleftheria Kahn, C. Ronald TI Reduction of the Cholesterol Sensor SCAP in the Brains of Mice Causes Impaired Synaptic Transmission and Altered Cognitive Function SO PLOS BIOLOGY LA English DT Article ID DIABETIC-RATS; NERVOUS-SYSTEM; RECEPTOR; INSULIN; DISEASE; HIPPOCAMPUS; METABOLISM; DYSFUNCTION; PHENOTYPE; DEMENTIA AB The sterol sensor SCAP is a key regulator of SREBP-2, the major transcription factor controlling cholesterol synthesis. Recently, we showed that there is a global down-regulation of cholesterol synthetic genes, as well as SREBP-2, in the brains of diabetic mice, leading to a reduction of cholesterol synthesis. We now show that in mouse models of type 1 and type 2 diabetes, this is, in part, the result of a decrease of SCAP. Homozygous disruption of the Scap gene in the brains of mice causes perinatal lethality associated with microcephaly and gliosis. Mice with haploinsufficiency of Scap in the brain show a 60% reduction of SCAP protein and similar to 30% reduction in brain cholesterol synthesis, similar to what is observed in diabetic mice. This results in impaired synaptic transmission, as measured by decreased paired pulse facilitation and long-term potentiation, and is associated with behavioral and cognitive changes. Thus, reduction of SCAP and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline and Alzheimer disease observed in diabetic states. C1 [Suzuki, Ryo; Ferris, Heather A.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Chee, Melissa J.; Maratos-Flier, Eleftheria] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Suzuki, R (reprint author), Univ Tokyo, Tokyo, Japan. EM c.ronald.kahn@joslin.harvard.edu FU Mary K. Iacocca Professorship [P30 DK036836, 5 T32 DK007260-34]; [R01 DK31036] FX This work was supported by R01 DK31036 and the Mary K. Iacocca Professorship (to CRK), P30 DK036836 (Joslin DERC Core Facilities), and 5 T32 DK007260-34 (to HAF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 13 Z9 13 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2013 VL 11 IS 4 AR e1001532 DI 10.1371/journal.pbio.1001532 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 140WT UT WOS:000318687800010 PM 23585733 ER PT J AU Momand, JR Xu, GG Walter, CA AF Momand, Jamila R. Xu, Guogang Walter, Christi A. TI The Paternal Age Effect: A Multifaceted Phenomenon SO BIOLOGY OF REPRODUCTION LA English DT Review DE DNA repair; mutagenesis; paternal age; spermatogenic cells; spermatogonial stem cells ID DE-NOVO MUTATIONS; MALE GERM-CELLS; SPERMATOGONIAL STEM-CELLS; NUCLEOTIDE EXCISION-REPAIR; APERT-SYNDROME; OSTEOGENESIS IMPERFECTA; HETEROZYGOUS MICE; COSTELLO-SYNDROME; CROUZON-SYNDROME; FGFR2 MUTATIONS AB Birth rates for older fathers have increased 30% since 1980. When combined with the increased risk for genetic and multifactorial disorders in children conceived by older fathers, paternal age has become an important health issue for modern society. Laboratory research in this area has been minimal, perhaps because of significant experimental barriers, not the least of which is inadequate access to fresh, disease-free human testicular tissue. Regardless, progress has been made and intriguing models supported by experimental evidence have been proposed. The putative mechanisms range from reduced DNA repair activity, leading to increased mutagenesis, to positive selection of germ cells harboring specific disease-causing mutations. There remain many important venues for research in this increasingly relevant phenomenon that impacts future generations. C1 [Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Momand, Jamila R.; Xu, Guogang; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walter@uthscsa.edu NR 101 TC 9 Z9 9 U1 1 U2 16 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2013 VL 88 IS 4 AR 108 DI 10.1095/biolreprod.112.103440 PG 9 WC Reproductive Biology SC Reproductive Biology GA 138EF UT WOS:000318490800014 PM 23515674 ER PT J AU Velligan, DI Castillo, D Lopez, L Manaugh, B Davis, C Rodriguez, J Milam, AC Dassori, A Miller, AL AF Velligan, Dawn I. Castillo, Desiree Lopez, Linda Manaugh, Bren Davis, Charlotte Rodriguez, Juanita Milam, A. Camis Dassori, Albana Miller, Alexander L. TI A Case Control Study of the Implementation of Change Model Versus Passive Dissemination of Practice Guidelines for Compliance in Monitoring for Metabolic Syndrome SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Metabolic syndrome monitoring; Practice guidelines; Community mental health; Atypical antipsychotics; Implementation of change model; Serious mental illness ID ANTIPSYCHOTIC MEDICATIONS; VENOUS THROMBOEMBOLISM; HEALTH-CARE; SCHIZOPHRENIA; STATEMENT; CATIE; RISK AB We developed an intervention to improve compliance with guidelines for monitoring metabolic syndrome and compared compliance prior to intervention and three times post-intervention at three community mental health clinics in Texas. One test clinic received intervention and two other clinics served as controls. Fifty random charts were reviewed from each clinic for three specific, 1-2 weeks periods over the course of 18 months. There were significant improvements in the ordering of labs, the presence of lab results in the chart, and documentation of blood pressure, body mass index and waist circumference in the intervention clinic over time in comparison to the control clinics. Documented evidence of physician action with respect to out of range values remained low. Metabolic monitoring is a multi-step process. Removing barriers, creating specific procedures, and dedicating staff resources can improve compliance with monitoring. C1 [Velligan, Dawn I.; Castillo, Desiree; Milam, A. Camis; Miller, Alexander L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Lopez, Linda; Manaugh, Bren; Davis, Charlotte; Rodriguez, Juanita; Milam, A. Camis] Ctr Hlth Care Serv, Bexar Cty, TX USA. [Dassori, Albana] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Velligan, DI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Mail Stop 7797,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM velligand@uthscsa.edu; castillod@uthscsa.edu; LLopez@chcsbc.org; BManaugh@chcsbc.org; Cdavis@chscbc.org; jlrodriguez@chcsbc.org; milama@uthscsa.edu; millera@uthscsa.edu FU NIMH NIH HHS [R24 MH072830] NR 18 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD APR PY 2013 VL 49 IS 2 BP 141 EP 149 DI 10.1007/s10597-011-9472-z PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 136MS UT WOS:000318366600001 PM 22350562 ER PT J AU Sylvia, L Kopeski, L Brown, C Bolton, P Laudate, C DiGangi, G Martin, P Reid, JA Martowski, JC Meade, A Sarmiento, IA Wang, JP Utschig, AC Siegel, A Neuhaus, EC AF Sylvia, Louisa G. Kopeski, Lynne Brown, Carrie Bolton, Paula Laudate, Corina DiGangi, Gina Martin, Paula Reid, James A. Martowski, Jules C. Meade, Amy Sarmiento, Ingrid A. Wang, Jianping Utschig, Angela C. Siegel, Arthur Neuhaus, Edmund C. TI An Adjunct Exercise Program for Serious Mental Illness: Who Chooses to Participate and is it Feasible? SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Serious mental illness; Exercise; Self-selection; Feasibility ID AUTOMATIC THOUGHTS QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIALS; BIPOLAR DISORDER; MEDICAL BURDEN; DEPRESSION; INTERVENTION; HOPELESSNESS; DISEASE; RISK AB Despite evidence that exercise is beneficial for serious mental illness, it continues to be an under utilized adjunct treatment strategy. Thus, the aims of this study were to examine if self-selected or volunteer exercise programs are feasible in a structured outpatient program and who might choose to participate in such a program. Individuals with serious mental illness admitted to a partial hospital program were offered an adjunct exercise group or a control, psychoeducation group. The exercise group (N = 38) met three times a week for 50 min. Individuals who chose not to exercise (N = 28), attended a psychoeducational control group. Those who self-selected the exercise group tended to have a higher level of education, employment rate and to be Caucasian. The control group had more medical problems, a higher body mass index and alcohol intake. The groups did not differ on age, sex, or use of cigarettes and caffeine. The exercise group was regularly attended. Both groups improved equally on all outcomes symptom and psychological well-being outcomes. These data highlight that certain individuals with serious mental illness may be more likely to exercise based on demographic opposed to clinical features, or illness characteristics. Thus, adjunct exercise programs for individuals with serious mental illness seem to be feasible, but certain groups of individuals (i.e., ethnic minorities, unemployed) should be targeted for recruitment as they are less likely to volunteer for such adjunct exercise programs. C1 [Sylvia, Louisa G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sylvia, Louisa G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Sylvia, Louisa G.; Siegel, Arthur; Neuhaus, Edmund C.] Harvard Univ, Sch Med, Boston, MA USA. [Kopeski, Lynne; Brown, Carrie; Laudate, Corina; DiGangi, Gina; Martin, Paula; Martowski, Jules C.; Meade, Amy; Sarmiento, Ingrid A.; Siegel, Arthur] McLean Hosp, Belmont, MA 02478 USA. [Bolton, Paula] McLean Hosp, Psychiat Neurotherapeut Program, Belmont, MA 02478 USA. [Reid, James A.] MCAS Beaufort, Mental Hlth Unit, Beaufort, SC 29902 USA. [Wang, Jianping] Beijing Normal Univ, Beijing 100875, Peoples R China. [Utschig, Angela C.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Sylvia, L (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org NR 34 TC 2 Z9 2 U1 2 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD APR PY 2013 VL 49 IS 2 BP 213 EP 219 DI 10.1007/s10597-012-9555-5 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 136MS UT WOS:000318366600011 PM 23064968 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_Brown@dfci.harvard.edu NR 0 TC 0 Z9 0 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2013 VL 27 IS 2 BP XIII EP XIV DI 10.1016/j.hoc.2013.01.009 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 138SK UT WOS:000318530100001 PM 23561479 ER PT J AU Improgo, MR Brown, JR AF Improgo, Ma. Reina Brown, Jennifer R. TI Genomic Approaches to Chronic Lymphocytic Leukemia SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Chronic lymphocytic leukemia; Genomics; Comparative genomic hybridization; Single-nucleotide polymorphism arrays; Linkage mapping; Genome-wide association studies; Whole-exome sequencing; Whole-genome sequencing ID SUSCEPTIBILITY LOCI; COMMON VARIATION; ATM MUTATIONS; P53 MUTATIONS; FOLLOW-UP; HYBRIDIZATION; FAMILIES; RISK; IMBALANCES; SURVIVAL AB This article discusses recent advances in genomic approaches used to understand chronic lymphocytic leukemia. Tools for analyzing DNA-level lesions are described, data obtained from these various platforms summarized, and the clinical relevance of these findings discussed. C1 [Improgo, Ma. Reina; Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,CLL Ctr, Boston, MA 02215 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,CLL Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_Brown@dfci.harvard.edu FU NIH [K23 CA115682] FX Funded by: NIH, Grant numbers: K23 CA115682. NR 57 TC 1 Z9 1 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2013 VL 27 IS 2 BP 157 EP + DI 10.1016/j.hoc.2013.01.001 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 138SK UT WOS:000318530100002 PM 23561468 ER PT J AU Davids, MS Brown, JR AF Davids, Matthew S. Brown, Jennifer R. TI Phosphoinositide 3 '-Kinase Inhibition in Chronic Lymphocytic Leukemia SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Lymphoid leukemia; Signaling therapies; Phosphoinositide 3 '-kinase; B-cell receptor ID B-CELL RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; ZAP-70 EXPRESSION; SURVIVAL SIGNALS; GENE-EXPRESSION; T-LYMPHOCYTES; P110 DELTA; CLL CELLS; PI3K; BCR AB Phosphoinositide 3'-kinase (PI3K) is a key node in the B-cell receptor pathway, which plays a crucial role in the trafficking, survival, and proliferation of chronic lymphocytic leukemia (CLL) cells. This article reviews the biology of PI3K, focusing on its relationship to the CLL microenvironment, and discusses the biological rationale for PI3K inhibition in CLL. Preliminary safety and efficacy data from early phase clinical trials is also discussed. Potential biomarkers for clinical response to PI3K inhibitors such as ZAP-70, IGHV status, and CCL3 are examined. Where PI3K inhibition may fit in the evolving landscape of CLL therapy is also explored. C1 [Davids, Matthew S.; Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,CLL Ctr, Boston, MA 02215 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, CLL Ctr, Dana Farber Canc Inst, 450 Brookline Ave,M232, Boston, MA 02215 USA. EM Jennifer_Brown@dfci.harvard.edu FU NCI NIH HHS [K23 CA115682, T32 CA009172] NR 48 TC 3 Z9 3 U1 0 U2 7 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 2013 VL 27 IS 2 BP 329 EP + DI 10.1016/j.hoc.2012.12.002 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 138SK UT WOS:000318530100010 PM 23561476 ER PT J AU Edlow, JA Caplan, LR O'Brien, K Tibbles, C AF Edlow, Jonathan A. Caplan, Louis R. O'Brien, Karen Tibbles, Carrie TI Neurological emergencies in pregnant and post-partum women in resource-poor settings Reply SO LANCET NEUROLOGY LA English DT Letter ID VENOUS THROMBOSIS C1 [Edlow, Jonathan A.] Harvard Univ, Sch Med, Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Caplan, Louis R.] Harvard Univ, Sch Med, Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [O'Brien, Karen] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Maternal & Fetal Med,Dept Obstet & Gynecol, Boston, MA 02215 USA. RP Edlow, JA (reprint author), Harvard Univ, Sch Med, Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. EM jedlow@bidmc.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2013 VL 12 IS 4 BP 330 EP 330 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 138SZ UT WOS:000318531600008 PM 23518326 ER PT J AU Lauer, A Pfeilschifter, W Schaffer, CB Lo, EH Foerch, C AF Lauer, Arne Pfeilschifter, Waltraud Schaffer, Chris B. Lo, Eng H. Foerch, Christian TI Intracerebral haemorrhage associated with antithrombotic treatment: translational insights from experimental studies SO LANCET NEUROLOGY LA English DT Review ID DIRECT THROMBIN INHIBITOR; PROTHROMBIN COMPLEX CONCENTRATE; ACTIVATED FACTOR-VII; RECOMBINANT FACTOR VIIA; FRESH-FROZEN PLASMA; PRIOR ANTIPLATELET THERAPY; REDUCED PLATELET ACTIVITY; BLOOD-CLOT FORMATION; ATRIAL-FIBRILLATION; INTRACRANIAL HEMORRHAGE AB Little is known about the pathophysiology of intracerebral haemorrhage that occurs during anticoagulant treatment. In observational studies, investigators have reported larger haematoma volumes and worse functional outcome in these patients than in those with intracerebral haemorrhage and a normal coagulation status. The need to prevent extensive haematoma enlargement by rapid reversal of the anticoagulation seems intuitive, although no evidence is available from randomised clinical trials. New oral anticoagulants, such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitor rivaroxaban, have been approved recently; however, intracerebral haemorrhage during dabigatran or rivaroxaban anticoagulation has not been characterised, and whether anticoagulation reversal can be beneficial in this scenario is unknown. In a translational approach, new experimental models have been developed to study anticoagulation-associated intracerebral haemorrhage in more detail and to test treatment strategies. Vitamin k antagonists enlarge haematoma volumes and worsen functional outcome in animal models. Rapid reversal of anticoagulation in the experimental setting prevents prolonged haematoma expansion and improves outcome. The new oral anticoagulants increase intracerbral haemorrhage volumes less than does warfarin. Haemostatic approaches that have been used for vitamin k-associated intracerebral haemorrhage also seem to be effective in intracerebral haemorrhage associated with the new anticoagulants. These experimental studies are valuable for filling gaps in knowledge, but the results need careful translation into routine clinical practice. C1 [Lauer, Arne; Pfeilschifter, Waltraud; Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60526 Frankfurt, Germany. [Lauer, Arne; Lo, Eng H.; Foerch, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA USA. [Schaffer, Chris B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. RP Foerch, C (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60526 Frankfurt, Germany. EM foerch@em.uni-frankfurt.de RI Schaffer, Chris/A-7409-2008 OI Schaffer, Chris/0000-0002-7800-9596 FU NINDS NIH HHS [R01 NS076694, P01 NS055104, R37 NS037074] NR 99 TC 17 Z9 18 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2013 VL 12 IS 4 BP 394 EP 405 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 138SZ UT WOS:000318531600015 PM 23518332 ER PT J AU Kumar, P Moy, B AF Kumar, Pallavi Moy, Beverly TI The Cost of Cancer Care-Balancing Our Duties to Patients Versus Society: Are They Mutually Exclusive? SO ONCOLOGIST LA English DT Editorial Material DE Health care costs; Ethical issues; Cancer care; Resource allocation; Decision-making ID QUALITY-OF-LIFE; BREAST-CANCER; DECISION-MAKING; FOLLOW-UP; CENTERED CARE; TRASTUZUMAB; TRIAL; PARTICIPATION; MULTICENTER; PREFERENCES C1 [Kumar, Pallavi; Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Moy, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Womens Canc, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM bmoy@partners.org NR 33 TC 3 Z9 3 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2013 VL 18 IS 4 BP 347 EP 349 DI 10.1634/theoncologist.2013-0078 PG 3 WC Oncology SC Oncology GA 136CB UT WOS:000318336200006 PM 23568002 ER PT J AU O'Toole, J Jammallo, LS Miller, CL Skolny, MN Specht, MC Taghian, AG AF O'Toole, Jean Jammallo, Lauren S. Miller, Cynthia L. Skolny, Melissa N. Specht, Michelle C. Taghian, Alphonse G. TI Screening for Breast Cancer-Related Lymphedema: The Need for Standardization SO ONCOLOGIST LA English DT Editorial Material ID ARM LYMPHEDEMA; LIMB VOLUME; SURVIVORS; DIAGNOSIS; SPECTROSCOPY; PREVALENCE; SECONDARY; IMPACT; COSTS; RISK C1 [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA. [Jammallo, Lauren S.; Miller, Cynthia L.; Skolny, Melissa N.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 18 TC 4 Z9 4 U1 1 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2013 VL 18 IS 4 BP 350 EP 352 DI 10.1634/theoncologist.2012-0387 PG 3 WC Oncology SC Oncology GA 136CB UT WOS:000318336200007 PM 23576481 ER PT J AU Ruddy, KJ Meyer, ME Giobbie-Hurder, A Emmons, KM Weeks, JC Winer, EP Partridge, AH AF Ruddy, Kathryn J. Meyer, Meghan E. Giobbie-Hurder, Anita Emmons, Karen M. Weeks, Jane C. Winer, Eric P. Partridge, Ann H. TI Long-Term Risk Perceptions of Women With Ductal Carcinoma In Situ SO ONCOLOGIST LA English DT Article DE Carcinoma; Intraductal; Noninfiltrating; Survivors; Anticipation; Psychological; Anxiety ID INTRADUCTAL BREAST-CANCER; SURGICAL ADJUVANT BREAST; TRIAL; TAMOXIFEN; DIAGNOSIS; THERAPY; DCIS AB Introduction. Previous research has demonstrated that many women with ductal carcinoma in situ (DCIS) overestimate their risk for future breast cancer at the time of diagnosis and soon thereafter. This study aims to evaluate risk perceptions after 5 years. Patients and Methods. In a longitudinal cohort study, we mailed long-term follow-up surveys to 315 women who had previously responded to a survey 18 months after they were diagnosed with DCIS, excluding those who had experienced recurrence and those not treated at our institution. We evaluated risk perceptions with items used previously in the cohort. Results. One hundred ninety-three women (61%) responded. The median time since diagnosis was 5.9 years. We excluded 12 because of recurrence. Of the 181 remaining, 32% perceived at least a moderate 5-year risk for developing DCIS again, 43% perceived at least a moderate lifetime risk for developing DCIS again, 27% perceived at least a moderate 5-year risk for invasive breast cancer, 38% perceived at least a moderate lifetime risk for invasive breast cancer, and 24% perceived at least a moderate risk for DCIS spreading to other body parts. In a multivariate model, worse financial status and higher perceived risk in the previous survey were the only predictors of at least a moderate perception of risk for DCIS spreading. Conclusion. Women with a history of DCIS continue to harbor in accurate perceptions of their risk for future breast cancer events even 5 years after diagnosis. The Oncologist 2013;18:362-368 C1 [Ruddy, Kathryn J.; Meyer, Meghan E.; Weeks, Jane C.; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kruddy@partners.org FU Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Breast Cancer [5P50CA89393-03] FX Funding was provided by the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Breast Cancer (5P50CA89393-03). The principal investigator for this grant was James D. Iglehart, M.D. However, the National Cancer Institute was not involved in the study design; collection, analysis, or interpretation of the data; manuscript preparation; or the decision to submit the manuscript for publication. No one other than the authors of the study contributed to the writing of this manuscript. NR 19 TC 3 Z9 3 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2013 VL 18 IS 4 BP 362 EP 368 DI 10.1634/theoncologist.2012-0376 PG 7 WC Oncology SC Oncology GA 136CB UT WOS:000318336200009 PM 23568001 ER PT J AU Wolpin, BM Ng, K Zhu, AX Abrams, T Enzinger, PC McCleary, NJ Schrag, D Kwak, EL Allen, JN Bhargava, P Chan, JA Goessling, W Blaszkowsky, LS Supko, JG Elliot, M Sato, K Regan, E Meyerhardt, JA Fuchs, CS AF Wolpin, Brian M. Ng, Kimmie Zhu, Andrew X. Abrams, Thomas Enzinger, Peter C. McCleary, Nadine J. Schrag, Deborah Kwak, Eunice L. Allen, Jill N. Bhargava, Pankaj Chan, Jennifer A. Goessling, Wolfram Blaszkowsky, Lawrence S. Supko, Jeffrey G. Elliot, Meaghan Sato, Kaori Regan, Eileen Meyerhardt, Jeffrey A. Fuchs, Charles S. TI Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer SO ONCOLOGIST LA English DT Editorial Material AB Background. Treatments that target the vascular endothelial growth factor (VEGF) pathway have efficacy in colorectal cancer. We evaluated tolerability and efficacy of tivozanib (an oral VEGF receptor-1, -2, -3 inhibitor) plus everolimus (an oral mammalian target of rapamycin inhibitor). Methods. The phase Ib study followed a 3 + 3 dose-escalation design with three dose levels. The primary objective in the follow-on phase II study was improvement in 2-month progression-free survival (PFS) from 30% (historical benchmark) to 50% in patients with refractory, metastatic colorectal cancer. Results. Dose-limiting toxicities in the phase Ib study were grade 3 fatigue and dehydration. Oral tivozanib (1 mg daily for 3 of 4 weeks) and oral everolimus (10 mg daily continuously) were advanced to a 40-patient phase II study. The most common grade 3-4 adverse events were thrombocytopenia and hypophosphatemia. The 2-month PFS rate was 50%, with 20 of 40 patients having stable disease (SD). Seven (18%) patients were treated for >= 6 months. Median PFS and overall survival (OS) times were 3.0 months (95% confidence interval [CI]: 1.9-3.6 months) and 5.6 months (95% CI: 4.4-10.6 months), respectively. Patients who developed grade 1+ hypertension had increased SD rates (65.2% vs. 29.4%) and longer OS times (10.6 vs. 3.7 months). Conclusions. The oral combination of tivozanib and everolimus was well tolerated, with stable disease achieved in 50% of patients with refractory, metastatic colorectal cancer. The Oncologist 2013;18:377-378 C1 [Wolpin, Brian M.; Ng, Kimmie; Abrams, Thomas; Enzinger, Peter C.; McCleary, Nadine J.; Schrag, Deborah; Bhargava, Pankaj; Chan, Jennifer A.; Goessling, Wolfram; Elliot, Meaghan; Sato, Kaori; Regan, Eileen; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Zhu, Andrew X.; Kwak, Eunice L.; Allen, Jill N.; Blaszkowsky, Lawrence S.; Supko, Jeffrey G.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Bhargava, Pankaj] AVEO Pharmaceut, Cambridge, MA USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org OI Goessling, Wolfram/0000-0001-9972-1569 FU NCI NIH HHS [K07 CA140790, K07 CA148894] NR 0 TC 17 Z9 19 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2013 VL 18 IS 4 BP 377 EP 378 DI 10.1634/theoncologist.2012-0378 PG 2 WC Oncology SC Oncology GA 136CB UT WOS:000318336200011 PM 23580238 ER PT J AU Zafar, SY Peppercorn, JM Schrag, D Taylor, DH Goetzinger, AM Zhong, XY Abernethy, AP AF Zafar, S. Yousuf Peppercorn, Jeffrey M. Schrag, Deborah Taylor, Donald H. Goetzinger, Amy M. Zhong, Xiaoyin Abernethy, Amy P. TI The Financial Toxicity of Cancer Treatment: A Pilot Study Assessing Out-of-Pocket Expenses and the Insured Cancer Patient's Experience SO ONCOLOGIST LA English DT Article DE Neoplasms; Cost; Chemotherapy; Indigency; Medical; Quality of health care; Financial support ID BREAST-CANCER; CARE; HEALTH; COSTS; ADULTS; WOMEN AB Purpose. Cancer patients carry rising burdens of health care-related out-of-pocket expenses, and a growing number of patients are considered "underinsured." Our objective was to describe experiences of insured cancer patients requesting copayment assistance and to describe the impact of health care expenses on well-being and treatment. Methods. We conducted baseline and follow-up surveys regarding the impact of health care costs on well-being and treatment among cancer patients who contacted a national copayment assistance foundation along with a comparison sample of patients treated at an academic medical center. Results. Among 254 participants, 75% applied for drug copayment assistance. Forty-two percent of participants reported a significant or catastrophic subjective financial burden; 68% cut back on leisure activities, 46% reduced spending on food and clothing, and 46% used savings to defray out-of-pocket expenses. To save money, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether. Copayment assistance applicants were more likely than nonapplicants to employ at least one of these strategies to defray costs (98% vs. 78%). In an adjusted analysis, younger age, larger household size, applying for copayment assistance, and communicating with physicians about costs were associated with greater subjective financial burden. Conclusion. Insured patients undergoing cancer treatment and seeking copayment assistance experience considerable subjective financial burden, and they may alter their care to defray out-of-pocket expenses. Health insurance does not eliminate financial distress or health disparities among cancer patients. Future research should investigate coverage thresholds that minimize adverse financial outcomes and identify cancer patients at greatest risk for financial toxicity. The Oncologist 2013;18:381-390 C1 [Zafar, S. Yousuf; Peppercorn, Jeffrey M.; Zhong, Xiaoyin; Abernethy, Amy P.] Ctr Learning Hlth Care, Duke Clin Res Inst, Div Med Oncol, Durham, NC USA. [Zafar, S. Yousuf; Peppercorn, Jeffrey M.; Zhong, Xiaoyin; Abernethy, Amy P.] Duke Canc Inst, Dept Med, Durham, NC 27710 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taylor, Donald H.] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. [Goetzinger, Amy M.] Univ N Carolina, Chapel Hill, NC USA. RP Zafar, SY (reprint author), Duke Canc Inst, Dept Med, Div Med Oncol, DUMC 3505,10 Byran Searle Dr,Seeley Mudd Bld,Room, Durham, NC 27710 USA. EM yousuf.zafar@duke.edu FU HealthWell Foundation FX This study was funded by the HealthWell Foundation. NR 23 TC 138 Z9 139 U1 5 U2 20 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 2013 VL 18 IS 4 BP 381 EP 390 DI 10.1634/theoncologist.2012-0279 PG 10 WC Oncology SC Oncology GA 136CB UT WOS:000318336200013 PM 23442307 ER PT J AU Rosenberg, TL Kelley, K Dowdall, JR Replogle, WH Liu, JC Raol, NP Zafereo, ME AF Rosenberg, Tara L. Kelley, Kanwar Dowdall, Jayme R. Replogle, William H. Liu, Jeffrey C. Raol, Nikhila P. Zafereo, Mark E. TI Section for Residents and Fellows-in-Training Survey Results SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT AAO-HNSF Annual Meeting and OTO EXPO CY SEP 09-12, 2012 CL Washington, DC SP AAO, HNSF, Off Res & Dev, Vet Hlth Adm, Dept Vet Affairs, MED-EL, Agcy Healthcare Res & Qual, Sect Residents & Fellows Training DE otolaryngology residents; section for residents and fellows; survey ID OTOLARYNGOLOGY-HEAD; NECK-SURGERY; WORKFORCE; ISSUES AB Objectives. (1) To present data from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Section for Residents and Fellows-in-Training (SRF) annual survey from 2002 to 2011. (2) To compare and analyze trends in resident demographics, residency experiences, and post-training career choices. Study Design. Review of cross-sectional survey data. Setting. Residents and Fellows registered as Members-in-Training through AAO-HNS. Methods. A review of data from surveys distributed between 2002 and 2011 was conducted. Respondent demographic data including age, postgraduate year, gender, and geographic distribution were analyzed. Responses about training experiences, fellowship selection, debt burden, and post-training practice choice were studied in order to elicit trends. Results. Respondents have consistently rated otolaryngology, anesthesia, and trauma/critical care as the most important intern rotations for otolaryngology residents. Each year, approximately 70% of respondents have reported interest in pursuing a fellowship. Pediatric otolaryngology fellowship is now the most popular fellowship among respondents. There has been a recent increase in the percentage of respondents who are interested in pursuing a career in academics. Location, family, and lifestyle have consistently been the most important factors in determining choice of practice. Respondents have reported increasing levels of educational debt. Conclusion. The AAO-HNS SRF survey collects important data regarding resident/fellow training. Several factors limit the generalizability of these results. Despite its limitations, these unique data provide valuable information for continual evaluation and improvement of physician training in the specialty. C1 [Rosenberg, Tara L.] Univ Mississippi, Med Ctr, Dept Otolaryngol & Communicat Sci, Jackson, MS 39216 USA. [Kelley, Kanwar] Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, Irvine, CA USA. [Dowdall, Jayme R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Replogle, William H.] Univ Mississippi, Med Ctr, Dept Family Med, Jackson, MS 39216 USA. [Liu, Jeffrey C.] Temple Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. [Raol, Nikhila P.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. [Zafereo, Mark E.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. RP Rosenberg, TL (reprint author), Univ Mississippi, Med Ctr, Dept Otolaryngol & Communicat Sci, 2500 North State St, Jackson, MS 39216 USA. EM trosenberg@umc.edu NR 10 TC 6 Z9 6 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2013 VL 148 IS 4 BP 582 EP 588 DI 10.1177/0194599813477353 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 136LG UT WOS:000318362800010 PM 23396591 ER PT J AU Hill, CA Ojha, S Maturo, S Maurer, R Bunting, G Hartnick, CJ AF Hill, Courtney A. Ojha, Shilpa Maturo, Stephen Maurer, Rie Bunting, Glenn Hartnick, Christopher J. TI Consistency of Voice Frequency and Perturbation Measures in Children SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE pediatric; voice ID SPEECH AB Objective. Evaluate normal pediatric voice frequency and perturbation measures with Voice Evaluation Suite (VES) and Multi Dimensional Voice Program (MDVP), determine the consistency of these measures over time, and understand which measures might be most useful for evaluating children with voice disorders. Study Design. Prospective, longitudinal study of normal voices of 50 children aged 4 to 17 years. Setting. Pediatric otolaryngology clinic within tertiary hospital. Subjects and Methods. Two tests of sustained utterances from each child were evaluated by 2 computerized voice analysis programs for frequency and perturbation. Intraclass correlation coefficient (ICC) was used to assess the reliability between the samples. Results. Children (male/female, 1.08:1) with a mean age of 8.34 years were tested on an average of 54.2 minutes apart. Each test included 4 utterances; 1 was analyzed by MDVP, and 3 grouped utterances were averaged and evaluated by VES. Fundamental frequency had excellent reliability (ICC = 0.95) in both VES and MDVP. Jitter, shimmer, and noise to harmonic ratio were poorly reliable (ICC <= 0.4) in MDVP but had good to excellent reliability (ICC 0.66-0.8) in VES. Conclusion. Single, sustained utterances in children provide consistent measures of frequency. Perturbation is not reliably measured by such testing, but averaging multiple samples yields improved consistency. Evaluating acoustic measure stability in spontaneous speech and in sustained utterances cued by a tuning frequency can provide further insight on pediatric voice consistency. C1 [Hill, Courtney A.] Dartmouth Hitchcock Med Ctr, Otolaryngol Sect, Lebanon, NH 03766 USA. [Ojha, Shilpa; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Maturo, Stephen] San Antonio Mil Med Ctr, Dept Otolaryngol, Ft Sam Houston, TX USA. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Invest, Boston, MA 02115 USA. [Maurer, Rie] Harvard Clin & Translat Sci Ctr, Harvard Catalyst, Boston, MA USA. [Bunting, Glenn] Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 14 TC 6 Z9 7 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2013 VL 148 IS 4 BP 637 EP 641 DI 10.1177/0194599813477829 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 136LG UT WOS:000318362800018 PM 23396592 ER PT J AU Slater, LH Hett, EC Mark, K Chumbler, NM Patel, D Lacy, DB Collier, RJ Hung, DT AF Slater, Louise H. Hett, Erik C. Mark, Kevin Chumbler, Nicole M. Patel, Deepa Lacy, D. Borden Collier, R. John Hung, Deborah T. TI Identification of Novel Host-Targeted Compounds That Protect from Anthrax Lethal Toxin-Induced Cell Death SO ACS CHEMICAL BIOLOGY LA English DT Article ID IN-VIVO; BACILLUS-ANTHRACIS; DEPENDENT PROCESS; BCL-2 INHIBITORS; MAMMALIAN-CELLS; TYROSINE KINASE; SMALL MOLECULES; CANCER-CELLS; EDEMA FACTOR; N-TERMINUS AB Studying how pathogens subvert the host to cause disease has contributed to the understanding of fundamental cell biology. Bacillus anthracis, the causative agent of anthrax, produces the virulence factor lethal toxin to disarm host immunity and cause pathology. We conducted a phenotypic small molecule screen to identify inhibitors of lethal toxin-induced macrophage cell death and used an ordered series of secondary assays to characterize the hits and determine their effects on cellular function. We identified a structurally diverse set of small molecules that act at various points along the lethal toxin pathway, including inhibitors of endocytosis, natural product inhibitors of organelle acidification (e.g., the botulinum neurotoxin inhibitor, toosendanin), and a novel proteasome inhibitor, 4MNB (4-methoxy-2-[2-(5-methoxy-2-nitrosophenyl)ethyl]-1-nitrosobenzene). Many of the compounds, including three drugs approved for use in humans, also protected against the related Clostridium difficile toxin TcdB, further demonstrating their value as novel tools for perturbation and study of toxin biology and host cellular processes and highlighting potential new strategies for intervening on toxin-mediated diseases. C1 [Slater, Louise H.; Hett, Erik C.; Mark, Kevin; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Slater, Louise H.; Hett, Erik C.; Mark, Kevin; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Slater, Louise H.; Hett, Erik C.; Mark, Kevin; Hung, Deborah T.] Broad Inst, Infect Dis Initiat, Cambridge, MA 02142 USA. [Slater, Louise H.; Hett, Erik C.; Mark, Kevin; Patel, Deepa; Collier, R. John; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Chumbler, Nicole M.; Lacy, D. Borden] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu OI Collier, R John/0000-0002-2427-4239 FU NIH National Research Service Award fellowship [F32AI084323]; NIH [U54 AI057159] FX The authors would like to thank A. Barker for help with production and purification of PA and LF, A. Clatworthy and S. Chiang for helpful discussions, and the Broad Institute chemical screening platform for technical help. E.C.H. was funded by an NIH National Research Service Award fellowship F32AI084323. This work was supported in part by NIH U54 AI057159 to the New England Center of Excellence/Biodefense and Emerging Infectious Diseases (D.T.H.). NR 77 TC 8 Z9 8 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD APR PY 2013 VL 8 IS 4 BP 812 EP 822 DI 10.1021/cb300555n PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 131NY UT WOS:000318001600020 PM 23343607 ER PT J AU Sengupta, S Kulkarni, A AF Sengupta, Shiladitya Kulkarni, Ashish TI Design Principles for Clinical Efficacy of Cancer Nanomedicine: A Look into the Basics SO ACS NANO LA English DT Editorial Material ID NANOPARTICLES; CHALLENGES; DELIVERY; DENSITY; DRUGS; PEG AB With recent advances in cancer nanomedicine, there is an increasing expectation for clinical translation. However, what are the parameters of a nanomedicine that will define clinical success, which will be measured by increased efficacy and not just ease of delivery or reduction in toxicity? In this Perspective, we build on a fundamental study by Stefanick et al. on the significance of the design principles in the engineering of a nanomedicine, such as peptide-PEG-linker length and ligand density in cellular uptake of liposomal nanoparticles. We address additional design parameters that can potentially facilitate clinical translation as well as how emerging insights into tumor biology will inspire next-generation cancer nanomedicines. C1 [Sengupta, Shiladitya; Kulkarni, Ashish] Harvard Univ, Sch Med,Lab Nanomed, Dana Farber Canc Ctr,Dept Med,Brigham & Womens Ho, Harvard MIT Div Hlth Sci Technol,Div Biomed Engn, Boston, MA 02139 USA. RP Sengupta, S (reprint author), Harvard Univ, Sch Med,Lab Nanomed, Dana Farber Canc Ctr,Dept Med,Brigham & Womens Ho, Harvard MIT Div Hlth Sci Technol,Div Biomed Engn, 65 Landsdowne St,Room 317, Boston, MA 02139 USA. EM shiladit@mit.edu FU NCI NIH HHS [1R01CA135242-01A2, R01 CA135242] NR 20 TC 29 Z9 30 U1 0 U2 59 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD APR PY 2013 VL 7 IS 4 BP 2878 EP 2882 DI 10.1021/nn4015399 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 133MU UT WOS:000318143300002 PM 23607425 ER PT J AU Coopey, S Tang, R Lei, L Kansal, K Colwell, A Gadd, M Specht, M Austen, W Smith, B AF Coopey, Suzanne Tang, Rong Lei, Lan Kansal, Kari Colwell, Amy Gadd, Michele Specht, Michelle Austen, William Smith, Barbara TI Eligibility for Nipple-Sparing Mastectomy May Be Safely Expanded SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Coopey, Suzanne; Tang, Rong; Lei, Lan; Kansal, Kari; Colwell, Amy; Gadd, Michele; Specht, Michelle; Austen, William; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 5 EP 6 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800006 ER PT J AU Dominici, L Shulman, L Ahn, SH Camp, M Cho, JY Coopey, S Kim, SB Caragacianu, D Valero, M Barkley, C Wang, JP Gong, GY Hevelone, N Baek, S Son, BH Golshan, M AF Dominici, Laura Shulman, Lawrence Ahn, Sei Hyun Camp, Melissa Cho, Ja Young Coopey, Suzanne Kim, Sung Bae Caragacianu, Diana Valero, Monica Barkley, Christina Wang, Jiping Gong, Gyung-yub Hevelone, Nathanael Baek, Seunghee Son, Byung Ho Golshan, Mehra TI Young Women With Breast Cancer in Boston and Seoul: Comparison of Demographics, Pathology, and Management SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Dominici, Laura; Shulman, Lawrence; Caragacianu, Diana; Valero, Monica; Barkley, Christina; Wang, Jiping; Hevelone, Nathanael; Golshan, Mehra] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Camp, Melissa; Coopey, Suzanne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ahn, Sei Hyun; Cho, Ja Young; Kim, Sung Bae; Gong, Gyung-yub; Baek, Seunghee; Son, Byung Ho] Asan Med Ctr, Seoul, South Korea. 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 37 EP 37 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800047 ER PT J AU Kansal, KJ Tang, R Lei, L Coopey, SB Colwell, AS Specht, MC Gadd, MA Taghian, A Austen, WG Smith, BL AF Kansal, Kari J. Tang, Rong Lei, Lan Coopey, Suzanne B. Colwell, Amy S. Specht, Michelle C. Gadd, Michele A. Taghian, Alphonse Austen, William G., Jr. Smith, Barbara L. TI Impact of Postmastectomy Radiation Therapy after Nipple-Sparing Mastectomy With Immediate Reconstruction SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Kansal, Kari J.; Tang, Rong; Lei, Lan; Coopey, Suzanne B.; Colwell, Amy S.; Specht, Michelle C.; Gadd, Michele A.; Taghian, Alphonse; Austen, William G., Jr.; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 62 EP 62 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800083 ER PT J AU Schubart, J Dominici, L Farnan, M Kelly, T Manahan, E Rahman, R Smith, JS Kass, R AF Schubart, Jane Dominici, Laura Farnan, Michelle Kelly, Tricia Manahan, Eric Rahman, Rakhshanda Smith, J. Stanley Kass, Rena TI Shared Decision Making in Breast Cancer: National Practice Patterns of Surgeons SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Schubart, Jane; Farnan, Michelle; Smith, J. Stanley; Kass, Rena] Penn State Coll Med, Hershey, PA USA. [Dominici, Laura] Brigham & Womens Canc Ctr, Dana Farber, Boston, MA USA. [Kelly, Tricia] St Lukes Univ Hlth Network, Allentown, PA USA. [Manahan, Eric] Dalton Surg Grp, Dalton, GA USA. [Rahman, Rakhshanda] Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA. RI sebastianovitsch, stepan/G-8507-2013 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 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 64 EP 65 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800085 ER PT J AU Miller, C Koerner, F West, J Freer, P Gudewicz, T Coopey, S Gadd, M Hughes, K Smith, B Rafferty, E Specht, M AF Miller, Cynthia Koerner, Frederick West, Jane Freer, Phoebe Gudewicz, Thomas Coopey, Suzanne Gadd, Michele Hughes, Kevin Smith, Barbara Rafferty, Elizabeth Specht, Michelle TI Upgrade Rate of Radial Scars Without Atypia Diagnosed by Core Biopsy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Miller, Cynthia; Koerner, Frederick; West, Jane; Freer, Phoebe; Gudewicz, Thomas; Coopey, Suzanne; Gadd, Michele; Hughes, Kevin; Smith, Barbara; Rafferty, Elizabeth; Specht, Michelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 82 EP 83 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800108 ER PT J AU Tang, R Saksena, M Coopey, S Fernandez, L Buckley, J Lei, L Aftreth, O Koerner, F Michaelson, J Brachtel, E Smith, B AF Tang, Rong Saksena, Mansi Coopey, Suzanne Fernandez, Leopoldo Buckley, Julliette Lei, Lan Aftreth, Owen Koerner, Frederick Michaelson, James Brachtel, Elena Smith, Barbara TI Microcomputed Tomography vs Mammography and Ultrasonography for Assessment of Breast Cancer Tumor Size SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 01-05, 2013 CL Chicago, IL SP Amer Soc Breast Surg C1 [Tang, Rong; Saksena, Mansi; Coopey, Suzanne; Fernandez, Leopoldo; Buckley, Julliette; Lei, Lan; Aftreth, Owen; Koerner, Frederick; Michaelson, James; Brachtel, Elena; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tang, Rong] Hunan Prov Tumor Hosp, Changsha, Hunan, Peoples R China. RI sebastianovitsch, stepan/G-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 SU 2 BP 111 EP 112 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 133XS UT WOS:000318174800143 ER PT J AU Jackevicius, CA Tu, JV Krumholz, HM AF Jackevicius, Cynthia A. Tu, Jack V. Krumholz, Harlan M. TI Statins: Is It Safe and Effective to Use Generic "Equivalents"? SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; DRUGS; ATORVASTATIN; METAANALYSIS; PERCEPTIONS; EFFICACY; ADULTS; RISK C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.; Tu, Jack V.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.; Tu, Jack V.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Tu, Jack V.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Cardiol, Schulich Heart Ctr, Toronto, ON, Canada. [Krumholz, Harlan M.] Sect Cardiovasc Med, Dept Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Yale New Haven Hosp, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Krumholz, Harlan M.] Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu OI Tu, Jack/0000-0003-0111-722X NR 17 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD APR PY 2013 VL 29 IS 4 BP 408 EP 410 DI 10.1016/j.cjca.2012.08.012 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133UQ UT WOS:000318166500002 PM 23062664 ER PT J AU Camp, ER Wang, C Little, EC Watson, PM Pirollo, KF Rait, A Cole, DJ Chang, EH Watson, DK AF Camp, E. R. Wang, C. Little, E. C. Watson, P. M. Pirollo, K. F. Rait, A. Cole, D. J. Chang, E. H. Watson, D. K. TI Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy SO CANCER GENE THERAPY LA English DT Article DE pancreatic cancer; transferrin; p53; nanoparticle ID SINGLE-INSTITUTION EXPERIENCE; CELLS IN-VITRO; 1423 PANCREATICODUODENECTOMIES; NANODELIVERY SYSTEM; INTERFERING RNA; CARCINOMA; IMMUNOLIPOPLEX; RESTORATION; XENOGRAFTS; EFFICACY AB To overcome gene therapy barriers such as low transfection efficiency and nonspecific delivery, liposomal nanoparticles targeted by a single-chain antibody fragment to the transferrin receptor (TfRscFv) delivering wild-type (wt) human p53 (SGT-53) were developed for tumor-specific targeting. We hypothesize that SGT-53 in combination with gemcitabine will demonstrate enhanced therapeutic benefit in an in vivo metastatic pancreatic cancer model. Intrasplenic injection of 1 x 10(6) Panc02 murine pancreatic cancer cells was used to generate in vivo hepatic metastatic tumors. Nanoparticle localization was assessed by tail vein injection of TfRscFv with fluorescently labeled oligonucleotides (6-carboxyfluorescein phosphoramidite (6FAM) ODN) imaged by Xenogen IVIS 200 scan. SGT-53 (equivalent to 30 mu g of p53 intravenously) and gemcitabine (20 mg/kg intraperitoneally) alone and in combination were administered biweekly and compared with untreated mice. Survival was determined by blinded daily assessment of morbidity. Human wtp53 expression and transferrin levels in the tumors were assessed by western blot analysis. Tumor burden was quantified by liver weight. Xenogen imaging demonstrated tumor-specific uptake of TfRscFv-6FAM ODN. Exogenous human wtp53 protein was detected in the SGT-53-treated tumors compared with control. Compared with untreated mice with metastatic tumors demonstrating median survival of 20 days, SGT-53, gemcitabine and the combination demonstrated improved median survival of 29, 30 and 37 days, respectively. The combination treatment prolonged median survival when compared with single drug treatment and decreased tumor burden. The tumor targeting liposomal-based SGT-53 nanoparticle is capable of sensitizing pancreatic cancer to conventional chemotherapy in pancreatic cancer models. This approach has the potential to be translated into a new, more effective therapy for pancreatic cancer. Further optimization is ongoing, moving towards a Phase 1B/2 clinical trial. Cancer Gene Therapy (2013) 20, 222-228; doi:10.1038/cgt.2013.9; published online 8 March 2013 C1 [Camp, E. R.; Wang, C.; Cole, D. J.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Camp, E. R.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Little, E. C.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Watson, P. M.; Watson, D. K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Pirollo, K. F.; Rait, A.; Chang, E. H.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Watson, D. K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC795, Charleston, SC 29425 USA. EM campe@musc.edu FU Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]; National Institutes of Health [5R01CA123159-05, 1K08CA142904] FX This work was supported in part by the Flow Cytometry and Cell Sorting and Molecular imaging Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313) and National Institutes of Health, 5R01CA123159-05 (DJC, DKW) and 1K08CA142904 (ERC). NR 30 TC 39 Z9 39 U1 2 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2013 VL 20 IS 4 BP 222 EP 228 DI 10.1038/cgt.2013.9 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 131OT UT WOS:000318003700002 PM 23470564 ER PT J AU Brennan-Minnella, AM Shen, Y Swanson, RA AF Brennan-Minnella, A. M. Shen, Y. Swanson, R. A. TI Phosphoinositide 3-kinase couples NMDA receptors to superoxide release in excitotoxic neuronal death SO CELL DEATH & DISEASE LA English DT Article DE Calcium; glutamate; NADPH oxidase; protein kinase C zeta; protein kinase M ID PROTEIN-KINASE-C; D-ASPARTATE RECEPTOR; CEREBELLAR GRANULE CELLS; RAT HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; NITRIC-OXIDE; GLUTAMATE NEUROTOXICITY; NADPH-OXIDASE; OXIDATIVE STRESS; NR2B SUBUNIT AB Sustained activation of neuronal N-methly D-aspartate (NMDA)-type glutamate receptors leads to excitotoxic cell death in stroke, trauma, and neurodegenerative disorders. Excitotoxic neuronal death results in part from superoxide produced by neuronal NADPH oxidase (NOX2), but how NMDA receptors are coupled to neuronal NOX2 activation is not well understood. Here, we identify a signaling pathway coupling NMDA receptor activation to NOX2 activation in primary neuron cultures. Calcium influx through the NR2B subunit of NMDA receptors leads to the activation of phosphoinositide 3-kinase (PI3K). Formation of phosphatidylinositol (3,4,5)-triphosphate (PI(3,4,5)P3) by PI3K activates the atypical protein kinase C, PKC zeta (PKC xi), which in turn phosphorylates the p47(phox) organizing subunit of neuronal NOX2. Calcium influx through NR2B-containing NMDA receptors triggered mitochondrial depolarization, NOX2 activation, superoxide formation, and cell death. However, equivalent magnitude calcium elevations induced by ionomycin did not induce NOX2 activation or neuronal death, despite causing mitochondrial depolarization. The PI3K inhibitor wortmannin prevented NMDA-induced NOX2 activation and cell death, without preventing cell swelling, calcium elevation, or mitochondrial depolarization. The effects of wortmannin were circumvented by exogenous supply of the PI3K product, PI(3,4,5)P3, and by transfection with protein kinase M, a constitutively active form of PKC xi. These findings demonstrate that superoxide formation and excitotoxic neuronal death can be dissociated from mitochondrial depolarization, and identify a novel role for PI3K in this cell death pathway. Perturbations in this pathway may either increase or decrease superoxide production in response to NMDA receptor activation, and may thereby impact neurological disorders, in which excitotoxicity is a contributing factor. Cell Death and Disease (2013) 4, e580; doi:10.1038/cddis.2013.111; published online 4 April 2013 C1 [Brennan-Minnella, A. M.; Shen, Y.; Swanson, R. A.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Neurol, San Francisco, CA 94121 USA. RP Brennan-Minnella, AM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM angela.brennan@ucsf.edu FU US National Institutes of Health [NS041421]; US Department of Veterans Affairs FX We thank J-Y Ahn, SM Massa, and S Finkbeiner for helpful discussions and C Hefner for technical assistance. This work was supported by funding from the US National Institutes of Health (NS041421) and by the US Department of Veterans Affairs. AMB-M designed and performed most of the experiments and prepared the initial manuscript. RAS conceived the project and prepared the final manuscript. The authors declare no competing financial interests. NR 60 TC 22 Z9 22 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD APR PY 2013 VL 4 AR e580 DI 10.1038/cddis.2013.111 PG 10 WC Cell Biology SC Cell Biology GA 132NL UT WOS:000318075500014 PM 23559014 ER PT J AU Brim, RL Pearson, SD AF Brim, Remy L. Pearson, Steven D. TI The use and reporting of patient-reported outcomes in phase III breast cancer trials SO CLINICAL TRIALS LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CLINICAL-TRIALS; CLINICALTRIALS.GOV; REGISTRATION; ONCOLOGY; ISSUES; STOCK AB Background Public and government attention to patient-centered research outcomes has been increasing, evidenced by the recent formation of the Patient Centered Outcomes Research Institute. Drug development clinical trials can be made more patient-centered by collecting patient-reported outcome measures that can inform decision making by patients and their health-care providers. Patient-reported outcomes are important to collect in trials of breast cancer therapeutics, which encompass a wide range of treatment regimens and side effects. Purpose We sought to determine recent trends in the use of patient-reported outcomes in drug trials for the treatment of breast cancer and evaluate the reporting of these data in study publications. Methods We searched ClinicalTrials.gov for phase Ill breast cancer drug trials, recording information on start date, primary completion date, primary outcome measure, primary sponsor, stage of cancer, and patient-reported outcome use. To assess the reporting of patient-reported outcome data, Google.com and PubMed. gov were searched for all publications resulting from included trials. Results We found 236 eligible trials, starting between May 1989 and December 2011. Of these trials, 83 (35%) stipulated patient-reported outcome use. The rate of patient-reported outcome use in recent years has shown no increase over earlier time periods: 37% (1989-2000) versus 36% (2004-2007) versus 30% (2008-2011) (p = 0.8). Trials with sponsorship led by the pharmaceutical industry and trials including patients with locally advanced or metastatic disease had the highest rates of patient-reported outcome use (40/87 (46%) and 44/102 (43%), respectively). Among the 83 trials that collected patient-reported outcome measures, 36 were completed a minimum of 2 years before our analysis; of these 36 studies, 19 (53%) had published patient-reported outcome data. Limitations Data were limited to self-reported descriptions of trials listed on the ClinicalTrial.gov database, which is the best compendium of trial information available, but it is neither a complete nor a fully accurate record of all trials. Conclusions Patient-reported outcome use and reporting in breast cancer drug trials has remained relatively low despite calls for more patient-centered research. Increasing the collection and availability of patient-reported outcome data to guide clinical decisions will require aligned support from trial sponsors, researchers, journal editors, regulators and patient advocacy groups, who can all play important roles in implementing change. Clinical Trials 2013; 10: 243-249. http://ctj.sagepub.com C1 [Brim, Remy L.; Pearson, Steven D.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Brim, RL (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM remy.brim@nih.gov FU Intramural Research Program of the National Institutes of Health Clinical Center FX This research was supported by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 32 TC 6 Z9 6 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2013 VL 10 IS 2 BP 243 EP 249 DI 10.1177/1740774513475529 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 135CJ UT WOS:000318263300006 PM 23539108 ER PT J AU Gmyrek, GB Graham, DB Sandoval, GJ Blaufuss, GS Akilesh, HM Fujikawa, K Xavier, RJ Swat, W AF Gmyrek, Grzegorz B. Graham, Daniel B. Sandoval, Gabriel J. Blaufuss, Gregory S. Akilesh, Holly M. Fujikawa, Keiko Xavier, Ramnik J. Swat, Wojciech TI Polarity gene discs large homolog 1 regulates the generation of memory T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Cell polarity; Discs large protein; Memory T cell; Ovalbumin; Transgenic T cells ID PDZ-CONTAINING PROTEINS; TRANSGENIC MICE; IMMUNOLOGICAL SYNAPSE; POSITIVE SELECTION; POTASSIUM CHANNEL; CUTTING EDGE; IN-VIVO; RECEPTOR; ACTIVATION; EFFECTOR AB Mammalian ortholog of Drosophila cell polarity protein, Dlg1, plays a critical role in neural synapse formation, epithelial cell homeostasis, and urogenital development. More recently, it has been proposed that Dlg1 may also be involved in the regulation of T-cell proliferation, migration, and Ag-receptor signaling. However, a requirement for Dlg1 in development and function of T lineage cells remains to be established. In this study, we investigated a role for Dlg1 during T-cell development and function using a combination of conditional Dlg1 KO and two different Cre expression systems where Dlg1 deficiency is restricted to the T-cell lineage only, or all hematopoietic cells. Here, using three different TCR models, we show that Dlg1 is not required during development and selection of thymocytes bearing functionally rearranged TCR transgenes. Moreover, Dlg1 is dispensable in the activation and proliferative expansion of Ag-specific TCR-transgenic CD4+ and CD8+ T cells in vitro and in vivo. Surprisingly, however, we show that Dlg1 is required for normal generation of memory T cells during endogenous response to cognate Ag. Thus, Dlg1 is not required for the thymocyte selection or the activation of primary T cells, however it is involved in the generation of memory T cells. C1 [Gmyrek, Grzegorz B.; Graham, Daniel B.; Sandoval, Gabriel J.; Blaufuss, Gregory S.; Akilesh, Holly M.; Swat, Wojciech] Washington Univ, Sch Med, Div Immunobiol, St Louis, MO 63110 USA. [Fujikawa, Keiko] Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Swat, Wojciech] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Swat, W (reprint author), Washington Univ, Sch Med, Div Immunobiol Lab & Genom Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM swat@wustl.edu RI Gmyrek, Grzegorz/C-3175-2011 FU National Institutes of Health [R01AI061077, R01AI073718]; Leukemia & Lymphoma Society Scholar; Special Fellow (D.B.G.) awards; NIH [DK043351, HL088297] FX This work was supported by National Institutes of Health grant nos. R01AI061077 (to W.S.), R01AI073718 (to W.S.), and Leukemia & Lymphoma Society Scholar (W.S.) and Special Fellow (D.B.G.) awards. R.J.X was supported by NIH grants DK043351 and HL088297. NR 46 TC 10 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2013 VL 43 IS 5 BP 1185 EP 1194 DI 10.1002/eji.201142362 PG 10 WC Immunology SC Immunology GA 135GM UT WOS:000318276500007 PM 23436244 ER PT J AU Cohen, J Malins, A Shahpurwala, Z AF Cohen, Joshua Malins, Ashley Shahpurwala, Zainab TI Compared To US Practice, Evidence-Based Reviews In Europe Appear To Lead To Lower Prices For Some Drugs SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; CANCER DRUGS; REIMBURSEMENT; ONCOLOGISTS; DECISIONS; COUNTRIES; COVERAGE; KINGDOM; IMPACT; WORTH AB In Europe drug reimbursement decisions often weigh how new drugs perform relative to those already on the market and how cost-effective they are relative to certain metrics. In the United States such comparative-effectiveness and cost-effectiveness evidence is rarely considered. Which approach allows patients greater access to drugs? In 2000-11 forty-one oncology drugs were approved for use in the United States and thirty-one were approved in Europe. We compared patients' access to the twenty-nine cancer drugs introduced into the health care systems of the United States and four European countries. Relative to the approach used in the US Medicare program in particular, the European evidence-based approach appears to have led to reduced prices for those drugs deemed worthy of approval and reimbursement. The result is improved affordability for payers and increased access for patients to those drugs that were available. The United States lacks a systematic approach to assessing such evidence in the coverage decision-making process, which may prove inadequate for controlling costs, improving outcomes, and reducing inequities in access to care. C1 [Cohen, Joshua] Tufts Univ, Ctr Study Drug Dev, Boston, MA 02111 USA. [Malins, Ashley] Dana Farber Canc Inst, Dis Ctr Operat, Boston, MA 02115 USA. [Shahpurwala, Zainab] Univ Mississippi, Dept Pharm Adm, University, MS 38677 USA. RP Cohen, J (reprint author), Tufts Univ, Ctr Study Drug Dev, Boston, MA 02111 USA. EM Joshua.cohen@tufts.edu FU Commonwealth Fund FX The authors thank the Commonwealth Fund for its financial support of this study. The views presented here are those of the authors and not necessarily those of the Commonwealth Fund, its directors, officers, or staff. NR 42 TC 5 Z9 5 U1 1 U2 8 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2013 VL 32 IS 4 BP 762 EP 770 DI 10.1377/hlthaff.2012.0707 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 131UU UT WOS:000318023100017 PM 23569057 ER PT J AU Sepucha, KR AF Sepucha, Karen R. TI To Err Is Health Care? Breaking The Silence SO HEALTH AFFAIRS LA English DT Book Review C1 [Sepucha, Karen R.] Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Div Gen Med, Boston, MA 02114 USA. [Sepucha, Karen R.] Harvard Univ, Sch Med, Boston, MA USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Div Gen Med, Boston, MA 02114 USA. EM ksepucha@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2013 VL 32 IS 4 BP 820 EP 821 DI 10.1377/hlthaff.2012.1343 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 131UU UT WOS:000318023100024 ER PT J AU Garg, A Burrell, L Tripodis, Y Goodman, E Brooks-Gunn, J Duggan, AK AF Garg, Arvin Burrell, Lori Tripodis, Yorghos Goodman, Elizabeth Brooks-Gunn, Jeanne Duggan, Anne K. TI Maternal Mental Health during Children's First Year of Life: Association with Receipt of Section 8 Rental Assistance SO HOUSING POLICY DEBATE LA English DT Article DE vouchers; underserved; low-income housing ID HOME VISITING PROGRAM; MEDICAL HOME; CAGE QUESTIONNAIRE; RANDOMIZED-TRIAL; FAMILY PROCESS; START PROGRAM; DEPRESSION; NEIGHBORHOOD; POVERTY; WOMEN AB Prior studies evaluating housing programs have found varied results for the impact of improved housing on maternal mental health. This study evaluated data from 169 families who participated in Hawaii's Healthy Start Program. The study's objective was to determine whether receipt of Section 8 rental assistance in the first year of a child's life decreased the risk of poor maternal mental health. Multivariable logistic regression was used to measure the association of Section 8 housing receipt with poor mental health. Overall, 50% of mothers had poor mental health at baseline, and 32% reported receipt of Section 8 housing at follow-up. Mothers who received Section 8 housing were significantly less likely to have poor maternal mental health at follow-up (adjusted odds ratio=.40; 95% confidence interval, .16.97; p < .05). Receipt of Section 8 rental assistance in the first year of a child's life may reduce the risk of poor mental health for mothers in housing need. C1 [Garg, Arvin] Boston Univ, Sch Med, Dept Pediat, Boston Med Ctr, Boston, MA 02118 USA. [Burrell, Lori; Duggan, Anne K.] Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD USA. [Tripodis, Yorghos] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Goodman, Elizabeth] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Brooks-Gunn, Jeanne] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Brooks-Gunn, Jeanne] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Garg, A (reprint author), Boston Univ, Sch Med, Dept Pediat, Boston Med Ctr, Boston, MA 02118 USA. EM arvin.garg@bmc.org NR 77 TC 1 Z9 1 U1 6 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1051-1482 J9 HOUS POLICY DEBATE JI Hous. Policy Debate PD APR 1 PY 2013 VL 23 IS 2 BP 281 EP 297 DI 10.1080/10511482.2012.762033 PG 17 WC Planning & Development; Urban Studies SC Public Administration; Urban Studies GA 130WZ UT WOS:000317952100002 ER PT J AU Mazzoni, M De Giorgio, R Latorre, R Vallorani, C Bosi, P Trevisi, P Barbara, G Stanghellini, V Corinaldesi, R Forni, M Faussone-Pellegrini, MS Sternini, C Clavenzani, P AF Mazzoni, Maurizio De Giorgio, Roberto Latorre, Rocco Vallorani, Claudia Bosi, Paolo Trevisi, Paolo Barbara, Giovanni Stanghellini, Vincenzo Corinaldesi, Roberto Forni, Monica Faussone-Pellegrini, Maria S. Sternini, Catia Clavenzani, Paolo TI Expression and regulation of alpha-transducin in the pig gastrointestinal tract SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE alpha-gustducin; taste receptors; enteroendocrine cells; chemosensing ID BITTER TASTE RECEPTORS; ENTEROENDOCRINE STC-1 CELLS; FOOD-INTAKE; ENDOCRINE RESPONSES; WEANLING PIGS; GUSTDUCIN; GHRELIN; SOMATOSTATIN; SECRETION; DEPRIVATION AB Taste signalling molecules are found in the gastrointestinal (GI) tract suggesting that they participate to chemosensing. We tested whether fasting and refeeding affect the expression of the taste signalling molecule, -transducin (Gtran), throughout the pig GI tract and the peptide content of Gtran cells. The highest density of Gtran-immunoreactive (IR) cells was in the pylorus, followed by the cardiac mucosa, duodenum, rectum, descending colon, jejunum, caecum, ascending colon and ileum. Most Gtran-IR cells contained chromogranin A. In the stomach, many Gtran-IR cells contained ghrelin, whereas in the upper small intestine many were gastrin/cholecystokinin-IR and a few somatostatin-IR. Gtran-IR and Ggust-IR colocalized in some cells. Fasting (24h) resulted in a significant decrease in Gtran-IR cells in the cardiac mucosa (29.3 +/- 0.8 versus 64.8 +/- 1.3, P<0.05), pylorus (98.8 +/- 1.7 versus 190.8 +/- 1.9, P<0.0l), caecum (8 +/- 0.01 versus 15.5 +/- 0.5, P<0.01), descending colon (17.8 +/- 0.3 versus 23 +/- 0.6, P<0.05) and rectum (15.3 +/- 0.3 versus 27.5 +/- 0.7, P<0.05). Refeeding restored the control level of Gtran-IR cells in the cardiac mucosa. In contrast, in the duodenum and jejunum, Gtran-IR cells were significantly reduced after refeeding, whereas Gtran-IR cells density in the ileum was not changed by fasting/refeeding. These findings provide further support to the concept that taste receptors contribute to luminal chemosensing in the GI tract and suggest they are involved in modulation of food intake and GI function induced by feeding and fasting. C1 [Mazzoni, Maurizio; Latorre, Rocco; Vallorani, Claudia; Forni, Monica; Clavenzani, Paolo] Univ Bologna, Dept Vet Med Sci, I-40126 Bologna, Italy. [De Giorgio, Roberto; Barbara, Giovanni; Stanghellini, Vincenzo; Corinaldesi, Roberto] Univ Bologna, Dept Med & Surg Sci, I-40126 Bologna, Italy. [Bosi, Paolo; Trevisi, Paolo] Univ Bologna, Dept Agri Food Protect & Improvement, I-40126 Bologna, Italy. [Faussone-Pellegrini, Maria S.] Univ Florence, Dept Anat Histol & Forens Med, Florence, Italy. [Sternini, Catia] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE DDRC,Dept Med, Los Angeles, CA 90095 USA. [Sternini, Catia] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE DDRC,Dept Neurobiol, Los Angeles, CA 90095 USA. [Sternini, Catia] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [De Giorgio, Roberto; Clavenzani, Paolo] Univ Bologna, CIRAU, I-40126 Bologna, Italy. RP Sternini, C (reprint author), Vet Adm Greater Los Angeles Hlth Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM csternin@ucla.edu RI Mazzoni, Maurizio/J-1918-2016; OI Mazzoni, Maurizio/0000-0002-7384-5990; TREVISI, PAOLO/0000-0001-7019-6828; Forni, Monica/0000-0003-1310-6202 FU NIH [DK79155, 41301]; Italian Ministry of Education, University and Research (MIUR); 'Fondazione Del Monte di Bologna e Ravenna', Italy; University of Bologna FX Grant support: The present work was supported by NIH grants DK79155 and 41301 (C. S.), and grants from the Italian Ministry of Education, University and Research (MIUR) (PRIN2009) (R. De G.), from 'Fondazione Del Monte di Bologna e Ravenna', Italy and funds from the University of Bologna (R. De G. and P. C.). We are grateful to Dr. Chiara Bernardini, Department of Medical Veterinary Sciences, University of Bologna, for her valuable technical assistance with Western blot experiments. NR 33 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD APR PY 2013 VL 17 IS 4 BP 466 EP 474 DI 10.1111/jcmm.12026 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 135KZ UT WOS:000318288300004 PM 23414137 ER PT J AU Tonetti, MS Van Dyke, TE AF Tonetti, Maurizio S. Van Dyke, Thomas E. CA Working Grp 1 Joint EFP AAP TI Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE atherosclerosis; bacteremia; cardiovascular diseases; clinical trials; C-reactive protein; epidemiology; inflammation; myocardial infarction; periodontal diseases; periodontitis; stroke ID OF-CARDIOLOGY; INTERVENTIONS; PROGRESSION; GUIDELINES; MANAGEMENT; HEALTH; ADULTS AB Background This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue. Aims This report examined biological plausibility, epidemiology and early results from intervention trials. Plausibility Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation. Epidemiology In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective. Intervention There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C-reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention. Conclusions It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed. C1 [Tonetti, Maurizio S.] European Res Grp Periodontol, I-16149 Genoa, Italy. [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA USA. RP Tonetti, MS (reprint author), European Res Grp Periodontol, WTC Tower Genoa,Via De Marini 1, I-16149 Genoa, Italy. EM maurizio.tonetti@ergoperio.eu OI Graziani, Filippo/0000-0001-8780-7306 FU Colgate-Palmolive; American Academy of Periodontology FX Group participants declare no conflict of interest. The workshop was funded by an unrestricted educational grant from Colgate-Palmolive to the European Federation of Periodontology and the American Academy of Periodontology. NR 14 TC 98 Z9 106 U1 1 U2 16 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 2013 VL 40 SU 14 SI SI BP S24 EP S29 DI 10.1111/jcpe.12089 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 135LX UT WOS:000318290700004 PM 23627332 ER PT J AU Van Dyke, TE van Winkelhoff, AJ AF Van Dyke, Thomas E. van Winkelhoff, Arie Jan TI Infection and inflammatory mechanisms SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE cardiovascular disease; infection; inflammation; pathogenesis; periodontitis; systemic diseases ID HUMAN PERIODONTAL-LIGAMENT; CORONARY-HEART-DISEASE; TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; ANTIINFLAMMATORY LIPID MEDIATORS; EDITORS CONSENSUS PERIODONTITIS; JOURNAL-OF-CARDIOLOGY; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS AB This introductory article examines the potential mechanisms that may play a role in the associations between periodontitis and the systemic conditions being considered in the EFP/AAP Workshop in Segovia, Spain. Three basic mechanisms have been postulated to play a role in these interactions; metastatic infections, inflammation and inflammatory injury, and adaptive immunity. The potential role of each alone and together is considered in in vitro and animal studies and in human studies when available. This is not a systematic or critical review, but rather an overview of the field to set the stage for the critical reviews in each of the working groups. C1 [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA 02142 USA. [van Winkelhoff, Arie Jan] Univ Groningen, Univ Med Ctr Groningen, Dept Dent & Oral Hyg, Groningen, Netherlands. RP Van Dyke, TE (reprint author), Forsyth Inst, 245 1st St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org OI Van Dyke, Thomas/0000-0003-0568-124X FU Colgate-Palmolive; American Academy of Periodontology FX The authors declare no conflict of interest. The workshop was funded by an unrestricted educational grant from Colgate-Palmolive to the European Federation of Periodontology and the American Academy of Periodontology. NR 92 TC 34 Z9 35 U1 0 U2 8 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 2013 VL 40 SU 14 SI SI BP S1 EP S7 DI 10.1111/jcpe.12088 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 135LX UT WOS:000318290700001 PM 23627321 ER PT J AU Grant, KW Walden, BE Summers, V Leek, MR AF Grant, Ken W. Walden, Brian E. Summers, Van Leek, Marjorie R. TI Auditory Models of Suprathreshold Distortion in Persons with Impaired Hearing Introduction SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Editorial Material ID SPEECH-RECEPTION THRESHOLD; NOISE; AID; LISTENERS; COGNITION; BENEFIT C1 [Grant, Ken W.; Summers, Van] Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, Bethesda, MD USA. [Walden, Brian E.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Grant, KW (reprint author), Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, Bethesda, MD USA. NR 24 TC 4 Z9 4 U1 0 U2 2 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD APR PY 2013 VL 24 IS 4 BP 254 EP 257 DI 10.3766/jaaa.24.4.2 PG 4 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 134JK UT WOS:000318206300002 PM 23636207 ER PT J AU Summers, V Makashay, MJ Theodoroff, SM Leek, MR AF Summers, Van Makashay, Matthew J. Theodoroff, Sarah M. Leek, Marjorie R. TI Suprathreshold Auditory Processing and Speech Perception in Noise: Hearing-Impaired and Normal-Hearing Listeners SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Compression; frequency selectivity; hearing impaired; hearing science; sensorineural hearing loss; speech perception; temporal fine structure sensitivity ID TEMPORAL FINE-STRUCTURE; FILTER SHAPES; FREQUENCY-SELECTIVITY; FLUCTUATING MASKERS; RECEPTION THRESHOLD; INTERFERING SPEECH; PHASE-LOCKING; INTELLIGIBILITY; NONLINEARITY; MODULATION AB Background: It is widely believed that suprathreshold distortions in auditory processing contribute to the speech recognition deficits experienced by hearing-impaired (HI). listeners in noise. Damage to outer hair cells and attendant reductions in peripheral compression and frequency selectivity may contribute to these deficits. In addition, reduced access to temporal fine structure (TFS) information in the speech waveform may play a role. Purpose: To examine how measures of peripheral compression, frequency selectivity, and TFS sensitivity relate to speech recognition performance by HI listeners. To determine whether distortions in processing reflected by these psychoacoustic measures are more closely associated with speech deficits in steady-state or modulated noise. Research Design: Normal-hearing (NH) and HI listeners were tested on tasks examining frequency selectivity (notched-noise task), peripheral compression (temporal masking curve task), and sensitivity to TFS information (frequency modulation [FM] detection task) in the presence of random amplitude modulation. Performance was tested at 500, 1000, 2000, and 4000 Hz at several presentation levels. The same listeners were tested on sentence recognition in steady-state and modulated noise at several signal-to-noise ratios. Study Sample: Ten NH and 18 HI listeners were tested. NH listeners ranged in age from 36 to 80 yr (M = 57.6). For HI listeners, ages ranged from 58 to 87 yr (M = 71.8). Results: Scores on the FM detection task at 1 and 2 kHz were significantly correlated with speech scores in both noise conditions. Frequency selectivity and compression measures were not as clearly associated with speech performance. Speech Intelligibility Index (SII) analyses indicated only small differences in speech audibility across subjects for each signal-to-noise ratio (SNR) condition that would predict differences in speech scores no greater than 10% at a given SNR. Actual speech scores varied by as much as 80% across subjects. Conclusions: The results suggest that distorted processing of audible speech cues was a primary factor accounting for differences in speech scores across subjects and that reduced ability to use TFS cues may be an important component of this distortion. The influence of TFS cues on speech scores was comparable in steady-state and modulated noise. Speech recognition was not related to audibility, represented by the SII, once high-frequency sensitivity differences across subjects (beginning at 5 kHz) were removed statistically. This might indicate that high-frequency hearing loss is associated with distortions in processing in lower-frequency regions. C1 [Summers, Van; Makashay, Matthew J.] Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, Bethesda, MD 20889 USA. [Theodoroff, Sarah M.; Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Summers, V (reprint author), Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM vsummers6@gmail.com FU Oticon Foundation, Smorum, Denmark; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX Supported by a grant from the Oticon Foundation, Smorum, Denmark. Additional support was provided by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Senior Research Career Scientist award [MRL]). The work was supported with resources and the use of facilities at the Portland VA Medical Center. NR 51 TC 14 Z9 16 U1 0 U2 24 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD APR PY 2013 VL 24 IS 4 BP 274 EP 292 DI 10.3766/jaaa.24.4.4 PG 19 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 134JK UT WOS:000318206300004 PM 23636209 ER PT J AU Bernstein, JGW Mehraei, G Shamma, S Gallun, FJ Theodoroff, SM Leek, MR AF Bernstein, Joshua G. W. Mehraei, Golbarg Shamma, Shihab Gallun, Frederick J. Theodoroff, Sarah M. Leek, Marjorie R. TI Spectrotemporal Modulation Sensitivity as a Predictor of Speech Intelligibility for Hearing-Impaired Listeners SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Fine structure; frequency selectivity; hearing loss; model; modulation; sensorineural; spectral; speech intelligibility; temporal ID TEMPORAL FINE-STRUCTURE; AUDITORY FILTER SHAPES; FREQUENCY-SELECTIVITY; STRUCTURE INFORMATION; CARRIER FREQUENCY; PHASE-LOCKING; NERVE FIBERS; NOISE; RECEPTION; RECOGNITION AB Background: A model that can accurately predict speech intelligibility for a given hearing-impaired (HI) listener would be an important tool for hearing-aid fitting or hearing-aid algorithm development. Existing speech-intelligibility models do not incorporate variability in suprathreshold deficits that are not well predicted by classical audiometric measures. One possible approach to the incorporation of such deficits is to base intelligibility predictions on sensitivity to simultaneously spectrally and temporally modulated signals. Purpose: The likelihood of success of this approach was evaluated by comparing estimates of spectrotemporal modulation (STM) sensitivity to speech intelligibility and to psychoacoustic estimates of frequency selectivity and temporal fine-structure (TFS) sensitivity across a group of HI listeners. Research Design: The minimum modulation depth required to detect STM applied to an 86 dB SPL four-octave noise carrier was measured for combinations of temporal modulation rate (4, 12, or 32 Hz) and spectral modulation density (0.5, 1, 2, or 4 cycles/octave). STM sensitivity estimates for individual HI listeners were compared to estimates of frequency selectivity (measured using the notched-noise method at 500, 1000, 2000, and 4000 Hz), TFS processing ability (2 Hz frequency-modulation detection thresholds for 500, 1000, 2000, and 4000 Hz carriers) and sentence intelligibility in noise (at a 0 dB signal-to-noise ratio) that were measured for the same listeners in a separate study. Study Sample: Eight normal-hearing (NH) listeners and 12 listeners with a diagnosis of bilateral sensorineural hearing loss participated. Data Collection and Analysis: STM sensitivity was compared between NH and HI listener groups using a repeated-measures analysis of variance. A stepwise regression analysis compared STM sensitivity for individual HI listeners to audiometric thresholds, age, and measures of frequency selectivity and TFS processing ability. A second stepwise regression analysis compared speech intelligibility to STM sensitivity and the audiogrann-based Speech Intelligibility Index. Results: STM detection thresholds were elevated for the HI listeners, but only for low rates and high densities. STM sensitivity for individual HI listeners was well predicted by a combination of estimates of frequency selectivity at 4000 Hz and TFS sensitivity at 500 Hz but was unrelated to audiometric thresholds. STM sensitivity accounted for an additional 40% of the variance in speech intelligibility beyond the 40% accounted for by the audibility-based Speech Intelligibility Index. Conclusions: Impaired STM sensitivity likely results from a combination of a reduced ability to resolve spectral peaks and a reduced ability to use TFS information to follow spectral-peak movements. Combining STM sensitivity estimates with audiometric threshold measures for individual HI listeners provided a more accurate prediction of speech intelligibility than audiometric measures alone. These results suggest a significant likelihood of success for an STM-based model of speech intelligibility for HI listeners. C1 [Bernstein, Joshua G. W.] Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, Bethesda, MD 20889 USA. [Mehraei, Golbarg] Harvard MIT Speech & Hearing Biosci & Technol Pro, Cambridge, MA USA. [Shamma, Shihab] Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. [Gallun, Frederick J.; Theodoroff, Sarah M.; Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Bernstein, JGW (reprint author), Walter Reed Natl Mil Med Ctr, Sci & Clin Studies Sect, Audiol & Speech Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM joshua.g.bernstein.civ@health.mil FU Oticon Foundation, Swum, Denmark; VA Rehabilitation Research & Development Service FX Supported by a grant from the Oticon Foundation, Swum, Denmark (J.G.W.B. and M.R.L.). Additional support was provided by the VA Rehabilitation Research & Development Service (Career Development grant [F.J.G.], Senior Research Career Scientist award [M.R.L.]), and some resources and facilities were provided by the Portland VA Medical Center and Walter Reed Army Medical Center. NR 63 TC 18 Z9 18 U1 3 U2 26 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD APR PY 2013 VL 24 IS 4 BP 293 EP 306 DI 10.3766/jaaa.24.4.5 PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 134JK UT WOS:000318206300005 PM 23636210 ER PT J AU Rehani, B Basu, P Ellenbogen, PH Sherin, C Cooper, JJ AF Rehani, Bhavya Basu, Pat Ellenbogen, Paul H. Sherin, Christopher Cooper, Joshua J. TI The Threat to Radiologists From the Multiple-Procedure Payment Reduction SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Rehani, Bhavya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA USA. [Basu, Pat] Virtual Radiol Corp, Eden Prairie, MN USA. [Ellenbogen, Paul H.] Amer Coll Radiol, Dallas, TX USA. [Ellenbogen, Paul H.] Texas Hlth Presbyterian Hosp Dallas, Dept Radiol, Radiol Associates North Texas, Dallas, TX USA. [Sherin, Christopher; Cooper, Joshua J.] Amer Coll Radiol, Washington, DC USA. RP Rehani, B (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM brehani@partners.org NR 0 TC 4 Z9 4 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 2013 VL 10 IS 4 BP 237 EP 238 DI 10.1016/j.jacr.2012.12.017 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 130UD UT WOS:000317944700005 PM 23545081 ER PT J AU Hempel, S Newberry, S Wang, Z Booth, M Shanman, R Johnsen, B Shier, V Saliba, D Spector, WD Ganz, DA AF Hempel, Susanne Newberry, Sydne Wang, Zhen Booth, Marika Shanman, Roberta Johnsen, Breanne Shier, Victoria Saliba, Debra Spector, William D. Ganz, David A. TI Hospital Fall Prevention: A Systematic Review of Implementation, Components, Adherence, and Effectiveness SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE fall prevention; implementation; hospital; systematic review ID QUALITY IMPROVEMENT; PATIENT SAFETY; CARE HOSPITALS; INTERVENTIONS; METAANALYSIS; INPATIENTS; WORK AB Objectives To systematically document the implementation, components, comparators, adherence, and effectiveness of published fall prevention approaches in U.S. acute care hospitals. Design Systematic review. Studies were identified through existing reviews, searching five electronic databases, screening reference lists, and contacting topic experts for studies published through August 2011. Setting U.S. acute care hospitals. Participants Studies reporting in-hospital falls for intervention groups and concurrent (e.g., controlled trials) or historic comparators (e.g., beforeafter studies). Intervention Fall prevention interventions. Measurements Incidence rate ratios (IRR, ratio of fall rate postintervention or treatment group to the fall rate preintervention or control group) and ratings of study details. Results Fifty-nine studies met inclusion criteria. Implementation strategies were sparsely documented (17% not at all) and included staff education, establishing committees, seeking leadership support, and occasionally continuous quality improvement techniques. Most interventions (81%) included multiple components (e.g., risk assessments (often not validated), visual risk alerts, patient education, care rounds, bed-exit alarms, and postfall evaluations). Fifty-four percent did not report on fall prevention measures applied in the comparison group, and 39% neither reported fidelity data nor described adherence strategies such as regular audits and feedback to ensure completion of care processes. Only 45% of concurrent and 15% of historic control studies reported sufficient data to compare fall rates. The pooled postintervention incidence rate ratio (IRR) was 0.77 (95% confidence interval=0.521.12, P=.17; eight studies; I2: 94%). Meta-regressions showed no systematic association between implementation intensity, intervention complexity, comparator information, or adherence levels and IRR. Conclusion Promising approaches exist, but better reporting of outcomes, implementation, adherence, intervention components, and comparison group information is necessary to establish evidence on how hospitals can successfully prevent falls. C1 [Hempel, Susanne; Newberry, Sydne; Wang, Zhen; Booth, Marika; Shanman, Roberta; Johnsen, Breanne; Shier, Victoria; Saliba, Debra; Ganz, David A.] RAND Corp, Santa Monica, CA 90407 USA. [Saliba, Debra; Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Saliba, Debra] Univ Calif Los Angeles, JH Borun Ctr, Los Angeles, CA USA. [Spector, William D.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hempel, S (reprint author), RAND Corp, Southern Calif Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90407 USA. EM susanne_hempel@rand.org RI Wang, Zhen/D-5991-2013 OI Wang, Zhen/0000-0002-9368-6149 FU AHRQ [HHSA290201000017I]; U.S. Department of Veterans Affairs, Veterans Health Administration, Veterans Affairs Health Services Research and Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence [VA CD2 08-012-1] FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This project was funded under Contract HHSA290201000017I TO #1 from the AHRQ. Additional support was provided through the U.S. Department of Veterans Affairs, Veterans Health Administration, Veterans Affairs Health Services Research and Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence (Project VA CD2 08-012-1 and a locally initiated project). NR 29 TC 30 Z9 30 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 483 EP 494 DI 10.1111/jgs.12169 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600001 PM 23527904 ER PT J AU Munshi, MN Pandya, N Umpierrez, GE DiGenio, A Zhou, R Riddle, MC AF Munshi, Medha N. Pandya, Naushira Umpierrez, Guillermo E. DiGenio, Andres Zhou, Rong Riddle, Matthew C. TI Contributions of Basal and Prandial Hyperglycemia to Total Hyperglycemia in Older and Younger Adults with Type 2 Diabetes Mellitus SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE basal hyperglycemia; insulin glargine; postprandial hyperglycemia; type 2 diabetes mellitus; older adults ID INSULIN GLARGINE; GLYCEMIC CONTROL; THERAPY; AGENTS; TRIAL; METFORMIN; PEOPLE AB Objectives To evaluate the relative contributions of basal and prandial components to total hyperglycemia in older and younger adults with type 2 diabetes mellitus. Design Participant-level data were pooled from six randomized studies of 24weeks or longer treatment with insulin glargine or an active comparator. Setting Prospective, randomized Phase 3 or 4 controlled trials. Participants One thousand six hundred ninety-nine individuals: 509 (30%) aged 65 and older and 1,190 (70%) younger than 65. Measurements Contributions of basal hyperglycemia (BHG) and postprandial hyperglycemia (PPHG) to total hyperglycemia, defined as the incremental area under the curve of daytime blood glucose (BG) from the overall glucose profile calculated from 7-point self-measured BG profiles, of participants aged 65 and older were compared with those of participants younger than 65. Results After 24weeks of treatment, glycosylated hemoglobin (HbA1c) decreased in the older (8.67.0%) and younger (8.77.1%) groups; the relative contribution of BHG was significantly lower in both age groups (P<.001). The relative contribution of BHG to that of PPHG was significantly smaller in older than in younger participants at baseline (75.4% vs 79.4%; P<.001) and 24weeks (37.6% vs 44.7%; P<.001). The relative contribution of BHG to total hyperglycemia was not correlated with HbA1c at baseline and after 24weeks of treatment in older participants but was positively correlated at baseline (correlation coefficient (r)=0.082; P=.005) and 24weeks (r=0.062; P=.03) in younger participants. A significantly lower proportion of older participants reported symptomatic, glucose-confirmed, and nocturnal hypoglycemia during 24weeks of treatment (P<.001). Conclusion The relative contribution of BHG was lower, and that of PPHG was greater in older than in younger participants, suggesting that different therapeutic approaches may be required to treat hyperglycemia effectively in these different age groups. C1 [Munshi, Medha N.] Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Munshi, Medha N.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Pandya, Naushira] Nova SE Univ, Coll Osteopath Med, Ft Lauderdale, FL 33314 USA. [Umpierrez, Guillermo E.] Emory Univ, Sch Med, Atlanta, GA USA. [DiGenio, Andres] Sanofi Aventis US Inc, Bridgewater, NJ USA. [Zhou, Rong] Medpace, Cincinnati, OH USA. [Riddle, Matthew C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Munshi, MN (reprint author), Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM medha.munshi@joslin.harvard.edu FU sanofi-aventis U.S., Inc.; sanofi-aventis; Merck; Eli Lilly; Novo Nordisk; Lilly; Amylin; GlaxoSmithKline; Oregon Health & Science University; Hoffmann La Roche FX The authors received writing and editorial support in the preparation of this manuscript from Katherine Roberts, PhD, of Excerpta Medica, funded by sanofi-aventis U.S., Inc.; Munshi: research grant support from sanofi-aventis. Pandya: speaker for sanofi-aventis and consultation fees for a research study sponsored by sanofi-aventis. Umpierrez: grant support from sanofi-aventis and Merck and consultant fees from sanofi-aventis, Eli Lilly, and Novo Nordisk. Zhou: employee at Medpace, which is under contract with sanofi-aventis. Riddle: research grant support from sanofi-aventis, Lilly, Amylin, and GlaxoSmithKline for clinical studies at Oregon Health & Science University. Honoraria for consulting for sanofi-aventis, Lilly, Amylin, and Hoffmann La Roche for research trial design, implementation, and interpretation of data. Presentations supported by sanofi-aventis at conferences associated with professional society meetings. NR 18 TC 6 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 535 EP 541 DI 10.1111/jgs.12167 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600007 PM 23581911 ER PT J AU Min, LL Wenger, N Walling, AM Blaum, C Cigolle, C Ganz, DA Reuben, D Shekelle, P Roth, C Kerr, EA AF Min, Lillian Wenger, Neil Walling, Anne M. Blaum, Caroline Cigolle, Christine Ganz, David A. Reuben, David Shekelle, Paul Roth, Carol Kerr, Eve A. TI When Comorbidity, Aging, and Complexity of Primary Care Meet: Development and Validation of the Geriatric CompleXity of Care Index SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE ambulatory care; utilization; comorbidity ID QUALITY-OF-CARE; VULNERABLE OLDER-PEOPLE; PRACTICE GUIDELINES; FUNCTIONAL DECLINE; ELDERS SURVEY; LAST YEAR; MULTIMORBIDITY; RISK; INTERVENTION; CONSEQUENCES AB Objectives To develop and validate the Geriatric CompleXity of Care Index (GXI), a comorbidity index of medical, geriatric, and psychosocial conditions that addresses disease severity and intensity of ambulatory care for older adults with chronic conditions. Design Development phase: variable selection and rating by clinician panel. Validation phase: medical record review and secondary data analysis. Setting Assessing the Care of Vulnerable Elders-2 study. Participants Six hundred forty-four older (75) individuals receiving ambulatory care. Measures Development: 32 conditions categorized according to severity, resulting in 117 GXI variables. A panel of clinicians rated each GXI variable with respect to the added difficulty of providing primary care for an individual with that condition. Validation: Modified versions of previously validated comorbidity measures (simple count, Charlson, Medicare Hierarchical Condition Category), longitudinal clinical outcomes (functional decline, survival), intensity of ambulatory care (primary, specialty care visits, polypharmacy, number of eligible quality indicators (NQI)) over 1year of care. Results The most-morbid individuals (according to quintiles of GXI) had more visits (7.0 vs 3.7 primary care, 6.2 vs 2.4 specialist), polypharmacy (14.3% vs 0% had 14 medications), and greater NQI (33 vs 25) than the least-morbid individuals. Of the four comorbidity measures, the GXI was the strongest predictor of primary care visits, polypharmacy, and NQI (P<.001, controlling for age, sex, function-based vulnerability). Conclusion Older adults with complex care needs, as measured by the GXI, have healthcare needs above what previously employed comorbidity measures captured. Healthcare systems could use the GXI to identify the most complex elderly adults and appropriately reimburse primary providers caring for older adults with the most complex care needs for providing additional visits and coordination of care. C1 [Min, Lillian; Cigolle, Christine] Univ Michigan, Dept Med, Div Geriatr, Sch Med, Ann Arbor, MI 48109 USA. [Min, Lillian; Cigolle, Christine] Vet Affairs Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Care Ctr, Ann Arbor, MI USA. [Wenger, Neil; Walling, Anne M.; Ganz, David A.; Shekelle, Paul] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Dept Med, Los Angeles, CA 90095 USA. [Wenger, Neil; Walling, Anne M.; Ganz, David A.; Shekelle, Paul; Roth, Carol] RAND Hlth, Santa Monica, CA USA. [Blaum, Caroline] NYU, Dept Med, Langone Med Ctr, New York, NY 10016 USA. [Blaum, Caroline] NYU, Dept Populat Hlth, Langone Med Ctr, New York, NY 10016 USA. [Ganz, David A.; Reuben, David] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, Los Angeles, CA 90095 USA. [Ganz, David A.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kerr, Eve A.] Univ Michigan, Div Gen Internal Med, Dept Med, Sch Med, Ann Arbor, MI 48109 USA. [Kerr, Eve A.] Vet Affairs Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. RP Min, LL (reprint author), Univ Michigan, Dept Med, Div Geriatr, 300 North Ingalls Bldg Wing E,Room 966, Ann Arbor, MI 48109 USA. EM lmin@med.umich.edu RI Kerr, Eve/I-3330-2013 FU Agency for Healthcare Research and Quality [Min R21 HS017621]; Claude Pepper Older Americans Independence Centers at the University of California at Los Angeles [NIA-K12 2006-2010]; University of Michigan; Hartford-AFAR Geriatric Scholars Research Outcomes Award; Veterans Affairs Greater Los Angeles Health Services Research and Development Center [CD208-012-1]; Pfizer, Inc FX This project was supported by the Agency for Healthcare Research and Quality (Min R21 HS017621). Dr. Min was supported by the Claude Pepper Older Americans Independence Centers at the University of California at Los Angeles (NIA-K12 2006-2010) and the University of Michigan (2010-2011) and a Hartford-AFAR Geriatric Scholars Research Outcomes Award (2005-2006). Dr. Ganz is funded by a Veterans Affairs Greater Los Angeles Health Services Research and Development Center of Excellence Career Development Award (CD208-012-1). The original ACOVE-2 study was supported by a contract from Pfizer, Inc. to RAND. These results were presented at the American Geriatrics Society and Society for General Internal Medicine Meetings in 2012. NR 41 TC 10 Z9 11 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 542 EP 550 DI 10.1111/jgs.12160 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600008 PM 23581912 ER PT J AU Andrews, JS Cenzer, IS Yelin, E Covinsky, KE AF Andrews, James S. Cenzer, Irena Stijacic Yelin, Edward Covinsky, Kenneth E. TI Pain as a Risk Factor for Disability or Death SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; functional limitations; activities of daily living; disability; quality of life ID LIVING OLDER PERSONS; LOW-BACK-PAIN; LAST 2 YEARS; MUSCULOSKELETAL PAIN; FUNCTIONAL DECLINE; DISABLED WOMEN; HEALTH; LIFE; DIFFICULTY; ADULTS AB Objectives To determine whether pain predicts future activity of daily living (ADL) disability or death in individuals aged 60 and older. Design Prospective cohort study. Setting The 1998 to 2008 Health and Retirement Study (HRS), a nationally representative study of older community-living individuals. Participants Twelve thousand six hundred thirty-one participants in the 1998 HRS aged 60 and older who did not need help in any ADL. Measurements Participants reporting that they had moderate or severe pain most of the time were defined as having significant pain. The primary outcome was time to development of ADL disability or death over 10yrs, assessed at five successive 2-year intervals. ADL disability was defined as needing help performing any ADL: bathing, dressing, transferring, toileting, eating, or walking across a room. A discrete hazards survival model was used to examine the relationship between pain and incident disability over each 2-year interval using only participants who started the interval with no ADL disability. Several potential confounders were adjusted for at the start of each interval: demographic factors, seven chronic health conditions, and functional limitations (ADL difficulty and difficulty with five measures of mobility). Results At baseline, 2,283 (18%) participants had significant pain. Participants with pain were more likely (all P<.001) to be female (65% vs 54%), have ADL difficulty (e.g., transferring 12% vs 2%, toileting 11% vs 2%), have difficulty walking several blocks (60% vs 21%), and have difficulty climbing one flight of stairs (40% vs 12%). Over 10years, participants with pain were more likely to develop ADL disability or death (58% vs 43%, unadjusted hazard ratio (HR)=1.67, 95% confidence interval(CI)=1.571.79), although after adjustment for confounders, participants with pain were not at greater risk for ADL disability or death (HR=0.98, 95% CI=0.911.07). Adjustment for functional status almost entirely explained the difference between the unadjusted and adjusted results. Conclusion Although there are strong cross-sectional relationships between pain and functional limitations, individuals with pain are not at higher risk of subsequent disability or death after accounting for functional limitations. Like many geriatric syndromes, pain and disability may represent interrelated phenomena that occur simultaneously and require unified treatment paradigms. C1 [Yelin, Edward] Univ Calif San Francisco, Div Rheumatol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Andrews, James S.] Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Andrews, JS (reprint author), 400 Parnassus Ave,Floor B1, San Francisco, CA 94143 USA. EM james.andrews@ucsf.edu FU NIAMD; NIA [U01AG009740]; University of California at San Francisco Multidisciplinary Clinical Research Center from the National Institute of Arthritis and Musculoskeletal Diseases (NIAMD) [P60AR-053308]; National Institute on Aging (NIA) [K24 AG029812] FX Dr. Yelin receives grant support from the NIAMD. Dr. Covinsky receives grant support from the NIA. The HRS is funded by the NIA (U01AG009740).; Supported in part by the University of California at San Francisco Multidisciplinary Clinical Research Center from the National Institute of Arthritis and Musculoskeletal Diseases (NIAMD) (P60AR-053308) and a Midcareer Research and Mentoring Award from the National Institute on Aging (NIA) (K24 AG029812). NR 29 TC 14 Z9 15 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 583 EP 589 DI 10.1111/jgs.12172 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600014 PM 23521614 ER PT J AU Hazzard, WR AF Hazzard, William R. TI As a Gerontologist Enters Old Age SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE gerontologist; old age; successful aging C1 [Hazzard, William R.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA USA. RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, 1660 S Columbian Way,S-182-GEC, Seattle, WA 98108 USA. EM william.hazzard@med.va.gov NR 0 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 639 EP 640 DI 10.1111/jgs.12176 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600020 PM 23581916 ER PT J AU Wells, RE Kerr, CE Wolkin, J Dossett, M Davis, RB Walsh, J Wall, RB Kong, J Kaptchuk, T Press, D Phillips, RS Yeh, G AF Wells, Rebecca Erwin Kerr, Catherine E. Wolkin, Jennifer Dossett, Michelle Davis, Roger B. Walsh, Jacquelyn Wall, Robert B. Kong, Jian Kaptchuk, Ted Press, Daniel Phillips, Russell S. Yeh, Gloria TI Meditation for Adults with Mild Cognitive Impairment: A Pilot Randomized Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID GRAY-MATTER; DISTRESS; DISEASE C1 [Wells, Rebecca Erwin] Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA. [Wells, Rebecca Erwin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kerr, Catherine E.] Brown Univ, Sch Med, Dept Family Med, Providence, RI 02912 USA. [Kerr, Catherine E.] Brown Univ, Sch Med, Mindfulness Wellness Program, Providence, RI 02912 USA. [Wolkin, Jennifer] NYU, Langone Med Ctr, New York, NY USA. [Dossett, Michelle; Davis, Roger B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Sch Med,Dept Med, Boston, MA 02215 USA. [Walsh, Jacquelyn] Harvard Univ, Brigham & Womens Hosp, Osher Ctr Integrat Med, Sch Med,Div Prevent Med, Boston, MA 02115 USA. [Wall, Robert B.] Commonwealth Care Alliance, Boston, MA USA. [Kong, Jian] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kaptchuk, Ted] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. [Press, Daniel] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Phillips, Russell S.; Yeh, Gloria] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Sch Med,Dept Med, Boston, MA 02215 USA. RP Wells, RE (reprint author), Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA. FU NCATS NIH HHS [8UL1TR000170-05, UL1 TR000170]; NCCIH NIH HHS [K01 AT003459, K01 AT003883, K24 AT000589, K24 AT004095, K24AT000589, KO1AT003883, R01 AT006364, R01AT006364, R03AT218317, R21 AT004497, R21AT004497, T32 AT000051, T32AT000051]; NCRR NIH HHS [UL1 RR025758, UL1 RR02758] NR 8 TC 15 Z9 15 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 IS 4 BP 642 EP 645 DI 10.1111/jgs.12179 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 130IN UT WOS:000317907600022 PM 23581918 ER PT J AU Yoshida, M Dickey, MW Sturt, P AF Yoshida, Masaya Dickey, Michael Walsh Sturt, Patrick TI Predictive processing of syntactic structure: Sluicing and ellipsis in real-time sentence processing SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article DE Sluicing; Ellipsis; Prediction; Gender mismatch effects ID EYE-TRACKING; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; CONSTRAINTS; INFORMATION; RECONSTRUCTION; DEPENDENCIES; PLAUSIBILITY; PARALLELISM; ASYMMETRIES AB This paper investigates the prediction of syntactic structure during sentence processing, using constructions that temporarily allow a sluicing interpretation in English. Making use of two well-known properties of sluicing and pronoun interpretation-connectivity effects and the local antecedent requirement on reflexives, respectively-we show that (1) the parser chooses a sluicing structure over other possible structures when sluicing is a possibility, and (2) the structure which the parser posits for sluicing involves detailed hierarchical syntactic structure. A self-paced reading experiment and three offline experiments (two acceptability rating studies and a sentence completion study) find evidence that readers immediately try to associate a reflexive pronoun embedded inside a wh-phrase with a potential antecedent in the preceding clause. However, this association is made only if a sluicing structure is a possible continuation of the sentence. This finding suggests that readers actively anticipated a sluicing structure when it was grammatically permissible, and that this structure is sufficiently detailed to license reflexive binding. This result adds to the increasing evidence that comprehenders make detailed predictions regarding upcoming linguistic structure. C1 [Yoshida, Masaya] Northwestern Univ, Dept Linguist, Evanston, IL USA. [Dickey, Michael Walsh] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Sturt, Patrick] Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, Edinburgh EH8 9YL, Midlothian, Scotland. RP Yoshida, M (reprint author), Northwestern Univ, Dept Linguist, 2016 Sheridan Rd, Eanston, IL 60208 USA. EM m-yoshida@northwestern.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 75 TC 14 Z9 14 U1 2 U2 17 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PD APR 1 PY 2013 VL 28 IS 3 SU S SI SI BP 272 EP 302 DI 10.1080/01690965.2011.622905 PG 31 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 113GE UT WOS:000316653800005 ER PT J AU Shek, SY Yeung, CK Chan, JCY Chan, HHL AF Shek, Samantha Y. Yeung, C. K. Chan, Johnny C. Y. Chan, Henry H. L. TI SAFETY AND EFFICACY EVALUATION OF A COMBINED DEVICE USING INFRARED LIGHT & BI-POLAR RADIOFREQUENCY AND SUBLATIVE RADIOFREQUENCY APPLICATORS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 33rd Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 03-07, 2013 CL Boston, MA SP Amer Soc Laser Med & Surg (ASLMS) C1 Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, 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 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2013 VL 45 IS 4 BP 280 EP 280 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 135RT UT WOS:000318306900045 ER PT J AU Ramos-Mendez, J Perl, J Faddegon, B Schumann, J Paganetti, H AF Ramos-Mendez, Jose Perl, Joseph Faddegon, Bruce Schuemann, Jan Paganetti, Harald TI Geometrical splitting technique to improve the computational efficiency in Monte Carlo calculations for proton therapy SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; variance reduction; proton therapy; TOPAS; treatment head ID DOSE-CALCULATION ALGORITHM; TRACK-REPEATING ALGORITHM; CLINICAL IMPLEMENTATION; VARIANCE REDUCTION; BEAM THERAPY; PHOTON; SIMULATIONS; DISTRIBUTIONS; RADIOTHERAPY; NOZZLE AB Purpose: To present the implementation and validation of a geometrical based variance reduction technique for the calculation of phase space data for proton therapy dose calculation. Methods: The treatment heads at the Francis H Burr Proton Therapy Center were modeled with a new Monte Carlo tool (TOPAS based on Geant4). For variance reduction purposes, two particle-splitting planes were implemented. First, the particles were split upstream of the second scatterer or at the second ionization chamber. Then, particles reaching another plane immediately upstream of the field specific aperture were split again. In each case, particles were split by a factor of 8. At the second ionization chamber and at the latter plane, the cylindrical symmetry of the proton beam was exploited to position the split particles at randomly spaced locations rotated around the beam axis. Phase space data in IAEA format were recorded at the treatment head exit and the computational efficiency was calculated. Depth-dose curves and beam profiles were analyzed. Dose distributions were compared for a voxelized water phantom for different treatment fields for both the reference and optimized simulations. In addition, dose in two patients was simulated with and without particle splitting to compare the efficiency and accuracy of the technique. Results: A normalized computational efficiency gain of a factor of 10-20.3 was reached for phase space calculations for the different treatment head options simulated. Depth-dose curves and beam profiles were in reasonable agreement with the simulation done without splitting: within 1% for depth-dose with an average difference of (0.2 +/- 0.4)%, 1 standard deviation, and a 0.3% statistical uncertainty of the simulations in the high dose region; 1.6% for planar fluence with an average difference of (0.4 +/- 0.5)% and a statistical uncertainty of 0.3% in the high fluence region. The percentage differences between dose distributions in water for simulations done with and without particle splitting were within the accepted clinical tolerance of 2%, with a 0.4% statistical uncertainty. For the two patient geometries considered, head and prostate, the efficiency gain was 20.9 and 14.7, respectively, with the percentages of voxels with gamma indices lower than unity 98.9% and 99.7%, respectively, using 2% and 2 mm criteria. Conclusions: The authors have implemented an efficient variance reduction technique with significant speed improvements for proton Monte Carlo simulations. The method can be transferred to other codes and other treatment heads. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4795343] C1 [Ramos-Mendez, Jose] Benemerita Univ Autonoma Puebla, Puebla 72750, Mexico. [Perl, Joseph] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. [Faddegon, Bruce] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Schuemann, Jan; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Schuemann, Jan; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ramos-Mendez, J (reprint author), Benemerita Univ Autonoma Puebla, 18 Sur & San Claudio Ave, Puebla 72750, Mexico. EM joserm84@gmail.com FU Consejo Nacional de Ciencia y Tecnologia (Mexico); Benemerita Universidad Autonoma de Puebla; National Institutes of Health/National Cancer Institute (NIH/NCI) [R01 CA 140735-01] FX J.R.M. acknowledges the Consejo Nacional de Ciencia y Tecnologia (Mexico) and H. Salazar-Ibarguen (Benemerita Universidad Autonoma de Puebla) for financial supporting for his visit to the Massachusetts General Hospital. J.R.M. thanks J. Shin (University of California San Francisco) for discussions on Geant4 topics. This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) under R01 CA 140735-01. NR 41 TC 11 Z9 11 U1 0 U2 6 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 2013 VL 40 IS 4 AR 041718 DI 10.1118/1.4795343 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 130UP UT WOS:000317945900024 PM 23556888 ER PT J AU Arroyo, JP Kahle, KT Gamba, G AF Pablo Arroyo, Juan Kahle, Kristopher T. Gamba, Gerardo TI The SLC12 family of electroneutral cation-coupled chloride cotransporters SO MOLECULAR ASPECTS OF MEDICINE LA English DT Review DE Diuretics; Hypertension; Epilepsy; WNK; Psoriasis; SLC12 ID NA+-CL-COTRANSPORTER; DISTAL CONVOLUTED TUBULE; SENSITIVE NA+; BLOOD-PRESSURE; MOLECULAR PHYSIOLOGY; TERMINAL DOMAIN; ANGIOTENSIN-II; CELL-VOLUME; WNK KINASES; HYPERTENSION AB The SLC12 family encodes electroneutral cation-coupled chloride cotransporters that are critical for several physiological processes including cell volume regulation, modulation of intraneuronal chloride concentration, transepithelial ion movement, and blood pressure regulation. Members of this family are the targets of the most commonly used diuretic drugs, have been shown to be the causative genes for inherited disease such as Gitelman, Bartter and Andermann syndromes, and potentially play a role in polygenic complex diseases like arterial hypertension, epilepsy, osteoporosis, and cancer. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Pablo Arroyo, Juan; Gamba, Gerardo] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gamba, G (reprint author), Mol Physiol Unit, Vasco de Quiroga 15, Mexico City 14000, DF, Mexico. EM gamba@biomedicas.unam.mx OI Arroyo, Juan Pablo/0000-0002-5992-5011 FU Swiss National Science Foundation through the National Center of Competence in Research (NCCR) TransCure, University of Bern, Switzerland; Wellcome Trust [091415]; Fondation Leducq; Mexican Council of Science and Technology [165815]; Transatlantic Network on Hypertension FX Publication in part sponsored by the Swiss National Science Foundation through the National Center of Competence in Research (NCCR) TransCure, University of Bern, Switzerland: Director Matthias A. Hediger: Web: http://www.transcure.ch.; We apologize to the authors of many studies on SLC12 cotransporters whose work was not directly discussed owing to the specific focus of this review. Due to limited references space, many original articles that already are discussed in the reviews we cite, were intentionally omitted to give space for more recent original work, not included in aforementioned reviews. Supported in part by the Wellcome Trust grant 091415, the Transatlantic Network on Hypertension funded by the Fondation Leducq, and the Mexican Council of Science and Technology grant No. 165815 to GG. JPA is a student in the Biomedical Science Ph.D Program of the UNAM. NR 70 TC 24 Z9 25 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0098-2997 J9 MOL ASPECTS MED JI Mol. Asp. Med. PD APR-JUN PY 2013 VL 34 IS 2-3 SI SI BP 288 EP 298 DI 10.1016/j.mam.2012.05.002 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 135AK UT WOS:000318258200013 PM 23506871 ER PT J AU Yoo, B Pagel, MD AF Yoo, Byunghee Pagel, Mark D. TI Lanthanide-Mediated Dephosphorylation Used for Peptide Cleavage during Solid Phase Peptide Synthesis SO MOLECULES LA English DT Article DE lanthanide; dephosphorylation; peptide synthesis; solid phase ID PHOSPHODIESTEROLYTIC ACTIVITY; PHOSPHATE-ESTERS; PHOSPHORIC-ACID; DNA-LIKE; HYDROLYSIS; COMPLEXES; IONS; CHROMATOGRAPHY; EXTRACTION; CATALYSIS AB Lanthanide(III) ions can accelerate the hydrolysis of phosphomonoesters and phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated dephosphorylation has been applied in aqueous media as an orthogonal cleavage condition that can be employed in conventional solid phase peptide synthesis (SPPS). A phosphorylated polymeric support for SPPS was developed using Boc chemistry. The cleavage of resin-bound phosphates was investigated with the addition of Eu(III), Yb(III), acid or base, a mixture of solvents or different temperatures. To demonstrate the utility of this approach for SPPS, a peptide sequence was synthesized on a phosphorylated polymeric support and quantitatively cleaved with lanthanide ions in neutral aqueous media. The protecting groups for side chains were retained during peptide cleavage using lanthanide ions. This new methodology provides a mild orthogonal cleavage condition of phosphoester as a linker during SPPS. C1 [Yoo, Byunghee] Massachusetts Gen Hosp East, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02129 USA. [Pagel, Mark D.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85724 USA. [Pagel, Mark D.] Univ Arizona, Dept Biomed Imaging, Tucson, AZ 85724 USA. [Pagel, Mark D.] Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA. RP Pagel, MD (reprint author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave, Tucson, AZ 85724 USA. EM byunghee@nmr.mgh.harvard.edu; mpagel@u.arizona.edu FU National Cancer Institute of the NIH [CA133455-01] FX We thank Josef Vagner and Lars Furenlid at the University of Arizona for inspirational discussions. This work was supported by the National Cancer Institute of the NIH (CA133455-01). NR 37 TC 1 Z9 1 U1 3 U2 18 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD APR PY 2013 VL 18 IS 4 BP 3894 EP 3905 DI 10.3390/molecules18043894 PG 12 WC Chemistry, Organic SC Chemistry GA 131TV UT WOS:000318020100018 PM 23549296 ER PT J AU Sendler, E Johnson, GD Mao, SH Goodrich, RJ Diamond, MP Hauser, R Krawetz, SA AF Sendler, Edward Johnson, Graham D. Mao, Shihong Goodrich, Robert J. Diamond, Michael P. Hauser, Russ Krawetz, Stephen A. TI Stability, delivery and functions of human sperm RNAs at fertilization SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-EJACULATED SPERMATOZOA; EARLY MOUSE EMBRYO; MESSENGER-RNA; GENE-EXPRESSION; ALTERNATIVE POLYADENYLATION; EPIGENETIC MODIFICATIONS; HUMAN SPERMATOGENESIS; CELL-DIFFERENTIATION; TARGET PREDICTION; HISTONE RETENTION AB Increasing attention has focused on the significance of RNA in sperm, in light of its contribution to the birth and long-term health of a child, role in sperm function and diagnostic potential. As the composition of sperm RNA is in flux, assigning specific roles to individual RNAs presents a significant challenge. For the first time RNA-seq was used to characterize the population of coding and non-coding transcripts in human sperm. Examining RNA representation as a function of multiple methods of library preparation revealed unique features indicative of very specific and stage-dependent maturation and regulation of sperm RNA, illuminating their various transitional roles. Correlation of sperm transcript abundance with epigenetic marks suggested roles for these elements in the pre- and post-fertilization genome. Several classes of non-coding RNAs including lncRNAs, CARs, pri-miRNAs, novel elements and mRNAs have been identified which, based on factors including relative abundance, integrity in sperm, available knockout data of embryonic effect and presence or absence in the unfertilized human oocyte, are likely to be essential male factors critical to early post-fertilization development. The diverse and unique attributes of sperm transcripts that were revealed provides the first detailed analysis of the biology and anticipated clinical significance of spermatozoal RNAs. C1 [Sendler, Edward; Johnson, Graham D.; Mao, Shihong; Goodrich, Robert J.; Krawetz, Stephen A.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Sendler, Edward; Mao, Shihong; Goodrich, Robert J.; Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Sch Med, Massachusetts Gen Hosp,Dept Environm Hlth,Vincent, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Krawetz, SA (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. EM steve@compbio.med.wayne.edu OI Diamond, Michael/0000-0001-6353-4489 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [25PM6]; LIFE Study Working Group, Division of Epidemiology, Statistics and Prevention Research; Harvard School of Public Health; National Institute of Environmental Health Sciences [ES017285]; Charlotte B. Failing Professorship; State of Michigan's 21st Century Fund Program FX The authors are grateful to Ester Anton Martorell and Meritxell Jodar Bifet for review and comments to the manuscript and Leah Sendler for her visual review and identification of many transcript features. Samples were also prepared for sequencing by Claudia Lalancette. Support by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Contract 25PM6 in collaboration with the LIFE Study Working Group, Division of Epidemiology, Statistics and Prevention Research, which provided some of the semen samples for analysis, is appreciated. Conceived and designed the experiments: M. P. D., R. H., S. A. K.; Performed the experiments: E. S., G.D.J., R.J.G.; Analyzed the data: E. S., G.D.J., S. M., S. A. K.; Contributed reagents/materials/analysis tools: M. P. D., R. H.; Wrote the manuscript: E. S., G.D.J., S. A. K.; Reviewed the manuscript: E. S., G.D.J., S. M., R.J.G., M. P. D., R. H., S. A. K.; GENI pilot grant from Harvard School of Public Health (to S. A. K. and R. H.); National Institute of Environmental Health Sciences [ES017285 to R. H.]; Charlotte B. Failing Professorship (to S. A. K.); Michigan Core Technology grant from the State of Michigan's 21st Century Fund Program (to the Wayne State University Applied Genomics Technology Center). Funding for open access charge: Charlotte B. Failing Professorship (to S. A. K.). NR 102 TC 69 Z9 72 U1 3 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2013 VL 41 IS 7 BP 4104 EP 4117 DI 10.1093/nar/gkt132 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133VD UT WOS:000318167900029 PM 23471003 ER PT J AU Yigit, E Zhang, QW Xi, LQ Grilley, D Widom, J Wang, JP Rao, A Pipkin, ME AF Yigit, Erbay Zhang, Quanwei Xi, Liqun Grilley, Dan Widom, Jonathan Wang, Ji-Ping Rao, Anjana Pipkin, Matthew E. TI High-resolution nucleosome mapping of targeted regions using BAC-based enrichment SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EUKARYOTIC GENOME; PAIR RESOLUTION; GENE-EXPRESSION; T-CELLS; DNA; ORGANIZATION; CHROMATIN; DIFFERENTIATION; POSITIONS; PERFORIN AB We report a target enrichment method to map nucleosomes of large genomes at unprecedented coverage and resolution by deeply sequencing locus-specific mononucleosomal DNA enriched via hybridization with bacterial artificial chromosomes. We achieved similar to 10 000-fold enrichment of specific loci, which enabled sequencing nucleosomes at up to similar to 500-fold higher coverage than has been reported in a mammalian genome. We demonstrate the advantages of generating high-sequencing coverage for mapping the center of discrete nucleosomes, and we show the use of the method by mapping nucleosomes during T cell differentiation using nuclei from effector T-cells differentiated from clonal, isogenic, naive, primary murine CD4 and CD8 T lymphocytes. The analysis reveals that discrete nucleosomes exhibit cell type-specific occupancy and positioning depending on differentiation status and transcription. This method is widely applicable to mapping many features of chromatin and discerning its landscape in large genomes at unprecedented resolution. C1 [Yigit, Erbay; Grilley, Dan; Widom, Jonathan] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Zhang, Quanwei; Xi, Liqun; Wang, Ji-Ping] Northwestern Univ, Dept Stat, Evanston, IL 60208 USA. [Rao, Anjana; Pipkin, Matthew E.] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. [Rao, Anjana; Pipkin, Matthew E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Rao, Anjana; Pipkin, Matthew E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pipkin, ME (reprint author), Scripps Res Inst, Dept Canc Biol, 130 Scripps Way, Jupiter, FL 33458 USA. EM jzwang@northwestern.edu; mpipkin@scripps.edu RI Xi, Liqun/I-7689-2014 FU National Institutes of Health [R01AI95634, U54CA143869, R01CA42471, R01AI 44432]; Cancer Research Institute FX National Institutes of Health grants [R01AI95634 to M. E. P., U54CA143869 to J.P.W and J.W., R01CA42471 and R01AI 44432 to A. R.]; Fellowship from the Cancer Research Institute (to E.Y.) Funding for open access charge: National Institutes of Health [R01AI95634 to M.E.P.]. NR 27 TC 8 Z9 8 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2013 VL 41 IS 7 AR e87 DI 10.1093/nar/gkt081 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133VD UT WOS:000318167900014 PM 23413004 ER PT J AU Liu, J Lloyd, SG AF Liu, Jian Lloyd, Steven G. TI High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats SO NUTRITION RESEARCH LA English DT Article DE Diet; Rat; Myocardial ischemia; Obesity; Mitochondria; Oxidative stress ID HIGH-PROTEIN-DIET; METABOLIC SYNDROME; MITOCHONDRIAL BIOGENESIS; NAD(P)H OXIDASE; ADIPONECTIN; IMPACT; DYSFUNCTION; HEART; ACCUMULATION; RECEPTORS AB Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that. there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats. These findings may have important implications for diet selection in obese patients with ischemic heart disease. Published by Elsevier Inc. C1 [Liu, Jian; Lloyd, Steven G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Lloyd, Steven G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Lloyd, SG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM sglloyd@uab.edu FU Scientist Development Grant from the American Heart Association [0735212N]; NIH Grant [P30DK056336] FX The present study was supported by Scientist Development Grant 0735212N from the American Heart Association and, in part, by NIH Grant P30DK056336. The authors would like to thank Qinglin Yang and C. Roger White for assistance with the experiment. NR 42 TC 13 Z9 14 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD APR PY 2013 VL 33 IS 4 BP 311 EP 321 DI 10.1016/j.nutres.2013.02.005 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 134EI UT WOS:000318192500009 PM 23602249 ER PT J AU Foley, OW Rauh-Hain, JA del Carmen, MG AF Foley, Olivia W. Rauh-Hain, J. Alejandro del Carmen, Marcela G. TI Recurrent Epithelial Ovarian Cancer: An Update on Treatment SO ONCOLOGY-NEW YORK LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; PLATINUM-BASED CHEMOTHERAPY; PRIMARY PERITONEAL CANCER; PLATINUM/PACLITAXEL-REFRACTORY OVARIAN; PEGYLATED LIPOSOMAL DOXORUBICIN; PACLITAXEL-RESISTANT OVARIAN; SINGLE-AGENT PACLITAXEL; FALLOPIAN-TUBE CANCER; ANTITUMOR-ACTIVITY AB An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months to 24 months. Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer. C1 [Foley, Olivia W.; Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 65 TC 35 Z9 35 U1 2 U2 4 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2013 VL 27 IS 4 BP 288 EP + PG 8 WC Oncology SC Oncology GA 132IJ UT WOS:000318060800007 PM 23781692 ER PT J AU Darden, PM Thompson, DM Roberts, JR Hale, JJ Pope, C Naifeh, M Jacobson, RM AF Darden, Paul M. Thompson, David M. Roberts, James R. Hale, Jessica J. Pope, Charlene Naifeh, Monique Jacobson, Robert M. TI Reasons for Not Vaccinating Adolescents: National Immunization Survey of Teens, 2008-2010 SO PEDIATRICS LA English DT Article DE adolescent; preventive health services; vaccination; immunization; adolescent health services; preventive health services; vaccines; meningococcal vaccines; papillomavirus vaccines; tetanus vaccine; diphtheria-tetanus vaccine; attitude to health; patient acceptance of health care; treatment refusal ID HUMAN-PAPILLOMAVIRUS VACCINE; AGED 13-17 YEARS; UNITED-STATES; ADVISORY-COMMITTEE; PRACTICES ACIP; COVERAGE; RECOMMENDATIONS; PARENT; PERTUSSIS; COMMUNICATION AB OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. METHODS: We analyzed the 2008-2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. RESULTS: The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including "Not recommended" and "Not needed or not necessary." For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including "Not sexually active" and "Safety concerns/Side effects." "Safety concerns/Side effects" increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason "Not Needed or Not Necessary" at 17.4% (95% CI: 15.7-19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04-1.13). CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents increasingly intend not to vaccinate female teens with HPV. The concern about safety of HPV grew with each year. Addressing specific and growing parental concerns about HPV will require different considerations than those for the other vaccines. C1 [Darden, Paul M.; Hale, Jessica J.; Naifeh, Monique] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA. [Thompson, David M.] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Coll Publ Hlth, Oklahoma City, OK USA. [Darden, Paul M.; Roberts, James R.] Med Univ S Carolina, Coll Med, Dept Pediat, Charleston, SC 29425 USA. [Pope, Charlene] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Pope, Charlene] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Jacobson, Robert M.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA. RP Darden, PM (reprint author), Suite 12400, Oklahoma City, OK 73104 USA. EM paul-darden@ouhsc.edu OI Jacobson, Robert/0000-0002-6355-8752 FU Pfizer; Novartis; Merck; US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC 21522] FX Dr Darden has been a consultant and served on an advisory board to Pfizer, Inc. in the past 3 years. Dr Jacobson has served in the past 3 years as a principal investigator for 2 multicenter vaccine studies funded by Pfizer as well as 1 funded by Novartis, all conducted at Mayo Clinic. He currently serves as a member of a safety review committee for 1 vaccine study as well as a member of a data and safety monitoring board for 2 other vaccine studies, all funded by Merck. The other authors have indicated they have no financial relationships relevant to this article to disclose.; Supported by grant R40 MC 21522 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. NR 30 TC 73 Z9 73 U1 5 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2013 VL 131 IS 4 BP 645 EP 651 DI 10.1542/peds.2012-2384 PG 7 WC Pediatrics SC Pediatrics GA 135EF UT WOS:000318269500048 PM 23509163 ER PT J AU Balk, SJ Fisher, DE Geller, AC AF Balk, Sophie J. Fisher, David E. Geller, Alan C. TI Teens and Indoor Tanning: A Cancer Prevention Opportunity for Pediatricians SO PEDIATRICS LA English DT Article DE indoor tanning; artificial tanning; teenagers; skin cancer; melanoma; prevention; tanning addiction; tanning legislation ID CUTANEOUS MALIGNANT-MELANOMA; BASAL-CELL CARCINOMAS; ULTRAVIOLET-RADIATION; SKIN-CANCER; UNITED-STATES; YOUNG-ADULTS; SUN EXPOSURE; FREQUENT TANNERS; BETA-ENDORPHIN; PLASMA-LEVELS AB In October 2011, California became the first US state to ban indoor tanning for minors under age 18 years. Vermont followed in May 2012. Increasingly, scientific evidence shows that artificial tanning raises the risk of skin cancer, including melanoma, a common cancer in adolescents and young adults and the type most likely to result in death. The World Health Organization, the American Academy of Pediatrics, the American Academy of Dermatology, the American Medical Association, and other organizations strongly recommend legislation to ban minors under age 18 from indoor tanning. Several nations have banned teen tanning. Yet, tanning in salons is still a prevalent practice in the United States, especially among teen girls, where rates for the oldest teens approach 40%. There is no federal legislation to restrict minors from salon tanning. More than 60% of states have some kind of legislation regarding minors' use of tanning salons, but only California and Vermont have passed complete bans of indoor tanning for minors. The Indoor Tanning Association, an industry advocacy group, has vigorously opposed legislative efforts. Pediatricians can play key roles in counseling families and with legislative efforts. In this update, we review the prevalence of salon tanning, association with skin cancer risk, tanning addiction, the roles of the federal and state governments in regulation and legislation, and responses to arguments created by industry to oppose legislation. Preventing exposure to artificial tanning may save lives, including young lives, and is a key cancer prevention opportunity for pediatricians. Pediatrics 2013;131:772-785 C1 [Balk, Sophie J.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Bronx, NY 10467 USA. [Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA USA. [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Balk, SJ (reprint author), 1621 Eastchester Rd, Bronx, NY 10461 USA. EM sbalk@montefiore.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 79 TC 14 Z9 16 U1 0 U2 17 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2013 VL 131 IS 4 BP 772 EP 785 DI 10.1542/peds.2012-2404 PG 14 WC Pediatrics SC Pediatrics GA 135EF UT WOS:000318269500063 PM 23509165 ER PT J AU Oaklander, AL Klein, MM AF Oaklander, Anne Louise Klein, Max M. TI Evidence of Small-Fiber Polyneuropathy in Unexplained, Juvenile-Onset, Widespread Pain Syndromes SO PEDIATRICS LA English DT Article DE peripheral nervous system disease; widespread chronic pain; dysautonomia ID INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; SOCIETIES/PERIPHERAL NERVE SOCIETY; PRACTICE PARAMETER EVALUATION; JOINT TASK-FORCE; SKIN BIOPSY; SENSORY NEUROPATHY; AMERICAN-ACADEMY; INTRAVENOUS IMMUNOGLOBULIN; ELECTRODIAGNOSTIC MEDICINE; ORTHOSTATIC HYPOTENSION AB OBJECTIVE: We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. METHODS: Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. RESULTS: Age at illness onset averaged 12.3 +/- 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). CONCLUSIONS: More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies. C1 [Oaklander, Anne Louise; Klein, Max M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, 275 Charles St Warren 310, Boston, MA 02114 USA. EM aoaklander@partners.org FU Public Health Service [K24NS059892]; Department of Defense [GW093049]; Bradley and Curvey Family Foundations FX Supported in part by the Public Health Service (K24NS059892), the Department of Defense (GW093049), and the Bradley and Curvey Family Foundations. NR 65 TC 19 Z9 19 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2013 VL 131 IS 4 BP E1091 EP E1100 DI 10.1542/peds.2012-2597 PG 10 WC Pediatrics SC Pediatrics GA 135EF UT WOS:000318269500006 PM 23478869 ER PT J AU Andreassen, OA Thompson, WK Schork, AJ Ripke, S Mattingsdal, M Kelsoe, JR Kendler, KS O'Donovan, MC Rujescu, D Werge, T Sklar, P Roddey, JC Chen, CH McEvoy, L Desikan, RS Djurovic, S Dale, AM AF Andreassen, Ole A. Thompson, Wesley K. Schork, Andrew J. Ripke, Stephan Mattingsdal, Morten Kelsoe, John R. Kendler, Kenneth S. O'Donovan, Michael C. Rujescu, Dan Werge, Thomas Sklar, Pamela Roddey, J. Cooper Chen, Chi-Hua McEvoy, Linda Desikan, Rahul S. Djurovic, Srdjan Dale, Anders M. CA PGC Bipolar Disorder Grp PGC Schizophrenia Working Grp TI Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; KRAEPELINIAN DICHOTOMY; CONFERRING RISK; DSM-V; DISEASES; LOCI; SUSCEPTIBILITY; PSYCHOSIS; INFERENCE AB Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the "missing heritability'' of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q-Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders. C1 [Andreassen, Ole A.; Mattingsdal, Morten; Djurovic, Srdjan] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway. [Andreassen, Ole A.; Djurovic, Srdjan] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Andreassen, Ole A.; Thompson, Wesley K.; Kelsoe, John R.; Chen, Chi-Hua; Dale, Anders M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Schork, Andrew J.; Roddey, J. Cooper; Chen, Chi-Hua; McEvoy, Linda; Desikan, Rahul S.; Dale, Anders M.] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Schork, Andrew J.] Univ Calif San Diego, Cognit Sci Grad Program, La Jolla, CA 92093 USA. [Schork, Andrew J.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Ripke, Stephan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [O'Donovan, Michael C.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany. [Werge, Thomas] Univ Copenhagen, MHC, Inst Biol Psychiat, Copenhagen, Denmark. [Sklar, Pamela] Mt Sinai Sch Med, Div Psychiat Genet & Genom, New York, NY USA. [Roddey, J. Cooper; McEvoy, Linda; Desikan, Rahul S.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Andreassen, OA (reprint author), Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway. EM o.a.andreassen@medisin.uio.no; amdale@ucsd.edu RI Hansen, Thomas/O-5965-2014; OI Hansen, Thomas/0000-0001-6703-7762; O'Donovan, Michael/0000-0001-7073-2379; Andreassen, Ole A./0000-0002-4461-3568 FU Research Council of Norway; South-East Norway Health Authority; Kristian Gerhard Jebsen Foundation; US-Norway Fulbright Foundation; National Institutes of Health (NIH) [T32 EB005970]; NIH [R01AG031224, R01EB000790, RC2DA29475] FX OAA was supported by grants from the Research Council of Norway (www.forskningsradet.no), the South-East Norway Health Authority (www.helse-sorost.no), the Kristian Gerhard Jebsen Foundation (http://www.stiftkgj.no), and the US-Norway Fulbright Foundation. RSD was supported by a grant from the National Institutes of Health (NIH; www.nih.gov T32 EB005970). AMD was supported by NIH grants R01AG031224, R01EB000790, and RC2DA29475. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 54 Z9 55 U1 1 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2013 VL 9 IS 4 AR e1003455 DI 10.1371/journal.pgen.1003455 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 132MS UT WOS:000318073300048 PM 23637625 ER PT J AU Becherel, OJ Yeo, AJ Stellati, A Heng, EYH Luff, J Suraweera, AM Woods, R Fleming, J Carrie, D McKinney, K Xu, XL Deng, CX Lavin, MF AF Becherel, Olivier J. Yeo, Abrey J. Stellati, Alissa Heng, Evelyn Y. H. Luff, John Suraweera, Amila M. Woods, Rick Fleming, Jean Carrie, Dianne McKinney, Kristine Xu, Xiaoling Deng, Chuxia Lavin, Martin F. TI Senataxin Plays an Essential Role with DNA Damage Response Proteins in Meiotic Recombination and Gene Silencing SO PLOS GENETICS LA English DT Article ID SEX-CHROMOSOME INACTIVATION; OCULOMOTOR APRAXIA TYPE-2; DOUBLE-STRAND BREAKS; CROSSING-OVER; GENOMIC INSTABILITY; GROWTH-RETARDATION; MAMMALIAN MEIOSIS; MISMATCH REPAIR; DEFICIENT MICE; PROPHASE-I AB Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx(-/-) revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome. C1 [Becherel, Olivier J.; Yeo, Abrey J.; Stellati, Alissa; Heng, Evelyn Y. H.; Luff, John; Suraweera, Amila M.; Woods, Rick; Lavin, Martin F.] Queensland Inst Med Res, Radiat Biol & Oncol Lab, Brisbane, Qld 4006, Australia. [Becherel, Olivier J.; Stellati, Alissa] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld, Australia. [Yeo, Abrey J.] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Fleming, Jean] Univ Otago, Dunedin, New Zealand. [Carrie, Dianne] Queensland Inst Med Res, QCF Transgen Lab, Brisbane, Qld 4006, Australia. [McKinney, Kristine] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Xu, Xiaoling; Deng, Chuxia] NIDDKD, Mammalian Genet Sect, NIH, Bethesda, MD 20892 USA. [Lavin, Martin F.] Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia. RP Becherel, OJ (reprint author), Queensland Inst Med Res, Radiat Biol & Oncol Lab, Brisbane, Qld 4006, Australia. EM Martin.Lavin@qimr.edu.au RI Lavin, Martin/F-5961-2014; Yeo, Abrey/D-9695-2015; deng, chuxia/N-6713-2016 OI Lavin, Martin/0000-0002-5940-4769; Yeo, Abrey/0000-0003-4470-4854; FU Australian National Health and Medical Research Council FX Funding was obtained from the Australian National Health and Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 32 Z9 33 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2013 VL 9 IS 4 AR e1003435 DI 10.1371/journal.pgen.1003435 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 132MS UT WOS:000318073300029 PM 23593030 ER PT J AU Liu, L Sabo, A Neale, BM Nagaswamy, U Stevens, C Lim, E Bodea, CA Muzny, D Reid, JG Banks, E Coon, H DePristo, M Dinh, H Fennel, T Flannick, J Gabriel, S Garimella, K Gross, S Hawes, A Lewis, L Makarov, V Maguire, J Newsham, I Poplin, R Ripke, S Shakir, K Samocha, KE Wu, YQ Boerwinkle, E Buxbaum, JD Cook, EH Devlin, B Schellenberg, GD Sutcliffe, JS Daly, MJ Gibbs, RA Roeder, K AF Liu, Li Sabo, Aniko Neale, Benjamin M. Nagaswamy, Uma Stevens, Christine Lim, Elaine Bodea, Corneliu A. Muzny, Donna Reid, Jeffrey G. Banks, Eric Coon, Hillary DePristo, Mark Dinh, Huyen Fennel, Tim Flannick, Jason Gabriel, Stacey Garimella, Kiran Gross, Shannon Hawes, Alicia Lewis, Lora Makarov, Vladimir Maguire, Jared Newsham, Irene Poplin, Ryan Ripke, Stephan Shakir, Khalid Samocha, Kaitlin E. Wu, Yuanqing Boerwinkle, Eric Buxbaum, Joseph D. Cook, Edwin H., Jr. Devlin, Bernie Schellenberg, Gerard D. Sutcliffe, James S. Daly, Mark J. Gibbs, Richard A. Roeder, Kathryn TI Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; SEQUENCING DATA; PRINCIPAL-COMPONENTS; FUNCTIONAL IMPACT; VARIANT ANALYSIS; COMMON VARIANTS; LARGE-SCALE; GENES AB We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. C1 [Liu, Li; Bodea, Corneliu A.; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Sabo, Aniko; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Dinh, Huyen; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Neale, Benjamin M.; Lim, Elaine; Ripke, Stephan; Samocha, Kaitlin E.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.; Lim, Elaine; Ripke, Stephan; Samocha, Kaitlin E.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Neale, Benjamin M.; Stevens, Christine; Lim, Elaine; Banks, Eric; DePristo, Mark; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Maguire, Jared; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Coon, Hillary] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Makarov, Vladimir; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY USA. [Makarov, Vladimir; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Newsham, Irene; Wu, Yuanqing] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. RP Liu, L (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM roeder@stat.cmu.edu RI Liu, Li/G-1897-2015; OI Sutcliffe, James/0000-0001-5200-6007; Buxbaum, Joseph/0000-0001-8898-8313 FU NIH [R01MH089208, R01 MH089025, R01 MH089004, R01 MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009, UL1 RR024975, P30 HD015052, U54 HG003273, U54 HG003067] FX This work was directly supported by NIH grants R01MH089208, R01 MH089025, R01 MH089004, R01 MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009, UL1 RR024975, P30 HD015052, U54 HG003273, and U54 HG003067 (www.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 43 Z9 43 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2013 VL 9 IS 4 AR e1003443 DI 10.1371/journal.pgen.1003443 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 132MS UT WOS:000318073300037 PM 23593035 ER PT J AU Stone, AEL Giugliano, S Schnell, G Cheng, LL Leahy, KF Golden-Mason, L Gale, M Rosen, HR AF Stone, Amy E. L. Giugliano, Silvia Schnell, Gretja Cheng, Linling Leahy, Katelyn F. Golden-Mason, Lucy Gale, Michael, Jr. Rosen, Hugo R. TI Hepatitis C Virus Pathogen Associated Molecular Pattern (PAMP) Triggers Production of Lambda-Interferons by Human Plasmacytoid Dendritic Cells SO PLOS PATHOGENS LA English DT Article ID ANTIVIRAL INNATE IMMUNITY; RIG-I; GENETIC-VARIATION; INFECTION; RECOGNITION; RNA; REPLICATION; IL28B; EXPRESSION; CLEARANCE AB Plasmacytoid Dendritic Cells (pDCs) represent a key immune cell in the defense against viruses. Through pattern recognition receptors (PRRs), these cells detect viral pathogen associated molecular patterns (PAMPs) and initiate an Interferon (IFN) response. pDCs produce the antiviral IFNs including the well-studied Type I and the more recently described Type III. Recent genome wide association studies (GWAS) have implicated Type III IFNs in HCV clearance. We examined the IFN response induced in a pDC cell line and ex vivo human pDCs by a region of the HCV genome referred to as the HCV PAMP. This RNA has been shown previously to be immunogenic in hepatocytes, whereas the conserved X-region RNA is not. We show that in response to the HCV PAMP, pDC-GEN2.2 cells upregulate and secrete Type III (in addition to Type I) IFNs and upregulate PRR genes and proteins. We also demonstrate that the recognition of this RNA is dependent on RIG-I-like Receptors (RLRs) and Toll-like Receptors (TLRs), challenging the dogma that RLRs are dispensable in pDCs. The IFNs produced by these cells in response to the HCV PAMP also control HCV replication in vitro. These data are recapitulated in ex vivo pDCs isolated from healthy donors. Together, our data shows that pDCs respond robustly to HCV RNA to make Type III Interferons that control viral replication. This may represent a novel therapeutic strategy for the treatment of HCV. C1 [Stone, Amy E. L.; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA. [Stone, Amy E. L.; Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hlth, Denver, CO USA. [Stone, Amy E. L.; Giugliano, Silvia; Cheng, Linling; Leahy, Katelyn F.; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado Denver, Hepatitis C Ctr, Dept Med, Div Gastroenterol & Hepatol, Aurora, CO USA. [Schnell, Gretja; Gale, Michael, Jr.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA USA. [Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Stone, AEL (reprint author), Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA. EM Hugo.Rosen@UCDENVER.edu OI Gale, Michael/0000-0002-6332-7436 FU VA Merit Review grant; NIH/NCATS Colorado CTSI [TL1 TR000155]; [U19 AI 1066328] FX This work was supported by U19 AI 1066328 and a VA Merit Review grant. Supported by NIH/NCATS Colorado CTSI Grant Number TL1 TR000155. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 35 Z9 35 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2013 VL 9 IS 4 AR e1003316 DI 10.1371/journal.ppat.1003316 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 132MN UT WOS:000318072700053 PM 23637605 ER PT J AU Kallet, RH Volsko, TA Hess, DR AF Kallet, Richard H. Volsko, Teresa A. Hess, Dean R. TI Respiratory Care Year in Review 2012: Invasive Mechanical Ventilation, Noninvasive Ventilation, and Cystic Fibrosis SO RESPIRATORY CARE LA English DT Review DE cystic fibrosis; mechanical ventilation; noninvasive ventilation; respiratory failure ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; POSITIVE-PRESSURE VENTILATION; LOWER TIDAL VOLUMES; UNPLANNED EXTUBATION; DEAD-SPACE; NUTRITIONAL-STATUS; DISTRESS-SYNDROME; PREVENTIVE USE AB For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, noninvasive ventilation, and cystic fibrosis. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Kallet, Richard H.] Univ Calif San Francisco, Dept Anesthesia, Resp Care Serv, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Volsko, Teresa A.] Akron Childrens Hosp, Resp Care Dept, Akron, OH USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org OI Volsko, Teresa/0000-0001-5111-898X NR 64 TC 2 Z9 2 U1 0 U2 11 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2013 VL 58 IS 4 BP 702 EP 711 DI 10.4187/respcare.02412 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 134HO UT WOS:000318201200018 PM 23564873 ER PT J AU Rogg, JG White, BA Biddinger, PD Chang, YC Brown, DFM AF Rogg, Jonathan G. White, Benjamin A. Biddinger, Paul D. Chang, Yuchiao Brown, David F. M. TI A Long-term Analysis of Physician Triage Screening in the Emergency Department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID IMPACT; THROUGHPUT; MORTALITY; FLOW AB Objectives The problem of emergency department (ED) crowding is well recognized; however, little data exist on the sustainability of potential solutions, including physician triage and screening. The authors hypothesized that a physician triage screening program (Supplemented Triage and Rapid Treatment [START]) sustainably improves standard ED performance metrics. Methods This retrospective, observational, before-and-after study compared performance measures over 4years in a tertiary care urban academic medical center with approximately 90,000 annual ED visits. Patients seen between December 2006 and November 2010 were included. Outcome measures included length of stay (LOS) for ED patients, percentage of patients who left without completing assessment (LWCA), percentage of patients treated and dispositioned by START without using monitored beds, and door-to-room time. Descriptive statistics were used. Results Median LOS for START patients was 56minutes/patient lower when comparing 2010 to 2007 (p<0.0001) and for non-START patients 22minutes/patient lower (p<0.0001). The percentage of patients who LWCA decreased from 4.8% to 2.9% (p<0.0001) during the same time period. In START's first half-year, 18% of patients were discharged without using monitored beds. This increased to 29% by year 3. In addition, median door-to-room time decreased from 18.4 to 9.9minutes during the same 3-year interval. Conclusions Physician screening appears to provide sustainable improvements in ED performance metrics including ED LOS, percentage of patients who LWCA, door-to-room time, and percentage of patients treated without using a monitored bed, despite increasing ED volume. Physician screening delivers additional incremental benefits for severalyears after implementation and can effectively increase ED capacity by allowing emergency physicians to more efficiently use monitored beds. ACADEMIC EMERGENCY MEDICINE 2013; 20: 374-380 (C) 2013 by the Society for Academic Emergency Medicine C1 [Rogg, Jonathan G.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [White, Benjamin A.; Biddinger, Paul D.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Div Gen Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [White, Benjamin A.; Biddinger, Paul D.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Chang, Yuchiao] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Biddinger, Paul D.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Gen Med, Boston, MA 02114 USA. EM dbrown2@partners.org NR 25 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2013 VL 20 IS 4 BP 374 EP 380 DI 10.1111/acem.12113 PG 7 WC Emergency Medicine SC Emergency Medicine GA 127EZ UT WOS:000317681000010 PM 23701345 ER PT J AU Singh, JA Jensen, M Lewallen, D AF Singh, Jasvinder A. Jensen, Matthew Lewallen, David TI Predictors of periprosthetic fracture after total knee replacement An analysis of 21,723 cases SO ACTA ORTHOPAEDICA LA English DT Article ID SUPRACONDYLAR FRACTURE; TOTAL HIP; ARTHROPLASTY; FEMUR; OUTCOMES; MORBIDITY; MORTALITY; INDEX; RISK; PAIN AB Background and purpose Periprosthetic fracture is a devastating complication of total knee replacement (TKR). Most published studies have not comprehensively assessed clinical and demographic predictors. We wanted to determine the incidence and predictors of postoperative periprosthetic fracture after primary and revision TKR. Patients and methods We used prospectively collected data in the Mayo Clinic Total Joint Registry on all patients who underwent primary or revision TKR at the Mayo Clinic, Rochester, from 1989 through 2008. We assessed incidence of postoperative periprosthetic fractures and modifiable (comorbidity, body mass index) and unmodifiable factors (age, sex, operative diagnosis, ASA class, previous cardiac disease, and previous thromboembolic disease) as predictors of postoperative periprosthetic fractures. We used multivariable-adjusted Cox regression analyses separately for primary and revision TKR. Results 12,914 patients underwent 17,633 primary TKRs and 3,286 patients underwent 4,090 revision TKRs during the period 1989-2008. 1.1% of patients (188/17,633) after primary TKR and 2.5% of patients (104/4,090) after revision TKR sustained a postoperative periprosthetic fracture on or after postoperative day 1. Older age was associated with lower risk of periprosthetic fractures after primary TKR (p < 0.001). Compared to = 60 years, risk was lower for ages 61-70 years (hazard ratio (HR) = 0.5, 95% confidence interval (CI): 0.3-0.7)) and 71-80 years (HR = 0.6, CI: 0.4-0.8), but not for age > 80 years (HR = 0.9, CI: 0.5-1.6). In revision TKR cohort, a diagnosis of non-union (HR = 4.9, CI: 1.2-20), infection (HR = 2.9, CI: 1.3-6.4) or previous surgery with components removed (HR = 2.1, CI: 1.3-3.4) increased the risk of postoperative periprosthetic fracture, compared to a diagnosis of loosening/wear/osteolysis. Interpretation We identified significant risk factors for periprosthetic fracture after primary and revision TKR. Patients with these risk factors can be informed by their surgeons of increased risk of this uncommon, but serious complication of TKR. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Jensen, Matthew] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health (NIH) Clinical Translational Science Award [1 KL2 RR024151-01] FX We thank Youlonda Lochler for assistance in identifying the cohort for analysis and Scott Harmsen for help with statistical analysis. This published material is the result of work supported by the National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and of the resources and use of facilities at the Birmingham VA Medical Center, AL, USA. NR 28 TC 5 Z9 7 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 J9 ACTA ORTHOP JI Acta Orthop. PD APR PY 2013 VL 84 IS 2 BP 170 EP 177 DI 10.3109/17453674.2013.788436 PG 8 WC Orthopedics SC Orthopedics GA 126ZF UT WOS:000317661500009 PM 23530873 ER PT J AU Barbu, AM Burns, JA Lopez-Guerra, G Landau-Zemer, T Friedman, AD Zeitels, SM AF Barbu, Anca M. Burns, James A. Lopez-Guerra, Gerardo Landau-Zemer, Tali Friedman, Aaron D. Zeitels, Steven M. TI Salvage Endoscopic Angiolytic KTP Laser Treatment of Early Glottic Cancer After Failed Radiotherapy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Rhinological-and-Otological-Society, Inc CY APR 20-21, 2012 CL San Diego, CA SP Amer Laryngolog Rhinolog & Otolog Soc, Inc DE glottic cancer; glottis; laryngeal cancer; laser; microlaryngoscopy; phonomicrosurgery; phonosurgery; radiation; vocal cord; vocal fold; voice ID CONSERVATION LARYNGEAL SURGERY; TUMOR ANGIOGENESIS; RADIATION FAILURE; CARCINOMA; MICROSURGERY; MANAGEMENT; RECURRENCE; VOICE; T1 AB Objectives: Management of early glottic cancer subsequent to failed radiotherapy is challenging, especially in balancing oncological control and function preservation. Patients frequently have been incentivized against surgical management and thus have undergone radiotherapy as initial treatment. This history compounds the difficulty of discussions about surgical management after recurrence. Typically, endoscopic salvage has less morbidity than transcervical partial laryngectomy and is clearly desirable over total laryngectomy. However, there are appropriate concerns about the efficacy of endoscopic salvage and the overarching impact on larynx preservation and survival. Given our success with endoscopic angiolytic KTP laser treatment of previously nonirradiated T1 and T2 glottic cancers, we examined our results from treating similar-sized lesions after failed radiotherapy. Methods: We performed a retrospective chart review of 20 patients from our cancer database who had undergone failed radiation therapy elsewhere for early glottic cancer and then underwent endoscopic angiolytic KTP laser treatment. Results: Analysis of the geographic tumor recurrence of the 20 patients revealed T1a NO MO cancer in 4 patients, T1b N0 M0 cancer in 1 patient, T2a N0 M0 cancer in 1 patient, and T2b N0 M0 cancer in 14 patients. After KTP laser salvage treatment, 4 patients (20%) had local recurrence (all T2b) and required subsequent total laryngectomy, and 3 of these patients (15%) ultimately died of disease. The remaining 16 patients (80%) were free of disease at least 2 years after endoscopic salvage (average follow-up, 39 months). Conclusions: Our investigation provides preliminary evidence that angiolytic KTP laser salvage treatment of early glottic cancer is an effective treatment after failed irradiation. Studies with larger cohorts and longer follow-up will be necessary to establish incontrovertible evidence of its efficacy. C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2013 VL 122 IS 4 BP 235 EP 239 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 125QD UT WOS:000317555400004 PM 23697320 ER PT J AU Khoury, MJ Lam, TK Ioannidis, JPA Hartge, P Spitz, MR Buring, JE Chanock, SJ Croyle, RT Goddard, KA Ginsburg, GS Herceg, Z Hiatt, RA Hoover, RN Hunter, DJ Kramer, BS Lauer, MS Meyerhardt, JA Olopade, OI Palmer, JR Sellers, TA Seminara, D Ransohoff, DF Rebbeck, TR Tourassi, G Winn, DM Zauber, A Schully, SD AF Khoury, Muin J. Lam, Tram Kim Ioannidis, John P. A. Hartge, Patricia Spitz, Margaret R. Buring, Julie E. Chanock, Stephen J. Croyle, Robert T. Goddard, Katrina A. Ginsburg, Geoffrey S. Herceg, Zdenko Hiatt, Robert A. Hoover, Robert N. Hunter, David J. Kramer, Barnet S. Lauer, Michael S. Meyerhardt, Jeffrey A. Olopade, Olufunmilayo I. Palmer, Julie R. Sellers, Thomas A. Seminara, Daniela Ransohoff, David F. Rebbeck, Timothy R. Tourassi, Georgia Winn, Deborah M. Zauber, Ann Schully, Sheri D. TI Transforming Epidemiology for 21st Century Medicine and Public Health SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER-EPIDEMIOLOGY; TRANSLATIONAL RESEARCH; KNOWLEDGE INTEGRATION; GENOMICS RESEARCH; UNITED-STATES; BIG-DATA; OPPORTUNITIES; SCIENCE; THINKING; LESSONS AB In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating "big data" science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits. Cancer Epidemiol Biomarkers Prev; 22(4); 508-16. (c) 2013 AACR. C1 [Khoury, Muin J.; Lam, Tram Kim; Croyle, Robert T.; Seminara, Daniela; Winn, Deborah M.; Schully, Sheri D.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hartge, Patricia; Chanock, Stephen J.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kramer, Barnet S.] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Dept Hlth Res & Policy,Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA. [Spitz, Margaret R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Buring, Julie E.] Brigham & Womens Hosp, Div Med, Boston, MA 02115 USA. [Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Cambridge, MA 02138 USA. [Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Goddard, Katrina A.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Ginsburg, Geoffrey S.] Duke Univ, Sch Med, Ctr Genom Med, Inst Genome Sci & Policy, Durham, NC USA. [Herceg, Zdenko] Int Agcy Res Canc, F-69372 Lyon, France. [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Olopade, Olufunmilayo I.] Univ Chicago Med, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL USA. [Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Off Director, Tampa, FL 33682 USA. [Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Tourassi, Georgia] Oak Ridge Natl Lab, Computat Sci & Engn Div, Oak Ridge, TN USA. [Zauber, Ann] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@CDC.GOV RI Lauer, Michael/L-9656-2013; OI Lauer, Michael/0000-0002-9217-8177; Palmer, Julie/0000-0002-6534-335X; Tourassi, Georgia/0000-0002-9418-9638 FU Novartis FX G.S. Ginsburg has a commercial research grant from Novartis. No potential conflicts of interest were disclosed by the other authors. NR 51 TC 50 Z9 52 U1 10 U2 80 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 2013 VL 22 IS 4 BP 508 EP 516 DI 10.1158/1055-9965.EPI-13-0146 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 130ZW UT WOS:000317960900005 PM 23462917 ER PT J AU Berkey, CS Willett, WC Tamimi, RM Rosner, B Frazier, AL Colditz, GA AF Berkey, Catherine S. Willett, Walter C. Tamimi, Rulla M. Rosner, Bernard Frazier, A. Lindsay Colditz, Graham A. TI Dairy Intakes in Older Girls and Risk of Benign Breast Disease in Young Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER-RISK; FOOD-CONSUMPTION; ADOLESCENT DIET; AMERICAN WOMEN; GROWTH; QUESTIONNAIRE; VALIDATION; PATTERNS; WEIGHT; COHORT AB Previous investigations found high dairy intakes in girls associated with rapid height growth and excess weight gain, which had opposite relationships with benign breast disease (BBD) in young women. We use data from the longitudinal Growing Up Today Study (GUTS) to investigate whether dairy intakes, in older children/adolescents, are associated with BBD risk in young women. GUTS includes 9,039 females, ages 9-15 years in 1996, who completed questionnaires annually through 2001, then in 2003, 2005, 2007, and 2010. Dietary food frequencies (1996-2001) obtained milk, yogurt, and cheese intakes. On 2005-2010 surveys, 7,011 females (18-29 years) reported whether a health care provider ever diagnosed them with BBD (n = 250) and if confirmed by breast biopsy (n 105). Logistic regression models estimated associations between prevalent biopsy-confirmed BBD and dairy intakes, adjusted for age and energy. Multivariable-adjusted models additionally included menarche age, childhood adiposity, adolescent alcohol consumption, and pregnancy. Further analyses stratified by family history. Age-energy-adjusted models of dairy (milk, yogurt, cheese, total dairy servings, dairy protein, dairy fat) intakes at 14 yr found no significant associations with BBD risk [milk: OR, 0.90/(serving/d); 95% confidence interval (CI), 0.76-1.05; dairy protein: OR, 0.98/(10 g/d); 95% CI, 0.82-1.17). Separate analyses of dairy intakes at 10 yr, intakes before the growth spurt, during the growth spurt, before menses-onset, and after menses-onset provided no significant associations with BBD. Multivariable adjustment, and family history stratification, did not alter the above findings. We conclude that dairy intakes by older girls have no strong relation with BBD risk in young women. Because of small number of cases, it is important to continue follow-up and re-examine later. Cancer Epidemiol Biomarkers Prev; 22(4); 670-4. (C) 2013 AACR. C1 [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard] Harvard Univ, Sch Med, Boston, MA USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Berkey, CS (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM Catherine.Berkey@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU Breast Cancer Research Foundation (NYC, NY); NIH (Bethesda, MD) [DK46834]; American Institute for Cancer Research; American Cancer Society FX The study was supported by a grant from The Breast Cancer Research Foundation (NYC, NY) and by DK46834 from the NIH (Bethesda, MD). A. L. Frazier was supported by an award from the American Institute for Cancer Research. G.A. Colditz was supported, in part, by an American Cancer Society Clinical Research Professorship. NR 25 TC 3 Z9 3 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2013 VL 22 IS 4 BP 670 EP 674 DI 10.1158/1055-9965.EPI-12-1133 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 130ZW UT WOS:000317960900024 PM 23542805 ER PT J AU Mondul, AM Shui, IM Yu, K Travis, RC Stevens, VL Campa, D Schumacher, FR Ziegler, RG Bueno-de-Mesquita, HB Berndt, S Crawford, ED Gapstur, SM Gaziano, JM Giovannucci, E Haiman, CA Henderson, BE Hunter, DJ Johansson, M Key, TJ Le Marchand, L Lindstrom, S McCullough, ML Navarro, C Overvad, K Palli, D Purdue, M Stampfer, MJ Weinstein, SJ Willett, WC Yeager, M Chanock, SJ Trichopoulos, D Kolonel, LN Kraft, P Albanes, D AF Mondul, Alison M. Shui, Irene M. Yu, Kai Travis, Ruth C. Stevens, Victoria L. Campa, Daniele Schumacher, Frederick R. Ziegler, Regina G. Bueno-de-Mesquita, H. Bas Berndt, Sonja Crawford, E. D. Gapstur, Susan M. Gaziano, J. Michael Giovannucci, Edward Haiman, Christopher A. Henderson, Brian E. Hunter, David J. Johansson, Mattias Key, Timothy J. Le Marchand, Loic Lindstroem, Sara McCullough, Marjorie L. Navarro, Carmen Overvad, Kim Palli, Domenico Purdue, Mark Stampfer, Meir J. Weinstein, Stephanie J. Willett, Walter C. Yeager, Meredith Chanock, Stephen J. Trichopoulos, Dimitrios Kolonel, Laurence N. Kraft, Peter Albanes, Demetrius TI Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer-Results from the Breast and Prostate Cancer Cohort Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; D-BINDING PROTEIN; SUSCEPTIBILITY LOCI; POLYMORPHISMS; PREVENTION; VARIANTS AB Background: Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. Methods: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. Results: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; P-trend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; P-trend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; P-trend = 0.003). Conclusions: In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. Impact: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 22(4); 688-96. (C) 2013 AACR. C1 [Mondul, Alison M.; Yu, Kai; Ziegler, Regina G.; Berndt, Sonja; Purdue, Mark; Weinstein, Stephanie J.; Yeager, Meredith; Chanock, Stephen J.; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Shui, Irene M.; Giovannucci, Edward; Hunter, David J.; Lindstroem, Sara; Stampfer, Meir J.; Willett, Walter C.; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Hunter, David J.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiovasc Dis, Boston, MA 02115 USA. [Giovannucci, Edward; Hunter, David J.; Stampfer, Meir J.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Travis, Ruth C.; Key, Timothy J.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Stevens, Victoria L.; Gapstur, Susan M.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Campa, Daniele] Univ Pisa, Dept Biol, Pisa, Italy. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Florence, Italy. [Schumacher, Frederick R.; Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Crawford, E. D.] Univ Colorado Hosp, Sect Urol Oncol, Aurora, CO USA. [Johansson, Mattias] IARC, Lyon, France. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Epidemiol Program, Ctr Canc, Honolulu, HI 96822 USA. [Navarro, Carmen] CIBERESP, Barcelona, Spain. [Navarro, Carmen] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain. [Overvad, Kim] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, Aarhus, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Dept Cardiol, Cardiovasc Res Ctr, Aalborg Hosp, DK-8000 Aarhus, Denmark. RP Mondul, AM (reprint author), NCI, NIH, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM mondulam@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Campa, Daniele/K-1617-2016; OI Campa, Daniele/0000-0003-3220-9944; Mondul, Alison/0000-0002-8843-1416; PALLI, Domenico/0000-0002-5558-2437 FU U.S. NIH, NCI [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]; NIH/NCI, Division of Cancer Epidemiology and Genetics; National Research Service Award from the NCI, NIH [T32 CA09001]; U.S. Army Department of Defense; NCI at the NIH; U.S. Public Health Service contracts from the NCI, NIH [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C, HHSN261200800001E] FX This work was supported by the U.S. NIH, NCI cooperative agreements U01-CA98233-07 (to D.J. Hunter), U01-CA98710-06 (to M.J. Thun), U01-CA98216-06 to (E. Riboli and R. Kaaks), and U01-CA98758-07 (to B.E. Henderson) and Intramural Research Program of NIH/NCI, Division of Cancer Epidemiology and Genetics. I.M. Shui was supported by a National Research Service Award (T32 CA09001) from the NCI, NIH and a U.S. Army Department of Defense Prostate Cancer Post-doctoral Fellowship. The ATBC Study was supported by the Intramural Research Program of the NCI at the NIH. In addition, this research was supported by U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C, and HHSN261200800001E) from the NCI, NIH. NR 28 TC 15 Z9 15 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2013 VL 22 IS 4 BP 688 EP 696 DI 10.1158/1055-9965.EPI-13-0007-T PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 130ZW UT WOS:000317960900027 PM 23377224 ER PT J AU Kinsey, CM Channick, CL AF Kinsey, C. Matthew Channick, Colleen L. TI Counterpoint: Are > 50 Supervised Procedures Required to Develop Competency in Performing Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Lung Cancer Staging? No SO CHEST LA English DT Editorial Material ID CONTROLLED-TRIAL; LYMPH-NODES; MEDIASTINOSCOPY C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Channick, CL (reprint author), Massachusetts Gen Hosp, Pulm Special Procedures Unit, 55 Fruit St,Bigelow 952, Boston, MA 02114 USA. EM cchannick@partners.org NR 13 TC 8 Z9 8 U1 0 U2 2 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 2013 VL 143 IS 4 BP 891 EP 893 DI 10.1378/chest.12-2464 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 129VG UT WOS:000317871500005 PM 23546479 ER PT J AU Kinsey, CM Channick, CL AF Kinsey, C. Matthew Channick, Colleen L. TI Rebuttal From Drs Kinsey and Channick SO CHEST LA English DT Editorial Material ID TRANSBRONCHIAL NEEDLE ASPIRATION; LEARNING-CURVE C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Channick, CL (reprint author), Massachusetts Gen Hosp, Pulm Special Procedures Unit, 55 Fruit St,Bigelow 952, Boston, MA 02114 USA. EM cchannick@partners.org NR 7 TC 0 Z9 0 U1 0 U2 2 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 2013 VL 143 IS 4 BP 894 EP 895 DI 10.1378/chest.12-2465 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 129VG UT WOS:000317871500007 ER PT J AU Lipton, A Cook, R Brown, J Body, JJ Smith, M Coleman, R AF Lipton, A. Cook, R. Brown, J. Body, J. J. Smith, M. Coleman, R. TI Skeletal-related Events and Clinical Outcomes in Patients with Bone Metastases and Normal Levels of Osteolysis: Exploratory Analyses SO CLINICAL ONCOLOGY LA English DT Article DE Bone marker; bone metastases; bone resorption; skeletal-related events; survival; zoledronic acid ID PLACEBO-CONTROLLED TRIAL; LONG-TERM EFFICACY; ZOLEDRONIC ACID; PROSTATE-CANCER; BREAST-CANCER; SOLID TUMORS; DOUBLE-BLIND; LUNG-CANCER; PHASE-III; MULTIPLE-MYELOMA AB Aims: High levels of bone resorption markers (e.g. N-telopeptide of type I collagen; NTX) have been correlated with increased risks of skeletal-related events and death in patients with bone metastases from solid tumours. However, the disease course has not been well characterised in patients with bone metastases but normal NTX levels. Therefore, the aim of this study was to evaluate the patterns of skeletal morbidity in patients with normal NTX levels. Materials and methods: Exploratory analyses were carried out on patients with bone metastases from breast cancer, castration-resistant prostate cancer, non-small cell lung cancer or other solid tumours treated with zoledronic acid (ZOL) in phase III trials. The effects of covariates on the relative risk of death were estimated using the Cox proportional hazard model. The prognostic values of covariates were compared between patients with normal (<64 nmol/mmol creatinine) versus elevated (>= 64 nmol/mmol creatinine) NTX levels. Results: Among patients with normal baseline NTX (n = 501), less than 10% developed elevated NTX levels before a skeletal-related event or death during ZOL treatment over 12 months. The prognostic factors identified in these analyses were mostly similar across NTX groups. However, some indicators of aggressive disease (e.g. visceral/cerebral metastases from breast cancer) were associated with poor clinical outcomes only in the normal NTX group. Conclusions: Skeletal-related events were generally not preceded or followed by transition to elevated NTX in patients treated with ZOL. Elevated baseline NTX and aggressive extraskeletal disease were independently associated with reduced survival. (C) 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Lipton, A.] Penn State Univ, Milton S Hershey Med Ctr, Penn State Canc Ctr, Div Hematol Oncol, Hershey, PA 17033 USA. [Cook, R.] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. [Brown, J.] St James Univ Hosp, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England. [Brown, J.; Coleman, R.] Univ Sheffield, Canc Res Ctr, Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England. [Body, J. J.] Univ Hosp Brugmann ULB, Dept Med, Brussels, Belgium. [Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Lipton, A (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Penn State Canc Ctr, Div Hematol Oncol, Room C-6830,500 Univ Dr, Hershey, PA 17033 USA. EM alipton@hmc.psu.edu RI sebastianovitsch, stepan/G-8507-2013 FU Novartis Pharmaceuticals Corporation FX The authors thank Ker-Ai Lee from the University of Waterloo for expert assistance with the statistical analyses. We thank Tamalette Loh, PhD, ProEd Communications, Inc.(R), for her medical editorial assistance with this manuscript. The statistical analysis was funded through a consulting contract between Novartis Pharmaceuticals Corporation and Dr Cook; funding for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. NR 23 TC 11 Z9 11 U1 1 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD APR PY 2013 VL 25 IS 4 BP 217 EP 226 DI 10.1016/j.clon.2012.11.004 PG 10 WC Oncology SC Oncology GA 130BY UT WOS:000317888900001 PM 23219232 ER PT J AU Herzlinger, S Horton, ES AF Herzlinger, Susan Horton, Edward S. TI Extraglycemic effects of glp-1-based therapeutics: Addressing metabolic and cardiovascular risks associated with type 2 diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Review DE Exenatide; Liraglutide; Glucagon-like peptide-1; GLP-1 receptor agonists; Cardiovascular comorbidities ID GLUCAGON-LIKE PEPTIDE-1; IMPAIRED GLUCOSE-TOLERANCE; HUMAN GLP-1 ANALOG; BETA-CELL FUNCTION; CORONARY-ARTERY-DISEASE; VEIN ENDOTHELIAL-CELLS; ONCE-DAILY LIRAGLUTIDE; OPEN-LABEL TRIAL; GLYCEMIC CONTROL; RECEPTOR AGONIST AB Context: To examine whether widespread tissue expression of the glucagon-like peptide (GLP)-1 receptor supports the possibility of differential effects of GLP-1-based therapeutics on cardiac function, blood pressure, food intake, gastric emptying, and other regulatory activities. GLP-1 receptor agonists (RAs) have demonstrated pleiotropic effects on over-weight/obesity, hypertension, dyslipidemia, and cardiovascular (CV) disease. Food-regulatory effects have been demonstrated in preclinical and clinical trials, including reduced gastric motility and food intake leading to body weight reductions. Native GLP-1 and GLP-1 RAs have demonstrated cardioprotective effects in preclinical models. Evidence acquisition: Using PubMed, we performed a search of the recent literature on GLP-1 and GLP-1 RAs. Evidence synthesis: Preliminary clinical data indicate native GLP-1 has beneficial effects on endothelial cell function and vascular inflammation. Native GLP-1 and GLP-1 RAs have demonstrated renoprotective and antihypertensive effects, and reductions in lipid parameters. The GLP-1 RA liraglutide has also demonstrated positive effects on such markers of endothelial dysfunction as tumor necrosis factor-alpha and plasminogen activator inhibitor-1. Conclusion: Preliminary data suggest GLP-1 RAs could benefit type 2 diabetes patients at risk for CV comorbidities. Additional studies are needed to confirm the extraglycemic and extrapancreatic effects and determine whether outcomes will translate into beneficial effects for patient care. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Herzlinger, Susan; Horton, Edward S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Horton, ES (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Edward.Horton@joslin.harvard.edu FU Novo Nordisk Inc; Amylin; Eli Lilly and Company FX Funding to support the preparation of this manuscript was provided by Novo Nordisk Inc. This manuscript was prepared according to the International Society for Medical Publication Professionals' "Good Publication Practice for Communicating Company-Sponsored Medical Research: the GPP2 Guidelines.'' The authors received no honorarium or payment for their authorship of this review.; ESH has served as an advisory board member and consultant to Amarin Corporation, PLC; Amylin Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Merck & CO. Inc. and Gilead Sciences, Inc. In addition, ESH has served on Data Safety Monitoring Boards for GI Dynamics, Inc.; Theracos, Inc. and Takeda Pharmaceuticals U. S. A, Inc.; is a member of the Merck speakers bureau; and has received research grant support from Amylin and Eli Lilly and Company. NR 93 TC 11 Z9 11 U1 2 U2 15 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 2013 VL 100 IS 1 BP 1 EP 10 DI 10.1016/j.diabres.2012.11.009 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 128BY UT WOS:000317744300010 PM 23332049 ER PT J AU Hou, JK Chang, M Nguyen, T Kramer, JR Richardson, P Sansgiry, S D'Avolio, LW El-Serag, HB AF Hou, Jason K. Chang, Mimi Thien Nguyen Kramer, Jennifer R. Richardson, Peter Sansgiry, Shubhada D'Avolio, Leonard W. El-Serag, Hashem B. TI Automated Identification of Surveillance Colonoscopy in Inflammatory Bowel Disease Using Natural Language Processing SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Ulcerative colitis; Machine learning; Automated retrieval console ID ULCERATIVE-COLITIS; GUIDELINES; DIAGNOSIS; SYSTEM AB Differentiating surveillance from non-surveillance colonoscopy for colorectal cancer in patients with inflammatory bowel disease (IBD) using electronic medical records (EMR) is important for practice improvement and research purposes, but diagnosis code algorithms are lacking. The automated retrieval console (ARC) is natural language processing (NLP)-based software that allows text-based document-level classification. The purpose of this study was to test the feasibility and accuracy of ARC in identifying surveillance and non-surveillance colonoscopy in IBD using EMR. We performed a split validation study of electronic reports of colonoscopy pathology for patients with IBD from the Michael E. DeBakey VA Medical Center. A gastroenterologist manually classified pathology reports as either derived from surveillance or non-surveillance colonoscopy. Pathology reports were randomly split into two sets: 70 % for algorithm derivation and 30 % for validation. An ARC generated classification model was applied to the validation set of pathology reports. The performance of the model was compared with manual classification for surveillance and non-surveillance colonoscopy. A total of 575 colonoscopy pathology reports were available on 195 IBD patients, of which 400 reports were designated as training and 175 as testing sets. Within the testing set, a total of 69 pathology reports were classified as surveillance by manual review, whereas the ARC model classified 66 reports as surveillance for a recall of 0.77, precision of 0.80, and specificity of 0.88. ARC was able to identify surveillance colonoscopy for IBD without customized software programming. NLP-based document-level classification may be used to differentiate surveillance from non-surveillance colonoscopy in IBD. C1 [Hou, Jason K.; Chang, Mimi; Kramer, Jennifer R.; Richardson, Peter; Sansgiry, Shubhada; El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Hou, Jason K.; Chang, Mimi; Kramer, Jennifer R.; Richardson, Peter; Sansgiry, Shubhada; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hou, Jason K.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Thien Nguyen; D'Avolio, Leonard W.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Cooperat Studies Coordinating Ctr, Jamaica Plain, MA USA. [D'Avolio, Leonard W.] Harvard Univ, Sch Med, Div Aging, Boston, MA USA. RP Hou, JK (reprint author), 1709 Dryden Rd,Suite 8-40, Houston, TX 77030 USA. EM jkhou@bcm.edu FU American College of Gastroenterology Junior Faculty Development Award; Houston VA HSR&D Center of Excellence [HFP90-020]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [MRP05-305]; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease Center [P30 DK56338, K24 DK078154-05] FX The research reported here was supported by the American College of Gastroenterology Junior Faculty Development Award to J.K. Hou, a pilot grant from the Houston VA HSR&D Center of Excellence (HFP90-020) to J.K. Hou, the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, grant MRP05-305 to J.R. Kramer, and the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease Center grant P30 DK56338, K24 DK078154-05. NR 9 TC 7 Z9 7 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2013 VL 58 IS 4 BP 936 EP 941 DI 10.1007/s10620-012-2433-8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126HX UT WOS:000317605800007 PM 23086115 ER PT J AU Kostic, AD Howitt, MR Garrett, WS AF Kostic, Aleksandar D. Howitt, Michael R. Garrett, Wendy S. TI Exploring host-microbiota interactions in animal models and humans SO GENES & DEVELOPMENT LA English DT Review DE microbiome; microbiota; model organisms; symbiosis ID HUMAN GUT MICROBIOME; INTESTINAL ALKALINE-PHOSPHATASE; INFLAMMATORY-BOWEL-DISEASE; SCOLOPES LIGHT ORGAN; TOLL-LIKE RECEPTORS; VIBRIO-FISCHERI; IMMUNE-SYSTEM; DROSOPHILA-MELANOGASTER; EUPRYMNA-SCOLOPES; COMMENSAL MICROBIOTA AB The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies. C1 [Kostic, Aleksandar D.; Howitt, Michael R.; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kostic, Aleksandar D.; Howitt, Michael R.; Garrett, Wendy S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kostic, Aleksandar D.; Howitt, Michael R.; Garrett, Wendy S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kostic, Aleksandar D.; Garrett, Wendy S.] Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02141 USA. RP Garrett, WS (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu OI Kostic, Aleksandar/0000-0002-0837-4360 FU NIH [AI078942, R01CA154426, R01DK092405, GM099531, F32DK098826]; Burroughs Wellcome Fund; Searle Scholars Program; Lavietes Fund; Cancer Research Institute FX We thank members of the Garrett laboratory for discussion. Work from our laboratory is supported by grants from the NIH (AI078942, R01CA154426, R01DK092405, and GM099531 to W.S.G., and F32DK098826 to M.H.), the Burroughs Wellcome Fund, the Searle Scholars Program, the Lavietes Fund, and the Cancer Research Institute to W.S.G. NR 168 TC 79 Z9 81 U1 12 U2 179 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2013 VL 27 IS 7 BP 701 EP 718 DI 10.1101/gad.212522.112 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 125YL UT WOS:000317578000001 PM 23592793 ER PT J AU Ni, M Chen, YW Fei, T Li, D Lim, E Liu, XS Brown, M AF Ni, Min Chen, Yiwen Fei, Teng Li, Dan Lim, Elgene Liu, X. Shirley Brown, Myles TI Amplitude modulation of androgen signaling by c-MYC SO GENES & DEVELOPMENT LA English DT Article DE breast cancer; cistrome; AR; MYC; TCF7L2; FOXA1 ID EMBRYONIC STEM-CELLS; BREAST-CANCER; TRANSCRIPTIONAL NETWORK; PATHWAYS; RECEPTOR; ACTIVATION; REPRESSION; FOXA1; EXPRESSION; ELEMENT AB Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program. However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive. Here we report a positive feed-forward loop that enhances breast cancer growth involving AR, AR coregulators, and downstream target genes. In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and represses the basal expression of AR target genes, including MYC. Direct AR regulation of MYC cooperates with AR-mediated activation of HER2/HER3 signaling. HER2/HER3 signaling increases the transcriptional activity of MYC through phosphorylation of MAD1, leading to increased levels of MYC/MAX heterodimers. MYC in turn reinforces the transcriptional activation of androgen-responsive genes. These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth. C1 [Ni, Min; Fei, Teng; Li, Dan; Lim, Elgene; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Ni, Min; Fei, Teng; Li, Dan; Lim, Elgene; Brown, Myles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Chen, Yiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM xsliu@jimmy.harvard.edu; myles_brown@dfci.harvard.edu RI Fei, Teng/G-5324-2015; OI Fei, Teng/0000-0001-5707-0673; Brown, Myles/0000-0002-8213-1658 FU Breast Cancer Research Foundation; National Cancer Institute [P01CA080111]; National Human Genome Research Institute [R01HG004069]; Department of Defense [W81XWH-10-1-0037] FX We thank members of the Brown laboratory for technical support and helpful discussions. This work was supported by funding from the Breast Cancer Research Foundation (to M. B.), the National Cancer Institute (P01CA080111 to M. B.), the National Human Genome Research Institute (R01HG004069 to X. S. L), and a Department of Defense Award (W81XWH-10-1-0037 to M.N.). NR 37 TC 30 Z9 32 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2013 VL 27 IS 7 BP 734 EP 748 DI 10.1101/gad.209569.112 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 125YL UT WOS:000317578000004 PM 23530127 ER PT J AU Swirski, FK Nahrendorf, M AF Swirski, Filip K. Nahrendorf, Matthias TI Imaging macrophage development and fate in atherosclerosis and myocardial infarction SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Review DE atherosclerosis; imaging; macrophage; myocardial infarction ID POSITRON-EMISSION-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; MATRIX-METALLOPROTEINASE ACTIVATION; STEM-CELL PROLIFERATION; IN-VIVO; HEMATOPOIETIC STEM; BONE-MARROW; CORONARY ATHEROSCLEROSIS; MONOCYTE ACCUMULATION; INFLAMMATORY SITES AB Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction (MI). In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In MI, which is caused by atherosclerosis, macrophages accumulate readily and have important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular and tissue levels. Here, we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease. Immunology and Cell Biology (20 1 3) 91, 297-303; doi:10.1038/icb.2012.72; published online 4 December 2012 C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swirski, FK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NHLBI [R01HL095612, R01HL095629, R01HL096576] FX This work was supported in part by NHLBI grants R01HL095612, R01HL095629 and R01HL096576. NR 74 TC 9 Z9 9 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR PY 2013 VL 91 IS 4 BP 297 EP 303 DI 10.1038/icb.2012.72 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 131NA UT WOS:000317999200006 PM 23207281 ER PT J AU Dalle, S Poulalhon, N Debarbieux, S Zaharia, D Mihm, MC Lacouture, ME Rosen, A Marghoob, AA Busam, KJ Depaepe, L Bringuier, PP Richez, P Baurain, JF Bressac-de Paillerets, B Balme, B Thomas, L AF Dalle, Stephane Poulalhon, Nicolas Debarbieux, Sebastien Zaharia, Daniela Mihm, Martin C. Lacouture, Mario E. Rosen, Alyx Marghoob, Ashfaq A. Busam, Klaus J. Depaepe, Lauriane Bringuier, Pierre-Paul Richez, Pauline Baurain, Jean-Francois Bressac-de Paillerets, Brigitte Balme, Brigitte Thomas, Luc TI Tracking of Second Primary Melanomas in Vemurafenib-Treated Patients SO JAMA DERMATOLOGY LA English DT Letter C1 [Dalle, Stephane; Poulalhon, Nicolas; Debarbieux, Sebastien; Zaharia, Daniela; Thomas, Luc] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Unit Dermatol, Lyon, France. [Dalle, Stephane; Zaharia, Daniela; Thomas, Luc] Univ Lyon 1, F-69365 Lyon, France. [Dalle, Stephane] Canc Res Ctr Lyon, Lyon, France. [Mihm, Martin C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Mihm, Martin C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lacouture, Mario E.; Rosen, Alyx; Marghoob, Ashfaq A.] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. [Busam, Klaus J.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Depaepe, Lauriane; Bringuier, Pierre-Paul; Balme, Brigitte] Hosp Civils Lyon, Hop Edouard Herriot, Ctr Hosp Lyon Sud, Unit Pathol, Lyon, France. [Richez, Pauline] Catholic Univ Louvain, Clin Univ St Luc, Ctr Canc, Dept Dermatol, B-1200 Brussels, Belgium. [Baurain, Jean-Francois] Catholic Univ Louvain, Clin Univ St Luc, Ctr Canc, Dept Oncol, B-1200 Brussels, Belgium. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Dept Biopathol, Serv Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] INSERM, U946, Genet Variat & Human Dis Unit, Paris, France. RP Dalle, S (reprint author), Ctr Hosp Lyon Sud, Serv Dermatol, F-69495 Lyon, France. EM stephane.dalle@chu-lyon.fr NR 5 TC 15 Z9 15 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2013 VL 149 IS 4 BP 488 EP 490 DI 10.1001/jamadermatol.2013.21 PG 4 WC Dermatology SC Dermatology GA 127XH UT WOS:000317731700025 PM 23715012 ER PT J AU Patel, SM Thames, AD Arbid, N Panos, SE Castellon, S Hinkin, CH AF Patel, Sapna M. Thames, April D. Arbid, Natalie Panos, Stella E. Castellon, Steven Hinkin, Charles H. TI The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE HIV; Neuropsychology; Comorbid risk factors; Aging; Cognition ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; INTIMA-MEDIA THICKNESS; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; DRUG-USE; METHAMPHETAMINE DEPENDENCE; NEUROCOGNITIVE DISORDERS; CARDIOVASCULAR-DISEASE AB This study developed and then cross-validated a novel weighting algorithm based on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C, HIV disease severity, cognitive reserve) to predict cognitive functioning among 366 HIV+ adults. The resultant risk severity score was used to differentially weight, as a function of age, the impact and magnitude of multiple risk factors on cognition. Among older adults (50 years) the risk severity index was differentially predictive of learning/memory and verbal fluency, whereas among younger adults it was linked to working memory and executive function. Cognitive reserve was found to be the most robust predictor of neurocognition. C1 [Patel, Sapna M.; Thames, April D.; Panos, Stella E.; Castellon, Steven; Hinkin, Charles H.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Patel, Sapna M.; Thames, April D.; Arbid, Natalie; Panos, Stella E.; Castellon, Steven; Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Patel, SM (reprint author), Univ Calif Los Angeles, 760 Westwood Plaza,C8-746, Los Angeles, CA 90095 USA. EM smpatel@mednet.ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU National Institute on Drug Abuse [R01 DA 13799]; National Institute of Mental Health [T32 MH19535]; NIMH [T32MH19535, K23MH095661] FX This study was supported by a grant from the National Institute on Drug Abuse (R01 DA 13799) and by the National Institute of Mental Health Training Grant (T32 MH19535; PI: Charles Hinkin). Dr. Patel and Dr. Panos are supported by the NIMH Institutional Training Grant (No. T32MH19535) and Dr. Thames is supported by NIMH Grant (No. K23MH095661). We would also like to acknowledge the help from members of our laboratory: Sara-Beth Lawrence, Tim Arentsen, and Vanessa Streiff. NR 89 TC 7 Z9 7 U1 3 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR 1 PY 2013 VL 35 IS 4 BP 421 EP 434 DI 10.1080/13803395.2013.783000 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 129LR UT WOS:000317841600008 PM 23547924 ER PT J AU Villamar, MF Wivatvongvana, P Patumanond, J Bikson, M Truong, DQ Datta, A Fregni, F AF Villamar, Mauricio F. Wivatvongvana, Pakorn Patumanond, Jayanton Bikson, Marom Truong, Dennis Q. Datta, Abhishek Fregni, Felipe TI Focal Modulation of the Primary Motor Cortex in Fibromyalgia Using 4x1-Ring High-Definition Transcranial Direct Current Stimulation (HD-tDCS): Immediate and Delayed Analgesic Effects of Cathodal and Anodal Stimulation SO JOURNAL OF PAIN LA English DT Article DE Fibromyalgia; chronic pain; transcranial direct current stimulation (tDCS); high-definition transcranial direct current stimulation (HD-tDCS); electrical brain stimulation; transcranial electrical stimulation (tES) ID NONINVASIVE BRAIN-STIMULATION; CHRONIC WIDESPREAD PAIN; DC STIMULATION; MAGNETIC STIMULATION; CENTRAL SENSITIZATION; GENERAL-POPULATION; TENDER POINTS; PERCEPTION; THRESHOLDS; PREVALENCE AB Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4x1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population. Perspective: 4x1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored. (C) 2013 by the American Pain Society C1 [Villamar, Mauricio F.; Wivatvongvana, Pakorn; Datta, Abhishek; Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Villamar, Mauricio F.; Wivatvongvana, Pakorn; Datta, Abhishek; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Villamar, Mauricio F.] Pontifical Catholic Univ Ecuador, Sch Med, Quito, Ecuador. [Wivatvongvana, Pakorn] Chiang Mai Univ, Fac Med, Dept Rehabil Med, Chiang Mai 50000, Thailand. [Wivatvongvana, Pakorn] Chiang Mai Univ, Fac Med, Clin Epidemiol & Clin Stat Unit, Chiang Mai 50000, Thailand. [Bikson, Marom; Truong, Dennis Q.; Datta, Abhishek] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Lab Neuromodulat, 125 Nashua St 726, Boston, MA 02114 USA. EM ffregni@post.harvard.edu FU Translational Research Award from the Wallace H. Coulter Foundation FX Funded by a Translational Research Award from the Wallace H. Coulter Foundation. NR 55 TC 39 Z9 42 U1 0 U2 15 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 2013 VL 14 IS 4 BP 371 EP 383 DI 10.1016/j.jpain.2012.12.007 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RP UT WOS:000317639200012 PM 23415877 ER PT J AU Chen, L Vo, T Seefeld, L Malarick, C Houghton, M Ahmed, S Zhang, Y Cohen, A Retamozo, C St Hilaire, K Zhang, V Mao, JR AF Chen, Lucy Trang Vo Seefeld, Lindsey Malarick, Charlene Houghton, Mary Ahmed, Shihab Zhang, Yi Cohen, Abigail Retamozo, Cynthia St Hilaire, Kristen Zhang, Vivian Mao, Jianren TI Lack of Correlation Between Opioid Dose Adjustment and Pain Score Change in a Group of Chronic Pain Patients SO JOURNAL OF PAIN LA English DT Article DE Opioid therapy; chronic pain; opioid dose adjustment; numeric pain score ID CHRONIC NONCANCER PAIN; NEUROPATHIC PAIN; THERAPY; EFFICACY; ESCALATION; MISUSE; ABUSE AB Despite the increasing use of opioid analgesics for chronic pain management, it is unclear whether opioid dose escalation leads to better pain relief during chronic opioid therapy. In this study, we retrospectively analyzed clinical data collected from the Massachusetts General Hospital Center for Pain Medicine over a 7-year period. We examined 1) the impact of opioid dose adjustment (increase or decrease) on clinical pain score; 2) gender and age differences in response to opioid therapy; and 3) the influence of clinical pain conditions on the opioid analgesic efficacy. A total of 109 subjects met the criteria for data collection. We found that neither opioid dose increase, nor decrease, correlated with point changes in clinical pain score in a subset of chronic pain patients over a prolonged course of opioid therapy (an average of 704 days). This lack of correlation was consistent regardless of the type of chronic pain including neuropathic, nociceptive, or mixed pain conditions. Neither gender nor age differences showed a significant influence on the clinical response to opioid therapy in these subjects. These results suggest that dose adjustment during opioid therapy may not necessarily alter long-term clinical pain score in a group of chronic pain patients and that individualized opioid therapy based on the clinical effectiveness should be considered to optimize the treatment outcome. Perspective: The study reports a relationship, or lack thereof, between opioid dose change and clinical pain score in a group of chronic pain patients. The study also calls for further investigation into the effectiveness of opioid therapy in the management of chronic nonmalignant pain conditions. (C) 2013 by the American Pain Society C1 [Chen, Lucy; Trang Vo; Seefeld, Lindsey; Malarick, Charlene; Houghton, Mary; Ahmed, Shihab; Zhang, Yi; Cohen, Abigail; Retamozo, Cynthia; St Hilaire, Kristen; Zhang, Vivian; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Chen, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM llchen@partners.org FU NIH [RO1 DA022576, P20 DA026002, RO1 AT005819] FX This work was supported by NIH grants RO1 DA022576, P20 DA026002, and RO1 AT005819. NR 29 TC 9 Z9 9 U1 0 U2 6 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 2013 VL 14 IS 4 BP 384 EP 392 DI 10.1016/j.jpain.2012.12.012 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RP UT WOS:000317639200013 PM 23452826 ER PT J AU Psutka, SP Cendron, M AF Psutka, Sarah P. Cendron, Marc TI Bladder diverticula in children SO JOURNAL OF PEDIATRIC UROLOGY LA English DT Review DE Bladder; Diverticulum; Bladder diverticula; Children; Paraureteral diverticulum ID EHLERS-DANLOS-SYNDROME; WILLIAMS-BEUREN-SYNDROME; PARAURETERAL DIVERTICULA; VESICAL DIVERTICULA; URINARY-BLADDER; VESICOURETERAL REFLUX; SOTOS-SYNDROME; DIAGNOSIS; OBSTRUCTION; MANAGEMENT AB This review of bladder diverticula in children includes: historical aspects of the condition, its presentation and diagnosis, as well as management options. The purpose of the review is to provide a comprehensive and in-depth understanding of a relatively infrequent but clinically challenging urologic abnormality that may affect not only the bladder but also the upper urinary tract and kidney. (C) 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. C1 [Psutka, Sarah P.] Childrens Hosp Boston, Dept Urol, Boston, MA 02115 USA. [Cendron, Marc] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Cendron, M (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM Marc.Cendron@childrens.harvard.edu NR 50 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1477-5131 J9 J PEDIATR UROL JI J. Pediatr. Urol PD APR PY 2013 VL 9 IS 2 BP 129 EP 138 DI 10.1016/j.jpurol.2012.02.013 PG 10 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 129KI UT WOS:000317837600010 PM 22658330 ER PT J AU Coit, DG Andtbacka, R Anker, CJ Bichakjian, CK Carson, WE Daud, A DiMaio, D Fleming, MD Guilds, V Halpern, AC Hodi, FS Kelley, MC Khushalani, NI Kudchadkar, RR Lange, JR Lind, A Martini, MC Olszanski, AJ Pruitt, SK Ross, MI Swetter, SM Tanabe, KK Thompson, JA Trisal, V Urist, MM McMillian, N Ho, M AF Coit, Daniel G. Andtbacka, Robert Anker, Christopher J. Bichakjian, Christopher K. Carson, William E., III Daud, Adil DiMaio, Dominick Fleming, Martin D. Guilds, Valerie Halpern, Allan C. Hodi, F. Stephen, Jr. Kelley, Mark C. Khushalani, Nikhil I. Kudchadkar, Ragini R. Lange, Julie R. Lind, Anne Martini, Mary C. Olszanski, Anthony J. Pruitt, Scott K. Ross, Merrick I. Swetter, Susan M. Tanabe, Kenneth K. Thompson, John A. Trisal, Vijay Urist, Marshall M. McMillian, Nicole Ho, Maria TI Melanoma, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID LYMPH-NODE BIOPSY; POSITRON-EMISSION-TOMOGRAPHY; STAGE-III MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; HIGH-RISK MELANOMA; METASTATIC MELANOMA; COMPUTED-TOMOGRAPHY; THIN MELANOMA; OPEN-LABEL; CUTANEOUS MELANOMA AB The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma. (JNCCN 2013;11:395-407) C1 [Coit, Daniel G.; Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Andtbacka, Robert; Anker, Christopher J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bichakjian, Christopher K.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Carson, William E., III] Solove Res Inst, Columbus, OH USA. [Daud, Adil] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [DiMaio, Dominick] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Fleming, Martin D.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Guilds, Valerie] Aim Melanoma, Plano, TX USA. [Hodi, F. Stephen, Jr.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Kelley, Mark C.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Khushalani, Nikhil I.] Roswell Pk Canc Inst, Buffalo, NY USA. [Kudchadkar, Ragini R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Lange, Julie R.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Lind, Anne] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Lind, Anne] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Martini, Mary C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Olszanski, Anthony J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Pruitt, Scott K.] Duke Canc Inst, Durham, NC USA. [Ross, Merrick I.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Swetter, Susan M.] Stanford Canc Inst, Stanford, CA USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Thompson, John A.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Trisal, Vijay] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Urist, Marshall M.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [McMillian, Nicole; Ho, Maria] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Coit, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RI Carson, William/E-2846-2011 FU Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer Health-Care Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; ARIAD Pharmaceuticals, Inc. FX Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer Health-Care Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; and ARIAD Pharmaceuticals, Inc. NR 52 TC 60 Z9 61 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2013 VL 11 IS 4 BP 395 EP 407 PG 13 WC Oncology SC Oncology GA 125ML UT WOS:000317543800007 PM 23584343 ER PT J AU Clark, PE Agarwal, N Biagio, MC Eisenberger, MA Greenberg, RE Herr, HW Inman, BA Kuban, DA Kuzel, TM Lele, SM Michalski, J Pagliaro, LC Pal, SK Patterson, A Plimack, ER Pohar, KS Porter, MP Richie, JP Sexton, WJ Shipley, WU Small, EJ Spiess, PE Trump, DL Wile, G Wilson, TG Dwyer, M Ho, M AF Clark, Peter E. Agarwal, Neeraj Biagio, Matthew C. Eisenberger, Mario A. Greenberg, Richard E. Herr, Harry W. Inman, Brant A. Kuban, Deborah A. Kuzel, Timothy M. Lele, Subodh M. Michalski, Jeff Pagliaro, Lance C. Pal, Sumanta K. Patterson, Anthony Plimack, Elizabeth R. Pohar, Kamal S. Porter, Michael P. Richie, Jerome P. Sexton, Wade J. Shipley, William U. Small, Eric J. Spiess, Philippe E. Trump, Donald L. Wile, Geoffrey Wilson, Timothy G. Dwyer, Mary Ho, Maria TI Bladder Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID TRANSITIONAL-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; PHASE-II TRIAL; RANDOMIZED CLINICAL-TRIALS; ADVANCED UROTHELIAL CANCER; INDIVIDUAL PATIENT DATA; REPEAT TRANSURETHRAL RESECTION; GEMCITABINE PLUS CISPLATIN; LONG-TERM OUTCOMES; NEOADJUVANT CHEMOTHERAPY AB Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management. (JNCCN 2013;11:446-475) C1 [Clark, Peter E.; Wile, Geoffrey] Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Biagio, Matthew C.; Sexton, Wade J.; Spiess, Philippe E.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Eisenberger, Mario A.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Greenberg, Richard E.; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Herr, Harry W.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Inman, Brant A.] Duke Canc Inst, Durham, NC USA. [Kuban, Deborah A.; Pagliaro, Lance C.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kuzel, Timothy M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lele, Subodh M.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Michalski, Jeff] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Michalski, Jeff] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Pal, Sumanta K.; Wilson, Timothy G.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Patterson, Anthony] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Pohar, Kamal S.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Porter, Michael P.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Shipley, William U.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Small, Eric J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Trump, Donald L.] Roswell Pk Canc Inst, Buffalo, NY USA. RP Clark, PE (reprint author), Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. RI Clark, Peter/E-1423-2011 OI Clark, Peter/0000-0002-8006-7015 FU Bristol-Myers Squibb Company; Genentech, Inc.; Agensys, Inc.; sanofi-aventis U.S. LLC; Endo Pharmaceuticals; GlaxoSmithKline plc; Bayer HealthCare; CureTech Ltd.; Eli Lilly and Company; Merck Co., Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals, Inc.; Alton Pharmaceuticals; Argos Therapeutics, Inc.; Biovex, Inc. FX Clinical Research Support: Bristol-Myers Squibb Company; Genentech, Inc.; Agensys, Inc.; and sanofi-aventis U.S. LLC; Endo Pharmaceuticals; GlaxoSmithKline plc; Bayer HealthCare; Bristol-Myers Squibb Company; CureTech Ltd.; Eli Lilly and Company; GlaxoSmithKline plc; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals, Inc.; Alton Pharmaceuticals; Argos Therapeutics, Inc.; and Biovex, Inc.; Endo Pharmaceuticals NR 101 TC 127 Z9 129 U1 0 U2 16 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2013 VL 11 IS 4 BP 446 EP 475 PG 30 WC Oncology SC Oncology GA 125ML UT WOS:000317543800011 PM 23584347 ER PT J AU King, MW Street, AE Gradus, JL Vogt, DS Resick, PA AF King, Matthew W. Street, Amy E. Gradus, Jaimie L. Vogt, Dawne S. Resick, Patricia A. TI Gender Differences in Posttraumatic Stress Symptoms Among OEF/OIF Veterans: An Item Response Theory Analysis SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SEX-DIFFERENCES; MENTAL-HEALTH; DISORDER; TRAUMA; PTSD; COMBAT; WOMEN; RISK AB Establishing whether men and women tend to express different symptoms of posttraumatic stress in reaction to trauma is important for both etiological research and the design of assessment instruments. Use of item response theory (IRT) can reveal how symptom reporting varies by gender and help determine if estimates of symptom severity for men and women are equally reliable. We analyzed responses to the PTSD Checklist (PCL) from 2,341 U.S. military veterans (51% female) who completed deployments in support of operations in Afghanistan and Iraq (Operation Enduring Freedom/Operation Iraqi Freedom [OEF/OIF]), and tested for differential item functioning by gender with an IRT-based approach. Among men and women with the same overall posttraumatic stress severity, women tended to report more frequent concentration difficulties and distress from reminders whereas men tended to report more frequent nightmares, emotional numbing, and hypervigilance. These item-level gender differences were small (on average d = 0.05), however, and had little impact on PCL measurement precision or expected total scores. For practical purposes, men's and women's severity estimates had similar reliability. This provides evidence that men and women veterans demonstrate largely similar profiles of posttraumatic stress symptoms following exposure to military-related stressors, and some theoretical perspectives suggest this may hold in other traumatized populations. C1 [King, Matthew W.; Street, Amy E.; Gradus, Jaimie L.; Vogt, Dawne S.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Street, Amy E.; Gradus, Jaimie L.; Vogt, Dawne S.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP King, MW (reprint author), VA Boston Healthcare Syst 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM matthew.king2@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 40 TC 9 Z9 9 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2013 VL 26 IS 2 BP 175 EP 183 DI 10.1002/jts.21802 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 123CP UT WOS:000317366200001 PM 23526678 ER PT J AU Avins, AL Lee, JY Meyers, CM Barry, MJ AF Avins, Andrew L. Lee, Jeannette Y. Meyers, Catherine M. Barry, Michael J. CA CAMUS Study Grp TI Safety and Toxicity of Saw Palmetto in the CAMUS Trial SO JOURNAL OF UROLOGY LA English DT Article DE prostate; Serenoa; prostatic hyperplasia; lower urinary tract symptoms; phytotherapy ID BENIGN PROSTATIC HYPERPLASIA; SERENOA-REPENS; INDUCED PANCREATITIS; EXTRACT; PHYTOTHERAPY; HERB AB Purpose: Extracts of the saw palmetto berry are used by many men in the United States as self-treatment for lower urinary tract symptoms due to benign prostatic hyperplasia. While the most recent data from double-blind clinical trials do not support efficacy superior to that of placebo, there are sparse data on saw palmetto toxicity. Materials and Methods: A total of 369 patients were randomized in the CAMUS (Complementary and Alternative Medicine for Urological Symptoms) trial, of whom 357 were included in this modified intent to treat analysis. Participants were randomized to 320, 640 and 960 mg daily of an ethanolic saw palmetto extract or to an identical-appearing placebo in an escalating manner at 6-month intervals for a total of 18 months of followup. Adverse event assessments, vital signs, and blood and urine laboratory tests were obtained at regular intervals. Results: There were no statistically significant differences between the groups in the rates of serious or nonserious adverse events, changes in vital signs, digital prostate examination findings or study withdrawal rates. Overall, there were no significant intergroup differences in laboratory test abnormalities, while differences in individual laboratory tests were rare and small in magnitude. No evidence of significant dose-response phenomena was identified. Conclusions: The saw palmetto extract used in the CAMUS trial showed no evidence of toxicity at doses up to 3 times the usual clinical dose during an 18-month period. C1 [Avins, Andrew L.] No Calif Kaiser Permanente Div Res, Oakland, CA 94612 USA. [Avins, Andrew L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Avins, Andrew L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Lee, Jeannette Y.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Meyers, Catherine M.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Avins, AL (reprint author), No Calif Kaiser Permanente Div Res, 2000 Broadway,3rd Floor, Oakland, CA 94612 USA. EM andrew.avins@ucsf.edu FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778, U01 DK63788]; National Center for Complementary and Alternative Medicine; Office of Dietary Supplements, National Institutes of Health FX Supported by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Cooperative Agreements U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778 and U01 DK63788, the National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements, National Institutes of Health. NR 27 TC 3 Z9 3 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2013 VL 189 IS 4 BP 1415 EP 1420 DI 10.1016/j.juro.2012.10.002 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 127TN UT WOS:000317721800064 PM 23063633 ER PT J AU Pashtan, I Mauch, PM Chen, YH Dorfman, DM Silver, B Ng, AK AF Pashtan, Itai Mauch, Peter M. Chen, Yu-Hui Dorfman, David M. Silver, Barbara Ng, Andrea K. TI Radiotherapy in the management of localized primary cutaneous B-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Primary cutaneous B-cell lymphoma; prognosis; radiation; dose; local control ID TREATMENT-OF-CANCER; WHO-EORTC CLASSIFICATION; EUROPEAN-ORGANIZATION; UNITED-STATES; PROPOSAL; SYSTEM AB The optimal therapy and radiation dose for patients with localized primary cutaneous B-cell lymphoma (PCBCL) are unknown. We retrospectively identified 23 patients with localized (T1-T2) PCBCL treated with definitive radiation to doses ranging from 30 to 44 Gy (median, 36 Gy). With a median follow-up of 4.8 years, the 5-year overall survival rate was 100%, the relapse-free survival rate was 71% (95% confidence interval, 46-86%) and there were no local recurrences, suggesting that radiotherapy to a dose of 30 Gy may be sufficient for cure. C1 [Pashtan, Itai] Harvard Radiat Oncol Program, Boston, MA USA. [Mauch, Peter M.; Silver, Barbara; Ng, Andrea K.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Mauch, Peter M.; Silver, Barbara; Ng, Andrea K.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dorfman, David M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Pashtan, I (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ipashtan@partners.org NR 14 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2013 VL 54 IS 4 BP 726 EP 730 DI 10.3109/10428194.2012.723707 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 103EP UT WOS:000315898100012 PM 22916994 ER PT J AU Cheng, G Servaes, S Zhuang, HM AF Cheng, Gang Servaes, Sabah Zhuang, Hongming TI Value of F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan versus diagnostic contrast computed tomography in initial staging of pediatric patients with lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE FDG PET/CT; lymphoma; Hodgkin disease; staging; pediatric ID FDG-PET; CHILDHOOD LYMPHOMA; HODGKINS-LYMPHOMA; MANAGEMENT; BONE; ADOLESCENTS; CHILDREN; UTILITY; IMPACT; CT AB Our objective was to evaluate the value of F-18-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) versus diagnostic contrast CT in the initial staging of pediatric Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL). Thirty patients with HD and 21 patients with NHL were included in this retrospective study. On nodal lesion analysis, PET/CT detected 94.8% (HD) and 88.3% (NHL) of total lesions, respectively, in contrast to 82.6% (HD) and 69.1% (NHL), respectively, for diagnostic contrast CT. PET/CT also detected more extranodal lesions. On the patient level, PET/CT detected additional lesions in 50% of patients with HD and in 42.9% of patients with NHL. In contrast, diagnostic contrast CT detected additional lesions in 16.7% (HD) and 23.8% (NHL) of total cases. FDG PET/CT led to upstaging in seven cases of HD and seven cases of NHL, while diagnostic contrast CT upstaged two cases of NHL. We conclude that FDG PET/CT outperforms diagnostic contrast CT in the initial staging of pediatric patients with lymphoma. C1 [Cheng, Gang] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Servaes, Sabah; Zhuang, Hongming] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. RP Cheng, G (reprint author), Philadelphia VA Med Ctr, Dept Radiol, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM gangcheng99@yahoo.com; zhuang@email.chop.edu NR 21 TC 13 Z9 13 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2013 VL 54 IS 4 BP 737 EP 742 DI 10.3109/10428194.2012.727416 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 103EP UT WOS:000315898100014 PM 22957898 ER PT J AU Fathi, AT Preffer, FI Sadrzadeh, H Ballen, KK Amrein, PC Attar, EC McAfee, SL Dillon, L Chen, YB Hasserjian, RP AF Fathi, Amir T. Preffer, Frederic I. Sadrzadeh, Hossein Ballen, Karen K. Amrein, Philip C. Attar, Eyal C. McAfee, Steven L. Dillon, Laura Chen, Yi-Bin Hasserjian, Robert P. TI CD30 expression in acute myeloid leukemia is associated with FLT3-internal tandem duplication mutation and leukocytosis SO LEUKEMIA & LYMPHOMA LA English DT Letter ID VARIANT CD30; RECEPTOR; PROGRESS; FLT3; AML C1 [Fathi, Amir T.; Preffer, Frederic I.; Sadrzadeh, Hossein; Ballen, Karen K.; Amrein, Philip C.; Attar, Eyal C.; McAfee, Steven L.; Dillon, Laura; Chen, Yi-Bin; Hasserjian, Robert P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org NR 15 TC 6 Z9 6 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2013 VL 54 IS 4 BP 860 EP 863 DI 10.3109/10428194.2012.728596 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 103EP UT WOS:000315898100030 PM 22966913 ER PT J AU Spindler, SR Mote, PL Flegal, JM Teter, B AF Spindler, Stephen R. Mote, Patricia L. Flegal, James M. Teter, Bruce TI Influence on Longevity of Blueberry, Cinnamon, Green and Black Tea, Pomegranate, Sesame, Curcumin, Morin, Pycnogenol, Quercetin, and Taxifolin Fed Iso-Calorically to Long-Lived, F1 Hybrid Mice SO REJUVENATION RESEARCH LA English DT Article ID LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; DROSOPHILA-MELANOGASTER; EXTRACT; HEALTH; ACID; EXPRESSION; CAFFEINE; SURVIVAL AB Phytonutrients reportedly extend the life span of Caenorhabditis elegans, Drosophila, and mice. We tested extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, and French maritime pine bark (Pycnogenol and taxifolin), as well as curcumin, morin, and quercetin for their effects on the life span of mice. While many of these phytonutrients reportedly extend the life span of model organisms, we found no significant effect on the life span of male F1 hybrid mice, even though the dosages used reportedly produce defined therapeutic end points in mice. The compounds were fed beginning at 12 months of age. The control and treatment groups were iso-caloric with respect to one another. A 40% calorically restricted and other groups not reported here did experience life span extension. Body weights were un-changed relative to controls for all but two supplemented groups, indicating most supplements did not change energy absorption or utilization. Tea extracts with morin decreased weight, whereas quercetin, taxifolin, and Pycnogenol together increased weight. These changes may be due to altered locomotion or fatty acid biosynthesis. Published reports of murine life span extension using curcumin or tea components may have resulted from induced caloric restriction. Together, our results do not support the idea that isolated phytonutrient anti-oxidants and anti-inflammatories are potential longevity therapeutics, even though consumption of whole fruits and vegetables is associated with enhanced health span and life span. C1 [Spindler, Stephen R.; Mote, Patricia L.] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. [Flegal, James M.] Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. [Teter, Bruce] VA Greater Los Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. RP Spindler, SR (reprint author), Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. EM spindler@ucr.edu OI Flegal, James/0000-0002-9960-8942 FU Alva, LLC FX The authors thank Ms. Carol Boyd for her invaluable help feeding and monitoring the mice. This work was funded by Alva, LLC, whose business is funding research. The funding organization and its members had no role in study design, data collection or analysis, decision to publish, or preparation of the manuscript. NR 60 TC 13 Z9 13 U1 3 U2 27 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR PY 2013 VL 16 IS 2 BP 143 EP 151 DI 10.1089/rej.2012.1386 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 129IM UT WOS:000317832600008 PM 23432089 ER PT J AU Khodneva, Y Pletcher, M Safford, M Schumacher, J Tucker, J Kertesz, S AF Khodneva, Yulia Pletcher, Mark Safford, Monika Schumacher, Joseph Tucker, Jalie Kertesz, Stefan TI Conjoint Trajectories of Drug Use and Trajectories of Depressive Symptoms in Adults: A 2-Decade Portrait of Comorbidity (the CARDIA study) SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Khodneva, Yulia; Tucker, Jalie; Kertesz, Stefan] Univ Alabama Birmingham, Birmingham, AL USA. [Pletcher, Mark; Safford, Monika; Schumacher, Joseph] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kertesz, Stefan] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PD APR 1 PY 2013 VL 34 IS 2 BP 215 EP 215 PG 1 WC Substance Abuse SC Substance Abuse GA 128BI UT WOS:000317742700038 ER PT J AU Park, TW Cheng, DM Samet, JH Winter, M Saitz, R AF Park, Tae Woo Cheng, Debbie M. Samet, Jeffrey H. Winter, Michael Saitz, Richard TI Effectiveness of Chronic Care Management for Substance Dependence in Primary Care Among Patients with Co-Occurring Mental Health Disorders SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PD APR 1 PY 2013 VL 34 IS 2 BP 215 EP 215 PG 1 WC Substance Abuse SC Substance Abuse GA 128BI UT WOS:000317742700039 ER PT J AU Ottum, A Sethi, AK Jacobs, E Zerbel, S Gaines, ME Safdar, N AF Ottum, Andrew Sethi, Ajay K. Jacobs, Elizabeth Zerbel, Sara Gaines, Martha E. Safdar, Nasia TI Engaging patients in the prevention of health care-associated infections: A survey of patients' awareness, knowledge, and perceptions regarding the risks and consequences of infection with methicillin-resistant Staphylococcus aureus and Clostridium difficile SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE MRSA; Clostridium difficile; Awareness ID EDUCATION MODEL; HOSPITALS AB Background and objective: Methicillin-resistant Staphylococcus aureus (MRSA) infections and Clostridium difficile infections (CDI) are major health care-associated infections (HAIs). Little is known about patients' knowledge of these HAIs. Therefore, we surveyed patients to determine awareness, knowledge, and perceptions of MRSA infections and CDI. Design: An interviewer-administered questionnaire. Setting: A tertiary care academic medical center. Participants: Adult patients who met at least one of the following criteria: at risk of CDI or MRSA infection, current CDI or colonization or current MRSA infection or colonization, or history of CDI or MRSA infection. Methods: Two unique surveys were developed and administered to 100 patients in 2011. Results: Overall, 76% of patients surveyed were aware of MRSA, whereas 44% were aware of C difficile. The strongest predictor of patients' awareness of these infections was having a history of HAI. Patients with a history of HAI were significantly more likely to have heard of both MRSA (odds ratio, 13.29; 95% confidence interval, 2.84-62.14; P = .001) and C difficile (odds ratio, 9.78; 95% confidence interval, 2.66-35.95; P = .001), than those patients without a history of HAI. There was also a significant positive association between having a history of HAI and greater knowledge of the risk factors, health consequences, and prevention techniques relative to CDI and MRSA infections. Conclusions: There are additional opportunities to engage patients about the risks and consequences of MRSA and CDIs, particularly those without a history of HAI. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Ottum, Andrew; Sethi, Ajay K.; Jacobs, Elizabeth] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Jacobs, Elizabeth; Safdar, Nasia] Univ Wisconsin, Dept Med, Madison, WI USA. [Zerbel, Sara; Safdar, Nasia] Univ Wisconsin, Univ Wisconsin Hosp & Clin, Madison, WI USA. [Gaines, Martha E.] Univ Wisconsin, Ctr Patient Partnerships, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Safdar, N (reprint author), 5221 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu NR 12 TC 6 Z9 6 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD APR PY 2013 VL 41 IS 4 BP 322 EP 326 DI 10.1016/j.ajic.2012.04.334 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 123UG UT WOS:000317416000008 PM 22884494 ER PT J AU Sips, PY Irie, T Zou, L Shinozaki, S Sakai, M Shimizu, N Nguyen, R Stamler, JS Chao, W Kaneki, M Ichinose, F AF Sips, Patrick Y. Irie, Tomoya Zou, Lin Shinozaki, Shohei Sakai, Michihiro Shimizu, Nobuyuki Nguyen, Rebecca Stamler, Jonathan S. Chao, Wei Kaneki, Masao Ichinose, Fumito TI Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE S-nitrosylation; sepsis; myocardial depression; GSNOR; genetically modified mice ID NITRIC-OXIDE SYNTHASE; RAT CARDIAC MYOCYTES; SOLUBLE GUANYLYL CYCLASE; SEPTIC SHOCK; SYSTEMIC INFLAMMATION; ENDOTOXIC-SHOCK; TREATED RATS; DYSFUNCTION; MICE; CALCIUM AB Sips PY, Irie T, Zou L, Shinozaki S, Sakai M, Shimizu N, Nguyen R, Stamler JS, Chao W, Kaneki M, Ichinose F. Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression. Am J Physiol Heart Circ Physiol 304: H1134-H1146, 2013. First published February 15, 2013; doi: 10.1152/ajpheart.00887.2012.-Myocardial depression is an important contributor to morbidity and mortality in septic patients. Nitric oxide (NO) plays an important role in the development of septic cardiomyopathy, but also has protective effects. Recent evidence has indicated that NO exerts many of its downstream effects on the cardiovascular system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation. We tested the hypothesis that reducing cardiomyocyte S-nitrosylation by increasing GSNOR activity can improve myocardial dysfunction during sepsis. Therefore, we generated mice with a cardiomyocyte-specific overexpression of GSNOR (GSNOR-CMTg mice) and subjected them to endotoxic shock. Measurements of cardiac function in vivo and ex vivo showed that GSNOR-CMTg mice had a significantly improved cardiac function after lipopolysaccharide challenge (LPS, 50 mg/kg) compared with wild-type (WT) mice. Cardiomyocytes isolated from septic GSNOR-CMTg mice showed a corresponding improvement in contractility compared with WT cells. However, systolic Ca2+ release was similarly depressed in both genotypes after LPS, indicating that GSNOR-CMTg cardiomyocytes have increased Ca2+ sensitivity during sepsis. Parameters of inflammation were equally increased in LPS-treated hearts of both genotypes, and no compensatory changes in NO synthase expression levels were found in GSNOR-overexpressing hearts before or after LPS challenge. GSNOR overexpression however significantly reduced total cardiac protein S-nitrosylation during sepsis. Taken together, our results indicate that increasing the denitrosylation capacity of cardiomyocytes protects against sepsis-induced myocardial depression. Our findings suggest that specifically reducing protein S-nitrosylation during sepsis improves cardiac function by increasing cardiac myofilament sensitivity to Ca2+. C1 [Sips, Patrick Y.; Irie, Tomoya; Zou, Lin; Shinozaki, Shohei; Sakai, Michihiro; Shimizu, Nobuyuki; Nguyen, Rebecca; Chao, Wei; Kaneki, Masao; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Sips, Patrick Y.; Irie, Tomoya; Zou, Lin; Shinozaki, Shohei; Sakai, Michihiro; Shimizu, Nobuyuki; Nguyen, Rebecca; Chao, Wei; Kaneki, Masao; Ichinose, Fumito] Harvard Univ, Sch Med, Charlestown, MA USA. [Stamler, Jonathan S.] Case Western Reserve Univ, Inst Transformat Mol Med, Cleveland, OH 44106 USA. [Stamler, Jonathan S.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. RP Sips, PY (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, CNY 149,Rm 4312,149 13th St, Charlestown, MA 02129 USA. EM psips@partners.org OI Sips, Patrick/0000-0001-9241-5980 FU American Heart Association; National Institute of Health [DK-05827, GM-079360, HL-101930] FX This work was supported by the American Heart Association - Philips Resuscitation Fellowship Award (P. Y. Sips) and National Institute of Health Grants DK-05827 (M. Kaneki), GM-079360 (F. Ichinose), and HL-101930 (F. Ichinose). NR 60 TC 10 Z9 10 U1 2 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2013 VL 304 IS 8 BP H1134 EP H1146 DI 10.1152/ajpheart.00887.2012 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 126GP UT WOS:000317601600010 PM 23417863 ER PT J AU Moye, J Marson, DC Edelstein, B AF Moye, Jennifer Marson, Daniel C. Edelstein, Barry TI Assessment of Capacity in an Aging Society SO AMERICAN PSYCHOLOGIST LA English DT Article DE capacity; competency; decision making; informed consent; assessment ID MILD COGNITIVE IMPAIRMENT; DECISION-MAKING CAPACITY; DECLINING FINANCIAL CAPACITY; DIFFERENT LEGAL STANDARDS; TRAUMATIC BRAIN-INJURY; TO-MODERATE DEMENTIA; ALZHEIMERS-DISEASE; OLDER-ADULTS; PROTOTYPE-INSTRUMENT; PHYSICIAN JUDGMENTS AB Over the past 40 years, the assessment and scientific study of capacity in older adults has emerged as a distinct field of clinical and research activity for psychologists. This new field reflects the convergence of several trends: the aging of American society, the growing incidence and prevalence of dementia, and the patient rights, deinstitutionalization, and disability rights movements. Because of these forces, capacity issues now permeate the fabric of everyday life, whether in the form of guardianship petitions, questions of capacity to consent to treatment, the ability to make a new will, or participation in human research. In seeking to resolve these issues, families, clinicians, and legal professionals increasingly turn to psychologists to assess a capacity and to provide empirically supported judgments that properly balance autonomy and protection for the individual. Psychologists have taken a leading role in the development of functional assessment instruments that measure important aspects of the capacity construct. In addition, psychology has been a major contributor to the scientific study of capacity. In collaboration with colleagues from medicine and law, psychologists have articulated crucial theoretical frameworks that integrate legal, clinical, and ethical dimensions of the capacity problem. This article focuses on the evolution of theory, law, science, and practice in the evaluation of capacity in older adults and its recent culmination in a series of interdisciplinary handbooks sponsored by the American Psychological Association and the American Bar Association. C1 [Moye, Jennifer] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Marson, Daniel C.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Marson, Daniel C.] Univ Alabama Birmingham, Alzheimers Dis Ctr, Birmingham, AL USA. [Edelstein, Barry] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Campus,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 Intramural VA [VA999999]; NIA NIH HHS [R56 AG021927, AG021927, R01 AG021927]; NICHD NIH HHS [HD053074, R01 HD053074]; NIMH NIH HHS [R29 MH057104] NR 106 TC 18 Z9 18 U1 3 U2 40 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2013 VL 68 IS 3 BP 158 EP 171 DI 10.1037/a0032159 PG 14 WC Psychology, Multidisciplinary SC Psychology GA 125EO UT WOS:000317522000004 PM 23586491 ER PT J AU Crivellari, D Gray, KP Dellapasqua, S Puglisi, F Ribi, K Price, KN Lang, I Gianni, L Spazzapan, S Pinotti, G Luthi, JM Gelber, RD Regan, MM Colleoni, M Castiglione-Gertsch, M Maibach, R Rabaglio, M Coates, AS Goldhirsch, A AF Crivellari, Diana Gray, Kathryn P. Dellapasqua, Silvia Puglisi, Fabio Ribi, Karin Price, Karen N. Lang, Istvan Gianni, Lorenzo Spazzapan, Simon Pinotti, Graziella Luethi, Jean-Marc Gelber, Richard D. Regan, Meredith M. Colleoni, Marco Castiglione-Gertsch, Monica Maibach, Rudolf Rabaglio, Manuela Coates, Alan S. Goldhirsch, Aron CA Int Breast Canc Study Grp TI Adjuvant pegylated liposomal doxorubicin for older women with endocrine nonresponsive breast cancer who are NOT suitable for a "standard chemotherapy regimen": The CASA randomized trial SO BREAST LA English DT Article DE Adjuvant treatment; Endocrine nonresponsive; Chemotherapy; Pegylated liposomal doxorubicin; Elderly; Breast cancer ID QUALITY-OF-LIFE; ELDERLY-PATIENTS PTS; INTERNATIONAL SOCIETY; GERIATRIC ONCOLOGY; CAPECITABINE X; IBANDRONATE I; MINI-COG; GBG 32; SURVIVAL; PHARMACOKINETICS AB There is no optimal treatment for breast cancers lacking estrogen (ER) and progesterone (PgR) receptors in elderly women with co-morbidities that prevent use of "standard chemotherapy regimens" such as AC or CMF. The CASA trial studied pegylated liposomal doxorubicin (PLD) and low dose, metronomic cyclophosphamide methotrexate (CM) for older (>65), vulnerable women with operable, ER and PgR-negative breast cancer. After two years the trial closed early, due to slow and inadequate accrual, with 77 patients (38:PLD, 36:CM, 3:nil). Sixty-eight percent completed PLD; 83% completed CM (both 16 weeks). Patients on PLD reported worse quality of life, cognitive and physical functioning than non-PLD regimens (primarily CM). At a median follow-up of 42 months, 81% of randomized patients remained free of any breast cancer recurrence. Based on our limited experience, PLD and CM may be reasonable options for further study for elderly vulnerable patients with endocrine nonresponsive breast cancer. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Crivellari, Diana; Spazzapan, Simon] Ctr Riferimento Oncol, I-33081 Aviano, Italy. [Gray, Kathryn P.; Gelber, Richard D.; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG, Ctr Stat, Boston, MA 02115 USA. [Gray, Kathryn P.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dellapasqua, Silvia; Colleoni, Marco] European Inst Oncol, Dept Med, Res Unit Med Senol, Milan, Italy. [Puglisi, Fabio] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy. [Ribi, Karin] Int Breast Canc Study Grp, Coordinating Ctr, Qual Life Off, Bern, Switzerland. [Price, Karen N.] Int Breast Canc Study Grp, Ctr Stat, Boston, MA USA. [Price, Karen N.; Maibach, Rudolf] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Gianni, Lorenzo] Osped Infermi Rimini, Dept Oncol, Rimini, Italy. [Gianni, Lorenzo] Ist Sci Romagnolo Studio & Cura Tumori, Rimini, Italy. [Pinotti, Graziella] Osped Circolo Varese, Varese, Italy. [Pinotti, Graziella] Fdn Macchi, Varese, Italy. [Luethi, Jean-Marc] Spital SIS AG, Thun, Switzerland. [Gelber, Richard D.; Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Castiglione-Gertsch, Monica] Univ Geneva, Dept Med Hop, Unite Oncogynecol Med, Geneva, Switzerland. [Maibach, Rudolf; Rabaglio, Manuela] Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. [Rabaglio, Manuela] Univ Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. RP Crivellari, D (reprint author), Ctr Riferimento Oncol, I-33081 Aviano, Italy. EM dcrivellari@cro.it OI Puglisi, Fabio/0000-0003-0573-4938 FU Schering-Plough Company FX Partial support was provided by Schering-Plough Company. The CASA trial was coordinated by the International Breast Cancer Study Group (IBCSG) on behalf of the Breast International Group (BIG); Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health and Medical Research Council); the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research (SAKK); the Swiss Cancer League; and the United States National Institutes of Health (CA-75362). NR 33 TC 19 Z9 19 U1 2 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2013 VL 22 IS 2 BP 130 EP 137 DI 10.1016/j.breast.2013.01.015 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126QA UT WOS:000317634900004 PM 23453899 ER PT J AU Ruddy, KJ Giobbie-Hurder, A Giordano, SH Goldfarb, S Kereakoglow, S Winer, EP Partridge, AH AF Ruddy, Kathryn J. Giobbie-Hurder, Anita Giordano, Sharon H. Goldfarb, Shari Kereakoglow, Sandra Winer, Eric P. Partridge, Ann H. TI Quality of life and symptoms in male breast cancer survivors SO BREAST LA English DT Article DE Breast neoplasms; Male; Hot flashes; Sexual dysfunction; Physiologic; Quality of life; Survivors ID PROSTATE-CANCER; WOMEN; TAMOXIFEN; DEPRESSION; THERAPY; ANXIETY AB Introduction: Little is known about quality of life and symptoms of male breast cancer survivors. Patients and methods: We recruited men with stage 0-4 breast cancer for an on-line survey through www.outoftheshadowofpink.com, www.malebreastcancer.org, and www.malebreastcancer.ca. Surveys included Expanded Prostate Cancer Index Composite (EPIC) Hormonal/Sexual Scales, Hospitalized Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy-Breast (FACT-B), sociodemographic/disease-related, genetic, and fertility-related items. Results: Forty-two responded. Mean EPIC Sexual and Hormonal scores were 44.5 and 81.3, respectively, suggesting symptom burden. Mean FACT-B score was 111.1, consistent with impaired overall quality of life. Conclusions: Male survivors experience substantial sexual and hormonal symptoms. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ruddy, Kathryn J.; Giobbie-Hurder, Anita; Kereakoglow, Sandra; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Giordano, Sharon H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Goldfarb, Shari] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kruddy@partners.org FU Dana-Farber Cancer Institute FX This study was supported by institutional funds at Dana-Farber Cancer Institute. NR 21 TC 3 Z9 4 U1 0 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2013 VL 22 IS 2 BP 197 EP 199 DI 10.1016/j.breast.2012.12.014 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126QA UT WOS:000317634900017 PM 23313328 ER PT J AU Vasdev, N Green, DE Vines, DC McLarty, K McCormick, PN Moran, MD Houle, S Wilson, AA Reilly, RM AF Vasdev, Neil Green, David E. Vines, Douglass C. McLarty, Kristin McCormick, Patrick N. Moran, Matthew D. Houle, Sylvain Wilson, Alan A. Reilly, Raymond M. TI Positron-Emission Tomography Imaging of the TSPO with [F-18]FEPPA in a Preclinical Breast Cancer Model SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE automation; breast cancer; [F-18]FEPPA; fluorine-18; peripheral benzodiazepine receptor; positron-emission tomography; translocator protein; TSPO ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; TRANSLOCATOR PROTEIN TSPO; MICROGLIAL ACTIVATION; IN-VIVO; 18 KDA; CELL-PROLIFERATION; PET RADIOLIGAND; BINDING-SITE; EXPRESSION; LOCALIZATION AB The present study aims to image the 18-kDa translocator protein (TSPO; formerly known as the peripheral benzodiazepine receptor) in a preclinical human breast cancer (BC) xenograft mouse model with positron-emission tomography (PET). An automated radiosynthesis of [F-18]-N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([F-18]FEPPA) was validated for human use using a commercial synthesis module and resulted in a high radiochemical yield (30%+/- 8%, uncorrected; n = 54) and specific activity (6 +/- 4 Ci/ mu mol). Tumor uptake of [F-18]FEPPA in mice bearing subcutaneous MDA-MB-231 BC xenografts was evaluated by PET-computed tomography imaging and ex vivo biodistribution studies. Although the tumor was successfully visualized, ex vivo biodistribution studies revealed low tumor uptake (0.7%ID/g), with the majority of radioactivity distributed in the spleen, muscle, and heart despite high TSPO expression in this cell line. Our laboratory routinely prepares [F-18]FEPPA for human-imaging studies in the central nervous system, and we envision that radiopharmaceuticals that target the TSPO have the potential for imaging macrophages in the tumor microenvironment. C1 [Vasdev, Neil; McCormick, Patrick N.; Moran, Matthew D.; Houle, Sylvain; Wilson, Alan A.] Ctr Addict & Mental Hlth, PET Ctr, Toronto, ON, Canada. [Vasdev, Neil; McCormick, Patrick N.; Moran, Matthew D.; Houle, Sylvain; Wilson, Alan A.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Vines, Douglass C.] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [McLarty, Kristin; Reilly, Raymond M.] Univ Toronto, Dept Pharmaceut Sci, Toronto, ON, Canada. [Reilly, Raymond M.] Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. [Green, David E.; Vines, Douglass C.] Princess Margaret Hosp, Radiat Med Program, STTARR Innovat Ctr, Toronto, ON M4X 1K9, Canada. [Reilly, Raymond M.] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu RI Wilson, Alan/A-1788-2011 FU Ontario Institute for Cancer Research; Government of Ontario FX This research was supported by grants from the Ontario Institute for Cancer Research (One Millimetre Cancer Challenge) with funding provided by the Government of Ontario. The authors gratefully acknowledge Armando Garcia and Winston Stableford for 18F production. The authors would like to thank Lisa DiDiodato for performing the CT imaging. NR 44 TC 4 Z9 4 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD APR PY 2013 VL 28 IS 3 BP 254 EP 259 DI 10.1089/cbr.2012.1196 PG 6 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 124PU UT WOS:000317478200011 PM 23350894 ER PT J AU Pusztaszeri, MP Sadow, PM Faquin, WC AF Pusztaszeri, Marc P. Sadow, Peter M. Faquin, William C. TI Association of CD1a-Positive Dendritic Cells With Papillary Thyroid Carcinoma in Thyroid Fine-Needle Aspirations A Cytologic and Immunocytochemical Evaluation SO CANCER CYTOPATHOLOGY LA English DT Article DE dendritic cells; Langerhans cells; thyroid; papillary carcinoma; cytopathology; fine-needle aspiration; CD1a; immunohistochemistry ID ANTIGEN-PRESENTING FUNCTION; LANGERHANS CELLS; HISTIOCYTOID CELLS; IMMUNE-RESPONSES; EXPRESS CD83; CLASS-II; TUMOR; CANCER; CD1A; MATURATION AB BACKGROUND: In contrast to other primary thyroid neoplasms and benign thyroid tissue, it has been demonstrated histologically that dendritic cells (DCs) are associated with papillary thyroid carcinoma (PTC). However, the presence and potential diagnostic value of DCs in thyroid fine-needle aspirations (FNAs) have not been previously described. METHODS: The authors quantitatively assessed for the presence of DCs that were positive for cluster of differentiation 1a (CD1a) (a 43-49 kD protein expressed on DCs and cortical thymocytes) in cytologic samples of histologically confirmed PTC (n = 31) and in a control group of benign thyroid nodules (BTNs) (n = 29) using immunocytochemical staining with antibodies against CD1a. A subset of the corresponding PTCs (n = 11) and BTNs (n = 10) from surgical resection specimens also were assessed immunohistochemically for both CD1a and Langerin (a type II transmembrane cell surface receptor produced by Langerhans cells). RESULTS: CD1a-positive DCs were identified in 97% PTCs (n = 30 of 31 PTCs) in thyroid FNA specimens. DCs were largely present in 2 distinct patterns: either as isolated DCs in the background (n = 29 of 31) and/or associated with tumor cells (n = 30 of 31). Tumor-associated DCs (mean +/- standard deviation: 6.44 +/- 6.13 DCs per tumor cluster) exhibited multiple dendritic cytoplasmic processes extending over and between malignant cells within groups. The 3 PTC cases with the least DCs corresponded to the follicular variant at excision. In contrast, only 31% of BTNs (n = 9 of 29 BTNs; P = .0048) contained CD1a-positive DCs. When DCs were present in BTN, they were isolated primarily in the background (27%; n = 8 of 29), although 17% of BTNs (n = 5 of 29) contained rare DCs among thyrocytes, revealing both patterns in 4 cases. Both thyrocyte-associated DCs and background DCs were more numerous in PTC FNAs than in BTN FNAs, but only the thyrocyte-associated group of DCs was statistically significant (P < .0001 and P = .1173, respectively). Similar findings were reported in histologic samples in which all PTCs examined (n = 11 of 11) contained both CD1a-positive and Langerin-positive DCs; only 20% of BTNs (n = 2 of 10) contained rare DCs. CONCLUSIONS: CD1a-positive DCs were present in FNA specimens of PTC, typically in close association with tumor cells, whereas they were rare in BTNs. The increased presence of CD1a-positive DCs in PTC may be a useful diagnostic adjuvant. Cancer (Cancer Cytopathol) 2013;121:206213. (c) 2012 American Cancer Society. C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Pusztaszeri, Marc P.; Sadow, Peter M.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pusztaszeri, Marc P.; Sadow, Peter M.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org FU Department of Pathology, Massachusetts General Hospital; Nuovo-Soldati Foundation FX This study was supported by the Mini-Vickery Award grant from the Department of Pathology, Massachusetts General Hospital. M. P. P. received support from the Nuovo-Soldati Foundation for his visiting fellowship to Massachusetts General Hospital. NR 45 TC 7 Z9 8 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR PY 2013 VL 121 IS 4 BP 206 EP 213 DI 10.1002/cncy.21239 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 129TN UT WOS:000317865500008 PM 23042745 ER PT J AU Meng, SS Zhang, XH Giovannucci, EL Ma, J Fuchs, CS Cho, EY AF Meng, Shasha Zhang, Xuehong Giovannucci, Edward L. Ma, Jing Fuchs, Charles S. Cho, Eunyoung TI No association between garlic intake and risk of colorectal cancer SO CANCER EPIDEMIOLOGY LA English DT Article DE Garlic intake; Colorectal cancer; Incidence; Prospective study; Garlic supplement; Carcinogenesis ID COLON-CANCER; HEALTH AB Background: Although experimental studies suggested beneficial role of garlic intake on colorectal carcinogenesis, limited prospective cohort studies have evaluated garlic intake in relation to colorectal cancer (CRC) incidence. Methods: We followed 76,208 women in the Nurses' Health Study and 45,592 men in the Health Professionals Follow-up Study for up to 24 years and examined garlic intake and garlic supplement use in relation to CRC risk. Information on garlic intake and supplement use was assessed using a validated food frequency questionnaire and a Cox proportional hazard regression model was used to estimate the multivariable hazard ratio (MV-HR) and 95% confidence intervals (95% CIs). Results: We documented 2368 (1339 women and 1029 men) incident CRC cases and found no association between garlic intake and CRC risk; the MV-HRs (95% CIs) associated with garlic (1 clove or 4 shakes per serving) intake >= 1/day compared with < 1/month were 1.21 (0.94-1.57; p-trend = 0.14) for women and 1.00 (0.71-1.42; p-trend = 0.89) for men. The MV-HRs (95% CIs) of CRC for garlic supplement use, which was used in 6% of the participants in each study, were 0.72 (0.48-1.07) for women and 1.22 (0.83-1.78) for men. Conclusion: Our prospective data do not support an important role of garlic intake or garlic supplement use in colorectal carcinogenesis. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Meng, Shasha; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Zhang, Xuehong; Giovannucci, Edward L.; Ma, Jing; Cho, Eunyoung] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Zhang, Xuehong; Giovannucci, Edward L.; Ma, Jing; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cho, EY (reprint author), Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 181 Longwood Ave, Boston, MA USA. EM eunyoung.cho@channing.harvard.edu FU National Institutes of Health [CA136950, CA87969, CA55075] FX This study was supported by research grant CA136950, CA87969, and CA55075 from the National Institutes of Health. There are no financial disclosures from any authors. NR 10 TC 6 Z9 7 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD APR PY 2013 VL 37 IS 2 BP 152 EP 155 DI 10.1016/j.canep.2012.11.002 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 123UD UT WOS:000317415700008 PM 23265869 ER PT J AU Tanwar, PS Kaneko-Tarui, T Lee, HJ Zhang, LH Teixeira, JM AF Tanwar, Pradeep S. Kaneko-Tarui, Tomoko Lee, Ho-Joon Zhang, LiHua Teixeira, Jose M. TI PTEN loss and HOXA10 expression are associated with ovarian endometrioid adenocarcinoma differentiation and progression SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; TUMOR-SUPPRESSOR GENE; BETA-CATENIN GENE; REPRODUCTIVE-TRACT; SURFACE EPITHELIUM; WNT/BETA-CATENIN; CELL TUMOR; COLI APC; CANCER; MOUSE AB Epithelial ovarian cancer is a heterogeneous disease that is subdivided into five major histotypes but the mechanisms driving their differentiation are not clear. Mutations in adenomatous polyposis coli (APC) and -catenin are commonly observed in the human ovarian endometrioid adenocarcinoma (OEA) patients. However, the mechanisms subsequent to APC deletion in ovarian tumorigenesis have not been well characterized. We have conditionally deleted APC in the murine ovarian surface epithelium (OSE) and showed that its loss leads to development of epithelial inclusion cysts. High-grade OEAs with tightly packed villoglandular histology were observed in older APC-deleted mice. Phosphatase and tensin homolog (PTEN) expression was elevated in the early lesions but lost after progression to the more advanced tumors. Knockdown of APC or expression of a gain-of-function -catenin similarly induced human OSE cells to develop tumors with endometrioid histology in xenografts. Expression of HOXA10 was induced in both the advanced APC-deleted murine tumors and in the tumor xenografts of human OSE cells with knocked-down APC. These results show that reduced APC activity is sufficient to induce formation of epithelial inclusion cysts and support OEA development and suggest that induced HOXA10 expression and loss of PTEN are key mechanisms driving endometrioid histotype differentiation and progression. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Teixeira, Jose M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Thier 931, 55 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU National Institutes of Health [HD052701]; Vincent Center Memorial Funds FX National Institutes of Health (HD052701) and Vincent Center Memorial Funds to J.M.T. NR 56 TC 11 Z9 13 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2013 VL 34 IS 4 BP 893 EP 901 DI 10.1093/carcin/bgs405 PG 9 WC Oncology SC Oncology GA 123PB UT WOS:000317401200020 PM 23276799 ER PT J AU Holland, JP Kang, A Cohrs, S Selivanova, SV Sephton, SM Betzel, T Frey, D Wieser, M Jaussi, R Kammerer, RA Schibli, R Fischer, E AF Holland, Jason P. Kang, Albert Cohrs, Susan Selivanova, Svetlana V. Sephton, Selena Milicevic Betzel, Thomas Frey, Daniel Wieser, Mara Jaussi, Rolf Kammerer, Richard A. Schibli, Roger Fischer, Eliane TI Synthesis and Evaluation of Biphenyl Compounds as Kinesin Spindle Protein Inhibitors SO CHEMISTRY & BIODIVERSITY LA English DT Article DE Kinesin spindle protein; Biphenyls; Inhibitors; Mitosis; Antiproliferative activity; Confocal fluorescence microscopy; Density-functional theory (DFT) ID CANCER-CELLS; MECHANISM; AGENTS; KSP AB Kinesin spindle protein (KSP), an ATP-dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle. KSP has emerged as a novel target for antimitotic anticancer drug development. In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression. Antiproliferation (MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)) assays, combined with fluorescence-assisted cell sorting (FACS) and Western blot studies analyzing cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity. However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines. Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7, exerts its pharmacologic effect specifically in the M phase and induces monoaster formation. These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds. C1 [Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Holland, Jason P.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Holland, Jason P.; Kang, Albert; Selivanova, Svetlana V.; Sephton, Selena Milicevic; Betzel, Thomas; Schibli, Roger] ETH, Inst Pharmaceut Sci, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland. [Cohrs, Susan; Schibli, Roger; Fischer, Eliane] Paul Scherrer Inst, Ctr Radiopharmaceut Sci, CH-5232 Villigen, Switzerland. [Frey, Daniel; Wieser, Mara; Jaussi, Rolf; Kammerer, Richard A.] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. EM holland.jason@mgh.harvard.edu; eliane.fischer@psi.ch RI Fischer, Eliane/M-2590-2013; OI Fischer, Eliane/0000-0002-3399-3737; Holland, Jason/0000-0002-0066-219X; Schibli, Roger/0000-0002-1537-3833 FU ETH Fellowship Program [FEL-01-10-1] FX Funded in part by the ETH Fellowship Program (FEL-01-10-1; JPH). We thank Dr. Aristeidis Chiotellis and Cindy Fischer for helpful discussions and advice regarding chemical synthesis and chromatography. We also thank Drs. Tobias Schwarz and Joaquim Hehl at the Light Microscopy Centre, ETH Zurich, for technical support regarding fluorescence microscopy studies. NR 21 TC 2 Z9 2 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1612-1872 EI 1612-1880 J9 CHEM BIODIVERS JI Chem. Biodivers. PD APR PY 2013 VL 10 IS 4 BP 538 EP 555 DI 10.1002/cbdv.201200400 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 126LD UT WOS:000317616400004 PM 23576341 ER PT J AU Wu, JHY Lemaitre, RN Manichaikul, A Guan, WH Tanaka, T Foy, M Kabagambe, EK Djousse, L Siscovick, D Fretts, AM Johnson, C King, IB Psaty, BM McKnight, B Rich, SS Chen, YDI Nettleton, JA Tang, WH Bandinelli, S Jacobs, DR Browning, BL Laurie, CC Gu, XJ Tsai, MY Steffen, LM Ferrucci, L Fornage, M Mozaffarian, D AF Wu, Jason H. Y. Lemaitre, Rozenn N. Manichaikul, Ani Guan, Weihua Tanaka, Toshiko Foy, Millennia Kabagambe, Edmond K. Djousse, Luc Siscovick, David Fretts, Amanda M. Johnson, Catherine King, Irena B. Psaty, Bruce M. McKnight, Barbara Rich, Stephen S. Chen, Yii-Der I. Nettleton, Jennifer A. Tang, Weihong Bandinelli, Stefania Jacobs, David R., Jr. Browning, Brian L. Laurie, Cathy C. Gu, Xiangjun Tsai, Michael Y. Steffen, Lyn M. Ferrucci, Luigi Fornage, Myriam Mozaffarian, Dariush TI Genome-Wide Association Study Identifies Novel Loci Associated With Concentrations of Four Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway Results From the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE epidemiology; fatty acids; genome-wide association study; lipogenesis ID MIDDLE-AGED ADULTS; ENDOPLASMIC-RETICULUM; ATHEROSCLEROSIS RISK; INTERMITTENT HYPOXIA; SYNTHASE INHIBITORS; ALCOHOL-CONSUMPTION; HEPATIC STEATOSIS; ADIPOSE-TISSUE; PPAR-ALPHA; ER STRESS AB Background-Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and monounsaturated fatty acids that affect cellular signaling and metabolic pathways. They are synthesized via de novo lipogenesis and are the main saturated and monounsaturated fatty acids in the diet. Levels of these fatty acids have been linked to diseases including type 2 diabetes mellitus and coronary heart disease. Methods and Results-Genome-wide association studies were conducted in 5 population-based cohorts comprising 8961 participants of European ancestry to investigate the association of common genetic variation with plasma levels of these 4 fatty acids. We identified polymorphisms in 7 novel loci associated with circulating levels of >= 1 of these fatty acids. ALG14 (asparagine-linked glycosylation 14 homolog) polymorphisms were associated with higher 16:0 (P=2.7x10(-11)) and lower 18:0 (P=2.2x10(-18)). FADS1 and FADS2 (desaturases) polymorphisms were associated with higher 16:1n-7 (P=6.6x10(-13)) and 18:1n-9 (P=2.2x10(-32)) and lower 18:0 (P=1.3x10(-20)). LPGAT1 (lysophosphatidylglycerol acyltransferase) polymorphisms were associated with lower 18:0 (P=2.8x10(-9)). GCKR (glucokinase regulator; P=9.8x10(-10)) and HIF1AN (factor inhibiting hypoxia-inducible factor-1; P=5.7x10(-9)) polymorphisms were associated with higher 16:1n-7, whereas PKD2L1 (polycystic kidney disease 2-like 1; P=5.7x10(-15)) and a locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7 (P=4.1x10(-8)). Conclusions-Our findings provide novel evidence that common variations in genes with diverse functions, including protein-glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose-and oxygen-sensing pathways, are associated with circulating levels of 4 fatty acids in the de novo lipogenesis pathway. These results expand our knowledge of genetic factors relevant to de novo lipogenesis and fatty acid biology. (Circ Cardiovasc Genet. 2013;6:171-183.) C1 [Wu, Jason H. Y.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. [Wu, Jason H. Y.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Lemaitre, Rozenn N.; Siscovick, David; Fretts, Amanda M.; Johnson, Catherine; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [McKnight, Barbara; Laurie, Cathy C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Browning, Brian L.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Div Biostat & Epidemiol, Charlottesville, VA USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Guan, Weihua] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Tang, Weihong; Jacobs, David R., Jr.; Steffen, Lyn M.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Tsai, Michael Y.] Univ Minnesota, Sch Publ Hlth, Lab Med & Pathol, Minneapolis, MN USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Foy, Millennia; Gu, Xiangjun; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Kabagambe, Edmond K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Mozaffarian, Dariush] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Chen, Yii-Der I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. RP Wu, JHY (reprint author), Harvard Univ, Sch Publ Hlth, Kresge Bldg 913,677 Huntington Ave, Boston, MA 02115 USA. EM jasonwu@hsph.harvard.edu RI Browning, Brian/A-1178-2010; Djousse, Luc/F-5033-2017 OI Browning, Brian/0000-0001-6454-6633; Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN2682011 00007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402, U01-HG-004729, U01-HG-004446, U01-HG-004424]; National Institutes of Health [HSN268200625226C]; NIH [UL1RR025005]; NIH Roadmap for Medical Research; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Center for Research Resources CTSI [UL 1RR033176]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on Aging [263 MD 9164, 263 MD 821336]; Intramural research program of the National Institute on Aging, National Institutes of Health; MESA; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [5K01DK082729-02]; National Heart, Lung, and Blood Institute [N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204, R01-HL-084099, N01-HC-95159, N01-HC-95169, RR-024156, N02-HL-6-4278]; [R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258]; [R01HL071259] FX The ARIC Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN2682011 00007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HSN268200625226C. The authors thank the staff and participants of the ARIC Study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The CHS research reported in this article was supported by the NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133, and grants HL080295, HL075366, HL087652, and HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping were supported, in part, by National Center for Research Resources CTSI grant UL 1RR033176 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Coronary Artery Risk Development in Young Adults CARDIA study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, and N01-HC-45204 from the NHLBI to the CARDIA investigators. Genotyping of the CARDIA participants was supported by grants U01-HG-004729, U01-HG-004446, and U01-HG-004424 from the National Human Genome Research Institute and R01-HL-084099 from the NHLBI to Dr Fornage. Statistical analyses and fatty acid measures were funded by R01-HL-084099 from the NHLBI to Dr Foy. The InCHIANTI Study baseline (1998-2000) was supported as a targeted project (ICS110.1/RF97.71) by the Italian Ministry of Health, in part by the US National Institute on Aging (contracts 263 MD 9164 and 263 MD 821336), and in part by the Intramural research program of the National Institute on Aging, National Institutes of Health. The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SHARe were supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the NHLBI. Funding for MESA SHARe genotyping was provided by NHLBI contract N02-HL-6-4278. MESA Family is conducted and supported in collaboration with MESA investigators, and support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, and R01HL071259. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Dr Nettleton is supported by a K01 from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-02).; The authors thank the other investigators, the staff, and the participants of the ARIC study, the CARDIA study, the CHS study, the MESA study, and the InCHIANTI study for their important contributions. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. A full list of principal CARDIA investigators and institutions can be found at http://www.cardia.dopm.uab.edu/study-information/participating-instituti ons. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The authors acknowledge the essential role of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium in the development and support of this manuscript. CHARGE members include National Heart, Lung, and Blood Institute's (NHLBI's) Atherosclerosis Risk in Communities (ARIC) Study, National Institute of Health (NIH) and Icelandic Heart Association's Age, Gene/Environment Susceptibility (AGES) Study, NHLBI's Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), and the Netherland's Rotterdam Study (RS). NR 74 TC 21 Z9 21 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2013 VL 6 IS 2 BP 171 EP + DI 10.1161/CIRCGENETICS.112.964619 PG 37 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 128AW UT WOS:000317741400006 PM 23362303 ER PT J AU Kramer, JR Fischbach, LA Richardson, P Alsarraj, A Fitzgerald, S Shaib, Y Abraham, NS Velez, M Cole, R Anand, B Verstovsek, G Rugge, M Parente, P Graham, DY El-Serag, HB AF Kramer, Jennifer R. Fischbach, Lori A. Richardson, Peter Alsarraj, Abeer Fitzgerald, Stephanie Shaib, Yasser Abraham, Neena S. Velez, Maria Cole, Rhonda Anand, Bhupinderjit Verstovsek, Gordana Rugge, Massimo Parente, Paola Graham, David Y. El-Serag, Hashem B. TI Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated With an Increased Risk of Barrett's Esophagus in White Men SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Visceral Obesity; Epidemiologic Study; Veterans Affairs; Risk Factors ID GASTROESOPHAGEAL-REFLUX DISEASE; GENERAL-POPULATION; METABOLIC SYNDROME; CENTRAL ADIPOSITY; HIATAL-HERNIA; FLAP VALVE; OBESITY; PREVALENCE; SYMPTOMS; ADENOCARCINOMA AB BACKGROUND & AIMS: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barrett's esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS: We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS: There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS: High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia. C1 [Kramer, Jennifer R.; Richardson, Peter; Alsarraj, Abeer; Fitzgerald, Stephanie; Abraham, Neena S.; El-Serag, Hashem B.] Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Abraham, Neena S.; Velez, Maria; Cole, Rhonda; Anand, Bhupinderjit; Graham, David Y.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Verstovsek, Gordana] Baylor Coll Med, Dept Pathol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Kramer, Jennifer R.; Richardson, Peter; Shaib, Yasser] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Shaib, Yasser; Abraham, Neena S.; Velez, Maria; Cole, Rhonda; Anand, Bhupinderjit; Graham, David Y.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Verstovsek, Gordana] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Fischbach, Lori A.] Univ Arkansas Med Sci, Dept Epidemiol, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. [Rugge, Massimo] Univ Padua, Surg Pathol & Cytopathol Unit, Dept Med DIMED, Padua, Italy. [Parente, Paola] Casa Sollievo Sofferenza, Dept Pathol, San Giovanni Rotondo, Italy. RP Kramer, JR (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jennifer.kramer@va.gov RI Rugge, Massimo/K-7525-2016 FU National Institutes of Health grant National Cancer Institute [R01 116845]; Houston VA HSR&D Center of Excellence [HFP90-020]; Texas Digestive Disease Center National Institutes of Health [DK58338]; National Institute of Diabetes and Digestive and Kidney Diseases [K24-04-107] FX Supported in part by National Institutes of Health grant National Cancer Institute R01 116845, the Houston VA HSR&D Center of Excellence (HFP90-020), and the Texas Digestive Disease Center National Institutes of Health (DK58338). Also supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K24-04-107 to H.B.E.-S.). 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 United States government. NR 37 TC 39 Z9 39 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2013 VL 11 IS 4 BP 373 EP + DI 10.1016/j.cgh.2012.11.028 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 123TK UT WOS:000317413700012 PM 23220167 ER PT J AU Lin, JH Zhang, SMM Rexrode, KM Manson, JE Chan, AT Wu, KN Tworoger, SS Hankinson, SE Fuchs, C Gaziano, JM Buring, JE Giovannucci, E AF Lin, Jennifer H. Zhang, Shumin M. Rexrode, Kathryn M. Manson, Joann E. Chan, Andrew T. Wu, Kana Tworoger, Shelley S. Hankinson, Susan E. Fuchs, Charles Gaziano, J. Michael Buring, Julie E. Giovannucci, Edward TI Association Between Sex Hormones and Colorectal Cancer Risk in Men and Women SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Estrogen; Incidence; Colorectal Cancer; Testosterone ID ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; BINDING GLOBULIN; PROSTATE-CANCER; SUBSEQUENT RISK; RECTAL-CANCER; THERAPY; METAANALYSIS; COLON; TESTOSTERONE AB BACKGROUND & AIMS: There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear. METHODS: We collected data on lifestyle, medical history, and diet (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and C-peptide among 730 women (293 cases of colorectal cancer and 437 healthy individuals as controls) and 1158 men (439 colorectal cancer cases and 719 controls) and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals. All statistical tests were 2-sided. RESULTS: Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with colorectal cancer in men after adjustments for matching and risk factors for colorectal cancer, including body mass index and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% confidence interval, 0.40-0.96), 0.65 for SHBG (95% confidence interval, 0.42-0.99), and 2.63 for the ratio (95% confidence interval, 1.58-4.36) (P values for trend <= .02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with colorectal cancer after adjustments for all factors (RR, 0.43; 95% confidence interval, 0.22-0.84; P value for trend = .03). CONCLUSIONS: On the basis of combined data from 4 population studies, there appears to be an association between levels of sex hormones and colorectal cancer risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and colorectal cancer in postmenopausal women. C1 [Lin, Jennifer H.; Zhang, Shumin M.; Rexrode, Kathryn M.; Manson, Joann E.; Gaziano, J. Michael; Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Chan, Andrew T.; Tworoger, Shelley S.; Hankinson, Susan E.; Fuchs, Charles; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. [Manson, Joann E.; Tworoger, Shelley S.; Hankinson, Susan E.; Buring, Julie E.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Wu, Kana; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Fuchs, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Lin, JH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02215 USA. EM jhlin@rics.bwh.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046; Rexrode, Kathryn/0000-0003-3387-8429 FU National Cancer Institute [CA126846, CA49449, CA47988, CA87969, CA55075, CA34944, CA40360, CA097193, CA123089, CA137178]; National Heart, Lung, and Blood Institute [HL043851, HL080467, HL26490, HL34595] FX Supported by grants CA126846, CA49449, CA47988, CA87969, CA55075, CA34944, CA40360, CA097193, CA123089, and CA137178 from the National Cancer Institute and grants HL043851, HL080467, HL26490, and HL34595 from the National Heart, Lung, and Blood Institute. NR 26 TC 28 Z9 30 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2013 VL 11 IS 4 BP 419 EP + DI 10.1016/j.cgh.2012.11.012 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 123TK UT WOS:000317413700020 PM 23200979 ER PT J AU Fett, N Neves, J AF Fett, Nicole Neves, Jennifer TI Multiple Eruptive Milia SO CUTIS LA English DT Article ID CLASSIFICATION; BOY AB Multiple eruptive milia (MEM) is a rare skin condition characterized by sudden onset of multiple milia occurring mainly on the head, neck, and trunk. Milia are small, benign, 1- to 4-mm, white keratinous cysts. The lesions generally are asymptomatic and may arise spontaneously or secondary to a number of processes. Multiple eruptive milia are cosmetically troublesome and difficult to treat. We report the case of a 40-year-old man with an abrupt onset of MEM on the face. Cutis. 2013; 91: 191-192. C1 [Fett, Nicole; Neves, Jennifer] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Fett, Nicole] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Fett, N (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Ste 1-330A,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM Nicole.fett@uphs.upenn.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD APR PY 2013 VL 91 IS 4 BP 191 EP 192 PG 2 WC Dermatology SC Dermatology GA 127QB UT WOS:000317712400009 PM 23763079 ER PT J AU O'Donovan, A Rush, G Hoatam, G Hughes, BM McCrohan, A Kelleher, C O'Farrelly, C Malone, KM AF O'Donovan, Aoife Rush, Gavin Hoatam, Gerard Hughes, Brian M. McCrohan, AnnMaria Kelleher, Cecily O'Farrelly, Cliona Malone, Kevin M. TI SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE depression; biological markers; mood disorders; stress; suicide; self-harm ID NATIONAL COMORBIDITY SURVEY; IMMUNE ACTIVATION; CANCER-PATIENTS; DSM-IV; INTERLEUKIN-6; STRESS; PREVALENCE; ATTEMPTERS; RESPONSES; CORTISOL AB Background Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers. Methods To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor- (TNF-), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender. Results Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial 2 = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial 2 = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial 2 = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts. Conclusions Suicidal ideation may be uniquely associated with inflammation in depressed patients. C1 [O'Donovan, Aoife; Malone, Kevin M.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 2, Ireland. [O'Donovan, Aoife; McCrohan, AnnMaria; Malone, Kevin M.] St Vincents Univ Hosp, Dept Psychiat Psychotherapy & Mental Hlth Res, Dublin 4, Ireland. [O'Donovan, Aoife] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA USA. [O'Donovan, Aoife] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Rush, Gavin] St Patricks Univ Hosp, Dublin, Ireland. [Hoatam, Gerard] Creighton Univ, Sch Med, Omaha, NE USA. [Hughes, Brian M.] Natl Univ Ireland, Dept Psychol, Galway, Ireland. [Kelleher, Cecily] Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, Dublin 2, Ireland. [O'Farrelly, Cliona] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland. RP O'Donovan, A (reprint author), Univ Calif San Francisco, Dept Psychiat, 3333 Calif St,Suite 465, San Francisco, CA 94143 USA. EM aoife.odonovan@ucsf.edu OI Malone, Kevin M/0000-0001-5665-4706 FU Craig Dobbin Newman Scholarship in Mental Health Research and Society in Science - The Branco Weiss Fellowship; Lundbeck Research Scholarship FX This study was supported by the Craig Dobbin Newman Scholarship in Mental Health Research and Society in Science - The Branco Weiss Fellowship to A.O.D. and by a Lundbeck Research Scholarship to G. R. The authors would like to thank Josh Woolley, M.D./Ph.D., Ashkan Ahmadian, B. A., and Kristen Nishimi, B. A., for helpful feedback on this manuscript. NR 44 TC 38 Z9 39 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2013 VL 30 IS 4 BP 307 EP 314 DI 10.1002/da.22087 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 126GJ UT WOS:000317600800004 PM 23504697 ER PT J AU Bleich, S Nanda, NC Hage, FG AF Bleich, Steven Nanda, Navin C. Hage, Fadi G. TI The Incremental Value of Three-Dimensional Transthoracic Echocardiography in Adult Congenital Heart Disease SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE three-dimensional echocardiography; congenital heart disease; atrial septal defect; ventricular septal defect; anomalous coronary artery; coarctation of aorta ID VENTRICULAR SEPTAL-DEFECTS; COR-TRIATRIATUM SINISTER; BICUSPID AORTIC-VALVE; OF-THE-ART; GREAT-ARTERIES; PULMONARY-ARTERY; FORAMEN-OVALE; MANAGEMENT; TRANSPOSITION; COARCTATION AB Imaging with echocardiography is useful in diagnosing congenital heart disease (CHD). Two-dimensional (2D) transthoracic echocardiography (TTE) has been the standard cardiac imaging modality, but it forces the reader to mentally create the three-dimensional (3D) cardiac anatomy to understand these complex diseases. 3D TTE, which has relatively recently emerged to address this limitation, is capable of providing clear and dynamic 3D views of these anatomic defects and offers more insight on how to manage them. This review article will address the benefit of utilizing 3D TTE for proper characterization of different types of CHD in the adult and as a guide to appropriate treatment. (Echocardiography 2013;30:483-494) C1 [Bleich, Steven] Univ Alabama Birmingham, Dept Med, Div Internal Med, Birmingham, AL 35249 USA. [Nanda, Navin C.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35249 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Nanda, NC (reprint author), Univ Alabama Birmingham, Heart Stn SWB S102, 619 19th St South, Birmingham, AL 35249 USA. EM nanda@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 51 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD APR PY 2013 VL 30 IS 4 BP 483 EP 494 DI 10.1111/echo.12130 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 123XS UT WOS:000317425900025 PM 23551608 ER PT J AU Swirski, FK AF Swirski, F. K. TI Monocyte subsets in chronic inflammation SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Swirski, F. K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, F. K.] Harvard Univ, Sch Med, Boston, 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 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2013 VL 43 SU 1 SI SI BP 11 EP 11 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 120AE UT WOS:000317141000031 ER PT J AU Copin, JC da Silva, RF Fraga-Silva, RA Capettini, L Quintao, S Lenglet, S Pelli, G Galan, K Burger, F Braunersreuther, V Schaller, K Deruaz, M Proudfoot, AE Dallegri, F Stergiopulos, N Santos, RAS Gasche, Y Mach, F Montecucco, F AF Copin, J. C. da Silva, R. F. Fraga-Silva, R. A. Capettini, L. Quintao, S. Lenglet, S. Pelli, G. Galan, K. Burger, F. Braunersreuther, V. Schaller, K. Deruaz, M. Proudfoot, A. E. Dallegri, F. Stergiopulos, N. Santos, R. A. S. Gasche, Y. Mach, F. Montecucco, F. TI The selective pharmacologic inhibition of CXC chemokines is associated with an improvement of histological features of vulnerability in mouse atherosclerotic plaques SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Copin, J. C.] Univ Hosp Geneva, Div Neurosurg, Geneva, Switzerland. [Copin, J. C.; Schaller, K.; Gasche, Y.] Univ Geneva, Geneva Neurosci Ctr, Geneva, Switzerland. [da Silva, R. F.; Fraga-Silva, R. A.; Capettini, L.; Quintao, S.; Stergiopulos, N.] Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland. [da Silva, R. F.; Fraga-Silva, R. A.; Capettini, L.; Quintao, S.; Santos, R. A. S.] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil. [Lenglet, S.; Pelli, G.; Galan, K.; Burger, F.; Braunersreuther, V.; Mach, F.; Montecucco, F.] Univ Geneva, Fdn Med Res, Div Cardiol, Geneva, Switzerland. [Deruaz, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Proudfoot, A. E.] Merck Serono Geneva Res Ctr, Geneva, Switzerland. [Dallegri, F.; Montecucco, F.] Univ Genoa, Dept Internal Med, Clin Internal Med 1, Sch Med, I-16126 Genoa, Italy. [Gasche, Y.] Univ Hosp Geneva, Div Intens Care Med, Geneva, Switzerland. RI LENGLET, Sebastien/N-8923-2013; Santos, Robson/C-9336-2011; Montecucco, Fabrizio/K-8543-2016 OI LENGLET, Sebastien/0000-0002-4853-8163; Santos, Robson/0000-0001-8738-5852; Montecucco, Fabrizio/0000-0003-0823-8729 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 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2013 VL 43 SU 1 SI SI BP 23 EP 23 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 120AE UT WOS:000317141000069 ER PT J AU Polasek, M Caravan, P AF Polasek, Miloslav Caravan, Peter TI Is Macrocycle a Synonym for Kinetic Inertness in Gd(III) Complexes? Effect of Coordinating and Noncoordinating Substituents on Inertness and Relaxivity of Gd(III) Chelates with DO3A-like Ligands SO INORGANIC CHEMISTRY LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; MRI CONTRAST AGENTS; LANTHANIDE COMPLEXES; WATER-EXCHANGE; AQUEOUS-SOLUTION; PHYSICOCHEMICAL PROPERTIES; LUMINESCENCE PROPERTIES; GADOLINIUM COMPLEX; STRUCTURAL ENTRY; SERUM-ALBUMIN AB Gadolinium chelates with octadentate ligands are widely used as contrast agents for magnetic resonance imaging (MRI), with macrocyclic ligands based on DO3A being preferred for the high kinetic inertness of their Gd chelates. A major challenge in the design of new bifunctional MM probes is the need to control the rotational motion of the chelate, which greatly affects its relaxivity. In this work we explored facile alkylation of a secondary amine in macrocyclic DO3A-like ligands to create a short, achiral linkage to limit the undesired internal motion of chelates within larger molecular constructs. The acetate moiety on the trans nitrogen was also replaced with either a bidentate (ethoxyacetate, L1 or methyl picolinate, L2) or bulky monodentate (methyl phosphonate, L3) donor arm to give octa- or heptadentate ligands, respectively. The resultant Gd(III) complexes were all monohydrated (q = 1) and exhibited water residency times that spanned 2 orders of magnitude (tau(M) = 2190 +/- 170, 3500 +/- 90, and 12.7 +/- 3.8 ns at 37 degrees C for GdL1, GdL2, and GdL3, respectively). Alkylation of the secondary amine with a noncoordinating biphenyl moiety resulted in coordinatively saturated q = 0 complexes of octadentate ligands L1 and L2. Relaxivities were limited by slow water exchange and/or lack of water coligand. All complexes showed decreased inertness compared to [Gd(DO3A)] despite higher ligand denticity, and inertness was further decreased upon N-alkylation. These results demonstrate that high kinetic inertness and in vivo safety of Gd chelates with macrocyclic ligands should not be generalized. C1 [Polasek, Miloslav; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu RI Polasek, Miloslav/G-5949-2014 FU National Institute of Biomedical Imaging and Bioengineering [R01EB009062] FX This work was supported in part by award R01EB009062 from the National Institute of Biomedical Imaging and Bioengineering. NR 73 TC 17 Z9 17 U1 1 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD APR 1 PY 2013 VL 52 IS 7 BP 4084 EP 4096 DI 10.1021/ic400227k PG 13 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 119JT UT WOS:000317094300074 PM 23517079 ER PT J AU Karolyi, M Seifarth, H Liew, G Schlett, CL Maurovich-Horvat, P Stolzmann, P Dai, GP Huang, SN Goergen, CJ Nakano, M Otsuka, F Virmani, R Hoffmann, U Sosnovik, DE AF Karolyi, Mihaly Seifarth, Harald Liew, Gary Schlett, Christopher L. Maurovich-Horvat, Pal Stolzmann, Paul Dai, Guangping Huang, Shuning Goergen, Craig J. Nakano, Masataka Otsuka, Fumiyuki Virmani, Renu Hoffmann, Udo Sosnovik, David E. TI Classification of Coronary Atherosclerotic Plaques Ex Vivo With T1, T2, and Ultrashort Echo Time CMR SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; CMR; coronary artery; plaque classification; ultrashort TE ID CARDIOVASCULAR MAGNETIC-RESONANCE; OPTICAL COHERENCE TOMOGRAPHY; SPIRAL COMPUTED-TOMOGRAPHY; IN-VIVO; CAROTID PLAQUE; HIGH-RESOLUTION; INTRAVASCULAR ULTRASOUND; INTRAPLAQUE HEMORRHAGE; VULNERABLE PLAQUE; FIBROUS CAP AB OBJECTIVES This study sought to determine whether the classification of human coronary atherosclerotic plaques with T1, T2, and ultrashort echo time (UTE) cardiac magnetic resonance (CMR) would correlate well with atherosclerotic plaque classification by histology. BACKGROUND CMR has been extensively used to classify carotid plaque, but its ability to characterize coronary plaque remains unknown. In addition, the detection of plaque calcification by CMR remains challenging. Here, we used T1, T2, and UTE CMR to evaluate atherosclerotic plaques in fixed post-mortem human coronary arteries. We hypothesized that the combination of T1, T2, and UTE CMR would allow both calcified and lipid-rich coronary plaques to be accurately detected. METHODS Twenty-eight plaques from human donor hearts with proven coronary artery disease were imaged at 9.4-T with a T1-weighted 3-dimensional fast low-angle shot (FLASH) sequence (250-mu m resolution), a T2-weighted rapid acquisition with refocused echoes (RARE) sequence (in-plane resolution 0.156 mm), and an UTE sequence (300-mu m resolution). Plaques showing selective hypointensity on T2-weighted CMR were classified as lipid-rich. Areas of hypointensity on the T1-weighted images, but not the UTE images, were classified as calcified. Hyperintensity on the T1-weighted and UTE images was classified as hemorrhage. Following CMR, histological characterization of the plaques was performed with a pentachrome stain and established American Heart Association criteria. RESULTS CMR showed high sensitivity and specificity for the detection of calcification (100% and 90%, respectively) and lipid-rich necrotic cores (90% and 75%, respectively). Only 2 lipid-rich foci were missed by CMR, both of which were extremely small. Overall, CMR-based classification of plaque was in complete agreement with the histological classification in 22 of 28 cases (weighted k = 0.6945, p < 0.0001). CONCLUSIONS The utilization of UTE CMR allows plaque calcification in the coronary arteries to be robustly detected. High-resolution CMR with T1, T2, and UTE contrast enables accurate classification of human coronary atherosclerotic plaque. (J Am Coll Cardiol Img 2013;6:466-74) (C) 2013 by the American College of Cardiology Foundation C1 [Karolyi, Mihaly; Seifarth, Harald; Liew, Gary; Schlett, Christopher L.; Maurovich-Horvat, Pal; Stolzmann, Paul; Hoffmann, Udo; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Dai, Guangping; Huang, Shuning; Goergen, Craig J.; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Nakano, Masataka; Otsuka, Fumiyuki; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu OI Maurovich-Horvat, Pal/0000-0003-0885-736X; Goergen, Craig/0000-0001-8883-7953 FU National Institutes of Health [P41RR14075, S10RR025563]; Deutsche Forschungsgemeinschaft [DFG Se 2029/1-1] FX The study was partially supported by National Institutes of Health grants P41RR14075 and S10RR025563. Dr. Seifarth was supported by a Deutsche Forschungsgemeinschaft grant (DFG Se 2029/1-1). Dr. Sosnovik has received research support from and is a consultant for Siemens Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first two authors, Drs. Karolyi and Seifarth, contributed equally to this work; Drs. Hoffmann and Sosnovik are joint senior authors. NR 37 TC 7 Z9 9 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 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2013 VL 6 IS 4 BP 466 EP 474 DI 10.1016/j.jcmg.2012.09.015 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 129LU UT WOS:000317842300007 PM 23498670 ER PT J AU Blecker, S Bhatia, RS You, JJ Lee, DS Alter, DA Wang, JT Wong, HJ Tu, JV AF Blecker, Saul Bhatia, R. Sacha You, John J. Lee, Douglas S. Alter, David A. Wang, Julie T. Wong, Hannah J. Tu, Jack V. TI Temporal Trends in the Utilization of Echocardiography in Ontario, 2001 to 2009 SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiovascular imaging; echocardiography; resource utilization ID APPROPRIATENESS USE CRITERIA; TRANSTHORACIC ECHOCARDIOGRAPHY; HEART-FAILURE; CARE; MEDICARE; RATES; CANADA AB The purpose of this study was to examine utilization and growth in echocardiography among the general population of Ontario between 2001 and 2009. The age- and sex-adjusted rates of echocardiography grew from 39.1 per 1,000 persons in 2001 to 59.9 per 1,000 persons in 2009, for an annual rate of increase of 5.5%. Repeat echocardiograms increased at a rate of 10.6% per year and accounted for 25.3% of all procedures in 2009 as compared to 18.5% in 2002. While significant increases in echocardiography utilization were observed, opportunities may exist to improve the clinical utility of the echocardiograms performed in Ontario. C1 [Blecker, Saul] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Blecker, Saul] NYU, Sch Med, Dept Med, New York, NY USA. [Bhatia, R. Sacha] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bhatia, R. Sacha; Wong, Hannah J.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatia, R. Sacha; You, John J.; Lee, Douglas S.; Alter, David A.; Wang, Julie T.; Tu, Jack V.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [You, John J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [You, John J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Lee, Douglas S.; Alter, David A.; Tu, Jack V.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Lee, Douglas S.] Toronto Gen Hosp, Univ Hlth Network, Div Cardiol, Toronto, ON, Canada. [Alter, David A.] Toronto Rehabil Inst, Cardiac Rehabil & Secondary Prevent Program, Toronto, ON, Canada. [Alter, David A.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Wong, Hannah J.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wong, Hannah J.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Wong, Hannah J.] Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON, Canada. [Tu, Jack V.] Sunnybrook Schulich Heart Ctr, Toronto, ON, Canada. RP Tu, JV (reprint author), Inst Clin Evaluat Sci, G106-2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM tu@ices.on.ca RI Lee, Douglas/J-4315-2014; OI Tu, Jack/0000-0003-0111-722X; Wong, Hannah/0000-0002-9740-0312 FU Ontario Ministry of Health and Long-Term Care; Canadian Institutes of Health Research; National Heart, Lung, and Blood Institute [5T32HL007024]; Clinician-Scientist Award from the Canadian Institutes of Health Research; Career Investigator Award from the Heart and Stroke Foundation of Ontario; Canada Research Chair in Health Services Research FX The Institute for Clinical Evaluative Sciences is supported by the Ontario Ministry of Health and Long-Term Care. The results and conclusions are those of the authors, and should not be attributed to any of the funding agencies. This project was supported by operating grants from the Ontario Ministry of Health and Long-Term Care and the Canadian Institutes of Health Research. Dr. Blecker was supported in part by National Heart, Lung, and Blood Institute Grant 5T32HL007024. Dr. Lee is supported by a Clinician-Scientist Award from the Canadian Institutes of Health Research. Dr. Alter is supported by a Career Investigator Award from the Heart and Stroke Foundation of Ontario. Dr. Tu is supported by a Canada Research Chair in Health Services Research and a Career Investigator Award from the Heart and Stroke Foundation of Ontario. All other authors have reported they have no relationships relevant to the contents of this paper to disclose. NR 29 TC 15 Z9 15 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2013 VL 6 IS 4 BP 515 EP 522 DI 10.1016/j.jcmg.2012.10.026 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 129LU UT WOS:000317842300014 PM 23579013 ER PT J AU Kumar, V Donahue, DM Patel, N AF Kumar, Vishesh Donahue, Dean Michael Patel, Neha TI An Unexpected Complication During Cardiac Catheterization Blood Clot Cast of the Tracheobronchial Tree: First Case During Cardiac Catheterization SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE anticoagulation; bleeding; respiratory failure ID THROMBUS C1 [Kumar, Vishesh] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Donahue, Dean Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. [Donahue, Dean Michael] North Shore Med Ctr, Salem, MA USA. [Patel, Neha] Signature Healthcare, Brockton Hosp, Brockton, MA USA. RP Kumar, V (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Plaza,185 Cambridge St,Room, Boston, MA 02114 USA. EM kumar.vishesh@mgh.harvard.edu NR 3 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 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD APR PY 2013 VL 6 IS 4 DI 10.1016/j.jcin.2012.11.007 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 124SX UT WOS:000317487900001 ER PT J AU Rosner, W Hankinson, SE Sluss, PM Vesper, HW Wierman, ME AF Rosner, William Hankinson, Susan E. Sluss, Patrick M. Vesper, Hubert W. Wierman, Margaret E. TI Challenges to the Measurement of Estradiol: An Endocrine Society Position Statement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER RISK; ENDOGENOUS SEX-HORMONES; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; SERUM ESTRADIOL; DIRECT RADIOIMMUNOASSAYS; CIRCULATING ESTRADIOL; ENDOMETRIAL CANCER; ESTROGEN-RECEPTORS AB Objective: The objective of the study was to evaluate the current state of clinical assays for estradiol in the context of their applications. Participants: The participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Evidence: Data were gathered from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), and the clinical and laboratory experience of the participants. Consensus Process: The statement was an effort of the committee and was reviewed by each member. The Clinical Affairs Committee, the Council of The Endocrine Society, and JCEM reviewers reviewed the manuscript and made recommendations. Conclusions: The measurement of estradiol in biological fluids is important in human biology from cradle to grave. In addition to its centrality in sexual development, it has significant effects on skin, blood vessels, bone, muscle, coagulation, hepatic cells, adipose tissue, the kidney, the gastrointestinal tract, brain, lung, and pancreas. Alterations in its plasma concentration have been implicated in coronary artery disease, stroke, and breast cancer. Although modern immunoassays and liquid chromatography/tandem mass spectrometry-based methods for estradiol are reasonably well suited to the diagnosis and management of infertility (nonetheless, imprecision and method-to-method differences remain problematic), the very low concentrations that appear to be crucial in nonreproductive tissues are a separate and more difficult issue. Such levels of estradiol are too low to be routinely measured accurately or precisely, and further evolution of analytical methods and the way in which estradiol is standardized is needed. (J Clin Endocrinol Metab 98: 1376-1387, 2013) C1 [Rosner, William] Columbia Univ, Coll Phys & Surg, New York, NY 10019 USA. [Rosner, William] St Lukes Roosevelt Hosp, New York, NY 10019 USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Div Network Med, Boston, MA 02115 USA. [Sluss, Patrick M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Vesper, Hubert W.] US Ctr Dis Control & Prevent, Div Sci Lab, Clin Chem Branch, Atlanta, GA 30341 USA. [Wierman, Margaret E.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Wierman, Margaret E.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Rosner, W (reprint author), St Lukes Roosevelt Hosp, Dept Med, AJA 403,1000 10th Ave, New York, NY 10019 USA. EM wr7@columbia.edu FU National Institutes of Health [R01 CA49449, R01 CA6762] FX S.E.H. is funded by National Institutes of Health Grants R01 CA49449 and R01 CA6762. W.R., P.M.S., H.W.V., and M.E.W. have no conflicts to declare. NR 86 TC 80 Z9 83 U1 2 U2 20 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2013 VL 98 IS 4 BP 1376 EP 1387 DI 10.1210/jc.2012-3780 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120TJ UT WOS:000317195600038 PM 23463657 ER PT J AU Ackerman, KE Pierce, L Guereca, G Slattery, M Lee, H Goldstein, M Misra, M AF Ackerman, Kathryn E. Pierce, Lisa Guereca, Gabriela Slattery, Meghan Lee, Hang Goldstein, Mark Misra, Madhusmita TI Hip Structural Analysis in Adolescent and Young Adult Oligoamenorrheic and Eumenorrheic Athletes and Nonathletes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOUBLY LABELED WATER; NECK BONE STRENGTH; PHYSICAL-ACTIVITY; FEMORAL-NECK; OSTEOPOROTIC FRACTURES; NUTRIENT DATABASE; STRESS-FRACTURES; GEOMETRY; FEMUR; PREDICTION AB Context: Stress fractures are common in endurance athletes. Whereas studies have described distal tibia bone structure in athletes, there are few data regarding hip geometric parameters. Hip structural analysis (HSA) using dual-energy x-ray absorptiometry is a validated technique to assess hip bone structure. Objectives: The purpose of this study was to compare hip geometry in young oligoamenorrheic athletes (AAs), eumenorrheic athletes (EAs), and nonathletes using HSA. We hypothesized that AAs would have impaired bone structure compared with that of EAs. Design: This was a cross-sectional study. Setting: The setting was a clinical research center. Subjects: We enrolled 55 AAs, 24 EAs, and 23 nonathletes of normal weight who were 14 to 22 years old. Athletes ran >= 20 miles/wk or were engaged in weight-bearing sports for >= 4 hours/wk. Main Outcome Measures: Dual-energy x-ray absorptiometry was used for HSA and hip areal bone mineral density (aBMD). Results: Hip aBMD Z-scores were lower in AAs and in nonathletes than in EAs (P = .002). A larger proportion of AAs than EAs and nonathletes had hip Z-scores <-1 (30.9, 4.2, 17.4%, P = .01). At the narrow neck, trochanteric region, and femoral shaft, subperiosteal width, cross-sectional moment of inertia, and section modulus were higher in EAs than in nonathletes; values in AAs did not differ from those of nonathletes. Cross-sectional area was lower in AAs and in nonathletes than in EAs. Groups did not differ for cortical thickness or buckling ratio. Group differences were lost after adjustment for lean mass but not aBMD. Conclusions: In an eugonadal state, athletic activity confers benefits for hip structure independent of aBMD. This advantage is lost in AAs, who do not differ from nonathletes for most parameters and fare worse than EAs for cross-sectional area. (J Clin Endocrinol Metab 98: 1742-1749, 2013) C1 [Ackerman, Kathryn E.; Pierce, Lisa; Guereca, Gabriela; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. [Goldstein, Mark] Massachusetts Gen Hosp, Dept Med, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA 02116 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU National Institutes of Health [1 UL1 RR025758, 1 R01 HD060827, 1 K24 HD071843] FX This work was supported by the National Institutes of Health (Grants 1 UL1 RR025758, 1 R01 HD060827, and 1 K24 HD071843). NR 30 TC 8 Z9 8 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2013 VL 98 IS 4 BP 1742 EP 1749 DI 10.1210/jc.2013-1006 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120TJ UT WOS:000317195600081 PM 23476076 ER PT J AU Crandall, CJ Tseng, CH Karlamangla, AS Finkelstein, JS Randolph, JF Thurston, RC Huang, MH Zheng, HY Greendale, GA AF Crandall, Carolyn J. Tseng, Chi-Hong Karlamangla, Arun S. Finkelstein, Joel S. Randolph, John F., Jr. Thurston, Rebecca C. Huang, Mei-Hua Zheng, Huiyong Greendale, Gail A. TI Serum Sex Steroid Levels and Longitudinal Changes in Bone Density in Relation to the Final Menstrual Period SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING GLOBULIN; FOLLICLE-STIMULATING-HORMONE; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; MENOPAUSAL TRANSITION; VERTEBRAL FRACTURES; CIRCULATING ANDROGENS; PERIMENOPAUSAL WOMEN; ENDOGENOUS ESTRADIOL; ESTROGEN DEFICIENCY AB Context: The associations of serum sex steroid and FSH levels with change of bone mineral density (BMD) across the complete menopausal transition are incompletely understood. Objective: The objective of the study was to examine the associations of annual serum levels of FSH, estradiol (E-2), T, and SHBG with the rates of bone loss in 3 phases: pretransmenopausal [baseline to 1 year before the final menstrual period (FMP)], transmenopausal (1 year before to 2 years after the FMP), later postmenopausal (>= 2 years after the FMP). Design: The design of the study was a repeated-measures, mixed-effects regression. Setting: This was a community-based observational study, with a 10-year follow-up. Participants: A total of 720 participants of the Study of Women's Health Across the Nation Bone Study participated in the study. Outcome Measures: Annualized lumbar spine (LS) and femoral neck (FN) BMD decline was measured. Results: The mean annual change in BMD was slowest in pretransmenopause (0.27%/year in FN) and fastest in transmenopause (2.16%/year in LS). In the pretransmenopausal phase, for every doubling of FSH level, LS BMD change was faster by -0.32%/year (P < .0001). In the transmenopausal phase, for every doubling of FSH level, LS BMD change was -0.35%/year faster (P < .0001); for every doubling of SHBG level, LS BMD change was -0.36%/year faster (P < .0001). In the later postmenopausal phase, for each doubling of the E-2 level, the LS BMD change was slower by +0.26%/year (P = .049); for each SHBG doubling, the LS BMD change was 0.21%/year slower (P = .048). The FN associations were weaker and inconsistent. Conclusions: Higher E-2 levels and lower FSH levels were associated with lower rates of LS bone loss in some but not all menopausal transition phases. (J Clin Endocrinol Metab 98: E654-E663, 2013) C1 [Crandall, Carolyn J.; Tseng, Chi-Hong] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. [Karlamangla, Arun S.; Huang, Mei-Hua; Greendale, Gail A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90024 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Randolph, John F., Jr.] Univ Michigan Hlth Syst, Div Reprod Endocrinol & Infertil, Ann Arbor, MI 48109 USA. [Zheng, Huiyong] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Thurston, Rebecca C.] Univ Pittsburgh, Sch Med, Dept Psychiat & Epidemiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Crandall, CJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Univ Calif Los Angeles Med GIM, 911 Broxton Ave,1st Floor, Los Angeles, CA 90024 USA. EM ccrandall@mednet.ucla.edu FU National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495] FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. NR 58 TC 5 Z9 5 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2013 VL 98 IS 4 BP E654 EP E663 DI 10.1210/jc.2012-3651 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120TJ UT WOS:000317195600006 PM 23443812 ER PT J AU Tsai, CL Lee, WY Delclos, GL Hanania, NA Camargo, CA AF Tsai, Chu-Lin Lee, Wen-Ya Delclos, George L. Hanania, Nicola A. Camargo, Carlos A., Jr. TI Comparative Effectiveness of Noninvasive Ventilation vs Invasive Mechanical Ventilation in Chronic Obstructive Pulmonary Disease Patients With Acute Respiratory Failure SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; POSITIVE-PRESSURE VENTILATION; ACUTE EXACERBATIONS; UNITED-STATES; WARD; MULTICENTER; OUTCOMES; SUCCESS; COPD AB BACKGROUND Limited evidence exists on the comparative effectiveness of noninvasive ventilation (NIV) vs invasive mechanical ventilation (IMV) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with respiratory failure. OBJECTIVES To characterize the use of NIV and IMV, and to compare the effectiveness of NIV vs IMV in AECOPD. DESIGN AND PATIENTS Retrospective cohort study using data from the 20062008 Nationwide Emergency Department Sample. Emergency department visits for AECOPD with acute respiratory failure were identified with codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. MEASURES The outcome measures were inpatient mortality, hospital length of stay, hospital charges, and complications. RESULTS There were an estimated 101,000 visits annually for AECOPD with acute respiratory failure; 96% were admitted to the hospital. Of these, NIV use increased from 14% in 2006 to 16% in 2008 (P=0.049). Use of NIV, however, varied widely between hospitals, ranging from 0% to 100% with a median of 11%. Noninvasive ventilation was more often used in highercase volume, Northeastern hospitals. In a propensity score analysis, NIV use, compared with IMV, was associated with lower inpatient mortality (risk ratio: 0.54, 95% confidence interval [CI]: 0.50-0.59), shortened hospital length of stay (3.2 days; 95% CI: 3.4 to 2.9 days), lower hospital charges ($35,012; 95% CI: $36,848 to $33,176), and lower risk of iatrogenic pneumothorax (0.05% vs 0.5%, P<0.001). CONCLUSIONS Although NIV use is increasing in US hospitals, its adoption remains low and varies widely between hospitals. Our observational study suggests NIV appears to be more effective and safer than IMV for AECOPD in the real-world setting. Journal of Hospital Medicine 2013;8:165172. (c) 2013 Society of Hospital Medicine C1 [Tsai, Chu-Lin; Lee, Wen-Ya; Delclos, George L.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Hanania, Nicola A.] Baylor Coll Med, Dept Med, Sect Pulm & Crit Care Med, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Tsai, CL (reprint author), Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, 1200 Herman Pressler,Suite W610, Houston, TX 77030 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality [R03HS020722] FX Partial results from this study were presented at the 2012 Society for Academic Emergency Medicine Annual Meeting, Chicago, Illinois, May 9-12, 2012. This project was supported by grant number R03HS020722 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. The authors have no conflicts of interest to disclose. NR 44 TC 12 Z9 15 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2013 VL 8 IS 4 BP 165 EP 172 DI 10.1002/jhm.2014 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 122ED UT WOS:000317298700001 PM 23401469 ER PT J AU Yallampalli, R Wilde, EA Bigler, ED McCauley, SR Hanten, G Troyanskaya, M Hunter, JV Chu, ZL Li, XQ Levin, HS AF Yallampalli, Ragini Wilde, Elisabeth A. Bigler, Erin D. McCauley, Stephen R. Hanten, Gerri Troyanskaya, Maya Hunter, Jill V. Chu, Zili Li, Xiaoqi Levin, Harvey S. TI Acute White Matter Differences in the Fornix Following Mild Traumatic Brain Injury Using Diffusion Tensor Imaging SO JOURNAL OF NEUROIMAGING LA English DT Article DE Diffusion tensor imaging; mild traumatic brain injury; fornix ID AXONAL INJURY; HIPPOCAMPAL; CONCUSSION; RESPONSES; ATROPHY; MEMORY AB The integrity of the fornix using diffusion tensor imaging (DTI) in adolescent participants with acute mild traumatic brain injury (mTBI) compared to a demographically matched control group was examined. Fractional anisotropy (FA) in the fornix was elevated in the mild traumatic brain injured group. Performance on the Automated Neuropsychological Assessment Metrics (ANAM) was lower in the group with mTBI. A relation was found between lower performance on cognitive tasks and higher FA. The potential role of fornix injury as a basis of memory and processing speed deficits in mTBI is discussed. C1 [Yallampalli, Ragini; Wilde, Elisabeth A.; McCauley, Stephen R.; Hanten, Gerri; Troyanskaya, Maya; Li, Xiaoqi; Levin, Harvey S.] Baylor Coll Med, Phys Med & Rehabil Alliance, Houston, TX 77030 USA. [Yallampalli, Ragini; Wilde, Elisabeth A.; McCauley, Stephen R.; Hanten, Gerri; Troyanskaya, Maya; Li, Xiaoqi; Levin, Harvey S.] Univ Texas Houston, Sch Med, Houston, TX USA. [Wilde, Elisabeth A.; McCauley, Stephen R.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Wilde, Elisabeth A.; Hunter, Jill V.; Chu, Zili] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [McCauley, Stephen R.; Levin, Harvey S.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Wilde, Elisabeth A.; Hunter, Jill V.; Chu, Zili] Texas Childrens Hosp, Dept Pediat Radiol, Houston, TX 77030 USA. [Wilde, Elisabeth A.; McCauley, Stephen R.; Troyanskaya, Maya; Levin, Harvey S.] Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Yallampalli, Ragini] Univ Houston, Dept Psychol, Houston, TX USA. [Bigler, Erin D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Bigler, Erin D.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Bigler, Erin D.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Bigler, Erin D.] Univ Utah, Utah Brain Inst, Salt Lake City, UT USA. RP Wilde, EA (reprint author), Baylor Coll Med, 1709 Dryden Rd,Ste 1200, Houston, TX 77030 USA. EM ewilde@bcm.edu FU National Institutes of Health [NS056202-02] FX This research was supported by Grant NS056202-02 awarded to Harvey S. Levin by the National Institutes of Health. We would also like to acknowledge the generous support by Mission Connect of the TIRR Foundation. We would also like to thank the patients and their families for involvement in this study. The information in this manuscript and the manuscript itself has never been published either electronically or in print. None of the authors have any financial or other relationship(s) that could be construed as a conflict of interest with respect to the content of this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 30 TC 23 Z9 23 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2013 VL 23 IS 2 BP 224 EP 227 DI 10.1111/j.1552-6569.2010.00537.x PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 126LN UT WOS:000317617800016 PM 21988147 ER PT J AU Shaikhouni, A Donoghue, JP Hochberg, LR AF Shaikhouni, Ammar Donoghue, John P. Hochberg, Leigh R. TI Somatosensory responses in a human motor cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE brain machine interfaces; decoding; stroke; plasticity ID REORGANIZATION FOLLOWING MOTOR; PYRAMIDAL TRACT NEURONS; SENSORIMOTOR CORTEX; PRECENTRAL CORTEX; SENSORY INPUT; UNANESTHETIZED MONKEY; SPATIAL-ORGANIZATION; DYNAMIC ORGANIZATION; CONSCIOUS MONKEYS; TARGET MUSCLES AB Shaikhouni A, Donoghue JP, Hochberg LR. Somatosensory responses in a human motor cortex. J Neurophysiol 109: 2192-2204, 2013. First published January 23, 2013; doi:10.1152/jn.00368.2012.-Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. C1 [Shaikhouni, Ammar; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Shaikhouni, Ammar; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Donoghue, John P.; Hochberg, Leigh R.] Ctr Neurorestorat & Neurotechnol, Dept Vet Affairs, Providence, RI USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. RP Shaikhouni, A (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, N1014 Doan Hall,410 West 10th Ave, Columbus, OH 43210 USA. EM ammar.shaikhouni@osumc.edu FU Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs; National Institutes of Health [N01 HD-53403, RC1 HD-063931, R01 DC-009899, R01 EB-007401, NS-25074]; National Center for Research Resources [C06 16549-01A1]; Doris Duke Charitable Foundation; Massachusetts General Hospital-Deane Institute of Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation; Cyberkinetics Neurotechnology Systems, Inc.; Massachusetts General and Spaulding Rehabilitation Hospitals; CKI FX This work is supported by the Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs. Additional support is provided by National Institutes of Health Grants N01 HD-53403, RC1 HD-063931, R01 DC-009899, R01 EB-007401, and NS-25074; National Center for Research Resources Grant C06 16549-01A1; the Doris Duke Charitable Foundation; the Massachusetts General Hospital-Deane Institute of Integrated Research on Atrial Fibrillation and Stroke; and the Katie Samson Foundation.; The pilot clinical trial from which these data are derived was sponsored in part by Cyberkinetics Neurotechnology Systems, Inc. J. P. Donoghue is a former Chief Scientific Officer and director of Cyberkinetics Neurotechnology Systems, Inc. (CKI); he held stocks and received compensation. L. R. Hochberg received research support from Massachusetts General and Spaulding Rehabilitation Hospitals, which in turn received clinical trial support from CKI. A. Shaikhouni was a contracted consultant for CKI and received compensation. CKI ceased operations in 2009. NR 60 TC 6 Z9 6 U1 2 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2013 VL 109 IS 8 BP 2192 EP 2204 DI 10.1152/jn.00368.2012 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 125XG UT WOS:000317574700019 PM 23343902 ER PT J AU Maule, AL Heaton, KJ Rodrigues, E Smith, KW McClean, MD Proctor, SP AF Maule, Alexis L. Heaton, Kristin J. Rodrigues, Ema Smith, Kristen W. McClean, Michael D. Proctor, Susan P. TI Postural Sway and Exposure to Jet Propulsion Fuel 8 Among US Air Force Personnel SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CLINICAL BALANCE TESTS; TRUNK SWAY; INHALATION EXPOSURE; URINARY BIOMARKERS; SOLVENT EXPOSURE; DERMAL EXPOSURE; WORKERS; JP-8; STABILITY; GAIT AB Objective: To determine whether short-term jet propulsion fuel 8 (JP-8) exposure is associated with balance measurements in JP-8-exposed air force personnel. Methods: As part of a larger neuroepidemiology study, balance tasks were completed by JP-8 exposed individuals (n = 37). Short-term JP-8 exposure was measured using personal breathing zone levels and urinary biomarkers. Multivariate linear regression analyses were conducted to examine the relationship between workday JP-8 exposure and postural sway. Results: Balance control decreased as the task became more challenging. Workday exposure to JP-8, measured by either personal air or urinary metabolite levels, was not significantly related to postural sway. Increases in workday postural sway were associated with demographic variables, including younger age, being a current smoker, and higher body mass index. Conclusion: Results suggest that short-term workday JP-8 exposure does not significantly contribute to diminished balance control. C1 [Maule, Alexis L.; Heaton, Kristin J.; Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Heaton, Kristin J.; Proctor, Susan P.] USA, Environm Med Res Inst, Natick, MA 01760 USA. [Rodrigues, Ema; Smith, Kristen W.; McClean, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Boston, MA USA. RP Proctor, SP (reprint author), USA, Mil Performance Div, Environm Med Res Inst, Kansas St,Bldg 42, Natick, MA 01760 USA. EM susan.proctor@us.army.mil RI sebastianovitsch, stepan/G-8507-2013; Heaton, Kristin/E-3660-2013; McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823 FU US Air Force; US Army Medical Research and Materiel Command/Neurotoxin Exposure Treatment Program [W81XWH-06-1-0105] FX The authors thank the US Air Force personnel for their support and generous participation in the project. They thank the additional Boston area study team personnel (N. Longcore, E. Kryskow, K. Merchant-Borna, H. MacDonald, and A. Graefe) and other personnel from local universities for their assistance in data collection at the respective US Air Force base locations. This work was supported by the US Army Medical Research and Materiel Command/Neurotoxin Exposure Treatment Program though a grant award (W81XWH-06-1-0105; principal investigator: S.P. Proctor) to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. NR 34 TC 3 Z9 3 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2013 VL 55 IS 4 BP 446 EP 453 DI 10.1097/JOM.0b013e31827db94b PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 124BT UT WOS:000317439500011 PM 23532195 ER PT J AU Collins, E Ebert, J Hentzen, K Johnson, D Stevenson, K AF Collins, E. Ebert, J. Hentzen, K. Johnson, D. Stevenson, K. TI Development of a telephone clinic for the management of neuropathic pain SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Collins, E.; Ebert, J.; Hentzen, K.; Johnson, D.; Stevenson, K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 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 2013 VL 14 IS 4 SU 1 BP S39 EP S39 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RR UT WOS:000317639400154 ER PT J AU Loggia, M Renella, CB Kim, J Cahalan, C Gollub, R Wasan, A Edwards, R Napadow, V AF Loggia, M. Renella, C. Berna Kim, J. Cahalan, C. Gollub, R. Wasan, A. Edwards, R. Napadow, V. TI Brain processing of pain and expectancy of relief in fibromyalgia is modulated by catastrophizing SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Loggia, M.; Renella, C. Berna; Kim, J.; Cahalan, C.; Gollub, R.; Wasan, A.; Edwards, R.; Napadow, V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 2013 VL 14 IS 4 SU 1 BP S49 EP S49 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RR UT WOS:000317639400192 ER PT J AU Sein, M Chen, L AF Sein, M. Chen, L. TI Opioid-induced hyperalgesia: the primary care physician's perspective SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Sein, M.; Chen, L.] Massachusetts Gen Hosp, Ctr Translat Pain Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 2013 VL 14 IS 4 SU 1 BP S5 EP S5 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RR UT WOS:000317639400021 ER PT J AU Hung, EW Mayes, MD Sharif, R Assassi, S Machicao, VI Hosing, C St Clair, EW Furst, DE Khanna, D Forman, S Mineishi, S Phillips, K Seibold, JR Bredeson, C Csuka, ME Nash, RA Wener, MH Simms, R Ballen, K Leclercq, S Storek, J Goldmuntz, E Welch, B Keyes-Elstein, L Castina, S Crofford, LJ Mcsweeney, P Sullivan, KM AF Hung, Emily W. Mayes, Maureen D. Sharif, Roozbeh Assassi, Shervin Machicao, Victor I. Hosing, Chitra St Clair, E. William Furst, Daniel E. Khanna, Dinesh Forman, Stephen Mineishi, Shin Phillips, Kristine Seibold, James R. Bredeson, Christopher Csuka, Mary Ellen Nash, Richard A. Wener, Mark H. Simms, Robert Ballen, Karen Leclercq, Sharon Storek, Jan Goldmuntz, Ellen Welch, Beverly Keyes-Elstein, Lynette Castina, Sharon Crofford, Leslie J. Mcsweeney, Peter Sullivan, Keith M. TI Gastric Antral Vascular Ectasia and Its Clinical Correlates in Patients with Early Diffuse Systemic Sclerosis in the SCOT Trial SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GASTRIC ANTRAL VASCULAR ECTASIA; GAVE; SYSTEMIC SCLEROSIS; VASCULOPATHY; ENDOSCOPY ID WATERMELON STOMACH; GAVE; CYCLOPHOSPHAMIDE AB Objective. To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; "watermelon stomach") in early diffuse systemic sclerosis (SSc). Methods. Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. Results. Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Sc170) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). Conclusion. Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Sc170 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc. (J Rheurnatol First Release Feb 15 2013; doi:10.3899/jrheum.121087) C1 [Hung, Emily W.] Rheumatol Associates Houston, Houston, TX USA. [Mayes, Maureen D.; Assassi, Shervin; Machicao, Victor I.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Sharif, Roozbeh] Univ Texas Med Branch, Galveston, TX 77555 USA. [Hosing, Chitra] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [St Clair, E. William; Sullivan, Keith M.] Duke Univ, Durham, NC USA. [Furst, Daniel E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Khanna, Dinesh; Mineishi, Shin; Phillips, Kristine] Univ Michigan, Ann Arbor, MI 48109 USA. [Forman, Stephen] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Seibold, James R.] Scleroderma Res Consultants LLC, Avon, CT USA. [Bredeson, Christopher] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Csuka, Mary Ellen] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Nash, Richard A.; Mcsweeney, Peter] Colorado Blood Canc Inst, Rocky Mt Blood & Marrow Transplant Program, Denver, CO USA. [Wener, Mark H.] Univ Washington, Seattle, WA 98195 USA. [Simms, Robert] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leclercq, Sharon; Storek, Jan] Univ Calgary, Calgary, AB, Canada. [Goldmuntz, Ellen; Welch, Beverly] NIAID, NIH, Bethesda, MD 20892 USA. [Keyes-Elstein, Lynette; Castina, Sharon] Rho, Chapel Hill, NC USA. [Crofford, Leslie J.] Univ Kentucky, Lexington, KY USA. RP Mayes, MD (reprint author), Univ Texas Hlth Sci Ctr Houston, 6431 Fannin St,Med Sch Bldg 5-270, Houston, TX 77030 USA. EM Maureen.d.mayes@uth.unc.edu RI Crofford, Leslie/J-8010-2013; OI Simms, Robert/0000-0002-0101-1807; Hosing, Chitra/0000-0003-0409-5556 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases (USA) [A1-05419, HHSN272201100025C] FX Supported by awards A1-05419 and HHSN272201100025C from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (USA). NR 15 TC 16 Z9 16 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2013 VL 40 IS 4 BP 455 EP 460 DI 10.3899/jrheum.121087 PG 6 WC Rheumatology SC Rheumatology GA 125LF UT WOS:000317540600018 PM 23418384 ER PT J AU Prowse, RL Dalbeth, N Kavanaugh, A Adebajo, AO Gaffo, AL Terkeltaub, R Mandell, BF Suryana, BPP Goldenstein-Schainberg, C Diaz-Torne, C Khanna, D Liote, F Mccarthy, G Kerr, GS Yamanaka, H Janssens, H Baraf, HF Chen, JH Vazquez-Mellado, J Harrold, LR Stamp, LK Van de Laar, MA Janssen, M Doherty, M Boers, M Edwards, NL Gow, P Chapman, P Khanna, P Helliwell, PS Grainger, R Schumacher, HR Neogi, T Jansen, TL Louthrenoo, W Sivera, F Taylor, WJ AF Prowse, Rebecca L. Dalbeth, Nicola Kavanaugh, Arthur Adebajo, Adewale O. Gaffo, Angelo L. Terkeltaub, Robert Mandell, Brian F. Suryana, Bagus P. P. Goldenstein-Schainberg, Claudia Diaz-Torne, Cesar Khanna, Dinesh Liote, Frederic Mccarthy, Geraldine Kerr, Gail S. Yamanaka, Hisashi Janssens, Hein Baraf, Herbert F. Chen, Jiunn-Horng Vazquez-Mellado, Janitzia Harrold, Leslie R. Stamp, Lisa K. Van de Laar, Mart A. Janssen, Matthijs Doherty, Michael Boers, Maarten Edwards, N. Lawrence Gow, Peter Chapman, Peter Khanna, Puja Helliwell, Philip S. Grainger, Rebecca Schumacher, H. Ralph Neogi, Tuhina Jansen, Tim L. Louthrenoo, Worawit Sivera, Francisca Taylor, William J. TI A Delphi Exercise to Identify Characteristic Features of Gout - Opinions from Patients and Physicians, the First Stage in Developing New Classification Criteria SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; CLASSIFICATION; CRITERIA; PATIENTS; PHYSICIANS ID DIAGNOSTIC-CRITERIA; FLUID ANALYSIS; RHEUMATOLOGY; PREVALENCE; ARTHRITIS; HEALTH AB Objective. To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout. Methods. Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index. Results. Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory. Conclusion. Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms. (First Release Feb 15 2013; J Rheumatol 2013;40:498-505; doi:10.3899/jrheum.121037) C1 Univ Otago, Dunedin, New Zealand. [Dalbeth, Nicola] Univ Auckland, Auckland 1, New Zealand. [Kavanaugh, Arthur] Univ Calif San Diego, Vet Affairs Healthcare Syst, San Diego, CA 92103 USA. [Adebajo, Adewale O.] Univ Sheffield, Sheffield, S Yorkshire, England. Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. [Mandell, Brian F.] Case Western Reserve Univ, Cleveland Clin, CCF Lerner Coll Med, Cleveland, OH 44106 USA. Brawijaya Univ, Malang, Indonesia. Dr Saiful Anwar Hosp, Malang, Indonesia. Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo, Brazil. [Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Khanna, Dinesh; Stamp, Lisa K.] Univ Michigan, Ann Arbor, MI 48109 USA. Univ Paris Diderot, Paris, France. Hop Lariboisiere, F-75475 Paris, France. [Mccarthy, Geraldine] Univ Coll Dublin, Dublin 2, Ireland. Georgetown Univ, Vet Affairs Med Ctr, Washington, DC USA. [Kerr, Gail S.] Howard Univ, Vet Affairs Med Ctr, Washington, DC 20059 USA. [Yamanaka, Hisashi] Tokyo Womens Med Univ, Tokyo, Japan. [Janssens, Hein] Radboud Univ Nijmegen, Med Ctr, Dept Primary & Community Care, NL-6525 ED Nijmegen, Netherlands. [Baraf, Herbert F.] Arthrit & Rheumatism Associates, Ctr Rheumatol & Bone Res, Wheaton, MA USA. [Chen, Jiunn-Horng] China Med Univ, China Med Univ Hosp, Taichung, Taiwan. [Vazquez-Mellado, Janitzia] Hosp Gen Mexico City, Mexico City, DF, Mexico. [Harrold, Leslie R.] Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Otago, Christchurch, New Zealand. [Van de Laar, Mart A.] Med Spectrum Twente, Dept Rheumatol & Clin Immunol, Enschede, Netherlands. [Janssen, Matthijs] Rijnstate, Dept Rheumatol, Arnhem, Netherlands. [Doherty, Michael] Univ Nottingham, Nottingham NG7 2RD, England. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Edwards, N. Lawrence] Univ Florida, Gainesville, FL USA. [Gow, Peter] Counties Manukau Dist Hlth Board, Auckland, New Zealand. [Chapman, Peter] Canterbury Dist Hlth Board, Christchurch, New Zealand. [Helliwell, Philip S.] Univ Leeds, Leeds, W Yorkshire, England. Univ Otago, Wellington, New Zealand. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Jansen, Tim L.] Radboud Univ Nijmegen, Med Centrum, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands. [Louthrenoo, Worawit] Chiang Mai Univ, Chiang Mai 50000, Thailand. Hosp Gen Elda, Alicante, Spain. Univ Miguel Hernandez, Alicante, Spain. RP Taylor, WJ (reprint author), Univ Otago Wellington, Dept Med, POB 7343, Wellington 6242, New Zealand. EM Will.taylor@otago.ac.nz RI Jansen, T.L.Th.A./L-4407-2015; OI Cesar, Diaz-Torne/0000-0001-6275-7699; Jansen, Tim/0000-0003-3026-3154; Neogi, Tuhina/0000-0002-9515-1711 FU Arthritis New Zealand FX R. Prowse was supported by a Summer Student Scholarship from Arthritis New Zealand. Dr. Kerr has participated in gout trials by Savient, Nuon, and Ardea. Dr. Doherty is a member of advisory boards for Ardea Biosciences, Ipsen, Menarini, Novartis, and Savient. NR 18 TC 14 Z9 16 U1 0 U2 7 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2013 VL 40 IS 4 BP 498 EP 505 DI 10.3899/jrheum.121037 PG 8 WC Rheumatology SC Rheumatology GA 125LF UT WOS:000317540600024 PM 23418379 ER PT J AU Hawryluk, EB O'Regan, KN Sheehy, N Guo, Y Dorosario, A Sakellis, CG Jacene, HA Wang, LDC AF Hawryluk, Elena B. O'Regan, Kevin N. Sheehy, Niall Guo, Ye Dorosario, Andrew Sakellis, Christopher G. Jacene, Heather A. Wang, Linda C. TI Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: A study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women's Cancer Center SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-05, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) DE computed tomography; 2-fluoro-[F-18]-deoxy-2-D-glucose; imaging; Merkel cell carcinoma; metastasis; positron emission tomography; staging ID F-18-FDG PET; MANAGEMENT; MELANOMA; FEATURES; IMPACT AB Background: Merkel cell carcinoma (MCC) is a rare and lethal cutaneous neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains a strong predictor of survival, as well as earlier detection of recurrence and progression, which are common despite aggressive management. There is no consensus on the role of initial and subsequent imaging for MCC. Objective: We sought to evaluate the use of 2-fluoro-[F-18]-deoxy-2-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the management of MCC. Methods: In all, 270 FDG-PET/CT studies were performed in 97 patients with pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center, Boston, Mass, from August 2003 to December 2010. Results: FDG-PET/CT scans were obtained as part of the initial (61 scans in 61 patients) and subsequent (209 scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and a mean maximum standardized uptake value of regional and distant metastases of 7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more common than previously reported, and were often undetected by CT. Limitations: Our study is limited by its retrospective design, and potential referral bias associated with a tertiary care center. Conclusions: FDG-PET/CT performed as part of the initial management strategy tended to upstage patients with more advanced disease. FDG-PET/CT performed as part of the subsequent treatment strategy identified metastatic disease, particularly in bone/bone marrow, which was not seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC management. (J Am Acad Dermatol 2013;68:592-9.) C1 [Hawryluk, Elena B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [O'Regan, Kevin N.; Sheehy, Niall; Sakellis, Christopher G.; Jacene, Heather A.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Imaging, Boston, MA USA. [Guo, Ye; Wang, Linda C.] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Dorosario, Andrew; Wang, Linda C.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Ctr Cutaneous Oncol, Boston, MA USA. RP Wang, LDC (reprint author), Mercy Med Ctr, Inst Canc Care, 301 St Paul Pl,McAuley POB,Suite 607, Baltimore, MD 21202 USA. EM lwang@mdmercy.com NR 27 TC 22 Z9 22 U1 0 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 2013 VL 68 IS 4 BP 592 EP 599 DI 10.1016/j.jaad.2012.08.042 PG 8 WC Dermatology SC Dermatology GA 120VL UT WOS:000317201100018 PM 23127473 ER PT J AU Liu, ZC Li, YQ Liu, BL Deperalta, DK Zhao, T Chong, W Duan, XZ Zhou, P Velmahos, GC Alam, HB AF Liu, Zhengcai Li, Yongqing Liu, Baoling Deperalta, Danielle K. Zhao, Ting Chong, Wei Duan, Xiuzhen Zhou, Peter Velmahos, George C. Alam, Hasan B. TI Synergistic effects of hypertonic saline and valproic acid in a lethal rat two-hit model SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the American-Association-for-the-Surgery-of-Trauma / Clinical Congress of Acute Care Surgery CY SEP 12-15, 2012 CL Kauai, HI SP Amer Assoc Surg Trauma DE Hemorrhagic shock; sepsis; valproic acid; hypertonic saline; rats ID ACUTE LUNG INJURY; HEMORRHAGIC-SHOCK; FLUID RESUSCITATION; NEUTROPHIL ACTIVATION; CECAL LIGATION; RODENT MODEL; SEPSIS; INFLAMMATION; TRAUMA; PENTRAXIN-3 AB BACKGROUND: Hemorrhagic shock (HS) followed by an infection ("second hit") can lead to severe systemic inflammatory response and multiple-organ failure. Studies have shown that resuscitation with hypertonic saline (HTS) can blunt the inflammatory response. We demonstrated that large doses of valproic acid (VPA, 300 mg/kg), a histone deacetylase inhibitor, improves survival in a rodent two-hit model (HS followed by cecal ligation and puncture [CLP]). In the present study, we examined whether combination of HTS with VPA would allow us to achieve survival advantage at a lower dose of VPA (200 mg/kg). METHODS: Male Sprague-Dawley rats were subjected to HS (50% blood loss) and randomized into five groups (n = 7-8 per group) as follows: (1) isotonic sodium chloride solution (ISCS), (2) 7.5% saline, (3) VPA, (4) ISCS + VPA, and (5) HTS + VPA. After 24 hours, they underwent CLP, followed by the same doses of ISCS, HTS, and/or VPA and were monitored for 10 days. In a parallel experiment, blood, peritoneal irrigation fluid and lung homogenate were subjected to enzyme-linked immunosorbent assay 3 hours and 24 hours after CLP to measure myeloperoxidase activity and proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta levels. Western blotting was performed to investigate the expression of pentraxin 3 protein in the lung homogenate at 24 hours after CLP. Hematoxylin and eosin staining of lungs at the 24 hours were performed to quantify the degree of acute lung injury. RESULTS: HTS + VPA treatment significantly improved survival (87.5%), compared with the other groups (14.3%; p < 0.05), while attenuating peritoneal myeloperoxidase levels and proinflammatory cytokine tumor necrosis factor alpha and interleukin 1 beta levels in the serum, peritoneal cavity, and lung. The degree of acute lung injury and expression of pentraxin 3 in the lung were significantly reduced in the HTS + VPA group. CONCLUSION: This is the first study to show that VPA and HTS can work synergistically to attenuate inflammation and improve survival in a lethal two-hit model. (J Trauma Acute Care Surg. 2013;74: 991-998. Copyright (c) 2013 by Lippincott Williams & Wilkins) C1 [Liu, Zhengcai; Li, Yongqing; Liu, Baoling; Deperalta, Danielle K.; Zhao, Ting; Chong, Wei; Zhou, Peter; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02115 USA. [Duan, Xiuzhen] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Alam, Hasan B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Chong, Wei] China Med Univ, Hosp 1, Emergency Dept, Shenyang, Peoples R China. [Liu, Zhengcai] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Peoples R China. RP Alam, HB (reprint author), Univ Michigan Hosp, Sect Gen Surg, 2920 Taubman Center-5331,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU NIGMS NIH HHS [R01 GM084127] NR 40 TC 7 Z9 8 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD APR PY 2013 VL 74 IS 4 BP 991 EP 997 DI 10.1097/TA.0b013e31828583e3 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 123SS UT WOS:000317411700009 PM 23511136 ER PT J AU Gilstrap, LG Malhotra, R Peltier-Saxe, D Slicas, D Pineda, E Culhane-Hermann, C Cook, N Fernandez-Golarz, C Wood, M AF Gilstrap, Lauren Gray Malhotra, Rajeev Peltier-Saxe, Donna Slicas, Donna Pineda, Eliana Culhane-Hermann, Catherine Cook, Nakela Fernandez-Golarz, Carina Wood, Malissa TI Community-Based Primary Prevention Programs Decrease the Rate of Metabolic Syndrome Among Socioeconomically Disadvantaged Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR-DISEASE; LIFE-STYLE; RISK; METAANALYSIS; PREVALENCE; HEALTH; TRENDS AB Background: Metabolic Syndrome (MetSyn) is one of the strongest predictors of type 2 diabetes (DM2) and cardiovascular disease (CVD). It is associated with a 4- to 10-fold increased risk of DM2 and a 2- to 3-fold increased risk of CVD. Low income and minority women have some of the highest rates of MetSyn. This study examines the effect of a unique, community based, primary prevention program on the rates of MetSyn and health habits. Methods: Sixty-four low income and minority women were enrolled in the HAPPY (Health Awareness and Primary Prevention in Your neighborhood) Heart Program in an eastern suburb of Boston. Over these 2 years, patients were evaluated by an interdisciplinary medical team: their primary physician, cardiologist, nutritionist, physical therapist, and health coach. The rate of MetSyn was measured at baseline, year 1, and year 2. Comparisons were made either using the paired t test for normally distributed variables or the Wilcoxon Sign test for non-normal variables. Results: The rate of MetSyn fell from 64.7% at baseline to 34.9% at year 1 (p = 0.01) and 28.2% at year 2 (p < 0.001). This was driven by increases in high-density lipoprotein (HDL-C) (p < 0.001) and decreases in blood pressure (p = 0.05). Fasting blood glucose trended down, but the hemoglobin A1c (HbA1c) reached significance (decreasing from 6 to 5.8, p < 0.01). Nutrition and exercise habits trended toward improvement. There were significant decreases in anxiety (p < 0.001), depression (p = 0.006) and stress (p = 0.002). Conclusion: This lifestyle intervention program is effective at decreasing MetSyn in a socioeconomically disadvantaged, largely minority, female population. This program also decreases anxiety, stress, and depression among participants. C1 [Gilstrap, Lauren Gray; Malhotra, Rajeev; Fernandez-Golarz, Carina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Malhotra, Rajeev; Wood, Malissa] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Peltier-Saxe, Donna; Slicas, Donna; Pineda, Eliana; Culhane-Hermann, Catherine] Massachusetts Gen Hosp, Revere Hlth Ctr, Boston, MA 02114 USA. [Cook, Nakela] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gilstrap, LG (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM lgilstrap@partners.org OI Malhotra, Rajeev/0000-0003-0120-4630 NR 36 TC 3 Z9 3 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2013 VL 22 IS 4 BP 322 EP 329 DI 10.1089/jwh.2012.3854 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 126FZ UT WOS:000317599700006 PM 23540328 ER PT J AU Galimberti, V Cole, BF Zurrida, S Viale, G Luini, A Veronesi, P Baratella, P Chifu, C Sargenti, M Intra, M Gentilini, O Mastropasqua, MG Mazzarol, G Massarut, S Garbay, JR Zgajnar, J Galatius, H Recalcati, A Littlejohn, D Bamert, M Colleoni, M Price, KN Regan, MM Goldhirsch, A Coates, AS Gelber, RD Veronesi, U AF Galimberti, Viviana Cole, Bernard F. Zurrida, Stefano Viale, Giuseppe Luini, Alberto Veronesi, Paolo Baratella, Paola Chifu, Camelia Sargenti, Manuela Intra, Mattia Gentilini, Oreste Mastropasqua, Mauro G. Mazzarol, Giovanni Massarut, Samuele Garbay, Jean-Remi Zgajnar, Janez Galatius, Hanne Recalcati, Angelo Littlejohn, David Bamert, Monika Colleoni, Marco Price, Karen N. Regan, Meredith M. Goldhirsch, Aron Coates, Alan S. Gelber, Richard D. Veronesi, Umberto CA Int Breast Canc Study Grp Trial 23 TI Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial SO LANCET ONCOLOGY LA English DT Article ID INTERNATIONAL EXPERT CONSENSUS; EARLY BREAST-CANCER; PRIMARY THERAPY; AMERICAN-COLLEGE; LYMPH-NODES; BIOPSY; HIGHLIGHTS; METASTASES; INVOLVEMENT; RECURRENCE AB Background For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (<= 2 mm) sentinel nodes and tumour of maximum 5 cm. Methods In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (<= 2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1.25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. Findings Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5.0 (IQR 3.6-7.3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and nine regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87.8% (95% CI 84.4-91.2) in the group without axillary dissection and 84.4% (80.7-88.1) in the group with axillary dissection (log-rank p=0.16; HR for no axillary dissection vs axillary dissection was 0.78, 95% CI 0.55-1.11, non-inferiority p=0.0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Interpretation Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. C1 [Galimberti, Viviana] European Inst Oncol, Mol Senol Unit, Senol Div, I-20141 Milan, Italy. [Zurrida, Stefano] European Inst Oncol, Breast Diag & Surg Unit, Senol Div, I-20141 Milan, Italy. [Luini, Alberto; Baratella, Paola; Chifu, Camelia; Sargenti, Manuela; Intra, Mattia; Gentilini, Oreste] European Inst Oncol, Senol Div, I-20141 Milan, Italy. [Veronesi, Paolo] European Inst Oncol, Senol Div, Integrated Breast Surg Unit, I-20141 Milan, Italy. [Viale, Giuseppe; Mastropasqua, Mauro G.; Mazzarol, Giovanni] European Inst Oncol, Div Pathol & Lab Med, IBCSG Cent Pathol Off, I-20141 Milan, Italy. [Colleoni, Marco] European Inst Oncol, Res Unit Med Senol, Dept Med, I-20141 Milan, Italy. [Goldhirsch, Aron] European Inst Oncol, Dept Med, I-20141 Milan, Italy. [Veronesi, Umberto] European Inst Oncol, I-20141 Milan, Italy. [Cole, Bernard F.] Univ Vermont, Dept Math & Stat, Coll Engn & Math Sci, Burlington, VT 05405 USA. [Cole, Bernard F.; Price, Karen N.; Regan, Meredith M.; Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. [Viale, Giuseppe; Veronesi, Paolo] Univ Milan, Milan, Italy. [Massarut, Samuele] Ctr Riferimento Oncol, Breast Surg Div, I-33081 Aviano, Italy. [Garbay, Jean-Remi] Inst Gustave Roussy, Dept Surg, Villejuif, France. [Zgajnar, Janez] Inst Oncol, Dept Surg Oncol, Ljubljana, Slovenia. [Galatius, Hanne] Herlev Hosp, Dept Breastsurg, DK-2730 Herlev, Denmark. [Recalcati, Angelo] Osped Alessandro Manzoni, Dept Surg, Lecce, Italy. [Littlejohn, David] Riverina Canc Care Ctr, Wagga Wagga, NSW, Australia. [Bamert, Monika] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Centennial Pk, NSW, Australia. [Coates, Alan S.] Univ Sydney, Centennial Pk, NSW, Australia. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Galimberti, V (reprint author), European Inst Oncol, Dept Surg, Via Ripamonti 435, I-20141 Milan, Italy. EM viviana.galimberti@ieo.it FU International Breast Cancer Study Group; Swiss Group for Clinical Cancer Research; Swiss Cancer League/Cancer Research Switzerland/Oncosuisse [ICP OCS 01688-03-2005]; Frontier Science and Technology Research Foundation; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); US National Institutes of Health [CA-75362]; Swedish Cancer Society; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX This clinical trial was supported by the medical institutions that enrolled women into the trial and the International Breast Cancer Study Group, which is funded in part by: Swiss Group for Clinical Cancer Research; Swiss Cancer League/Cancer Research Switzerland/Oncosuisse (Grant ID: ICP OCS 01688-03-2005), Frontier Science and Technology Research Foundation; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); US National Institutes of Health (grant number CA-75362); Swedish Cancer Society; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). There was no pharmaceutical company support for this trial. We thank the patients, physicians, nurses, and data managers who have participated in the International Breast Cancer Study Group Trial 23-01. We thank Sandra Lippert for data management and Don Ward for help with the English. NR 29 TC 296 Z9 322 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2013 VL 14 IS 4 BP 297 EP 305 DI 10.1016/S1470-2045(13)70035-4 PG 9 WC Oncology SC Oncology GA 123LD UT WOS:000317390300037 PM 23491275 ER PT J AU Adesina, A Chumba, D Nelson, AM Orem, J Roberts, DJ Wabinga, H Wilson, M Rebbeck, TR AF Adesina, Adekunle Chumba, David Nelson, Ann M. Orem, Jackson Roberts, Drucilla J. Wabinga, Henry Wilson, Michael Rebbeck, Timothy R. TI Improvement of pathology in sub-Saharan Africa SO LANCET ONCOLOGY LA English DT Article ID DEVELOPING-COUNTRIES AB In the coming decades, cancer will be a major clinical and public health issue in sub-Saharan Africa. However, clinical and public health infrastructure and services in many countries are not positioned to deal with the growing cancer burden. Pathology is a core service required to serve many needs related to cancer in sub-Saharan Africa. Cancer diagnosis, treatment, and research all depend on adequate pathology. Pathology is also necessary for cancer registration, which is needed to accurately estimate cancer incidence and mortality. Cancer registry data directly guide policy-makers' decisions for cancer control and the allocation of clinical and public health services. Despite the centrality of pathology in many components of cancer care and control, countries in sub-Saharan Africa have at best a tenth of the pathology coverage of that in high-income countries. Equipment, processes, and services are lacking, and there is a need for quality assurance for the definition and implementation of high-quality, accurate diagnosis. Training and advocacy for pathology are also needed. We propose approaches to improve the status of pathology in sub-Saharan Africa to address the needs of patients with cancer and other diseases. C1 [Adesina, Adekunle] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Chumba, David] Moi Univ, Sch Med, Eldoret, Kenya. [Nelson, Ann M.] Joint Pathol Ctr, Washington, DC USA. [Orem, Jackson] Uganda Canc Inst, Kampala, Uganda. [Wabinga, Henry] Mulago Hosp, Kampala, Uganda. [Wabinga, Henry] Makerere Univ, Kampala, Uganda. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, Michael] Denver Hlth Med Ctr, Dept Pathol, Denver, CO USA. [Wilson, Michael] Univ Colorado, Sch Med, Aurora, CO USA. [Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Rebbeck, TR (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM rebbeck@upenn.edu FU African Organisation for Research and Training in Cancer; American Association for Cancer Research Landon Foundation; US Department of State Fulbright Program FX We thank the African Organisation for Research and Training in Cancer for its support of the Pathology Special Interest Group in Africa. Support for the Special Interest Group was provided by the American Association for Cancer Research Landon Foundation and the US Department of State Fulbright Program (both to TRR). NR 14 TC 44 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2013 VL 14 IS 4 BP E152 EP E157 PG 6 WC Oncology SC Oncology GA 123LD UT WOS:000317390300012 PM 23561746 ER PT J AU de Larrea, CF Kyle, RA Durie, BGM Ludwig, H Usmani, S Vesole, DH Hajek, R San Miguel, JF Sezer, O Sonneveld, P Kumar, SK Mahindra, A Comenzo, R Palumbo, A Mazumber, A Anderson, KC Richardson, PG Badros, AZ Caers, J Cavo, M Leleu, X Dimopoulos, MA Chim, CS Schots, R Noeul, A Fantl, D Mellqvist, UH Landgren, O Chanan-Khan, A Moreau, P Fonseca, R Merlini, G Lahuerta, JJ Blade, J Orlowski, RZ Shah, JJ AF Fernandez de Larrea, C. Kyle, R. A. Durie, B. G. M. Ludwig, H. Usmani, S. Vesole, D. H. Hajek, R. San Miguel, J. F. Sezer, O. Sonneveld, P. Kumar, S. K. Mahindra, A. Comenzo, R. Palumbo, A. Mazumber, A. Anderson, K. C. Richardson, P. G. Badros, A. Z. Caers, J. Cavo, M. Leleu, X. Dimopoulos, M. A. Chim, C. S. Schots, R. Noeul, A. Fantl, D. Mellqvist, U-H Landgren, O. Chanan-Khan, A. Moreau, P. Fonseca, R. Merlini, G. Lahuerta, J. J. Blade, J. Orlowski, R. Z. Shah, J. J. CA Int Myeloma Working Grp TI Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group SO LEUKEMIA LA English DT Review DE plasma cell leukemia; cytogenetics; bortezomib; transplantation; myeloma; prognosis ID BONE-MARROW MICROENVIRONMENT; IN-SITU HYBRIDIZATION; OF-THE-LITERATURE; C-MYC ONCOGENE; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; GENETIC ABERRATIONS; CLINICAL-FEATURES; SINGLE-CENTER AB Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (>= 20%) and absolute number (>= 2 x 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. Leukemia (2013) 27, 780-791; doi:10.1038/leu.2012.336 C1 [Fernandez de Larrea, C.; Blade, J.] Hosp Clin Barcelona, Dept Hematol, Amyloidosis & Myeloma Unit, IDIBAPS, E-08036 Barcelona, Spain. [Kyle, R. A.; Kumar, S. K.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Durie, B. G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Southwest Oncol Grp, Int Myeloma Fdn, Los Angeles, CA USA. [Ludwig, H.] Wilhelminenspital Stadt Wien, Dept Med, Ctr Oncol & Hematol, Vienna, Austria. [Usmani, S.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Vesole, D. H.] Hackensack Univ Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Hajek, R.] Univ Hosp Ostrava, Dept Haematooncol, Ostrava, Czech Republic. [Hajek, R.] Sch Med Univ, Ostrava, Czech Republic. [San Miguel, J. F.] Hosp Univ Salamanca, Serv Hematol, CIC, IBMCC USAL CSIC, Salamanca, Spain. [Sezer, O.] Univ Hamburg, Univ Med Ctr, Hamburg, Germany. [Sonneveld, P.] Erasmus Univ, Dept Hematol, Med Ctr, Rotterdam, Netherlands. [Mahindra, A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Comenzo, R.] Tufts Med Ctr, Boston, MA USA. [Palumbo, A.] Univ Turin, Myeloma Unit, Div Hematol, Turin, Italy. [Mazumber, A.] NYU Comprehens Canc Ctr, New York, NY USA. [Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Badros, A. Z.] Univ Maryland, Dept BMT, Baltimore, MD 21201 USA. [Caers, J.] Ctr Hosp Univ Liege, Dept Hematol, Liege, Belgium. [Cavo, M.] S Orsolas Univ Hosp, Bologna Sch Med, Seragnoli Inst Haematol, Bologna, Italy. [Leleu, X.] Hosp Claude Huriez, Dept Hematol, Lille, France. [Dimopoulos, M. A.] Univ Athens, Dept Clin Therapeut, Sch Med Athens, GR-10679 Athens, Greece. [Chim, C. S.] Queen Mary Hosp, Div Haematol & Med Oncol, Hong Kong, Hong Kong, Peoples R China. [Schots, R.] Univ Ziekenhuis Brussels, Dept Clin Hematol, Brussels, Belgium. [Noeul, A.] Hospital Ruiz & Paez, Bolivar, Venezuela. [Fantl, D.] Hosp Italiano Buenos Aires, Caba, Argentina. [Mellqvist, U-H] Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden. [Landgren, O.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Chanan-Khan, A.] Mayo Clin, Div Hematol Oncol, Jacksonville, FL 32224 USA. [Moreau, P.] Univ Hosp, Dept Clin Hematol, Nantes, France. [Fonseca, R.] Mayo Clin Scottsdale, Div Hematol Oncol, Scottsdale, AZ USA. [Merlini, G.] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Lahuerta, J. J.] Hosp Univ 12 Octubre, Dept Hematol, Madrid, Spain. [Orlowski, R. Z.; Shah, J. J.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Div Canc Med, Houston, TX 77030 USA. RP de Larrea, CF (reprint author), Hosp Clin Barcelona, Dept Hematol, Villarroel 170, E-08036 Barcelona, Spain. EM cfernan1@clinic.ub.es; jjshah@mdanderson.org RI Kumar, Shaji/A-9853-2008; richard, chrystelle/K-8595-2015; Garcia-Sanz, Ramon/B-7986-2017; OI Kumar, Shaji/0000-0001-5392-9284; Garcia-Sanz, Ramon/0000-0003-4120-2787; SAN MIGUEL, JESUS/0000-0002-9183-4857; Fonseca, Rafael/0000-0002-5938-3769; CAVO, MICHELE/0000-0003-4514-3227; Merlini, Giampaolo/0000-0001-7680-3254; nahi, hareth/0000-0003-4711-5094 FU Hospital Clinic de Barcelona; Instituto de Salud Carlos III, Spain [RD12/0036/0046] FX This work has been supported in part by 'Josep Font' Grant from Hospital Clinic de Barcelona and RD12/0036/0046 from Instituto de Salud Carlos III, Spain. Meeting on Plasma Cell Leukemia was supported by the International Myeloma Foundation. NR 92 TC 39 Z9 41 U1 0 U2 23 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 2013 VL 27 IS 4 BP 780 EP 791 DI 10.1038/leu.2012.336 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 124NT UT WOS:000317472200005 ER PT J AU Chen, L Deshpande, AJ Banka, D Bernt, KM Dias, S Buske, C Olhava, EJ Daigle, SR Richon, VM Pollock, RM Armstrong, SA AF Chen, L. Deshpande, A. J. Banka, D. Bernt, K. M. Dias, S. Buske, C. Olhava, E. J. Daigle, S. R. Richon, V. M. Pollock, R. M. Armstrong, S. A. TI Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l SO LEUKEMIA LA English DT Article DE MLL-AF10; CALM-AF10; MLL fusions; leukemia; Dot1l; EPZ004777 ID ACUTE MYELOID-LEUKEMIA; MLL-MUTANT MICE; T(10-11) TRANSLOCATION; LEUCINE-ZIPPER; UP-REGULATION; SET DOMAIN; METHYLATION; AF10; CLATHRIN; FUSION AB The t(10;11)(p12;q23) translocation and the t(10;11)(p12;q14) translocation, which encode the MLL (mixed lineage leukemia)-AF10 and CALM (clathrin assembly lymphoid myeloid leukemia)-AF10 fusion oncoproteins, respectively, are two recurrent chromosomal rearrangements observed in patients with acute myeloid leukemia and acute lymphoblastic leukemia. Here, we demonstrate that MLL-AF10 and CALM-AF10-mediated transformation is dependent on the H3K79 methyltransferase Dot1l using genetic and pharmacological approaches in mouse models. Targeted disruption of Dot1l using a conditional knockout mouse model abolished in vitro transformation of murine bone marrow cells and in vivo initiation and maintenance of MLL-AF10 or CALM-AF10 leukemia. The treatment of MLL-AF10 and CALM-AF10 transformed cells with EPZ004777, a specific small-molecule inhibitor of Dot1l, suppressed expression of leukemogenic genes such as Hoxa cluster genes and Meis1, and selectively impaired proliferation of MLL-AF10 and CALM-AF10 transformed cells. Pretreatment with EPZ004777 profoundly decreased the in vivo spleen-colony-forming ability of MLL-AF10 or CALM-AF10 transformed bone marrow cells. These results show that patients with leukemia-bearing chromosomal translocations that involve the AF10 gene may benefit from small-molecule therapeutics that inhibit H3K79 methylation. Leukemia (2013) 27, 813-822;doi:10.1038/leu.2012.327 C1 [Chen, L.; Deshpande, A. J.; Banka, D.; Bernt, K. M.; Dias, S.; Armstrong, S. A.] Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Chen, L.; Deshpande, A. J.; Banka, D.; Bernt, K. M.; Dias, S.; Armstrong, S. A.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, L.] Harvard Univ, Dept Mol & Cellular Biol, Boston, MA 02115 USA. [Deshpande, A. J.; Banka, D.; Bernt, K. M.; Dias, S.; Armstrong, S. A.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Buske, C.] Comprehens Canc Ctr Ulm, Inst Expt Canc Res, Ulm, Germany. [Olhava, E. J.; Daigle, S. R.; Richon, V. M.; Pollock, R. M.] Epizyme Inc, Cambridge, MA USA. [Armstrong, S. A.] Harvard Stem Cell Inst, Boston, MA USA. RP Armstrong, SA (reprint author), Childrens Hosp, Karp Family Res Labs, 1 Blackfan Circle, Boston, MA 02215 USA. EM armstros@mskcc.org RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 FU National Cancer Institute [U01CA105423, R01CA140575]; American Cancer Society; Leukemia and Lymphoma Society; NCI; NHLBI; William Lawrence and Blanche Hughes Foundation FX We would like to thank Ronald Mathieu and Mahnaz Pakhtinat for their excellent technical assistance with flow cytometry. This work was supported by grants from the National Cancer Institute (U01CA105423, R01CA140575), the American Cancer Society and the Leukemia and Lymphoma Society to SAA. AJD was supported by a grant to the American Cancer Society and the NCI Howard Temin Pathway to Independence Award. KMB was supported by NHLBI Career Development Award and funding from the William Lawrence and Blanche Hughes Foundation. NR 33 TC 44 Z9 45 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2013 VL 27 IS 4 BP 813 EP 822 DI 10.1038/leu.2012.327 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 124NT UT WOS:000317472200008 PM 23138183 ER PT J AU Krivtsov, AV Figueroa, ME Sinha, AU Stubbs, MC Feng, Z Valk, PJM Delwel, R Dohner, K Bullinger, L Kung, AL Melnick, AM Armstrong, SA AF Krivtsov, A. V. Figueroa, M. E. Sinha, A. U. Stubbs, M. C. Feng, Z. Valk, P. J. M. Delwel, R. Doehner, K. Bullinger, L. Kung, A. L. Melnick, A. M. Armstrong, S. A. TI Cell of origin determines clinically relevant subtypes of MLL-rearranged AML SO LEUKEMIA LA English DT Article DE MLL; cell of origin; gene expression; DNA methylation; chemotherapy; drug resistance ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELL; ACUTE MYELOGENOUS LEUKEMIA; EXPRESSION PROFILES; DNA METHYLATION; MOUSE MODELS; GENE; CANCER; TRANSFORMATION; PROGENITOR AB Mixed lineage leukemia (MLL)-fusion proteins can induce acute myeloid leukemias (AMLs) from either hematopoietic stem cells (HSCs) or granulocyte-macrophage progenitors (GMPs), but it remains unclear whether the cell of origin influences the biology of the resultant leukemia. MLL-AF9-transduced single HSCs or GMPs could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSCs or GMPs had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC-derived LGMP. The gene expression signature of LGMP derived from HSCs was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5'-mC levels were elevated in HSC-derived leukemias as compared with GMP-derived leukemias. This mirrored a difference seen in 5'-mC between MLL-rearranged human leukemias that are either EVI1 positive or EVI1 negative. Finally, HSC-derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias. Leukemia (2013) 27, 852-860; doi:10.1038/leu.2012.363 C1 [Krivtsov, A. V.; Sinha, A. U.; Stubbs, M. C.; Feng, Z.; Armstrong, S. A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Krivtsov, A. V.; Sinha, A. U.; Feng, Z.; Armstrong, S. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Krivtsov, A. V.; Sinha, A. U.; Armstrong, S. A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Krivtsov, A. V.; Sinha, A. U.; Armstrong, S. A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Figueroa, M. E.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Figueroa, M. E.; Melnick, A. M.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Valk, P. J. M.; Delwel, R.] Erasmus Univ, Dept Hematol, Med Ctr, Rotterdam, Netherlands. [Doehner, K.; Bullinger, L.] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany. [Kung, A. L.] Columbia Univ, Div Pediat Hematol Oncol Stem Cell Transplantat, New York, NY USA. RP Armstrong, SA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, HOPP Z-561,417 E 68th St, New York, NY 10065 USA. EM armstros@mskcc.org OI Kung, Andrew/0000-0002-9091-488X FU National Cancer Institute [5P01CA66996]; Leukemia and Lymphoma Society; American Cancer Society; Harvard Stem Cell Institute; German Research Foundation (DFG Heisenberg-Stipendium) [BU 1339/3-1] FX We thank Renee Wright for technical help and Megan Smith for administrative assistance. This work was supported in part by the National Cancer Institute (5P01CA66996), the Leukemia and Lymphoma Society, the American Cancer Society and the Harvard Stem Cell Institute, and the German Research Foundation (DFG Heisenberg-Stipendium BU 1339/3-1). NR 51 TC 53 Z9 54 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2013 VL 27 IS 4 BP 852 EP 860 DI 10.1038/leu.2012.363 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 124NT UT WOS:000317472200013 PM 23235717 ER PT J AU Azab, AK Weisberg, E Sahin, I Liu, F Awwad, R Azab, F Liu, Q Griffin, JD Ghobrial, IM AF Azab, A. K. Weisberg, E. Sahin, I. Liu, F. Awwad, R. Azab, F. Liu, Q. Griffin, J. D. Ghobrial, I. M. TI The influence of hypoxia on CML trafficking through modulation of CXCR4 and E-cadherin expression SO LEUKEMIA LA English DT Letter ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW MICROENVIRONMENT; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; MULTIPLE-MYELOMA; STEM-CELLS; INHIBITION; IMATINIB; STROMA; PROGENITORS C1 [Azab, A. K.; Azab, F.] Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, St Louis, MO 63130 USA. [Weisberg, E.; Sahin, I.; Griffin, J. D.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liu, F.; Liu, Q.] Chinese Acad Sci, High Magnet Field Lab, Hefei, Peoples R China. [Awwad, R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Azab, AK (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, St Louis, MO 63130 USA. EM aazab@radonc.wustl.edu OI liu, qing song/0000-0002-7829-2547 NR 15 TC 8 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2013 VL 27 IS 4 BP 961 EP 964 DI 10.1038/leu.2012.353 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 124NT UT WOS:000317472200029 PM 23212153 ER PT J AU Lane, AA Odejide, O Kopp, N Kim, S Yoda, A Erlich, R Wagle, N Abel, GA Rodig, SJ Antin, JH Weinstock, DM AF Lane, A. A. Odejide, O. Kopp, N. Kim, S. Yoda, A. Erlich, R. Wagle, N. Abel, G. A. Rodig, S. J. Antin, J. H. Weinstock, D. M. TI Low frequency clonal mutations recoverable by deep sequencing in patients with aplastic anemia SO LEUKEMIA LA English DT Letter ID FOLLICULAR LYMPHOMA; BETA-2-MICROGLOBULIN; INDIVIDUALS; CELLS C1 [Lane, A. A.; Odejide, O.; Kopp, N.; Kim, S.; Yoda, A.; Wagle, N.; Abel, G. A.; Antin, J. H.; Weinstock, D. M.] Dept Med Oncol, Boston, MA USA. [Lane, A. A.; Wagle, N.; Abel, G. A.; Rodig, S. J.; Antin, J. H.; Weinstock, D. M.] Harvard Univ, Sch Med, Boston, MA USA. [Erlich, R.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Rodig, S. J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Lane, AA (reprint author), Dept Med Oncol, Boston, MA USA. EM dweinstock@partners.org FU NCI NIH HHS [T32 CA009172] NR 10 TC 19 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2013 VL 27 IS 4 BP 968 EP 971 DI 10.1038/leu.2013.30 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 124NT UT WOS:000317472200031 PM 23370706 ER PT J AU Tomov, S Lazarchick, J Self, SE Bruner, ET Budisavljevic, MN AF Tomov, S. Lazarchick, J. Self, S. E. Bruner, E. T. Budisavljevic, M. N. TI Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim SO LUPUS LA English DT Article DE Thrombotic microangiopathy; antiphospholipid syndrome; thrombotic thrombocytopenic purpura; romiplostim; acute renal failure; systemic lupus erythematosus; plasma exchange ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEMOLYTIC-UREMIC SYNDROME; THROMBOCYTOPENIC PURPURA; ANTIPHOSPHOLIPID SYNDROME; IMMUNE THROMBOCYTOPENIA; VASCULAR-LESIONS; NEPHRITIS; ADAMTS13; THROMBOPOIETIN; ANEMIA AB We present the case of a 19 year-old Caucasian female with history of systemic lupus erythematosus (SLE) and normal baseline kidney function who developed severe acute renal failure following treatment of thrombocytopenia with the thrombopoietic agent romiplostim. Percutaneous kidney biopsy revealed thrombotic microangiopathy (TMA) without immune complex lupus glomerulonephritis. We discuss pathogenesis and differential diagnosis of TMA in patients with SLE and raise concerns regarding the use of thrombopoietic agents in such patients. Based on favorable long-term outcome in our case aggressive treatment and in particular prolonged use of plasma exchange in these patients are advocated. Lupus (2013) 22, 504-509. C1 [Tomov, S.; Budisavljevic, M. N.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lazarchick, J.; Self, S. E.; Bruner, E. T.] Pathol & Lab Med Med Univ South Carolina, Charleston, SC USA. [Budisavljevic, M. N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Budisavljevic, MN (reprint author), Med Univ S Carolina, Div Nephrol, 171 Ashley Ave, Charleston, SC 29425 USA. EM budisamn@musc.edu NR 37 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD APR PY 2013 VL 22 IS 5 BP 504 EP 509 DI 10.1177/0961203313477900 PG 6 WC Rheumatology SC Rheumatology GA 122TV UT WOS:000317341900014 PM 23554039 ER PT J AU de Villiers, TJ Gass, MLS Haines, CJ Hall, JE Lobo, RA Pierroz, DD Rees, M AF de Villiers, T. J. Gass, M. L. S. Haines, C. J. Hall, J. E. Lobo, R. A. Pierroz, D. D. Rees, M. TI Global Consensus Statement on menopausal hormone therapy SO MATURITAS LA English DT Editorial Material C1 [de Villiers, T. J.] MediClin Panorama, Cape Town, South Africa. [de Villiers, T. J.] Univ Stellenbosch, Dept Obstet & Gynecol, Cape Town, South Africa. [Gass, M. L. S.] Case Western Reserve Univ, Sch Med, Dept Surg, Cleveland Clin,Lerner Coll Med, Cleveland, OH 44106 USA. [Haines, C. J.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynecol, Shatin, Hong Kong, Peoples R China. [Hall, J. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hall, J. E.] Harvard Univ, Sch Med, Boston, MA USA. [Lobo, R. A.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Pierroz, D. D.] Univ Geneva, CH-1211 Geneva 4, Switzerland. [Rees, M.] Univ Oxford, Oxford OX1 2JD, England. RP de Villiers, TJ (reprint author), MediClin Panorama, ZA-7500 Parow, South Africa. OI Hall, Janet/0000-0003-4644-3061 NR 0 TC 37 Z9 38 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD APR PY 2013 VL 74 IS 4 BP 391 EP 392 DI 10.1016/j.maturitas.2013.02.001 PG 2 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 124II UT WOS:000317456600016 PM 23497918 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Horace Magoun-Neuroanatomist and Neurophysiologist SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2013 VL 88 IS 4 BP E33 EP E33 DI 10.1016/j.mayocp.2012.01.027 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 122QJ UT WOS:000317332500001 PM 23541022 ER PT J AU Gat-Viks, I Chevrier, N Wilentzik, R Eisenhaure, T Raychowdhury, R Steuerman, Y Shalek, AK Hacohen, N Amit, I Regev, A AF Gat-Viks, Irit Chevrier, Nicolas Wilentzik, Roni Eisenhaure, Thomas Raychowdhury, Raktima Steuerman, Yael Shalek, Alex K. Hacohen, Nir Amit, Ido Regev, Aviv TI Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli SO NATURE BIOTECHNOLOGY LA English DT Article ID QUANTITATIVE TRAIT LOCI; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; RIG-I; EXPRESSION; CELLS; RESPONSES; IDENTIFICATION; RECOGNITION; REGULATORS AB Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli. C1 [Gat-Viks, Irit; Chevrier, Nicolas; Eisenhaure, Thomas; Raychowdhury, Raktima; Hacohen, Nir; Amit, Ido; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Gat-Viks, Irit; Wilentzik, Roni; Steuerman, Yael] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Chevrier, Nicolas] Harvard Univ, Sch Med, Div Med Sci, Grad Program Immunol, Boston, MA USA. [Chevrier, Nicolas] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Eisenhaure, Thomas; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Shalek, Alex K.] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [Shalek, Alex K.] Harvard Univ, Dept Biol Chem, Cambridge, MA 02138 USA. [Shalek, Alex K.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA. RP Gat-Viks, I (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM iritgv@post.tau.ac.il; ido.amit@weizmann.ac.il; aregev@broad.mit.edu OI Shalek, Alex K./0000-0001-5670-8778 FU Human Frontiers Science Program postdoctoral fellowships; Howard Hughes Medical Institute; US National Institutes of Health; Burroughs-Wellcome Fund Career Award at the Scientific Interface; Center for Excellence in Genome Science from the National Human Genome Research Institute [5P50HG006193-02]; Klarman Cell Observatory at the Broad Institute; New England Regional Center for Excellence/Biodefense and Emerging Infectious Disease [U54 AI057159]; Israeli Centers of Research Excellence (I-CORE) Gene Regulation in Complex Human Disease [41/11]; Human Frontiers Science Program Career Development Award; Israeli Science Foundation Bikura Institutional Research Grant Program; Edmond J. Safra Center for Bioinformatics at Tel-Aviv University FX We thank C. (Jimmie) Ye, J. Pickerel, M. Daly and E. Lander for comments and discussions. I.G.-V. and I.A. were supported by Human Frontiers Science Program postdoctoral fellowships. Work was supported by Howard Hughes Medical Institute, a US National Institutes of Health PIONEER award, a Burroughs-Wellcome Fund Career Award at the Scientific Interface (A.R.), a Center for Excellence in Genome Science grant 5P50HG006193-02 from the National Human Genome Research Institute (N.H. and A.R.), the Klarman Cell Observatory at the Broad Institute (A.R.), the New England Regional Center for Excellence/Biodefense and Emerging Infectious Disease U54 AI057159 (N.H.), the Israeli Centers of Research Excellence (I-CORE) Gene Regulation in Complex Human Disease, Center No. 41/11 (I.G.-V., R.W. and Y.S.), the Human Frontiers Science Program Career Development Award and an Israeli Science Foundation Bikura Institutional Research Grant Program (I.A.) and the Edmond J. Safra Center for Bioinformatics at Tel-Aviv University (R.W. and Y.S.). A.R. is a fellow of the Merkin Foundation for Stem Cell Research at the Broad Institute. I.G.-V. is a Faculty Fellow of the Edmond J. Safra Center for Bioinformatics at Tel Aviv University and an Alon Fellow. NR 50 TC 19 Z9 19 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2013 VL 31 IS 4 BP 342 EP + DI 10.1038/nbt.2519 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 120TI UT WOS:000317195500028 PM 23503680 ER PT J AU Huang, LF Jin, JM Deighan, P Kiner, E McReynolds, L Lieberman, J AF Huang, Linfeng Jin, Jingmin Deighan, Padraig Kiner, Evgeny McReynolds, Larry Lieberman, Judy TI Efficient and specific gene knockdown by small interfering RNAs produced in bacteria SO NATURE BIOTECHNOLOGY LA English DT Article ID DOUBLE-STRANDED RNAS; SHORT HAIRPIN RNAS; CAENORHABDITIS-ELEGANS; MAMMALIAN-CELLS; EXPRESSION; SIRNAS; PLANTS; INHIBITION; INVASION; DUPLEXES AB Synthetic small interfering RNAs (siRNAs) are an indispensable tool to investigate gene function in eukaryotic cells(1,2) and may be used for therapeutic purposes to knock down genes implicated in disease(3). Thus far, most synthetic siRNAs have been produced by chemical synthesis. Here we present a method to produce highly potent siRNAs in Escherichia coli. This method relies on ectopic expression of p19, an siRNA-binding protein found in a plant RNA virus(4,5). When expressed in E. coli, p19 stabilizes an similar to 21-nt siRNA-like species produced by bacterial RNase III. When mammalian cells are transfected by them, siRNAs that were generated in bacteria expressing p19 and a hairpin RNA encoding 200 or more nucleotides of a target gene reproducibly knock down target gene expression by similar to 90% without immunogenicity or off-target effects. Because bacterially produced siRNAs contain multiple sequences against a target gene, they may be especially useful for suppressing polymorphic cellular or viral genes. C1 [Huang, Linfeng; Kiner, Evgeny; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Huang, Linfeng; Kiner, Evgeny; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Jin, Jingmin; McReynolds, Larry] New England Biolabs Inc, Ipswich, MA USA. [Deighan, Padraig] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Deighan, Padraig] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. RP Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015; OI Huang, Linfeng/0000-0002-0322-4929 FU National Institutes of Health [AI087431]; GSK-IDI Alliance fellowship FX The authors thank J. Carrington (Donald Danforth Plant Science Center) for the p19 clone, C. Zhang and G. Ruvkun (Massachusetts General Hospital) for L4440 plasmid and HT115(DE3) strain, S. Kushner (University of Georgia) for SK7622 strain, D. Higgins (Harvard Medical School) for pLIV-1 plasmid, and S. Ranjbar (Boston Children's Hospital) for HIV strains and cell lines. We thank L.M. Mazzola, J.M. Bybee and D.B. Munafo from New England Biolabs for assistance with RNA deep sequencing and Z. Ansara for technical help. We thank A. Hochschild (Harvard Medical School) for suggestions and critical reading of the manuscript and Lieberman Lab members for technical assistance, helpful discussions and comments on the manuscript. This work was supported by National Institutes of Health grant AI087431 (J.L.) and a GSK-IDI Alliance fellowship (L.H.). NR 33 TC 16 Z9 16 U1 1 U2 44 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2013 VL 31 IS 4 BP 350 EP + DI 10.1038/nbt.2537 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 120TI UT WOS:000317195500029 PM 23475073 ER PT J AU DeKosky, ST Blennow, K Ikonomovic, MD Gandy, S AF DeKosky, Steven T. Blennow, Kaj Ikonomovic, Milos D. Gandy, Sam TI Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers SO NATURE REVIEWS NEUROLOGY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; AMYLOID-BETA ACCUMULATION; PITTSBURGH COMPOUND-B; SEVERE BRAIN-INJURY; HEAD-INJURY; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; COGNITIVE DECLINE; PRECURSOR PROTEIN AB Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)-which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression-has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE. DeKosky, S. T. et al. Nat. Rev. Neurol. 9, 192-200 (2013); doi:10.1038/nrneurol.2013.36 C1 [DeKosky, Steven T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Clin Neurochem Lab, Inst Neurosci & Physiol,Sahlgrenska Univ Hosp, SE-43180 Molndal, Sweden. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Gandy, Sam] James J Peters Med Ctr, Icahn Sch Med, Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] James J Peters Med Ctr, Icahn Sch Med, Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam] James J Peters Med Ctr, Icahn Sch Med, Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. RP DeKosky, ST (reprint author), Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. EM dekosky@virginia.edu FU NIH [P01NS30318, P01AG14449, P50AG05133]; VA MERIT review grants [1I01BX000348, 1I01RX000511]; Cure Alzheimer's Fund; US NIH [P50 AG05138] FX The authors gratefully acknowledge the support of NIH grants P01NS30318, P01AG14449 and P50AG05133 (S. T. DeKosky and M. D. Ikonomovic), and VA MERIT review grants 1I01BX000348 (S. Gandy) and 1I01RX000511 (M. D. Ikonomovic). S. Gandy also acknowledges the support of the Cure Alzheimer's Fund and of US NIH P50 AG05138. The authors thank P. Davies (North Shore-Hofstra) for helpful discussions. NR 96 TC 77 Z9 79 U1 10 U2 66 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD APR PY 2013 VL 9 IS 4 BP 192 EP 200 DI 10.1038/nrneurol.2013.36 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 121TV UT WOS:000317268100007 PM 23558985 ER PT J AU McDougle, CJ AF McDougle, Christopher J. TI Recent progress in autism spectrum disorder FOREWORD SO NEUROPSYCHIATRY LA English DT Editorial Material C1 [McDougle, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [McDougle, Christopher J.] Lurie Ctr Autism, Lexington, MA 02421 USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM cmcdougle@partners.org NR 12 TC 1 Z9 1 U1 1 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD APR PY 2013 VL 3 IS 2 BP 119 EP 122 DI 10.2217/NPY.13.17 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126QM UT WOS:000317636300001 ER PT J AU Mody, M Manoach, DS Guenther, FH Kenet, T Bruno, KA McDougle, CJ Stigler, KA AF Mody, Maria Manoach, Dara S. Guenther, Frank H. Kenet, Tal Bruno, Katelyn A. McDougle, Christopher J. Stigler, Kimberly Ann TI Speech and language in autism spectrum disorder: a view through the lens of behavior and brain imaging SO NEUROPSYCHIATRY LA English DT Review ID HIGH-FUNCTIONING AUTISM; WHITE-MATTER; RIGHT-HEMISPHERE; SENTENCE COMPREHENSION; CORTICAL ACTIVATION; AUDITORY LANGUAGE; EARLY RECOGNITION; EARLY-CHILDHOOD; MISMATCH FIELD; COMPLEX SOUNDS AB Numerous studies have examined the brain bases of autism; few, however, have specifically examined the neurobiology of speech and language impairments in children and adults on the spectrum, especially those characterized as low functioning or minimally verbal, due to compliance issues. With exciting new advances in the development of paradigms and tools, and the ability to image children at risk for autism as young as 6 months of age, functional neuroimaging (EEG, magnetoencephalography and functional MRI) holds tremendous promise. Findings of reduced activation and structural and functional connectivity in the language network, together with deficits in social reciprocity and motivation, and a preference for visual over verbal information, appear to be carving out a neurobiological profile for the impaired social communication brain in autism. C1 [Mody, Maria] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Mody, Maria] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mody, Maria] Lurie Ctr Autism, Charlestown, MA 02129 USA. [Mody, Maria; Manoach, Dara S.; Kenet, Tal] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Manoach, Dara S.; Kenet, Tal] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Guenther, Frank H.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Guenther, Frank H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Bruno, Katelyn A.] Spaulding Rehabil Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. [Bruno, Katelyn A.] Massachusetts Gen Hosp Children, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Dept Psychiat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Dept Pediat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Lurie Ctr Autism, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lexington, MA 02421 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Lexington, MA 02421 USA. [Stigler, Kimberly Ann] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Dept Psychiat, Indianapolis, IN 46202 USA. RP Mody, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St,CNY 2301, Charlestown, MA 02129 USA. EM maria@nmr.mgh.harvard.edu FU Bristol-Myers Squibb Co.; Eli Lilly Co.; Forest Research Institute; Janssen; Novartis; Seaside Therapeutics; SynapDx FX KA Stigler receives research support from Bristol-Myers Squibb Co., Eli Lilly & Co., Forest Research Institute, Janssen, Novartis, Seaside Therapeutics and SynapDx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 126 TC 5 Z9 5 U1 6 U2 63 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD APR PY 2013 VL 3 IS 2 BP 223 EP 232 DI 10.2217/NPY.13.19 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126QM UT WOS:000317636300015 ER PT J AU Vahabzadeh, A Buxton, D McDougle, CJ Stigler, KA AF Vahabzadeh, Arshya Buxton, David McDougle, Christopher J. Stigler, Kimberly A. TI Current state and future prospects of pharmacological interventions for autism SO NEUROPSYCHIATRY LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; OPEN-LABEL TRIAL; PLACEBO-CONTROLLED TRIAL; DEFICIT HYPERACTIVITY DISORDER; PSYCHOTROPIC MEDICATION USE; SELF-INJURIOUS-BEHAVIOR; SPECTRUM DISORDERS; DOUBLE-BLIND; D-CYCLOSERINE; YOUNG-ADULTS AB Autism spectrum disorder (ASD) is a group of heterogeneous developmental disorders manifesting in early childhood. They are associated with a range of core and associated symptoms, including repetitive behaviors, hyperactivity and irritability. This review will describe the current evidence for psychopharmacological management of individuals with ASD. Additionally, some of the future treatment prospects will be discussed. Safety issues, adverse effects and limitations of the current literature will also be highlighted. C1 [Vahabzadeh, Arshya] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Buxton, David] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. [Stigler, Kimberly A.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Stigler, Kimberly A.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. RP Stigler, KA (reprint author), Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. EM kstigler@iupui.edu FU Bristol-Myers Squibb Co.; Eli Lilly Co.; Forest Research Institute; Janssen; Novartis; Seaside Therapeutics; SynapDx FX KA Stigler receives research support from Bristol-Myers Squibb Co., Eli Lilly & Co., Forest Research Institute, Janssen, Novartis, Seaside Therapeutics and SynapDx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 94 TC 2 Z9 2 U1 2 U2 15 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD APR PY 2013 VL 3 IS 2 BP 245 EP 259 DI 10.2217/NPY.13.22 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126QM UT WOS:000317636300017 ER PT J AU Villar, CC Lin, AL Cao, Z Zhao, XR Wu, LA Chen, S Sun, Y Yeh, CK AF Villar, C. C. Lin, A. L. Cao, Z. Zhao, X-R Wu, L-A Chen, S. Sun, Y. Yeh, C-K TI Anticandidal activity and biocompatibility of a rechargeable antifungal denture material SO ORAL DISEASES LA English DT Article DE anticandidal; rechargeable denture material; denture stomatitis; Candida albicans; epithelial cells ID ORAL EPITHELIAL-CELLS; SECRETED PROTEINASE GENES; CANDIDA-ALBICANS; IN-VITRO; TISSUE CONDITIONERS; BIOFILM FORMATION; SILVER-ZEOLITE; DRUG-RELEASE; MICONAZOLE; INFECTION AB OBJECTIVES: Candida-associated denture stomatitis is a recurrent and debilitating oral mucosal disease. Development of anticandidal denture materials represents a promising strategy to manage this condition. We have previously shown that miconazole incorporated in methacrylic acid (MAA) copolymerized diurethane dimethacrylate (UDMA) denture materials has long-term anticandidal activity. In this study, we examined the ability of culture medium conditioned with drug-free-or miconazole-MAA-UDMA discs to prevent Candida infection in an in vitro oral epithelial cell/Candida albicans coculture system. MATERIALS AND METHODS: Candida albicans (C. albicans)-induced OKF6/TERT-2 cell damage was quantified by the release of lactate dehydrogenase from epithelial cells, cytokine production was quantified using protein cytokine arrays, and the expression of C. albicans genes was measured by RT-qPCR. RESULTS: Candida albicans had limited growth with altered expression levels of secreted aspartyl proteinase-2 and -5 in culture medium conditioned by miconazole-MAA-UDMA discs. Significantly, the ability of C. albicans to induce oral epithelial cell damage and trigger epithelial proinflammatory cytokine production was also inhibited by miconazole disc conditioned media. CONCLUSION: Miconazole released from MAA-UDMA denture materials effectively prevents the development of candidal infection in an in vitro oral epithelial system. Further characterization of this drug-rechargeable denture material is warranted. Oral Diseases (2013) 19, 287--295 C1 [Villar, C. C.; Zhao, X-R] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Lin, A. L.; Yeh, C-K] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Cao, Z.; Sun, Y.] Univ S Dakota, Dept Biomed Engn Program, Sioux Falls, SD USA. [Wu, L-A; Chen, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Dev Dent, San Antonio, TX 78229 USA. [Yeh, C-K] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM yeh@uthscsa.edu RI Villar, Cristina/D-6353-2013 OI Villar, Cristina/0000-0002-5905-5079 FU NIDCR/NIH [R01 DE021084, R01DE019892]; NCRR/NIH [UL1RR025767] FX We are grateful to Drs. Brian Wickes (Department of Microbiology, UTHSCSA) and Spencer Redding (Comprehensive Dentistry, UTHSCSA) for their support and useful discussion during this research. Cell line OKF6/TERT-2 was a gift from Dr. Jim. Rhienwald (Brigham and Women's Hospital, Harvard Medical. School, Boston, MA). We would also like to thank Ms. Shuko Lee for her assistance in statistical analysis. This research is support by NIDCR/NIH grants R01 DE021084 (Y. Sun and C-K. Yeh), R01DE019892 (S. Chen), and NCRR/NIH grant UL1RR025767 (C.C. Villar). Dr. Zhengbing Cao current address is Medetech Development Corporation, 12527 MUKILTEO SPEEDWAY STE 103 LYNNWOOD, WA 98087-1532, USA (zhengbing@medetech.com). NR 52 TC 3 Z9 3 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD APR PY 2013 VL 19 IS 3 BP 287 EP 295 DI 10.1111/odi.12000 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 124TP UT WOS:000317490300008 PM 22957799 ER PT J AU Koolaee, RM Schumacher, H Shoemaker, MJ Mooar, SK Pullman-Mooar, S AF Koolaee, R. M. Schumacher, H., Jr. Shoemaker, M. J. Mooar, S. K. Pullman-Mooar, S. TI FACTORS PREDICTING THE EFFICACY OF VISCOSUPPLEMENTATION IN KNEE OSTEOARTHRITIS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) CY APR 18-21, 2013 CL Philadelphia, PA SP OsteoArthritis Res Soc Int (OARSI) C1 [Koolaee, R. M.; Schumacher, H., Jr.; Mooar, S. K.; Pullman-Mooar, S.] Univ Penn, Philadelphia, PA 19104 USA. [Koolaee, R. M.; Schumacher, H., Jr.; Mooar, S. K.; Pullman-Mooar, S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Shoemaker, M. J.] Grand Valley State Univ, Grand Rapids, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2013 VL 21 SU S BP S258 EP S258 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 130TF UT WOS:000317942300526 ER PT J AU Mootanah, R Hillstrom, HJ Gross, KD Niu, J Nevitt, MC Lewis, CE Torner, J Hietpas, J Felson, D AF Mootanah, R. Hillstrom, H. J. Gross, K. D. Niu, J. Nevitt, M. C. Lewis, C. E. Torner, J. Hietpas, J. Felson, D. TI STANCE AND SINGLE SUPPORT TIME ASYMMETRY IDENTIFY UNILATERAL KNEE OA AND THE INVOLVED LIMB: THE MULTICENTER OSTEOARTHRITIS STUDY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) CY APR 18-21, 2013 CL Philadelphia, PA SP OsteoArthritis Res Soc Int (OARSI) C1 [Mootanah, R.; Hillstrom, H. J.] Anglia Ruskin Univ, Chelmsford, Essex, England. [Mootanah, R.; Hillstrom, H. J.] Hosp Special Surg, New York, NY 10021 USA. [Gross, K. D.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Niu, J.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Nevitt, M. C.; Hietpas, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lewis, C. E.] Univ Alabama Hosp & Clin, Birmingham, AL USA. [Torner, J.] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2013 VL 21 SU S BP S246 EP S247 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 130TF UT WOS:000317942300498 ER PT J AU Suri, P Hunter, DJ Rainville, J Guermazi, A Katz, JN AF Suri, P. Hunter, D. J. Rainville, J. Guermazi, A. Katz, J. N. TI ASSOCIATIONS BETWEEN SELF-REPORTED PHYSICAL ACTIVITY AND LUMBAR FACET JOINT OSTEOARTHRITIS: THE FRAMINGHAM STUDY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) CY APR 18-21, 2013 CL Philadelphia, PA SP OsteoArthritis Res Soc Int (OARSI) C1 [Suri, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hunter, D. J.] Univ Sydney, Sydney, NSW 2006, Australia. [Rainville, J.] New England Baptist Hosp, Boston, MA USA. [Guermazi, A.] Boston Univ, Boston, MA 02215 USA. [Katz, J. N.] Harvard Univ, Sch Med, 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 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2013 VL 21 SU S BP S279 EP S279 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 130TF UT WOS:000317942300576 ER PT J AU Dowben, JS Grant, JS Froelich, KD Keltner, NL AF Dowben, Jonathan S. Grant, Joan S. Froelich, Kimberly D. Keltner, Norman L. TI Biological Perspectives Hydroxyzine for Anxiety: Another Look at an Old Drug SO PERSPECTIVES IN PSYCHIATRIC CARE LA English DT Article DE Hydroxyzine; anxiety ID GENERALIZED ANXIETY; DISORDER; EFFICACY; PLACEBO C1 [Dowben, Jonathan S.] Brooke Army Med Ctr, Pediat & Adolescent Behav Hlth Serv, San Antonio, TX USA. [Grant, Joan S.; Keltner, Norman L.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Froelich, Kimberly D.] Birmingham VA Med Ctr, Patient Care Serv, Birmingham, AL USA. RP Keltner, NL (reprint author), Univ Alabama Birmingham, Birmingham, AL 35294 USA. EM nkeltner@uab.edu OI Grant, Joan/0000-0001-6000-4060 NR 9 TC 4 Z9 4 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-5990 J9 PERSPECT PSYCHIATR C JI Perspect. Psychiatr. Care PD APR PY 2013 VL 49 IS 2 BP 75 EP 77 DI 10.1111/ppc.12012 PG 3 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 122DE UT WOS:000317295600002 PM 23557449 ER PT J AU Yeh, H Moore, DJ Markmann, JF Kim, JI AF Yeh, Heidi Moore, Daniel J. Markmann, James F. Kim, James I. TI Mechanisms of regulatory T cell counter-regulation by innate immunity SO TRANSPLANTATION REVIEWS LA English DT Article ID INDUCED TNF RECEPTOR; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; CUTTING EDGE; DENDRITIC CELLS; ALLOGRAFT ACCEPTANCE; IN-VIVO; TRANSPLANTATION TOLERANCE; COSTIMULATION BLOCKADE AB One of the most significant advances in the field of immunology in the last decade is delineation of the pivotal role of regulatory T cells (Tregs) in the maintenance of self-tolerance. While Tregs are just now being applied therapeutically in early phase clinical trials, data gleaned from basic and translational studies to-date suggest enormous potential to intervene in human disease. Data from our work and the work of others suggest that the innate immune system plays an important role in the differentiation and function of Tregs, largely through the production of cytokines but also through expression of cell surface ligands. These molecules are expressed differentially depending on whether the stimulus includes trauma, ischemia/necrosis, and microbial infection, and have opposing effects on Tregs, in contrast to those associated with dendritic cell maturation and somatic cell apoptosis, which promote Treg differentiation and function. We refer to the former process as Treg counter-regulation. Since the transplantation procedure involves surgical trauma, organ ischemia, and exposure to environmental microbes, Treg counter-regulation represents a key area of intervention to improve strategies for promoting allograft tolerance. (C) 2013 Elsevier Inc. All rights reserved. C1 [Yeh, Heidi; Markmann, James F.; Kim, James I.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Moore, Daniel J.] Vanderbilt Childrens Hosp, Dept Pediat, Ian Burr Div Endocrinol & Diabet, Nashville, TN 37232 USA. RP Kim, JI (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jkim35@partners.org RI Moore, Daniel/A-4924-2008 OI Moore, Daniel/0000-0002-6889-9345 FU NIH [2R56AI048820, 5R01AI048820, 1F32DK083161]; Vanderbilt Physician Scientist Development Program FX Supported in part by: NIH 2R56AI048820 (JFM), 5R01AI048820 (JFM), 1F32DK083161 (DJM) and the Vanderbilt Physician Scientist Development Program (DJM). NR 78 TC 2 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-470X J9 TRANSPLANT REV-ORLAN JI Transplant. Rev. PD APR PY 2013 VL 27 IS 2 BP 61 EP 64 DI 10.1016/j.trre.2013.02.001 PG 4 WC Immunology; Transplantation SC Immunology; Transplantation GA 124CK UT WOS:000317441200007 PM 23474287 ER PT J AU Lu, T Zwicker, L Kwena, Z Bukusi, E Mwaura-Muiru, E Dworkin, SL AF Lu, Tiffany Zwicker, Lindsey Kwena, Zachary Bukusi, Elizabeth Mwaura-Muiru, Esther Dworkin, Shari L. TI ASSESSING BARRIERS AND FACILITATORS OF IMPLEMENTING AN INTEGRATED HIV PREVENTION AND PROPERTY RIGHTS PROGRAM IN WESTERN KENYA SO AIDS EDUCATION AND PREVENTION LA English DT Article ID WOMENS EMPOWERMENT; MICROFINANCE; IMPACT AB Despite the recognized need for structural HIV prevention interventions, few scientific programs have integrated women's property and inheritance rights with HIV prevention and treatment. The current study focused on a community-led land and property rights intervention that was implemented in two rural areas of Western Kenya with high HIV prevalence rates (24-30%). The program was designed to respond to women's property rights violations in order to reduce HIV risk at the local level. Through in-depth interviews with twenty program leaders, we identified several facilitators to program implementation, including the leadership of home-based HIV caregivers and involvement of traditional leaders in mediating property rights disputes. We also identified the voluntary basis of the intervention and its lack of integration with the formal justice system as implementation barriers. Our findings can guide future research and design of structural HIV prevention strategies that integrate women's economic empowerment through property and inheritance rights. C1 [Lu, Tiffany] Massachusetts Gen Hosp, Dept Med, Residency Training Program, Boston, MA 02114 USA. [Zwicker, Lindsey] Univ Calif San Francisco, San Francisco Sch Med, Bixby Ctr Reprod Hlth, San Francisco, CA 94143 USA. [Kwena, Zachary; Bukusi, Elizabeth] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya. [Mwaura-Muiru, Esther] GROOTS Kenya, Nairobi, Kenya. [Dworkin, Shari L.] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA 94143 USA. RP Lu, T (reprint author), Massachusetts Gen Hosp, Dept Med, Residency Training Program, 15 Parkman St,WAC-615, Boston, MA 02114 USA. EM TLu4@partners.org FU NIAID NIH HHS [P30 AI027763] NR 30 TC 5 Z9 5 U1 2 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD APR PY 2013 VL 25 IS 2 BP 151 EP 163 PG 13 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 116ZO UT WOS:000316922100006 PM 23514082 ER PT J AU Chakrabarti, AK Feeney, K Abueg, C Brown, DA Czyz, E Tendera, M Janosi, A Giugliano, RP Kloner, RA Weaver, WD Bode, C Godlewski, J Merkely, B Gibson, CM AF Chakrabarti, Anjan K. Feeney, Kristin Abueg, Cassandra Brown, David A. Czyz, Ewa Tendera, Michal Andras Janosi Giugliano, Robert P. Kloner, Robert A. Weaver, W. Douglas Bode, Christoph Godlewski, Jacek Bela Merkely Gibson, C. Michael TI Rationale and design of the EMBRACE STEMI Study: A phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy of intravenous Bendavia on reperfusion injury in patients treated with standard therapy including primary percutaneous coronary intervention and stenting for ST-segment elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID PREVENTS MITOCHONDRIAL DEPOLARIZATION; NO-REFLOW PHENOMENON; APOPTOSIS; PEPTIDES; SALVAGE; IMPACT; TIME AB Background Although significant efforts have been made to improve ST-segment elevation myocardial infarction (STEMI) outcomes by reducing symptom-onset-to-reperfusion times, strategies to decrease the clinical impact of ischemic reperfusion injury have demonstrated limited success. Bendavia, an intravenously administered mitochondrial targeting peptide, has been shown to reduce myocardial infarct size and attenuate coronary no-reflow in experimental modelswhen given before reperfusion. Design The EMBRACE STEMI study is a phase 2a, randomized, double-blind, placebo-controlled trial enrolling 300 patients with a first-time anterior STEMI and an occluded proximal or mid-left anterior descending artery undergoing primary percutaneous coronary intervention (PCI) within 4 hours of symptom onset. Patients will be randomized to receive either Bendavia at 0.05 mg/kg per hour or an identically appearing placebo administered as an intravenous infusion at 60 mL/h. The primary end point is infarct size measured by the area under the creatine kinase-MB enzyme curve calculated from measurements from the central clinical chemistry laboratory obtained over the initial 72 hours after the primary PCI procedure, and the major secondary end point is infarct size calculated by the volume of infarcted myocardium (late contrast gadolinium enhancement) on the day 4 +/- 1 cardiac magnetic resonance imaging. Summary EMBRACE-STEMI is testing the hypothesis that Bendavia, in conjunction with standard-of-care therapy, is superior to placebo for the reduction of myocardial infarction size among patients with first time, acute, anterior wall STEMI who undergo successful reperfusion with primary PCI and stenting. (Am Heart J 2013;165:509-514.e7.) C1 [Chakrabarti, Anjan K.; Feeney, Kristin; Abueg, Cassandra; Gibson, C. Michael] Harvard Univ, Sch Med, Dept Med,PERFUSE Study Grp, Cardiovasc Div,Beth Israel Deaconess Med, Boston, MA USA. [Brown, David A.] E Carolina Univ, Dept Physiol, Brody Sch Med, Greenville, NC USA. [Czyz, Ewa] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Cardiol & Angiol, D-55122 Mainz, Germany. [Tendera, Michal] Med Univ Silesia, Cardiol Div, Katowice, Poland. [Andras Janosi] Gottsegen Gyorgy Natl Inst Cardiol, Budapest, Hungary. [Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. [Kloner, Robert A.] Univ So Calif, Good Samaritan Hosp, Inst Heart, Los Angeles, CA USA. [Kloner, Robert A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Weaver, W. Douglas] Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA. [Bode, Christoph] Tech Univ Bergakad Freiberg, Ctr Heart, D-09596 Freiberg, Germany. [Godlewski, Jacek] Jagiellonian Univ, Inst Cardiol, Sch Med, Krakow, Poland. [Bela Merkely] Semmelweis Univ, Ctr Heart, H-1085 Budapest, Hungary. RP Gibson, CM (reprint author), Beth Israel Deaconess Med Ctr, 185 Pilgrim Rd,Deaconess 319, Boston, MA 02215 USA. EM mgibson@perfuse.org FU Stealth Peptides Inc. FX The EMBRACE-STEMI trial is supported by Stealth Peptides Inc. The authors are solely responsible for all study analyses, the drafting and editing of the manuscript, and its final contents. NR 39 TC 40 Z9 42 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2013 VL 165 IS 4 BP 509 EP + DI 10.1016/j.ahj.2012.12.008 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120PV UT WOS:000317184300011 PM 23537966 ER PT J AU Vedantham, S Goldhaber, SZ Kahn, SR Julian, J Magnuson, E Jaff, MR Murphy, TP Cohen, DJ Comerota, AJ Gornik, HL Razavi, MK Lewis, L Kearon, C AF Vedantham, Suresh Goldhaber, Samuel Z. Kahn, Susan R. Julian, Jim Magnuson, Elizabeth Jaff, Michael R. Murphy, Timothy P. Cohen, David J. Comerota, Anthony J. Gornik, Heather L. Razavi, Mahmood K. Lewis, Lawrence Kearon, Clive TI Rationale and design of the ATTRACT Study: A multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; VENOUS THROMBOSIS; DETERMINANTS; SEVERITY; DISEASE; HEPARIN; BURDEN; STREPTOKINASE; DEFINITION; VILLALTA AB Background Current standard therapy for patients with acute proximal deep vein thrombosis (DVT) consists of anticoagulant therapy and graduated elastic compression stockings. Despite use of this strategy, the postthrombotic syndrome (PTS) develops frequently, causes substantial patient disability, and impairs quality of life. Pharmacomechanical catheter-directed thrombolysis (PCDT), which rapidly removes acute venous thrombus, may reduce the frequency of PTS. However, this hypothesis has not been tested in a large multicenter randomized trial. Study design The ATTRACT Study is an ongoing National Institutes of Health-sponsored, Phase III, multicenter, randomized, open-label, assessor-blinded, parallel two-arm, controlled clinical trial. Approximately 692 patients with acute proximal DVT involving the femoral, common femoral, and/or iliac vein are being randomized to receive PCDT + standard therapy versus standard therapy alone. The primary study hypothesis is that PCDT will reduce the proportion of patients who develop PTS within 2 years by one-third, assessed using the Villalta Scale. Secondary outcomes include safety, general and venous disease-specific quality of life, relief of early pain and swelling, and cost-effectiveness. Conclusion ATTRACT will determine if PCDT should be routinely used to prevent PTS in patients with symptomatic proximal DVT above the popliteal vein. (Am Heart J 2013;165:523-530.e3.) C1 [Vedantham, Suresh] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA. [Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kahn, Susan R.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Julian, Jim; Kearon, Clive] McMaster Univ, Hamilton, ON, Canada. [Magnuson, Elizabeth; Cohen, David J.] Univ Missouri Kansas City, St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Murphy, Timothy P.] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. [Comerota, Anthony J.] Univ Michigan, Toledo, OH USA. [Gornik, Heather L.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Razavi, Mahmood K.] St Josephs Vasc Inst, Orange, CA USA. [Lewis, Lawrence] Washington Univ, Sch Med, St Louis, MO USA. RP Vedantham, S (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, 510 S Kingshighway Blvd,Box 8131, St Louis, MO 63130 USA. EM vedanthams@mir.wustl.edu FU National Heart, Lung, and Blood Institute (NIH) [U01-HL088476, U01-HL088118]; Bayer Healthcare; BSN Medical; Covidien; Genentech FX The ATTRACT Study is supported by awards U01-HL088476 and U01-HL088118 from the National Heart, Lung, and Blood Institute (NIH). The contents of this article are solely the responsibility of the authors and do not represent the official views of the National Heart, Lung, and Blood Institute or NIH. Additional support for the study was provided by Bayer Healthcare, BSN Medical, Covidien, and Genentech. The authors wish to recognize the Society of Interventional Radiology Foundation, including Drs Stephen Kee and John Rundback, for its support for the planning and conduct of the ATTRACT Study. NR 30 TC 50 Z9 53 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2013 VL 165 IS 4 BP 523 EP + DI 10.1016/j.ahj.2013.01.024 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120PV UT WOS:000317184300013 PM 23537968 ER PT J AU Bui, AL Grau-Sepulveda, MV Hernandez, AF Peterson, ED Yancy, CW Bhatt, DL Fonarow, GC AF Bui, Anh L. Grau-Sepulveda, Maria V. Hernandez, Adrian F. Peterson, Eric D. Yancy, Clyde W. Bhatt, Deepak L. Fonarow, Gregg C. TI Admission heart rate and in-hospital outcomes in patients hospitalized for heart failure in sinus rhythm and in atrial fibrillation SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; GUIDELINES PROGRAM; PREDICTIVE VALUE; RISK-FACTOR; MORTALITY; ASSOCIATION; TRIAL AB Background Prior studies have suggested an association between higher heart rate and higher mortality, particularly in chronic heart failure (HF). Whether this relationship holds true in patients hospitalized with HF and differs between patients in sinus rhythm (SR) and atrial fibrillation (AF) has not been well studied. Methods We examined 145,221 admissions for HF from 295 hospitals enrolled in Get With The Guidelines-Heart Failure from January 2005 through September 2011. The associations of admission heart rate with in-hospital outcomes were evaluated overall and by heart rhythm. Results Patients presenting at higher heart rate tended to be younger and have less comorbidities. In-hospital mortality had a J-shaped relationship with heart rate, with the lowest mortality rate associated with heart rates between 70 and 75. However, the relationship differed between patients presenting in SR and AF: at heart rates above 100, the mortality curve for AF plateaued, whereas that for SR continued to rise. Higher heart rate was independently associated with higher mortality (SR adjusted OR 1.21, 95% CI 1.15-1.28 per 10 beat per minute increase in heart rate between 70-105; AF adjusted OR 1.20, 95% CI 1.14-1.27). Findings were similar when stratifying patients by ischemic etiology, diabetes, ejection fraction, blood pressure, and beta-blocker use. Conclusions Higher admission heart rate is independently associated with worse outcomes in patients admitted for HF, including those in SR and AF. Whether early heart rate reduction improves outcomes in patients hospitalized with HF is worthy of investigation. (Am Heart J 2013;165:567-574.e6.) C1 [Bui, Anh L.] Kaiser Permanente Med Ctr, Dept Cardiol, Los Angeles, CA 90034 USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Yancy, Clyde W.] Northwestern Univ, Sch Med, Div Cardiol, Chicago, IL USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, UCLA Med Ctr, Los Angeles, CA 90095 USA. RP Fonarow, GC (reprint author), Ahmanson UCLA Cardiomyopathy Ctr, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Medtronic; GlaxoSmithKline; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable FX The GWTG-HF program is provided by the American Heart Association. GWTG-HF has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. NR 25 TC 13 Z9 15 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2013 VL 165 IS 4 BP 567 EP + DI 10.1016/j.ahj.2013.01.007 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120PV UT WOS:000317184300019 PM 23537974 ER PT J AU Soni, RK Palevsky, PM AF Soni, Ritu K. Palevsky, Paul M. TI THE SMARTPHONE IN NEPHROLOGY: PRELIMINARY SURVEY ON CURRENT TRENDS AND PERCEIVED NEEDS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT International Conference on Glomerular Diseases CY APR 27, 2012 CL Hofstra N Shore LIJ Sch Med, Div Kidney Dis & Hypertens, Great Neck, NY SP N Shore LIJ Hlth Syst, Natl Kidney Fdn HO Hofstra N Shore LIJ Sch Med, Div Kidney Dis & Hypertens C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2013 VL 61 IS 4 MA 302 BP A91 EP A91 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 121WG UT WOS:000317274900304 ER PT J AU Chang, TI Li, SY Chen, SC Peralta, CA Shlipak, MG Fried, LF Whaley-Connell, AT McCullough, PA Tamura, MK AF Chang, Tara I. Li, Suying Chen, Shu-Cheng Peralta, Carmen A. Shlipak, Michael G. Fried, Linda F. Whaley-Connell, Adam T. McCullough, Peter A. Tamura, Manjula Kurella CA KEEP Investigators TI Risk Factors for ESRD in Individuals With Preserved Estimated GFR With and Without Albuminuria: Results From the Kidney Early Evaluation Program (KEEP) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Albuminuria; blood pressure; chronic kidney disease; diabetes; dialysis risk factors; end-stage renal disease; public health. ID STAGE RENAL-DISEASE; BLOOD-PRESSURE CONTROL; GLOMERULAR-FILTRATION-RATE; COMPETING RISK; PROGRESSION; PROTEINURIA; FAILURE; TRIAL; NEPHROPATHY; POPULATION AB Background: Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD. Methods: This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR >= 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death. Results: During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure. Conclusions: In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease. Am J Kidney Dis. 61(4)(S2): S4-S11. (C) 2013 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Chang, Tara I.; Tamura, Manjula Kurella] Stanford Univ, Sch Med, Div Nephrol, Dept Med, Palo Alto, CA 94304 USA. [Li, Suying; Chen, Shu-Cheng] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Whaley-Connell, Adam T.] Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA. [Whaley-Connell, Adam T.] Univ Missouri, Columbia Sch Med, Div Nephrol & Hypertens, Columbia, MO USA. [McCullough, Peter A.] St John Providence Hlth Syst, Providence Pk Heart Inst, Novi, MI USA. RP Chang, TI (reprint author), Stanford Univ, Sch Med, Div Nephrol, 777 Welch Rd,Ste DE,Rm D100, Palo Alto, CA 94304 USA. EM tichang@stanford.edu RI Kurella Tamura, Manjula/C-8284-2014; OI Kurella Tamura, Manjula/0000-0001-5227-2479; Whaley-Connell, Adam/0000-0001-8955-5560 FU National Kidney Foundation Inc; Abbott; Amgen; LifeScan; Siemens; Genentech; GMFoundation; Nephroceuticals; Pfizer; American Heart Association National Scientist Development Grant [12SDG11670032]; T. FranklinWilliams Scholarship Award [CDA-2 BB47, AG040638]; Atlantic Philanthropies Inc; John A. Hartford Foundation; ASP; ASN; Novartis Corp. FX KEEP is a program of the National Kidney Foundation Inc and is supported by Abbott, Amgen, LifeScan, Siemens, Genentech, GMFoundation, Nephroceuticals, and Pfizer. Dr Chang is supported by an American Heart Association National Scientist Development Grant (12SDG11670032). Department of Veterans Affairs CDA-2 BB47, National Institutes of Health AG040638, and the American Society of Nephrology- Association of Specialty Professors (ASN-ASP) Development Grant in Geriatric Nephrology to Dr Whaley-Connell are supported by a T. FranklinWilliams Scholarship Award, funding provided by Atlantic Philanthropies Inc, the John A. Hartford Foundation, the ASP, and the ASN. This research was also supported by Novartis Corp. NR 30 TC 17 Z9 17 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2013 VL 61 IS 4 SU 2 BP S4 EP S11 DI 10.1053/j.ajkd.2012.12.016 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 121US UT WOS:000317270600002 PM 23507268 ER PT J AU Birdsall, HH AF Birdsall, Holly H. TI Women as Leaders and Investigators in VA Research SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Birdsall, Holly H.] US Dept Vet Affairs, Washington, DC USA. [Birdsall, Holly H.] Baylor Coll Med, Houston, TX 77030 USA. RP Birdsall, HH (reprint author), US Dept Vet Affairs, Washington, DC USA. NR 1 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 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2013 VL 126 IS 4 BP E9 EP E9 DI 10.1016/j.amjmed.2012.08.022 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 115IR UT WOS:000316806300004 PM 23507219 ER PT J AU McCarren, M Goldman, S AF McCarren, Madeline Goldman, Steven TI Women as Leaders and Investigators in VA Research Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [McCarren, Madeline] US Dept Vet Affairs, Pharm Benefits Management Serv 10P4P, Hines, IL USA. [Goldman, Steven] US Dept Vet Affairs, Southern Arizona VA Healthcare Syst 111C, Tucson, AZ USA. RP McCarren, M (reprint author), US Dept Vet Affairs, Pharm Benefits Management Serv 10P4P, Hines, IL 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 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2013 VL 126 IS 4 BP E11 EP E11 DI 10.1016/j.amjmed.2012.09.007 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 115IR UT WOS:000316806300005 PM 23507209 ER PT J AU Masuzawa, A Black, KM Pacak, CA Ericsson, M Barnett, RJ Drumm, C Seth, P Bloch, DB Levitsky, S Cowan, DB McCully, JD AF Masuzawa, Akihiro Black, Kendra M. Pacak, Christina A. Ericsson, Maria Barnett, Reanne J. Drumm, Ciara Seth, Pankaj Bloch, Donald B. Levitsky, Sidney Cowan, Douglas B. McCully, James D. TI Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardioprotection; ischemia; mitochondria; myocardial infarction ID PROTEOMIC ANALYSIS; STROMAL CELLS; RABBIT HEART; STEM-CELLS; CARDIOPROTECTION; CARDIOPLEGIA; RESPIRATION; SKELETAL; MYOCARDIUM; DYSTROPHIN AB Masuzawa A, Black KM, Pacak CA, Ericsson M, Barnett RJ, Drumm C, Seth P, Bloch DB, Levitsky S, Cowan DB, McCully JD. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am J Physiol Endocrinol Metab 304: H966-H982, 2013. First published January 25, 2013; doi:10.1152/ajpheart.00883.2012.-Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 +/- 1.7 x 10(6)/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 +/- 2.9%) compared with RI-vehicle (34.2 +/- 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2-8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. C1 [Masuzawa, Akihiro; Black, Kendra M.; Barnett, Reanne J.; Drumm, Ciara; Levitsky, Sidney; McCully, James D.] Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Dept Surg, Boston, MA 02215 USA. [Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.; McCully, James D.] Harvard Univ, Sch Med, Boston, MA USA. [Pacak, Christina A.; Cowan, Douglas B.] Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Ericsson, Maria] Harvard Univ, Sch Med, Electron Microscopy Facil, Dept Cell Biol, Boston, MA USA. [Seth, Pankaj] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Dept Med, Boston, MA 02215 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP McCully, JD (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, 330 Brookline Ave,DA 0734, Boston, MA 02215 USA. EM james_mccully@hms.harvard.edu FU National Heart, Lung, and Blood Institute [HL-103642, HL-088206] FX This study was supported by National Heart, Lung, and Blood Institute Grants HL-103642 and HL-088206. NR 42 TC 29 Z9 30 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2013 VL 304 IS 7 BP H966 EP H982 DI 10.1152/ajpheart.00883.2012 PG 17 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 118DH UT WOS:000317002500007 PM 23355340 ER PT J AU Thompson, BT Matthay, MA AF Thompson, B. Taylor Matthay, Michael A. TI The Berlin Definition of ARDS versus Pathological Evidence of Diffuse Alveolar Damage SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; CLINICAL-TRIAL; VENTILATION C1 [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Matthay, Michael A.] Univ San Francisco, Cardiovasc Res Inst, San Francisco, CA 94117 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [R37 HL051856] NR 15 TC 25 Z9 27 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2013 VL 187 IS 7 BP 675 EP 677 DI 10.1164/rccm.201302-0385ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 122KE UT WOS:000317316200006 PM 23540876 ER PT J AU Bogoch, II Andrews, JR Speich, B Utzinger, J Ame, SM Ali, SM Keiser, J AF Bogoch, Isaac I. Andrews, Jason R. Speich, Benjamin Utzinger, Juerg Ame, Shaali M. Ali, Said M. Keiser, Jennifer TI Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NEGLECTED TROPICAL DISEASES; EFFICACY AB We created a mobile phone microscope and assessed its accuracy for the diagnosis of soil-transmitted helminths compared with conventional microscopy. Mobile phone microscopy has a sensitivity of 69.4% for detecting any helminth egg and sensitivities of 81.0%, 54.4%, and 14.3% for the diagnosis of Ascaris lumbricoides, Trichuris trichiura and hookworm respectively. C1 [Bogoch, Isaac I.] Toronto Gen Hosp, Div Internal Med, Toronto, ON M5G 2C4, Canada. [Bogoch, Isaac I.] Toronto Gen Hosp, Div Infect Dis, Toronto, ON M5G 2C4, Canada. [Andrews, Jason R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Speich, Benjamin; Keiser, Jennifer] Swiss Trop & Publ Hlth Inst, Dept Med Parasitol & Infect Biol, Basel, Switzerland. [Speich, Benjamin; Utzinger, Juerg; Keiser, Jennifer] Univ Basel, Basel, Switzerland. [Utzinger, Juerg] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Ame, Shaali M.; Ali, Said M.] Publ Hlth Lab, Pemba Isl, Zanzibar, Tanzania. RP Bogoch, II (reprint author), Toronto Gen Hosp, 14EN-209,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM isaac.bogoch@uhn.ca; jandrews6@partners.org; benjamin.speich@unibas.ch; juerg.utzinger@unibas.ch; shaaliame@yahoo.com; saidmali2003@yahoo.com; jennifer.keiser@unibas.ch FU Medicor Foundation; Swiss National Science Foundation (SNSF) [PPOOA-114941, PPOOP3_135170] FX This work was supported by The Medicor Foundation. J.K. is financially supported by the Swiss National Science Foundation (SNSF; projects PPOOA-114941 and PPOOP3_135170). NR 19 TC 41 Z9 42 U1 0 U2 13 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2013 VL 88 IS 4 BP 626 EP 629 DI 10.4269/ajtmh.12-0742 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 118KP UT WOS:000317024700005 PM 23478580 ER PT J AU Leung, DT Das, SK Malek, MA Ahmed, D Khanam, F Qadri, F Faruque, ASG Ryan, ET AF Leung, Daniel T. Das, Sumon K. Malek, M. A. Ahmed, Dilruba Khanam, Farhana Qadri, Firdausi Faruque, A. S. G. Ryan, Edward T. TI Non-Typhoidal Salmonella Gastroenteritis at a Diarrheal Hospital in Dhaka, Bangladesh, 1996-2011 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ANTIMICROBIAL RESISTANCE; CHILDHOOD DIARRHEA; ASIAN COUNTRIES; INFECTIONS; CHILDREN; DISEASE; SURVEILLANCE; BACTEREMIA; AFRICA; ENTEROPATHOGENS AB Data on non-typhoidal Salmonella (NTS) infection in South Asia are limited. We used data gathered prospectively from 1996 to 2011 as part of a hospital surveillance system in Dhaka, Bangladesh, to identify diarrheal patients with NTS isolated from stool. NTS was isolated in 1.3% (468 of 37,439) of diarrheal patients; 47% of total cases of NTS were in children <5 years of age, although older adults (>= 60 years) had the highest isolation rates. NTS isolation peaked in the monsoon months of July and August. Over the study period, rates of multidrug resistance decreased, whereas rates of decreased susceptibility to ciprofloxacin increased. Compared with control patients, NTS patients were older and wealthier; however, no differences in type of housing or exposure to animals were found. NTS patients had increased inflammatory cells in stool and required more fluid resuscitation. C1 [Leung, Daniel T.; Khanam, Farhana; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Bangladesh ICDDR B, Dhaka 1000, Bangladesh. [Das, Sumon K.; Malek, M. A.; Faruque, A. S. G.] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Bangladesh ICDDR B, Dhaka 1000, Bangladesh. [Ahmed, Dilruba] Int Ctr Diarrhoeal Dis Res, Clin Microbiol Lab, Bangladesh ICDDR B, Dhaka 1000, Bangladesh. [Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Leung, DT (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Bangladesh ICDDR B, GPO Box 128, Dhaka 1000, Bangladesh. EM dleung@icddrb.org; sumon@icddrb.org; mamalek@icddrli.org; dahmed@icddrb.org; farhanak@icddrb.org; fqadri@icddrb.org; gfaruque@icddrb.org; etryan@partners.org OI leung, daniel/0000-0001-8401-0801 FU ICDDR,B; National Institutes of Health; National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI100923, AI100023, AI077883]; National Institutes of Health, Fogarty International Center [TW005572]; American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund FX This work was supported by the ICDDR,B and its donors, which provide Unrestricted support to ICDDR,B for its operations and research. Current donors providing unrestricted support include the Australian Agency for 'International Development (AusAID), the Government of the People's Republic of Bangladesh, the Canadian International Development Agency (CIDA), the Swedish International Development Cooperation Agency (Sida), and the Department for International Development, United Kingdom (DFID). This study was also supported by grants from the National Institutes of Health, including National Institute of Allergy and Infectious Diseases Grants AI100923 (to D.T.L), AI100023 (to E.T.R.), and AI077883 (to E.T.R.) and Fogarty International Center Grant TW005572 (to F.K., F.Q., and E.T.R.), and a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund (to D.T.L.). NR 39 TC 6 Z9 7 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2013 VL 88 IS 4 BP 661 EP 669 DI 10.4269/ajtmh.12-0672 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 118KP UT WOS:000317024700010 PM 23358644 ER PT J AU Cserti-Gazdewich, CM Dhabangi, A Musoke, C Ssewanyana, I Ddungu, H Nakiboneka-Ssenabulya, D Nabukeera-Barungi, N Mpimbaza, A Dzik, WH AF Cserti-Gazdewich, Christine M. Dhabangi, Aggrey Musoke, Charles Ssewanyana, Isaac Ddungu, Henry Nakiboneka-Ssenabulya, Deborah Nabukeera-Barungi, Nicolette Mpimbaza, Arthur Dzik, Walter H. TI Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LIFE-THREATENING MALARIA; AFRICAN CHILDREN; CEREBRAL MALARIA; INFECTED ERYTHROCYTES; CLINICAL-FEATURES; CHILDHOOD MALARIA; ENDOTHELIAL-CELLS; GABONESE CHILDREN; PROGNOSTIC VALUE; LACTIC-ACIDOSIS AB Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory interrelationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov). C1 Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Musoke, Charles; Nabukeera-Barungi, Nicolette] Makerere Univ, Coll Hlth Sci, Mulago Hosp, Dept Paediat & Child Hlth, Kampala, Uganda. Joint Clin Res Ctr, Kampala, Uganda. [Ddungu, Henry] Uganda Canc Inst, Kampala, Uganda. [Ddungu, Henry] African Palliat Care Assoc, Kampala, Uganda. [Dzik, Walter H.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. [Cserti-Gazdewich, Christine M.] Toronto Gen Hosp, Univ Hlth Network, Dept Lab Hematol, Blood Transfus Med Lab, Toronto, ON, Canada. [Cserti-Gazdewich, Christine M.] Toronto Gen Hosp, Univ Hlth Network, Dept Med & Hematol, Toronto, ON, Canada. [Dhabangi, Aggrey] Child Hlth & Dev Ctr, Kampala, Uganda. [Ssewanyana, Isaac] Cent Publ Hlth Labs, Kampala, Uganda. [Nakiboneka-Ssenabulya, Deborah] London Sch Hyg & Trop Med, London WC1, England. [Mpimbaza, Arthur] Makerere Univ, Coll Hlth Sci, Child Hlth & Dev Ctr, Mulago Hosp, Kampala, Uganda. RP Dzik, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, J224,55 Fruit St, Boston, MA 02114 USA. EM christine.cserti@uhn.ca; adhabangi@gmail.com; jxyug@yahoo.com; sewyisaac@yahoo.co.uk; hddungu@gmail.com; debsenabulya@yahoo.com; nicbarungi@yahoo.com; arthurwakg@yahoo.com; sdzik@partners.org FU International Society of Blood Transfusion; National Blood Foundation; University of Toronto Dean's Fund; Evelyn and Robert Luick Fund FX This study was supported by the International Society of Blood Transfusion, the National Blood Foundation, the University of Toronto Dean's Fund, and the Evelyn and Robert Luick Fund. NR 37 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2013 VL 88 IS 4 BP 747 EP 756 DI 10.4269/ajtmh.12-0668 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 118KP UT WOS:000317024700025 PM 23358640 ER PT J AU Tsai, CL Delclos, GL Huang, JS Hanania, NA Camargo, CA AF Tsai, Chu-Lin Delclos, George L. Huang, Jamie S. Hanania, Nicola A. Camargo, Carlos A., Jr. TI Age-related differences in asthma outcomes in the United States, 1988-2006 SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID SERUM 25-HYDROXYVITAMIN D; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; OLDER US ADULTS; VITAMIN-D; NHANES-III; BRONCHODILATOR RESPONSIVENESS; CANCER-MORTALITY; REFERENCE VALUES; LUNG-FUNCTION AB Background: Relatively little is known about the effect of age on asthma outcomes in adults, particularly at a national level. Objective: To investigate age-related differences in asthma outcomes in a nationally representative, longitudinal study. Methods: We analyzed data from the Third National Health and Nutrition Examination Survey (1988-1994) with linked mortality files through 2006. Adults with physician-diagnosed asthma were identified and were divided into 2 age groups: younger adults (17-54 years of age) and older adults (55 years or older). The outcome measures were both cross-sectional (health care use, comorbidity, and lung function) and longitudinal (all-cause mortality). Results: There were an estimated 9,566,000 adults with current asthma. Of these, 73% were younger adults and 27% older adults. Compared with younger adults, older adults had more hospitalizations in the past year, more comorbidities, and poorer lung function (eg, lower forced expiratory volume in 1 second) (P<.05 for all). During a median follow-up of 15 years, significant baseline predictors of higher all-cause mortality included older age (>= 55 vs <55 years old: adjusted hazard ratio [HR], 6.77; 95% confidence interval [CI], 3.15-14.54), poor health status (fair and poor vs excellent health status: adjusted HR, 10.07; 95% CI, 3.75-27.01), and vitamin D deficiency (vitamin D level <30 vs >= 50 nmol/L: adjusted HR,2.19; 95% CI, 1.05-4.58), whereas Mexican American ethnicity (adjusted HR, 0.31; 95% CI, 0.14-0.65) was associated with lower mortality. Controlling for age, asthma was not associated with increased all-cause mortality (adjusted HR, 1.28; 95% CI, 0.99-1.65). Conclusion: Older adults with asthma have a substantial burden of morbidity and increased mortality. The ethnic differences in asthma mortality and the vitamin Demortality link merit further investigation. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin; Delclos, George L.; Huang, Jamie S.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Hanania, Nicola A.] Baylor Coll Med, Dept Med, Sect Pulm & Crit Care Med, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Tsai, CL (reprint author), Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, 1200 Herman Pressler,Ste W610, Houston, TX 77030 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 45 TC 13 Z9 13 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2013 VL 110 IS 4 BP 240 EP + DI 10.1016/j.anai.2013.01.002 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 121VY UT WOS:000317274000006 PM 23535086 ER PT J AU Muniappan, A Wain, JC Wright, CD Donahue, DM Gaissert, H Lanuti, M Mathisen, DJ AF Muniappan, Ashok Wain, John C. Wright, Cameron D. Donahue, Dean M. Gaissert, Henning Lanuti, Michael Mathisen, Douglas J. TI Surgical Treatment of Nonmalignant Tracheoesophageal Fistula: A Thirty-Five Year Experience SO ANNALS OF THORACIC SURGERY LA English DT Article ID MANAGEMENT; REPAIR AB Background. Acquired nonmalignant tracheoesophageal fistula in the adult patient develops in a variety of conditions. We have applied surgical closure with success for 35 years. Methods. From 1975 to 1991, 38 patients underwent surgical repair of a tracheoesophageal fistula. A retrospective study of 36 additional patients undergoing surgical repair from 1992 to 2010 was conducted. Results. The most common causes were postintubation injury (n = 17, 47%), trauma (n = 6, 17%), prior laryngectomy (n = 6,17%), and prior esophagectomy (n = 4,11%). Four patients presented after failing fistula control with an endoluminal stent. The tracheal defect was closed with resection and reconstruction (n = 17, 41%), laryngotracheal resection (n = 5, 12%), membranous tracheal repair (n = 17, 41%), or repair over a tracheal T tube (n = 2, 5%), while esophageal repair consisted of 2-layer closure (n. = 31, 78%), 1-layer closure (n = 6, 15%), esophagostomy (n = 1, 3%), end-to-end esophageal anastomosis (n = 1, 3%), or full thickness skin graft reconstruction (n = 1, 3%). The esophageal and tracheal repairs were buttressed by interposing pedicled muscle or omental flaps in all patients. There was 1 postoperative death (3%). Recurrence after repair developed only in fistulas arising after esophagectomy or laryngectomy (n = 4, 11%). Fistula closure was ultimately successful in 34 patients (94%). Twenty-nine patients (83%) resumed oral intake and 25 patients (71%) were breathing without a tracheal appliance. Conclusions. Successful closure of benign tracheoesophageal fistula is achieved with several surgical techniques based on buttressed repair and restoration of normal breathing and swallowing. Closure of complex postsurgical fistula may fail. Endoluminal stenting was not found useful. (Ann Thorac Surg 2013;95:1141-6) (C) 2013 by The Society of Thoracic Surgeons C1 [Muniappan, Ashok; Wain, John C.; Wright, Cameron D.; Donahue, Dean M.; Gaissert, Henning; Lanuti, Michael; Mathisen, Douglas J.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Muniappan, A (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM amuniappan@partners.org NR 15 TC 18 Z9 18 U1 0 U2 8 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 2013 VL 95 IS 4 BP 1141 EP 1146 DI 10.1016/j.athoracsur.2012.07.041 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 120DI UT WOS:000317150600001 PM 23000263 ER PT J AU Rankin, JS He, X O'Brien, SM Jacobs, JP Welke, KF Filardo, G Shahian, DM AF Rankin, J. Scott He, Xia O'Brien, Sean M. Jacobs, Jeffrey P. Welke, Karl F. Filardo, Giovanni Shahian, David M. TI The Society of Thoracic Surgeons Risk Model for Operative Mortality After Multiple Valve Surgery SO ANNALS OF THORACIC SURGERY LA English DT Article ID MITRAL-VALVE; ATRIAL-FIBRILLATION; CARDIAC DATABASE; REPAIR; REPLACEMENT; REOPERATION; SURVIVAL; FAILURE; TRENDS AB Background. This study was undertaken to develop The Society of Thoracic Surgeons (STS) mortality risk models for multiple valve procedures, which comprise 12% of total valve operations. Methods. Data were obtained from the STS Adult Cardiac Surgery Database for 50,231 patients undergoing combinations of aortic (A), mitral (M), and tricuspid (T) surgery between January 1, 2004, and December 31, 2010, divided into developmental (2004 to 2009) and validation (2010) samples. Pulmonary valve operations, aortic root replacements, and dissection procedures were excluded, and insufficient AT procedures were available to model. Using stepwise logistic regression, the risk of operative mortality was estimated for each valve surgery type: AM, n = 27,035; MT, n = 18,686; and AMT, n = 4,510. Two separate models were estimated, one that included only patient characteristics and status at presentation, and thereby would be suitable for performance profiling; and another that added discretionary operative variables such as arrhythmia ablation or valve repair. Results. Unadjusted operative mortality was 7.6% for MT, 9.4% for AM, and 13.1% for AMT procedures. Significant risk factors for mortality included emergency presentation, advanced age, renal failure, reoperation, endocarditis, diabetes mellitus, severe chronic lung disease, peripheral vascular disease, coronary artery disease, and female sex. In models containing intraoperative variables, performance of arrhythmia ablation and atrioventricular valve repair were protective for mortality. In the validation sample, the model exhibited acceptable discrimination in each of the three procedural subgroups (C = 0.711 to 0.727). Conclusions. Risk models were developed to predict operative mortality for patients having multiple valve procedures. These models may be useful for outcome assessment, quality improvement, patient counseling, shared decision making, and research. (Ann Thorac Surg 2013;95:1484-90) (c) 2013 by The Society of Thoracic Surgeons C1 Vanderbilt Univ, Centennial Med Ctr, Nashville, TN 37205 USA. Duke Clin Res Inst, Durham, NC USA. Univ S Florida, Congenital Heart Inst Florida, All Childrens Hosp, Tampa, FL USA. Seattle Childrens Hosp, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rankin, JS (reprint author), Vanderbilt Univ, 320 Lynnwood Blvd, Nashville, TN 37205 USA. EM jsrankinmd@cs.com RI O'Brien, Sean/H-6268-2013 NR 25 TC 16 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2013 VL 95 IS 4 BP 1484 EP 1490 DI 10.1016/j.athoracsur.2012.11.077 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 120DI UT WOS:000317150600062 PM 23522221 ER PT J AU Rosenberg, M Noonan, S DeGutis, J Esterman, M AF Rosenberg, Monica Noonan, Sarah DeGutis, Joseph Esterman, Michael TI Sustaining visual attention in the face of distraction: a novel gradual-onset continuous performance task SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Sustained attention; Attentional fluctuations; Inhibition; Vigilance ID SELECTIVE ATTENTION; VIGILANCE DECREMENT; MINDFULNESS; VARIABILITY; FAILURES; LAPSES; BRAIN; MINDLESSNESS; ADHD; MIND AB Sustained attention is a fundamental aspect of human cognition and has been widely studied in applied and clinical contexts. Despite a growing understanding of how attention varies throughout task performance, moment-to-moment fluctuations are often difficult to assess. In order to better characterize fluctuations in sustained visual attention, in the present study we employed a novel continuous performance task (CPT), the gradual-onset CPT (gradCPT). In the gradCPT, a central face stimulus gradually transitions between individuals at a constant rate (1,200 ms), and participants are instructed to respond to each male face but not to a rare target female face. In the distractor-present version, the background distractors consist of scene images, and in the distractor-absent condition, of phase-scrambled scene images. The results confirmed that the gradCPT taxes sustained attention, as vigilance decrements were observed over the task's 12-min duration: Participants made more commission errors and showed increasingly variable response latencies (RTs) over time. Participants' attentional states also fluctuated from moment to moment, with periods of higher RT variability being associated with increased likelihood of errors and greater speed-accuracy trade-offs. In addition, task performance was related to self-reported mindfulness and the propensity for attention lapses in everyday life. The gradCPT is a useful tool for studying both low- and high-frequency fluctuations in sustained visual attention and is sensitive to individual differences in attentional ability. C1 [Rosenberg, Monica; Noonan, Sarah; DeGutis, Joseph; Esterman, Michael] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Noonan, Sarah; Esterman, Michael] Boston Univ, Sch Med, Boston, MA 02118 USA. [DeGutis, Joseph] Harvard Univ, Cambridge, MA 02138 USA. RP Rosenberg, M (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 182 JP, Boston, MA 02130 USA. EM monica.rosenberg@yale.edu OI Esterman, Michael/0000-0002-9000-3920 NR 73 TC 22 Z9 22 U1 2 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD APR PY 2013 VL 75 IS 3 BP 426 EP 439 DI 10.3758/s13414-012-0413-x PG 14 WC Psychology; Psychology, Experimental SC Psychology GA 122GQ UT WOS:000317306800005 PM 23299180 ER PT J AU Schendan, HE Tinaz, S Maher, SM Stern, CE AF Schendan, Haline E. Tinaz, Sule Maher, Stephen M. Stern, Chantal E. TI Frontostriatal and Mediotemporal Lobe Contributions to Implicit Higher-Order Spatial Sequence Learning Declines in Aging and Parkinson's Disease SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE Parkinson's disease; aging; implicit learning; medial temporal lobe; striatum; prefrontal cortex ID REACTION-TIME-TASK; MEDIAL TEMPORAL-LOBE; POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA; OLDER-ADULTS; MOTOR-SEQUENCE; ASSOCIATIVE DEFICIT; COGNITIVE DEFICITS; AGE-DIFFERENCES; MEMORY-SYSTEMS AB Sequence learning depends on the striatal system, but recent findings also implicate the mediotemporal lobe (MTL) system. Schendan, Searl, Melrose, and Stern (2003) found higher-order associative, learning-related activation in the striatum, dorsolateral prefrontal cortex, and the MTL during the early acquisition phase of both implicit and explicit variants of a serial response time task. This functional MRI (fMRI) study capitalized on this task to determine how changes in MTL function observed in aging and compromised frontostriatal function characteristic of patients with Parkinson's disease (PD) impacts sequence learning and memory under implicit instructions. Brain activity was compared between "sequence" and "random" conditions in 12 nondemented patients with PD and education-and gender-matched healthy control participants of whom 12 were age matched (MC) and 14 were younger (YC). Behaviorally, sequence-specific learning of higher-order associations was reduced with aging and changed further with PD and resulted primarily in implicit knowledge in the older participants. fMRI revealed reduced intensity and extent of sequence learning-related activation in older relative to younger people in frontostriatal circuits and the MTL. This was because signal was greater for the sequence than random condition in younger people, whereas older people, especially those with PD, showed the opposite pattern. Both older groups also showed increased activation to the task itself relative to baseline fixation. In addition, right MTL showed hypoactivation and left MTL hyperactivation in PD relative to the MC group. The results suggest changes in frontostriatal and MTL activity occur during aging that affect task-related activity and the initial acquisition phase of implicit higher-order sequence learning. In addition, the results suggest that Parkinson's disease adversely affects processes in the MTL including sequence learning and memory. C1 [Schendan, Haline E.] Univ Plymouth, Sch Psychol, Ctr Brain Cognit & Behav, Cognit Inst, Plymouth PL4 8AA, Devon, England. [Schendan, Haline E.; Tinaz, Sule; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Tinaz, Sule; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Maher, Stephen M.] Tufts Univ, Dept Psychol, Medford, MA USA. [Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Stern, Chantal E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Schendan, HE (reprint author), Univ Plymouth, Sch Psychol, Ctr Brain Cognit & Behav, Cognit Inst, Portland Sq A208, Plymouth PL4 8AA, Devon, England. EM Haline.Schendan@plymouth.ac.uk OI Schendan, Haline/0000-0001-8925-5605 FU NIMH [R21 MH066213]; Plymouth University; EU [PCIG09-GA-2011-294144-COGNITSIMS] FX Research was supported by NIMH Award R21 MH066213 to C.E.S. and H.E.S. and an International Research, Networking and Collaboration grant from Plymouth University and EU FP7 Marie Curie award PCIG09-GA-2011-294144-COGNITSIMS to H.E.S. We acknowledge imaging support from the Athinoula A. Martinos Center for Biomedical Imaging and NCRR P41RR14075. We thank Kim C. Willment, PhD, for assisting with analyzing the neuroimaging data and preparing earlier drafts of the manuscript. We thank Alice Cronin-Golomb, PhD, for assistance with participant recruitment and visual and cognitive clinical assessment and Robert Ross, PhD, for his assistance with the study. We are also extremely grateful for the generous time and cooperation of the PD patients and the MC individuals who participated in this research. NR 76 TC 11 Z9 11 U1 1 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2013 VL 127 IS 2 BP 204 EP 221 DI 10.1037/a0032012 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 119VY UT WOS:000317128600008 PM 23565935 ER PT J AU Radhakrishnan, K Bhatia, M Geyer, MB del Toro, G Jin, ZZ Baker, C Harrison, L Morris, E Baxter-Lowe, LA Cairo, MS AF Radhakrishnan, Kavita Bhatia, Monica Geyer, Mark B. del Toro, Gustavo Jin, Zhezhen Baker, Courtney Harrison, Lauren Morris, Erin Baxter-Lowe, Lee Ann Cairo, Mitchell S. TI Busulfan, Fludarabine, and Alemtuzumab Conditioning and Unrelated Cord Blood Transplantation in Children with Sickle Cell Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Letter ID RECIPIENTS; DONORS C1 [Radhakrishnan, Kavita; Bhatia, Monica; Baker, Courtney] Columbia Univ, Dept Pediat, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY 10027 USA. [Jin, Zhezhen] Columbia Univ, Dept Biostat, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY USA. [Geyer, Mark B.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [del Toro, Gustavo] Wyckoff Hts Med Ctr, Dept Pediat, New York, NY USA. [Baxter-Lowe, Lee Ann] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Harrison, Lauren; Morris, Erin; Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. RP Cairo, MS (reprint author), New York Med Coll, Dept Pediat, Room 110A, Valhalla, NY 10595 USA. EM Mitchell_cairo@nymc.edu OI Geyer, Mark/0000-0001-5248-9117 NR 10 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2013 VL 19 IS 4 BP 676 EP 677 DI 10.1016/j.bbmt.2013.02.002 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 120IH UT WOS:000317163500026 PM 23403308 ER PT J AU Budde, LE Zhang, MM Shustov, AR Pagel, JM Gooley, TA Oliveira, GR Chen, TL Knudsen, NL Roden, JE Kammerer, BE Frayo, SL Warr, TA Boyd, TE Press, OW Gopal, AK AF Budde, Lihua E. Zhang, Michelle M. Shustov, Andrei R. Pagel, John M. Gooley, Ted A. Oliveira, George R. Chen, Tara L. Knudsen, Nancy L. Roden, Jennifer E. Kammerer, Britt E. Frayo, Shani L. Warr, Thomas A. Boyd, Thomas E. Press, Oliver W. Gopal, Ajay K. TI A phase I study of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE 2 stage design; clinical trial; lymphoma; phase I; vorinostat ID HISTONE DEACETYLASE INHIBITOR; B-CELL LYMPHOMA; SUBEROYLANILIDE HYDROXAMIC ACID; HODGKINS-LYMPHOMA; FOLLICULAR LYMPHOMA; ADVANCED CANCER; EXPRESSION; TRANSPLANTATION; ANGIOGENESIS; SURVIVAL AB Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that 2 center dot 5mol/l concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high-dose vorinostat could safely augment the anti-tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400mg/d to 700mg bid for 5d in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty-nine patients [median age 56years, median 2 prior therapies, 14 chemoresistant (of 27 evaluable), 2 prior transplants] were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500mg twice dailyx5d. Common dose limiting toxicities included infection (n=2), hypokalaemia (n=2), and transaminitis (n=2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4 center dot 5mol/l (range 4 center dot 26 center dot 0mol/l) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High-dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted. C1 [Budde, Lihua E.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Knudsen, Nancy L.; Kammerer, Britt E.; Frayo, Shani L.; Press, Oliver W.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Budde, Lihua E.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Roden, Jennifer E.; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Dept Med, Seattle, WA 98109 USA. [Zhang, Michelle M.] Valley Med Ctr, Renton, WA USA. [Oliveira, George R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chen, Tara L.] Univ Washington, Serv Pharm, Seattle, WA 98109 USA. [Warr, Thomas A.] Great Falls Clin, Great Falls, MT USA. [Boyd, Thomas E.] Yakima Reg Med & Cardiac Ctr, Yakima, WA USA. [Budde, Lihua E.] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA. RP Gopal, AK (reprint author), Univ Washington, Med Ctr, Dept Med, 825 Eastlake Ave E,G3-200, Seattle, WA 98109 USA. EM agopal@u.washington.edu FU Merck Sharp Dohme Corp USA; Washington State Life Sciences Discovery Fund; NIH PO1 [CA44991]; Lymphoma Research Foundation Mantle Cell Lymphoma Initiative, a SCOR [7040]; Leukemia and Lymphoma Society; Wright Memorial Research Fund; Clinical Research of the Leukemia and Lymphoma Society FX This work was supported by Merck Sharp & Dohme Corp USA, the Washington State Life Sciences Discovery Fund, an NIH PO1 grant (CA44991), a grant from the Lymphoma Research Foundation Mantle Cell Lymphoma Initiative, a SCOR grant (7040) from the Leukemia and Lymphoma Society, the Mary A. Wright Memorial Research Fund, a donation from Frank and Betty Vandermeer. L.E.B is a Special Fellow in Clinical Research of the Leukemia and Lymphoma Society. A.K.G is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 28 TC 9 Z9 9 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2013 VL 161 IS 2 BP 183 EP 191 DI 10.1111/bjh.12230 PG 9 WC Hematology SC Hematology GA 119UN UT WOS:000317124200006 PM 23356514 ER PT J AU Hartmann, AS Hilbert, A AF Hartmann, A. S. Hilbert, A. TI Child and adolescent obesity, psychosocial consequences and treatment strategies SO BUNDESGESUNDHEITSBLATT-GESUNDHEITSFORSCHUNG-GESUNDHEITSSCHUTZ LA German DT Article DE Obesity; Childhood and adolescence; Psychosocial factors; Therapeutic strategies; Overweight ID GERMAN HEALTH INTERVIEW; QUALITY-OF-LIFE; OVERWEIGHT CHILDREN; DUTCH ADOLESCENTS; EATING-DISORDER; WEIGHT STATUS; PREVENTION; SAMPLE; KIGGS; RISK AB Being overweight and obese in childhood and adolescence is associated with various somatic and psychosocial sequelae. Psychosocial problems can negatively influence the future weight trajectory. Therefore, weight reduction or stabilization should be complemented by the treatment of significant psychosocial problems. This review provides an overview of the psychosocial problems associated with being overweight and obese in childhood and adolescence. Evidence on weight-related stigmatization and discrimination, eating disorder symptoms, general psychopathology, impaired quality of life, lowered self-esteem, social skill deficits, as well as academic problems is summarized. Furthermore, state-of-the-art diagnostic and therapeutic procedures for the psychosocial problems are summarized. Future research should focus on the development of interventions targeting the destigmatization of obesity, as experiences of stigmatization and discrimination likely aggravate the psychosocial sequelae of overweight and obesity. C1 [Hartmann, A. S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hartmann, A. S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hilbert, A.] Univ Med Leipzig, Integriertes Forsch & Behandlungszentrum Adiposit, Leipzig, Germany. RP Hartmann, AS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2200,Simches Res Bldg, Boston, MA 02114 USA. EM andrea.sabrina.hartmann@gmail.com NR 60 TC 0 Z9 0 U1 3 U2 39 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1436-9990 J9 BUNDESGESUNDHEITSBLA JI Bundesgesundheitsblatt-Gesund. PD APR PY 2013 VL 56 IS 4 BP 532 EP 538 DI 10.1007/s00103-012-1637-6 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 114MH UT WOS:000316744900009 PM 23529599 ER PT J AU Ahmed, N AF Ahmed, Na'eem TI Scientific publishing needs disruption SO CLINICAL MEDICINE LA English DT Editorial Material C1 [Ahmed, Na'eem] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ahmed, Na'eem] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ahmed, Na'eem] Kings Coll Hosp, London, England. RP Ahmed, N (reprint author), NHS Commissioning Board, 4-8 Maple St, London W1T 5HD, England. EM naeem.ahmed@nhs.net NR 3 TC 0 Z9 0 U1 0 U2 1 PU ROY COLL PHYS LONDON EDITORIAL OFFICE PI LONDON PA 11 ST ANDREWS PLACE REGENTS PARK, LONDON NW1 4LE, ENGLAND SN 1470-2118 J9 CLIN MED JI Clin. Med. PD APR PY 2013 VL 13 IS 2 BP 125 EP 125 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 122JQ UT WOS:000317314800002 PM 23681856 ER PT J AU Khoshbin, S Herring, A Holmes, GL Schomer, D Hoch, D Dooling, EC Vining, EPG Holmes, LB AF Khoshbin, Shahram Herring, Amy Holmes, Gregory L. Schomer, Donald Hoch, Daniel Dooling, Elizabeth C. Vining, Eileen P. G. Holmes, Lewis B. TI Inter-rater agreement for diagnoses of epilepsy in pregnant women SO EPILEPSY & BEHAVIOR LA English DT Article DE Types of seizures; Adult and pediatric neurologists; Log-linear modeling ID SEIZURES; CLASSIFICATION; RELIABILITY; CHILDHOOD; CHILDREN; SCALE AB We report on inter-rater agreement in assessing the types of seizures exhibited by one hundred mothers ascertained in a study of the teratogenicity of maternal epilepsy and antiepileptic drugs. A summary of each woman's medical record and a one-page report of her responses to questions about her epilepsy were reviewed independently by six neurologists, three in pediatric neurology and three in adult neurology. Agreement was measured by the kappa statistic and log-linear modeling techniques. The adult neurologists agreed with each other 59% of the time, with the agreement higher when all three used information from the patients' records, such as an EEG, rather than when depending on the patients' responses to questions about their epilepsy. The pediatric neurologists agreed with each other 44% of the time and tended to rely more heavily on information in the patients' records, such as an EEG or a prior diagnosis, compared with the adult neurologists. (C) 2013 Elsevier Inc. All rights reserved. C1 [Khoshbin, Shahram] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Herring, Amy] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Holmes, Gregory L.] Childrens Hosp, Dept Neurol, Boston, MA USA. [Schomer, Donald] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. [Hoch, Daniel] Massachusetts Gen Hosp, Epilepsy Ctr, Boston, MA 02114 USA. [Dooling, Elizabeth C.] Massachusetts Gen Hosp, Div Pediat Neurol, Dept Neurol, Boston, MA 02114 USA. [Vining, Eileen P. G.] Johns Hopkins Med Inst, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD USA. [Holmes, Lewis B.] MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu OI Hoch, Daniel/0000-0002-4294-024X FU NCRR NIH HHS [M01 RR001066]; NICHD NIH HHS [R24 HD050924] NR 22 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2013 VL 27 IS 1 BP 148 EP 153 DI 10.1016/j.yebeh.2012.12.030 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 118MG UT WOS:000317029000028 PM 23416992 ER PT J AU Sullivan, RJ Flaherty, KT AF Sullivan, Ryan J. Flaherty, Keith T. TI Resistance to BRAF-targeted therapy in melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Melanoma; BRAF inhibitor resistance; Molecular targeted therapy ID RANDOMIZED DISCONTINUATION TRIAL; INHIBITOR AZD6244 ARRY-142886; CHRONIC MYELOID-LEUKEMIA; B-RAF; METASTATIC MELANOMA; PHASE-II; MULTIKINASE INHIBITOR; MALIGNANT-MELANOMA; ADVANCED CANCERS; OPEN-LABEL AB BRAF mutations are identified in 40-50% of patients with melanoma. Treatment of these patients with either of two BRAF inhibitors (vemurafenib, dabrafenib) or the MEK inhibitor trametinib is associated with improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III trials. Unfortunately, most patients, including those who experience initial, profound tumour regression, have evidence of disease progression within 6-8 months after commencing therapy with one of these agents. The mechanisms of resistance are varied and include activation of alternative signalling pathways as well as reactivating the MAP kinase pathway through alternative means. This review describes relevant aspects of MAP kinase pathway signalling, summarises the clinical data with BRAF and MEK inhibitors, presents the known resistance mechanisms to BRAF inhibitor therapy, and provides some strategies for how resistance may be overcome. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sullivan, Ryan J.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Henri & Belinda Termeer Ctr Targeted Therapies, 55 Fruit St, Boston, MA 02114 USA. EM kflaherty@partners.org NR 64 TC 124 Z9 128 U1 2 U2 44 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 2013 VL 49 IS 6 BP 1297 EP 1304 DI 10.1016/j.ejca.2012.11.019 PG 8 WC Oncology SC Oncology GA 120RF UT WOS:000317188600016 PM 23290787 ER PT J AU Konijeti, GG Deshpande, V Bunker, CJ AF Konijeti, Gauree Gupta Deshpande, Vikram Bunker, Cheryl J. TI An Unusual Case of Chronic Diarrhea Answer to the Clinical Challenges and Images in GI Question: Image 3 (page 696): Lansoprazole-induced Microscopic Colitis SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Konijeti, Gauree Gupta; Bunker, Cheryl J.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Konijeti, GG (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. FU NIDDK NIH HHS [T32 DK007191, T32DK007191] NR 0 TC 0 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2013 VL 144 IS 4 BP 696 EP + DI 10.1053/j.gastro.2012.11.002 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JB UT WOS:000316735800026 PM 23491834 ER PT J AU Peters, U Jiao, S Schumacher, FR Hutter, CM Aragaki, AK Baron, JA Berndt, SI Bezieau, S Brenner, H Butterbach, K Caan, BJ Campbell, PT Carlson, CS Casey, G Chan, AT Chang-Claude, J Chanock, SJ Chen, LS Coetzee, GA Coetzee, SG Conti, DV Curtis, KR Duggan, D Edwards, T Fuchs, CS Gallinger, S Giovannucci, EL Gogarten, SM Gruber, SB Haile, RW Harrison, TA Hayes, RB Henderson, BE Hoffmeister, M Hopper, JL Hudson, TJ Hunter, DJ Jackson, RD Jee, SH Jenkins, MA Jia, WH Kolonel, LN Kooperberg, C Kuery, S Lacroix, AZ Laurie, CC Laurie, CA Le Marchand, L Lemire, M Levine, D Lindor, NM Liu, Y Ma, J Makar, KW Matsuo, K Newcomb, PA Potter, JD Prentice, RL Qu, CH Rohan, T Rosse, SA Schoen, RE Seminara, D Shrubsole, M Shu, XO Slattery, ML Taverna, D Thibodeau, SN Ulrich, CM White, E Xiang, YB Zanke, BW Zeng, YX Zhang, B Zheng, W Hsu, L AF Peters, Ulrike Jiao, Shuo Schumacher, Fredrick R. Hutter, Carolyn M. Aragaki, Aaron K. Baron, John A. Berndt, Sonja I. Bezieau, Stephane Brenner, Hermann Butterbach, Katja Caan, Bette J. Campbell, Peter T. Carlson, Christopher S. Casey, Graham Chan, Andrew T. Chang-Claude, Jenny Chanock, Stephen J. Chen, Lin S. Coetzee, Gerhard A. Coetzee, Simon G. Conti, David V. Curtis, Keith R. Duggan, David Edwards, Todd Fuchs, Charles S. Gallinger, Steven Giovannucci, Edward L. Gogarten, Stephanie M. Gruber, Stephen B. Haile, Robert W. Harrison, Tabitha A. Hayes, Richard B. Henderson, Brian E. Hoffmeister, Michael Hopper, John L. Hudson, Thomas J. Hunter, David J. Jackson, Rebecca D. Jee, Sun Ha Jenkins, Mark A. Jia, Wei-Hua Kolonel, Laurence N. Kooperberg, Charles Kuery, Sebastien Lacroix, Andrea Z. Laurie, Cathy C. Laurie, Cecelia A. Le Marchand, Loic Lemire, Mathieu Levine, David Lindor, Noralane M. Liu, Yan Ma, Jing Makar, Karen W. Matsuo, Keitaro Newcomb, Polly A. Potter, John D. Prentice, Ross L. Qu, Conghui Rohan, Thomas Rosse, Stephanie A. Schoen, Robert E. Seminara, Daniela Shrubsole, Martha Shu, Xiao-Ou Slattery, Martha L. Taverna, Darin Thibodeau, Stephen N. Ulrich, Cornelia M. White, Emily Xiang, Yongbing Zanke, Brent W. Zeng, Yi-Xin Zhang, Ben Zheng, Wei Hsu, Li CA Colon Canc Family Registry Genetics Epidemiology Colorectal TI Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis SO GASTROENTEROLOGY LA English DT Article DE Colon Cancer; Genetics; Risk Factors; SNP ID STRANDED-DNA-BINDING; BASE-LINE CHARACTERISTICS; CANCER SCREENING TRIAL; REPLICATION PROTEIN-A; ASSOCIATION SCAN; COLON-CANCER; WOMENS HEALTH; EPITHELIAL-CELLS; RANDOMIZED-TRIAL; MEAT CONSUMPTION AB BACKGROUND & AIMS: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS: We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS: Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 X 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 X 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 X 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 X 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 X 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 X 10(-7)). CONCLUSIONS: In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to beta-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation. C1 [Peters, Ulrike; Hutter, Carolyn M.; Aragaki, Aaron K.; Carlson, Christopher S.; Curtis, Keith R.; Harrison, Tabitha A.; Kooperberg, Charles; Lacroix, Andrea Z.; Makar, Karen W.; Newcomb, Polly A.; Potter, John D.; Prentice, Ross L.; Qu, Conghui; Rosse, Stephanie A.; Ulrich, Cornelia M.; White, Emily; Hsu, Li] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Gogarten, Stephanie M.; Laurie, Cathy C.; Laurie, Cecelia A.; Levine, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Peters, Ulrike; Hutter, Carolyn M.; Carlson, Christopher S.; Newcomb, Polly A.; Rosse, Stephanie A.; Ulrich, Cornelia M.; White, Emily] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Schumacher, Fredrick R.; Casey, Graham; Coetzee, Gerhard A.; Coetzee, Simon G.; Conti, David V.; Gruber, Stephen B.; Haile, Robert W.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Brenner, Hermann; Butterbach, Katja; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Campbell, Peter T.] Amer Canc Soc, Atlanta, GA 30329 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.; Ma, Jing] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.; Ma, Jing] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chen, Lin S.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Duggan, David; Taverna, Darin] Translat Genom Res Inst, Phoenix, AZ USA. [Edwards, Todd; Shrubsole, Martha; Shu, Xiao-Ou; Zhang, Ben] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gallinger, Steven] Toronto Gen Hosp, Dept Surg, Toronto, ON, Canada. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melborne Sch Populat Hlth, Melbourne, Vic, Australia. [Hudson, Thomas J.; Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Jee, Sun Ha] Yonsei Univ, Inst Hlth Promot, Seoul 120749, South Korea. [Jia, Wei-Hua; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Lindor, Noralane M.] Mayo Clin Scottsdale, Dept Hlth Sci Res, Scottsdale, AZ USA. [Liu, Yan] Stephens & Associates, Carrollton, GA USA. [Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Ulrich, Cornelia M.] German Canc Res Ctr, Heidelberg, Germany. [Xiang, Yongbing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Zanke, Brent W.] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M4-B402,POB 19024, Seattle, WA 98109 USA. EM upeters@fhcrc.org; lih@fhcrc.org RI Gallinger, Steven/E-4575-2013; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Shrubsole, Martha/K-5052-2015; Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; Coetzee, Simon/C-1218-2014; OI Gogarten, Stephanie/0000-0002-7231-9745; Hayes, Richard/0000-0002-0918-661X; Matsuo, Keitaro/0000-0003-1761-6314; Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; Shrubsole, Martha/0000-0002-5591-7575; Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Coetzee, Simon/0000-0003-4267-5930; Potter, John/0000-0001-5439-1500 FU National Cancer Institute, National Institutes of Health; US Department of Health and Human Services [U01 CA137088, R01 CA059045]; Japanese Ministry of Education, Culture, Sports, Science and Technology [17015018, 221S0001]; Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte Contre le Cancer; Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer; National Institutes of Health [U01 CA074783, R01 CA60987, RFA CA-95-011, R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364, P50CA95103, R01CA121060, K05 CA154337]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; National Cancer Institute, National Institutes of Health [U01 CA122839]; Vanderbilt University School of Medicine; Vanderbilt-Ingram Cancer Center [P30 CA 68485]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX The Genetics and Epidemiology of Colorectal Cancer Consortium study was supported by the National Cancer Institute, National Institutes of Health, and the US Department of Health and Human Services (U01 CA137088; R01 CA059045). The Asian Consortium was supported by a Grant-in-aid for Cancer Research, the Grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (17015018 and 221S0001). The french Association STudy Evaluating RISK for sporadic colorectal cancer was supported by a Hospital Clinical Research Program (PHRC) and by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte Contre le Cancer, the Association Anne de Bretagne Genetique, and the Ligue Regionale Contre le Cancer. The Assessment of Risk in Colorectal Tumours in Canada study was supported by the National Institutes of Health through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783; see the Colon Cancer Family Registry support section below); and by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, by a Cancer Risk Evaluation Program grant from the Canadian Cancer Society Research Institute, and by Senior Investigator Awards (T.J.H. and B.W.Z.) from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Economic Development and Innovation. The Hawaii Colorectal Cancer Studies 2 and 3 studies were supported by the National Institutes of Health (R01 CA60987). The Colon Cancer Family Registry was supported by the National Institutes of Health (RFA CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health (U01 CA122839). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the cancer family registries, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the cancer family registries. The following colon cancer family registries centers contributed data to this article and were supported by National Institutes of Health: the Australasian Colorectal Cancer Family Registry (U01 CA097735), Seattle Colorectal Cancer Family Registry (U01 CA074794), and the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). The Darmkrebs: Chancen der Verhutung durch Screening study was supported by the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). The Diet, Activity, and Lifestyle Study was supported by the National Institutes of Health (R01 CA48998 to M. L. S.); Guangzhou-1 was supported by the National Key Scientific and Technological Project (2011ZX09307-001-04) and the National Basic Research Program (2011CB504303) was supported by the People's Republic of China.; The Health Professionals Follow-up Study was supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003), the Nurses' Health Study was supported by the National Institutes of Health (R01 137178, P01 CA 087969, and P50 CA 127003), and the Physicians' Health Study was supported by the National Institutes of Health (CA42182). The Korean Cancer Prevention Study-II study was supported by the National R&D Program for cancer control (1220180), and the Seoul R&D Program (10526, Republic of Korea). The Multiethnic Cohort study was supported by the National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464). The Prostate, Lung, Colorectal Cancer, and Ovarian Cancer Screening Trial was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility prostate cancer scan, supported by the Intramural Research Program of the National Cancer Institute. The data sets used in this analysis were accessed with appropriate approval through the dbGaP online resource (http://www.cgems.cancer.gov/data_acess.html) through dbGaP accession number 000207v.1p1. Control samples also were genotyped as part of the GWAS of Lung Cancer and Smoking (Yeager, M et al. Nat Genet 2008;124:161-170). Support for this work was provided through the National Institutes of Health, Genes, Environment and Health Initiative (Z01 CP 010200). The human subjects participating in the genome-wide association study were derived from the Prostate, Lung, Colon, and Ovarian Screening Trial and the study was supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, Geneva Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the National Institutes of Health, Genes, Environment and Health Initiative (U01 HG 004438). The data sets used for the analyses described in this article were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000093 v2.p2. The Postmenopausal Hormone Study was supported by the National Institutes of Health (R01 CA076366 to P.A.N.). The Shanghai-1 and Shanghai-2 studies were supported by the National Institutes of Health (R37CA070867, R01CA082729, R01CA124558, R01CA148667, and R01CA122364), as well as an Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. The Tennessee Colorectal Polyp Study was supported by the National Institutes of Health (P50CA95103 and R01CA121060) and was conducted by the Survey and Biospecimen Shared Resource, which was supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA 68485). The VITamins And Lifestyle study was supported by the National Institutes of Health (K05 CA154337).; The Women's Health Initiative program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 106 TC 121 Z9 122 U1 4 U2 47 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 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2013 VL 144 IS 4 BP 799 EP + DI 10.1053/j.gastro.2012.12.020 PG 33 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JB UT WOS:000316735800039 PM 23266556 ER PT J AU Sia, D Hoshida, Y Villanueva, A Roayaie, S Ferrer, J Tabak, B Peix, J Sole, M Tovar, V Alsinet, C Cornella, H Klotzle, B Fan, JB Cotsoglou, C Thung, SN Fuster, J Waxman, S Garcia-Valdecasas, JC Bruix, J Schwartz, ME Beroukhim, R Mazzaferro, V Llovet, JM AF Sia, Daniela Hoshida, Yujin Villanueva, Augusto Roayaie, Sasan Ferrer, Joana Tabak, Barbara Peix, Judit Sole, Manel Tovar, Victoria Alsinet, Clara Cornella, Helena Klotzle, Brandy Fan, Jian-Bing Cotsoglou, Christian Thung, Swan N. Fuster, Josep Waxman, Samuel Carlos Garcia-Valdecasas, Juan Bruix, Jordi Schwartz, Myron E. Beroukhim, Rameen Mazzaferro, Vincenzo Llovet, Josep M. TI Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes SO GASTROENTEROLOGY LA English DT Article DE Liver Cancer; Molecular Classification; Whole-Genome Profiling; Prognosis ID BILIARY-TRACT CANCER; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; PROMOTER METHYLATION; THERAPEUTIC TARGETS; LIVER; PATHWAY; CELLS; CLASSIFICATION; IDENTIFICATION AB BACKGROUND & AIMS: Cholangiocarcinoma, the second most common liver cancer, can be classified as intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma. We performed an integrative genomic analysis of ICC samples from a large series of patients. METHODS: We performed a gene expression profile, high-density single-nucleotide polymorphism array, and mutation analyses using formalin-fixed ICC samples from 149 patients. Associations with clinicopathologic traits and patient outcomes were examined for 119 cases. Class discovery was based on a non-negative matrix factorization algorithm and significant copy number variations were identified by Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. Gene set enrichment analysis was used to identify signaling pathways activated in specific molecular classes of tumors, and to analyze their genomic overlap with hepatocellular carcinoma (HCC). RESULTS: We identified 2 main biological classes of ICC. The inflammation class (38% of ICCs) is characterized by activation of inflammatory signaling pathways, overexpression of cytokines, and STAT3 activation. The proliferation class (62%) is characterized by activation of oncogenic signaling pathways (including RAS, mitogen-activated protein kinase, and MET), DNA amplifications at 11q13.2, deletions at 14q22.1, mutations in KRAS and BRAF, and gene expression signatures previously associated with poor outcomes for patients with HCC. Copy number variation-based clustering was able to refine these molecular groups further. We identified high-level amplifications in 5 regions, including 1p13 (9%) and 11q13.2 (4%), and several focal deletions, such as 9p21.3 (18%) and 14q22.1 (12% in coding regions for the SAV1 tumor suppressor). In a complementary approach, we identified a gene expression signature that was associated with reduced survival times of patients with ICC; this signature was enriched in the proliferation class (P < .001). CONCLUSIONS: We used an integrative genomic analysis to identify 2 classes of ICC. The proliferation class has specific copy number alterations, activation of oncogenic pathways, and is associated with worse outcome. Different classes of ICC, based on molecular features, therefore might require different treatment approaches. C1 [Sia, Daniela; Villanueva, Augusto; Peix, Judit; Sole, Manel; Tovar, Victoria; Alsinet, Clara; Cornella, Helena; Fuster, Josep; Bruix, Jordi; Llovet, Josep M.] Univ Barcelona, Hosp Clin, Barcelona Clin Liver Canc Grp,Pathol Dept, HCC Translat Res Lab,Liver Unit,Inst Invest Biome, Barcelona, Catalonia, Spain. [Sia, Daniela; Cotsoglou, Christian; Mazzaferro, Vincenzo] Natl Canc Inst, Dept Expt Oncol, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy. [Hoshida, Yujin; Roayaie, Sasan; Thung, Swan N.; Waxman, Samuel; Schwartz, Myron E.; Llovet, Josep M.] Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Surg Oncol,Mt Sinai Liver Canc Program, Dept Pathol,Tisch Canc Inst,Dept Med,Div Liver Di, New York, NY USA. [Villanueva, Augusto; Peix, Judit; Bruix, Jordi; Llovet, Josep M.] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain. [Ferrer, Joana; Fuster, Josep; Carlos Garcia-Valdecasas, Juan] Hosp Clin Barcelona, Dept Surg, Barcelona, Catalonia, Spain. [Tabak, Barbara; Beroukhim, Rameen] Broad Inst, Canc Program, Cambridge, MA USA. [Klotzle, Brandy; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Div Canc Biol, Div Med Oncol, Boston, MA 02115 USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. RP Llovet, JM (reprint author), Hosp Clin, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi & Sunyer, Barcelona Clin Liver Canc BCLC Grp,Liver Unit, Villarroel 170, Catalonia 08036, Spain. EM jmllovet@clinic.cat RI Augusto, Villanueva/F-9378-2012; Llovet, Josep M /D-4340-2014; Mazzaferro, Vincenzo/C-2726-2017; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; Mazzaferro, Vincenzo/0000-0002-4013-8085; Bruix, Jordi/0000-0002-9826-0753 FU Asociacion Espanola Contra el Cancer; Instituto de Salud Carlos III [ISCIII/FIS FI10/00143, ISCIII/FIS FI09/00605]; US National Cancer Institute [K08CA122833, U54CA143798]; V Foundation Scholarship; Instituto Carlos III [ISCIII/FIS PI 11/01830]; Italian Association for Cancer Research; Oncology Research Project of the Italian Ministry of Health; US National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK076986-01]; European Commission [259744]; Samuel Waxman Cancer Research Foundation; Spanish National Health Institute [SAF-2010-16055] FX The study has been supported by a grant from the Asociacion Espanola Contra el Cancer. Helena Cornella is supported by a fellowship from the Instituto de Salud Carlos III (ISCIII/FIS FI10/00143); Clara Alsinet is supported by a fellowship from Instituto de Salud Carlos III (ISCIII/FIS FI09/00605); Rameen Beroukhim is supported by grants from the US National Cancer Institute (K08CA122833 and U54CA143798) and a V Foundation Scholarship; Jordi Bruix is supported by a grant from the Instituto Carlos III (ISCIII/FIS PI 11/01830); Vincenzo Mazzaferro is supported by grants from the Italian Association for Cancer Research and the Oncology Research Project of the Italian Ministry of Health; Josep Llovet is supported by grants from the Asociacion Espanola Contra el Cancer, the US National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), European Commission-FP7 Framework (HEPTROMIC, proposal no. 259744), the Samuel Waxman Cancer Research Foundation, and the Spanish National Health Institute (SAF-2010-16055). NR 51 TC 101 Z9 105 U1 1 U2 17 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 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2013 VL 144 IS 4 BP 829 EP 840 DI 10.1053/j.gastro.2013.01.001 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JB UT WOS:000316735800042 PM 23295441 ER PT J AU Townamchai, K Berkowitz, R Bhagwat, M Damato, AL Friesen, S Lee, LJ Matulonis, U O'Farrell, D Viswanathan, AN AF Townamchai, Kanokpis Berkowitz, Ross Bhagwat, Mandar Damato, Antonio L. Friesen, Scott Lee, Larissa J. Matulonis, Ursula O'Farrell, Desmond Viswanathan, Akila N. TI Vaginal brachytherapy for early stage uterine papillary serous and clear cell endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Vaginal brachytherapy; Uterine papillary serous cancer; High-dose-rate brachytherapy ID HIGH-DOSE-RATE; ADJUVANT RADIATION-THERAPY; CARBOPLATIN/PACLITAXEL CHEMOTHERAPY; INTRAVAGINAL RADIATION; AMERICAN BRACHYTHERAPY; SURVIVAL OUTCOMES; I PATIENTS; CARCINOMA; RADIOTHERAPY; MANAGEMENT AB Objective. To report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer. Methods. A retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24 Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%). Results. The median follow up time was 24.8 months (range, 2.0 to 71.5 months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 893% and 100%, respectively. Conclusion. HDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective. (C) 2012 Elsevier Inc. All rights reserved. C1 [Townamchai, Kanokpis; Bhagwat, Mandar; Damato, Antonio L.; Friesen, Scott; Lee, Larissa J.; O'Farrell, Desmond; Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Berkowitz, Ross] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Gynecol Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Matulonis, Ursula] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 28 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2013 VL 129 IS 1 BP 18 EP 21 DI 10.1016/j.ygyno.2012.12.026 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 119IH UT WOS:000317090500005 PM 23262378 ER PT J AU Rauh-Hain, JA Nitschmann, CC Worley, MJ Bradford, LS Berkowitz, RS Schorge, JO Campos, SM del Carmen, MG Horowitz, NS AF Rauh-Hain, J. Alejandro Nitschmann, Caroline C. Worley, Micheal J., Jr. Bradford, Leslie S. Berkowitz, Ross S. Schorge, John O. Campos, Susana M. del Carmen, Marcela G. Horowitz, Neil S. TI Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Platinum resistance; Neoadjuvant chemotherapy ID SURGICAL CYTOREDUCTION; CANCER; METAANALYSIS; SENSITIVITY; THERAPY AB Objective. Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) for a subset of women with advanced ovarian cancer. It remains unresolved whether NACT-IDS increases the risk of platinum resistance. We compared response to chemotherapy in patients that received NACT-IDS vs. PDS. Methods. From our Cancer Registry database we identified patients with stages IIIC and IV epithelial ovarian cancer who underwent treatment from January, 2005 to December, 2010. Standard univariate analyses were performed, as were multivariable analysis with logistic regression. The Kaplan-Meier method was used to generate survival data. Results. The study population consisted of 425 patients, 95 (22.3%) underwent NACT-IDS and 330 (77.6%) PDS. After the initial platinum-based chemotherapy, 42 (44.2%) women in the NACT-IDS group were considered to have platinum resistant disease, compared to 103 (31.2%) in the PDS group (P=0.01). When multivariate logistic regression was used to control for factors independently associated with platinum resistance, NACT-IDS was no longer associated with an initial increased risk. However, in women that had a recurrence and were retreated with platinum-based chemotherapy, 32 (88.8%) in the NACT-IDS group had developed a recurrence within six months and were considered platinum resistant, compared to 62 (55.3%) in the PDS (P<0.001). Conclusion. In women with EOC that have a recurrence and are treated again with platinum-based chemotherapy, NACT-IDS appears to increase the risk of platinum resistance. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Nitschmann, Caroline C.; Bradford, Leslie S.; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. [Nitschmann, Caroline C.; Worley, Micheal J., Jr.; Berkowitz, Ross S.; Campos, Susana M.; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. RP Horowitz, NS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org NR 23 TC 27 Z9 30 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2013 VL 129 IS 1 BP 63 EP 68 DI 10.1016/j.ygyno.2013.01.009 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 119IH UT WOS:000317090500014 PM 23337490 ER PT J AU Worley, MJ Guseh, SH Rauh-Hain, JA Williams, KA Muto, MG Feltmate, CM Berkowitz, RS Horowitz, NS AF Worley, Michael J., Jr. Guseh, Stephanie H. Rauh-Hain, J. Alejandro Williams, Kristina A. Muto, Michael G. Feltmate, Colleen M. Berkowitz, Ross S. Horowitz, Neil S. TI Does neoadjuvant chemotherapy decrease the risk of hospital readmission following debulking surgery? SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Neoadjuvant chemotherapy; Ovarian-cancer; Elderly; Readmission ID EPITHELIAL OVARIAN-CANCER; CYTOREDUCTIVE SURGERY; ELDERLY-WOMEN; OLDER PATIENTS; SURVIVAL; AGE; CARCINOMA; MORBIDITY; PATTERNS AB Objective. To compare primary debulking surgery (PDS) vs. neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among elderly patients with ovarian/fallopian tube/primary peritoneal carcinoma. Methods. Medical records of patients >= 70 years old with epithelial ovarian/fallopian tube/primary peritoneal carcinoma between January 2000 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures and postoperative and oncologic outcomes were compared. Surgical procedures were given a complexity score based on a previously published method. Results. Of 165 patients, 125 (75.8%) underwent PDS and 40(24.2%) underwent NACT-IDS. Patients undergoing NACT-IDS were more likely to have a pleural effusion (without cytology) and stage 4 disease. Median CA-125 at diagnosis was greater for those undergoing NACT-IDS. The NACT-IDS group was associated with less intraoperative blood loss (250 vs. 400 mL, p = 0.001), a greater chance of achieving no residual disease (40% vs. 16%, p=0.005) and a shorter hospital length of stay (LOS) (5 vs. 7 days, p<0.001). PFS (17 vs. 15 months, p = 0.708) and OS (29 vs. 33 months, p = 0.827) were similar between the two groups. Readmission rates within 30 days of surgery were greater in those undergoing PDS (17.6% vs. 2.5%, p = 0.016). After readmission, the median hospital LOS was 6 days (range: 1-41). Conclusions. Elderly patients undergoing PDS have similar oncologic outcomes when compared to patients undergoing NACT-IDS. The risk of readmission within 30 days of surgery is significantly greater among patients undergoing PDS. (C) 2013 Elsevier Inc. All rights reserved. C1 [Worley, Michael J., Jr.; Muto, Michael G.; Feltmate, Colleen M.; Berkowitz, Ross S.; Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Guseh, Stephanie H.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Rauh-Hain, J. Alejandro] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Williams, Kristina A.] Harvard Univ, Sch Med, Boston, MA USA. RP Horowitz, NS (reprint author), Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org NR 31 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2013 VL 129 IS 1 BP 69 EP 73 DI 10.1016/j.ygyno.2013.01.012 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 119IH UT WOS:000317090500015 PM 23375727 ER PT J AU Armoundas, AA Weiss, EH Sayadi, O Laferriere, S Sajja, N Mela, T Singh, JP Barrett, CD Heist, EK Merchant, FM AF Armoundas, Antonis A. Weiss, Eric H. Sayadi, Omid Laferriere, Shawna Sajja, Naveen Mela, Theofanie Singh, Jagmeet P. Barrett, Conor D. Heist, E. Kevin Merchant, Faisal M. TI A novel pacing method to suppress repolarization alternans in vivo: Implications for arrhythmia prevention SO HEART RHYTHM LA English DT Article DE Repolarization alternans; Ventricular tachycardia/ventricular fibrillation; Cardiac pacing; Heart failure; Sudden cardiac death ID T-WAVE ALTERNANS; CARDIAC CONTRACTILITY MODULATION; VENTRICULAR TACHYARRHYTHMIAS; DISCORDANT ALTERNANS; HEART; FIBRILLATION; ELECTROGRAMS; MECHANISMS; THERAPY; GENESIS AB BACKGROUND Repolarization alternans (RA), a pattern of ventricular repolarization that repeats on an every other beat basis, has been closely linked with the substrate associated with ventricular tachycardia/ventricular fibrillation. OBJECTIVE To evaluate a novel method to suppress RA. METHODS We have developed a novel method to dynamically (on R-wave detection) trigger pacing pulses during the absolute refractory period. We have tested the ability of this method to control RA in a structurally normal swine heart in vivo. RESULTS RA induced by triggered pacing can be measured from both intracardiac and body surface leads and the amplitude of R-wave triggered pacing-induced alternans can be locally modulated by varying the amplitude and width of the pacing pulse. We have estimated that to induce a 1 mu V change in alternans voltage on the body surface, coronary sinus, and left ventricle leads, a triggered pacing pulse delivered in the right ventricle of 0.04 +/- 0.02, 0.05 +/- 0.025, and 0.06 +/- 0.033 mu C, respectively, is required. Similarly, to induce a 1 unit change in K-score (ratio of alternans peak to noise), a pacing stimulus of 0.93 +/- 0.73, 0.32 +/- 0.29, and 0.33 +/- 0.37 mu C, respectively, is required. We have been able to demonstrate that RA can be suppressed by R-wave triggered pacing from a site that is within or across ventricles. lastly, we have demonstrated that the proposed method can be used to suppress spontaneously occurring alternans in the diseased heart. CONCLUSION We have developed a novel method to suppress RA in vivo. C1 [Armoundas, Antonis A.; Weiss, Eric H.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Armoundas, Antonis A.; Sayadi, Omid; Laferriere, Shawna; Sajja, Naveen; Mela, Theofanie; Singh, Jagmeet P.; Barrett, Conor D.; Heist, E. Kevin; Merchant, Faisal M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org FU American Heart Association [0635127N, 12POST9310001, 0815767D]; National Institute of Aging [1R21AG035128]; National Institutes of Health [1RO1HL103961]; Center for Integration of Medicine and Innovative Technology (CIMIT); Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Cardiovascular Research Society; St Jude Medical; Medtronic; Boston Scientific; Biotronik; Guidant; Sorin FX This work was supported by a Scientist Development Grant (#0635127N), by a postdoctoral fellowship (#12POST9310001) and a predoctoral fellowship (#0815767D) from the American Heart Association, by National Institute of Aging grant 1R21AG035128 and National Institutes of Health grant 1RO1HL103961. This work was also supported by a fellowship and a science award from the Center for Integration of Medicine and Innovative Technology (CIMIT), the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and the Cardiovascular Research Society.; Dr Mela has received honoraria from Medtronic, Biotronik, and St Jude. Dr Singh has received research grants from St Jude Medical, Medtronic, Boston Scientific, and Biotronik and honoraria/speaker fees from Medtronic, Biotronik, Guidant, St Jude Medical, and Sorin; he is the advisory board member/steering committee member/consultant at Boston Scientific, Biotronik, St Jude Medical, Medtronic, CardioInsight, Thoratec, Biosense Webster. Dr Heist has received honoraria from Biotronik, Boston Scientific, Medtronic, Sorin, and St Jude Medical and research grants from Biotronik, Boston Scientific, and St Jude Medical; he is a consultant at Boston Scientific, Sanofi, Sorin, and St Jude Medical. NR 26 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD APR PY 2013 VL 10 IS 4 BP 564 EP 572 DI 10.1016/j.hrthm.2012.12.026 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 121XE UT WOS:000317277700023 PM 23274372 ER PT J AU Russo, AM Stainback, RF Bailey, SR Epstein, AE Heidenreich, PA Jessup, M Kapa, S Kremers, MS Lindsay, BD Stevenson, LW Bailey, SR Russo, AM Kapa, S Alexander, MB Bailey, SR Birgersdotter-Green, U Brown, AS Grimm, RA Hauptman, PJ Hunt, SA Lampert, R Lindenfeld, J Malenka, DJ Mani, K Marine, JE Martin, ET Page, RL Rich, MW Varosy, PD Walsh, MN Wolk, MJ Bailey, SR Doherty, JU Douglas, PS Hendel, RC Kramer, CM Min, JK Patel, MR Shaw, L Stainback, RF Allen, JM AF Russo, Andrea M. Stainback, Raymond F. Bailey, Steven R. Epstein, Andrew E. Heidenreich, Paul A. Jessup, Mariell Kapa, Suraj Kremers, Mark S. Lindsay, Bruce D. Stevenson, Lynne Warner Bailey, Steven R. Russo, Andrea M. Kapa, Suraj Alexander, Michael B. Bailey, Steven R. Birgersdotter-Green, Ulrika Brown, Alan S. Grimm, Richard A. Hauptman, Paul J. Hunt, Sharon A. Lampert, Rachel Lindenfeld, JoAnn Malenka, David J. Mani, Kartik Marine, Joseph E. Martin, Edward T. Page, Richard L. Rich, Michael W. Varosy, Paul D. Walsh, Mary Norine Wolk, Michael J. Bailey, Steven R. Doherty, John U. Douglas, Pamela S. Hendel, Robert C. Kramer, Christopher M. Min, James K. Patel, Manesh R. Shaw, Leslee Stainback, Raymond F. Allen, Joseph M. CA Amer Geriatrics Soc TI ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance SO HEART RHYTHM LA English DT Article DE ACCF appropriate use criteria; CRT; electrophysiology; heart failure; ICD; implantable defibrillator; sudden death ID ACUTE MYOCARDIAL-INFARCTION; MONOMORPHIC VENTRICULAR-TACHYCARDIA; DUAL-CHAMBER; QRS DURATION; TASK-FORCE; NUCLEAR CARDIOLOGY; PRIMARY PREVENTION; UNIVERSAL DEFINITION; COMPLICATION RATES; THORACIC-SURGEONS AB The American College of Cardiology Foundation in collaboration with the Heart Rhythm Society and key specialty and subspecialty societies conducted a review of common clinical scenarios where implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are frequently considered. The clinical scenarios covered in this document address secondary prevention, primary prevention, comorbidities, generator replacement at elective replacement indicator, dual-chamber ICD, and CRT. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining device implantation. The 369 indications in this document were developed by a multidisciplinary writing group and scored by a separate independent technical panel on a scale of 1 to 9 to designate care that is Appropriate (median 7 to 9), May Be Appropriate (median 4 to 6), and Rarely Appropriate (median 1 to 3). The final ratings reflect the median score of the 17 technical panel members: 45% of the indications were rated as Appropriate, 33% were rated May Be Appropriate and 22% were rated Rarely Appropriate. In general, Appropriate designations were assigned to scenarios for which clinical trial evidence and/or clinical experience was available that supported device implantation. By contrast, scenarios for which clinical trial evidence was limited or device implantation seemed reasonable for extenuating reasons were categorized as May Be Appropriate. Scenarios for which there were data showing harm, or no data were available, and medical judgment deemed device therapy ill-advised were categorized as Rarely Appropriate. For example, comorbidities including life expectancy and cognitive function impacted appropriateness ratings. The Appropriate Use Criteria for ICD/CRT have the potential to enhance physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of clinical scenarios rated as May Be Appropriate facilitates the identification of areas that would benefit from future research. C1 [Russo, Andrea M.; Russo, Andrea M.] UMDNJ, Robert Wood Johnson Med Sch, Piscataway, NJ USA. [Russo, Andrea M.; Russo, Andrea M.] Cooper Univ Hosp, Cardiac Electrophysiol Serv, Camden, NJ USA. [Russo, Andrea M.; Russo, Andrea M.] Cooper Univ Hosp, Arrhythmia Serv, Camden, NJ USA. [Stainback, Raymond F.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. [Stainback, Raymond F.] Baylor Coll Med, Houston, TX 77030 USA. [Bailey, Steven R.; Bailey, Steven R.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Bailey, Steven R.; Bailey, Steven R.] Univ Texas Hlth Sci Ctr San Antonio, Janey Briscoe Distinguished Chair, San Antonio, TX 78229 USA. [Epstein, Andrew E.] Univ Penn, Electrophysiol Sect, Cardiovasc Div, Philadelphia, PA 19104 USA. [Epstein, Andrew E.] Philadelphia VA Med Ctr, Cardiol Sect, Philadelphia, PA USA. [Heidenreich, Paul A.] Stanford Univ, Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Jessup, Mariell] Univ Penn, Heart & Vasc Ctr, Philadelphia, PA 19104 USA. [Kapa, Suraj; Kapa, Suraj] Univ Penn, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. [Kremers, Mark S.] Mid Carolina Cardiol, Charlotte, NC USA. [Lindsay, Bruce D.] Cleveland Clin Fdn Cardiovasc Med, Cleveland, OH USA. [Stevenson, Lynne Warner] Brigham & Womens Hosp, Cardiomyopathy & Heart Failure Program, Cardiovasc Div, Boston, MA 02115 USA. [Alexander, Michael B.] Cigna HealthCare, Blue Bell, PA USA. [Birgersdotter-Green, Ulrika] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Birgersdotter-Green, Ulrika] Univ Calif San Diego, Med Ctr, Pacemaker & ICD Clin, La Jolla, CA 92093 USA. [Brown, Alan S.] Midwest Heart Dis Prevent Ctr, Naperville, IL USA. [Brown, Alan S.] Loyola Univ, Stritch Sch Med, Naperville, IL USA. [Grimm, Richard A.] Cleveland Clin, Sect Cardiovasc Imaging, Cardiovasc Med Heart & Vasc Inst, Cleveland, OH 44106 USA. [Hauptman, Paul J.] St Louis Univ Hosp, Heart Failure & Transplant Program, St Louis, MO USA. [Hauptman, Paul J.] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. [Hunt, Sharon A.] Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA. [Lampert, Rachel] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Lindenfeld, JoAnn] Univ Colorado, Hlth Sci Ctr, Cardiac Transplant Program, Aurora, CO USA. [Malenka, David J.] Dartmouth Inst Hlth Policy & Clin Practice, Dartmouth Med Sch, Lebanon, NH USA. [Mani, Kartik] Mercy Med Ctr, Roseburg, OR USA. [Marine, Joseph E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Martin, Edward T.] Oklahoma Heart Inst, Cardiovasc MRI, Tulsa, OK USA. [Martin, Edward T.] Univ Oklahoma, Tulsa, OK USA. [Page, Richard L.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Rich, Michael W.] Washington Univ, Sch Med, St Louis, MO USA. [Varosy, Paul D.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Varosy, Paul D.] Univ Colorado, Denver, CO 80202 USA. [Walsh, Mary Norine] St Vincent Heart Ctr Indiana, Indianapolis, IN USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. VA Med Ctr, Heart Failure Program, Minneapolis, MN USA. Johns Hopkins Med Inst, Cardiac Elect Training Program, Baltimore, MD 21205 USA. Ctr Med Technol Policy, Baltimore, MD USA. Los Angeles Biomed Res Inst, Torrance, CA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Clin Electrophysiol Lab, Boston, MA 02215 USA. Cardiac Arrhythmia Serv, Baltimore, MD USA. Electrophysiol Lab, Baltimore, MD USA. Johns Hopkins ARVD C Program, Baltimore, MD USA. SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA. RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 NR 61 TC 46 Z9 47 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD APR PY 2013 VL 10 IS 4 BP E11 EP E58 DI 10.1016/j.hrthm.2013.01.008 PG 48 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 121XE UT WOS:000317277700001 PM 23473952 ER PT J AU Li, Y Chang, XY Zhou, WX Xiao, Y Nakatsuka, LN Chen, J Lauwers, GY AF Li, Yuan Chang, Xiaoyan Zhou, Weixun Xiao, Yu Nakatsuka, Laura N. Chen, Jie Lauwers, Gregory Y. TI Gastric intestinal metaplasia with basal gland atypia: a morphological and biologic evaluation in a large Chinese cohort SO HUMAN PATHOLOGY LA English DT Article DE Stomach; Adenocarcinoma; Intestinal metaplasia; Basal gland atypia; Dysplasia; Gastric pit dysplasia ID BARRETTS-ESOPHAGUS; ULCERATIVE-COLITIS; DYSPLASIA; LESIONS; CANCER; EXPRESSION; CLASSIFICATION; INDEFINITE; NEOPLASIA; MUCOSA AB Gastric intestinal metaplasia can display cytoarchitectural atypia that falls short of qualifying for dysplasia but can be classified as indefinite for dysplasia. Yet few studies have evaluated the prevalence, the morphologic, and biologic characteristics of this variant. Out of a cohort of 554 biopsies with chronic atrophic gastritis and/or dysplasia, we categorized the cases as either (1) simple intestinal metaplasia; (2) intestinal metaplasia with hyperplasia; (3) intestinal metaplasia with basal gland atypia; and (4) gastric dysplasia. The relationship between the subtypes and various clinicopathologic features, mucin immunophenotypes, and biologic characteristics was evaluated. The final cohort consisted of 424 cases of simple intestinal metaplasia, 93 intestinal metaplasia with hyperplasia, 16 intestinal metaplasia with basal gland atypia, and 21 gastric dysplasia. Intestinal metaplasia with basal gland atypia had a prevalence of 2.8% and similar to gastric dysplasia, 3.7%. Both of these lesions were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). Intestinal metaplasia with basal gland atypia and gastric dysplasia seem to share some biologic similarities but with a lower frequency of alpha-methylacyl-CoA racemase expression (25% versus 62%), p53 expression (6.3% versus 47.6%), and increased Ki-67 index on surface/pit and isthmus in intestinal metaplasia with basal gland atypia. Alternatively, simple intestinal metaplasia and intestinal metaplasia with hyperplasia did not differ statistically with regard to the various characteristics evaluated. We concluded that gastric intestinal metaplasia can be divided into 2 broad categories that are readily defined by cytoarchitectural and biologic characteristics. Based on the characteristics of intestinal metaplasia with basal gland atypia and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that needs further evaluation. (C) 2013 Elsevier Inc. All rights reserved. C1 [Li, Yuan; Chang, Xiaoyan; Zhou, Weixun; Xiao, Yu; Chen, Jie] Beijing Union Med Coll Hosp, Chinese Acad Med Sci, Peking Union Med Coll, Dept Pathol, Beijing 100730, Peoples R China. [Li, Yuan; Nakatsuka, Laura N.; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02144 USA. EM xhblk@163.com; glauwers@partners.org FU Scientific Research Special Projects of the Health Industry of China, People's Republic of China [200802011] FX Supported by a grant (200802011) from the Scientific Research Special Projects of the Health Industry of China, People's Republic of China. NR 35 TC 5 Z9 6 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2013 VL 44 IS 4 BP 578 EP 590 DI 10.1016/j.humpath.2012.07.002 PG 13 WC Pathology SC Pathology GA 121LQ UT WOS:000317246700015 PM 23079203 ER PT J AU Ting, JY Remenschneider, A Holbrook, EH AF Ting, Jonathan Y. Remenschneider, Aaron Holbrook, Eric H. TI Management of severe epistaxis after Young's procedure: a case report SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE nasal closure; modified Young's procedure; epistaxis; hereditary hemorrhagic telangiectasia; Osler-Weber-Rendu disease ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; PULSED DYE-LASER; NOSTRIL CLOSURE; THERAPY; BEVACIZUMAB; SECONDARY AB Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting multiple organ systems, with epistaxis being the most common manifestation. Multiple procedures have been used for the management of epistaxis in the setting of HHT, including closure of the anterior nares via a Young's procedure. While this procedure results in loss of smell and permanent nasal obstruction, proponents note significant improvement in patient symptomatology. Methods Case report. Results A 70-year-old female with a history of HHT presented to an outside hospital with bleeding into the nasopharynx 2 months after undergoing a modified Young's procedure at an unaffiliated institution. She was transfused with 2 units of packed red blood cells (PRBCs) and transferred to our facility. Due to persistent epistaxis and need for airway protection, the patient was intubated and her throat was packed. She also developed aspiration pneumonia and hypotensive shock requiring vasopressors. Twenty-four hours following bilateral internal maxillary and sphenopalatine artery embolization, she developed significant epistaxis requiring reversal of the Young's procedure on the left and placement of an anterior-posterior pack at the bedside. Upon packing removal several days later in the operating room, she was noted to have significant bleeding that necessitated reversal of the Young's procedure on the right side to obtain adequate exposure and hemostasis. Conclusion We report a case of significant, life-threatening epistaxis following a modified Young's procedure that requiring multiple transfusions, bilateral embolization, and ultimately reversal of the Young's procedure for control of epistaxis. Although recognized as a potential complication, to our knowledge this is the first report in the English literature of such a case. (C) 2013 ARS-AAOA, LLC. C1 [Ting, Jonathan Y.; Remenschneider, Aaron; Holbrook, Eric H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Ting, JY (reprint author), 243 Charles St, Boston, MA 02114 USA. EM jonathan_ting@meei.harvard.edu NR 34 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD APR PY 2013 VL 3 IS 4 BP 334 EP 337 DI 10.1002/alr.21099 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 123BK UT WOS:000317362900012 PM 23109496 ER PT J AU Garshick, E AF Garshick, E. TI EPIDEMIOLOGY OF CANCER AND DIESEL EXHAUST SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Garshick, E.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Channing Div Network Med, Boston, MA 02115 USA. [Garshick, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A7 EP A7 PG 1 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000019 ER PT J AU Greenblatt, EE Venegas, JG AF Greenblatt, E. E. Venegas, J. G. TI ANALYSIS OF AEROSOL DEPOSITION USING ANATOMICALLY DERIVED REGIONS OF INTEREST (ROIs): BEYOND BLACK AND WHITE SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Greenblatt, E. E.] MIT, Boston, MA USA. [Greenblatt, E. E.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A34 EP A35 PG 2 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000094 ER PT J AU Greenblatt, EE Harris, RS Winkler, T Kelly, VJ Kone, M Katz, I Martin, A Caillibotte, G Venegas, JG AF Greenblatt, E. E. Harris, R. S. Winkler, T. Kelly, V. J. Kone, M. Katz, I. Martin, A. Caillibotte, G. Venegas, J. G. TI RELATIONSHIP BETWEEN REGIONAL VENTILATION AND AEROSOL DEPOSITION IN BRONCHOCONSTRICTED SUBJECTS WITH ASTHMA SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Greenblatt, E. E.] MIT, Boston, MA USA. [Greenblatt, E. E.; Harris, R. S.; Winkler, T.; Kelly, V. J.; Kone, M.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.; Winkler, T.; Kelly, V. J.; Kone, M.; Venegas, J. G.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, I.; Martin, A.; Caillibotte, G.] Air Liquide R&D, Jouy En Josas, France. RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A34 EP A34 PG 1 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000092 ER PT J AU Hess, DR AF Hess, D. R. TI MODES OF NONINVASIVE POSITIVE PRESSURE VENTILATION AND MASK INTERFACES EMPLOYED SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Hess, D. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hess, D. R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A3 EP A3 PG 1 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000006 ER PT J AU Venegas, JG Greenblatt, EE Winkler, T Kelly, VJ Kone, M Katz, I Martin, A Caillibotte, G Harris, RS AF Venegas, J. G. Greenblatt, E. E. Winkler, T. Kelly, V. J. Kone, M. Katz, I. Martin, A. Caillibotte, G. Harris, R. S. TI EFFECT OF CARRIER GAS ON THE RELATIONSHIP BETWEEN REGIONAL VENTILATION AND AEROSOL DEPOSITION IN BRONCHOCONSTRICTED SUBJECTS WITH ASTHMA SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Venegas, J. G.; Greenblatt, E. E.; Winkler, T.; Kelly, V. J.; Kone, M.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Katz, I.; Martin, A.; Caillibotte, G.] Air Liquide R&D, Jouy En Josas, France. RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A34 EP A34 PG 1 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000093 ER PT J AU Venegas, JG Greenblatt, EE Winkler, T Kelly, VJ Kone, M Harris, RS AF Venegas, J. G. Greenblatt, E. E. Winkler, T. Kelly, V. J. Kone, M. Harris, R. S. TI AEROSOL IMAGING WITH PET-CT: FROM DEPOSITION TO TISSUE DOSING SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Meeting Abstract C1 [Venegas, J. G.; Greenblatt, E. E.; Winkler, T.; Kelly, V. J.; Kone, M.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.; Winkler, T.; Kelly, V. J.; Kone, M.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR PY 2013 VL 26 IS 2 BP A15 EP A16 PG 2 WC Respiratory System SC Respiratory System GA 118QI UT WOS:000317040000044 ER PT J AU Cattaneo, F Recher, M Masneri, S Baxi, SN Fiorini, C Antonelli, F Wysocki, CA Calderon, JG Eibel, H Smith, AR Bonilla, FA Tsitsikov, E Giliani, S Notarangelo, LD Pai, SY AF Cattaneo, Federica Recher, Mike Masneri, Stefania Baxi, Sachin N. Fiorini, Claudia Antonelli, Francesca Wysocki, Christian A. Calderon, Jose G. Eibel, Hermann Smith, Angela R. Bonilla, Francisco A. Tsitsikov, Erdyni Giliani, Silvia Notarangelo, Luigi D. Pai, Sung-Yun TI Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Severe combined immunodeficiency; cytokine signaling; maternal engraftment ID SEVERE COMBINED-IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; RECEPTOR-GAMMA-CHAIN; IMMUNOLOGICAL MANIFESTATIONS; OMENN-SYNDROME; LYMPHOCYTES; DEFICIENCY; DISEASE; JAK3; IDENTIFICATION AB Background: Mutations in Janus kinase 3 (JAK3) are a cause of severe combined immunodeficiency, but hypomorphic JAK3 defects can result in a milder clinical phenotype, with residual development and function of autologous T cells. Maternal T-cell engraftment is a common finding in infants with severe combined immunodeficiency but is not typically observed in patients with residual T-cell development. Objective: We sought to study in detail the molecular, cellular, and humoral immune phenotype and function of 3 patients with hypomorphic JAK3 mutations. Methods: We analyzed the distribution and function of T and B lymphocytes in 3 patients and studied the in vitro and in vivo responses of maternal T lymphocytes in 1 patient with maternal T-cell engraftment and residual production of autologous T lymphocytes. Results: B cells were present in normal numbers but with abnormal distribution of marginal zone-like and memory B cells. B-cell differentiation to plasmablasts in vitro in response to CD40 ligand and IL-21 was abolished. In 2 patients the T-cell repertoire was moderately restricted. Surprisingly, 1 patient showed coexistence of maternal and autologous T lymphocytes. By using an mAb recognizing the maternal noninherited HLA-A2 antigen, we found that autologous cells progressively accumulated in vivo but did not compete with maternal cells in vitro. Conclusion: The study of 3 patients with hypomorphic JAK3 mutations suggests that terminal B-cell maturation/differentiation requires intact JAK3 function, even if partially functioning T lymphocytes are present. Maternal T-cell engraftment can occur in patients with JAK3 mutations despite the presence of autologous T cells. (J Allergy Clin Immunol 2013; 131:1136-45.) C1 [Cattaneo, Federica; Fiorini, Claudia; Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Recher, Mike; Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Recher, Mike; Baxi, Sachin N.; Bonilla, Francisco A.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Tsitsikov, Erdyni] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. [Masneri, Stefania; Antonelli, Francesca; Giliani, Silvia] Univ Brescia, A Nocivelli Inst Mol Med, Brescia, Italy. [Masneri, Stefania; Antonelli, Francesca; Giliani, Silvia] Spedali Civil Brescia, Lab Genet Disorders Childhood, I-25125 Brescia, Italy. [Wysocki, Christian A.; Calderon, Jose G.] Yale Univ, Sch Med, Yale New Haven Hosp, Sect Allergy & Clin Immunol, New Haven, CT USA. [Eibel, Hermann] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiencies, Freiburg, Germany. [Smith, Angela R.] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Pai, SY (reprint author), Boston Childrens Hosp, Karp Family Res Labs, 1 Blackfan Circle,Rm 08214, Boston, MA 02115 USA. EM sung-yun.pai@childrens.harvard.edu RI sebastianovitsch, stepan/G-8507-2013; Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Fiorini, Claudia/0000-0003-4878-2438 FU Translational Investigator Service at Boston Children's Hospital; Manton Foundation; National Institutes of Health [U54AI082973]; FondazioneNocivelli; Swiss National Science Foundation (SNSF/SSMBS) [PASMP3-127678]; National Institute of Allergy and Infectious Diseases and from Translational Research Program at Boston Children's Hospital FX Supported by the Translational Investigator Service at Boston Children's Hospital (to S.-Y.P.), the Manton Foundation (to L.D.N.), the National Institutes of Health (U54AI082973 to S.-Y.P. and L.D.N.), and FondazioneNocivelli (to S. G). M. R. was supported by the Swiss National Science Foundation (SNSF/SSMBS) grant PASMP3-127678.; Disclosure of potential conflict of interest: M. Recher has been supported by one or more grants from the Swiss National Science Foundation (SNSF/SSMBS; Nrz PASMP3127678). C. A. Wysocki has been supported by one or more grants from the National Institutes of Health. L. D. Notarangelo has received one or more grants from the National Institutes of Health and from the Manton Foundation, is a Board member for the Immune Disease Institute, is employed by Boston Children's Hospital, has received one or more grants from or has one or more grants pending with the Wiskott-Aldrich Foundation and with the March of Dimes, and has received royalties from UpToDate. S.-Y. Pai has been supported by one or more grants from the National Institute of Allergy and Infectious Diseases and from Translational Research Program at Boston Children's Hospital. The rest of the authors declare that they have no relevant conflicts of interest. NR 41 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 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2013 VL 131 IS 4 BP 1136 EP 1145 DI 10.1016/j.jaci.2012.12.667 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 120QT UT WOS:000317187200024 PM 23384681 ER PT J AU Henderson, LA Frugoni, F Hopkins, G Al-Herz, W Weinacht, K Comeau, AM Bonilla, FA Notarangelo, LD Pai, SY AF Henderson, Lauren A. Frugoni, Francesco Hopkins, Gregory Al-Herz, Waleed Weinacht, Katja Comeau, Anne Marie Bonilla, Francisco A. Notarangelo, Luigi D. Pai, Sung-Yun TI First reported case of Omenn syndrome in a patient with reticular dysgenesis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID SEVERE COMBINED IMMUNODEFICIENCY; ADENYLATE KINASE 2; SENSORINEURAL DEAFNESS; ALEUKOCYTOSIS C1 [Henderson, Lauren A.; Frugoni, Francesco; Bonilla, Francisco A.; Notarangelo, Luigi D.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Hopkins, Gregory; Weinacht, Katja; Pai, Sung-Yun] Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA USA. [Notarangelo, Luigi D.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Allergy & Clin Immunol Unit, Kuwait, Kuwait. [Weinacht, Katja; Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Comeau, Anne Marie] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Worcester, MA USA. RP Henderson, LA (reprint author), Childrens Hosp Boston, Div Immunol, Boston, MA USA. EM Sung-Yun.Pai@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Frugoni, Francesco/0000-0002-1769-8121 FU NCEH CDC HHS [1U01EH00362, U01 EH000362]; NIAID NIH HHS [U54 AI082973, U54AI082973] NR 10 TC 10 Z9 10 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2013 VL 131 IS 4 BP 1227 EP 1230 DI 10.1016/j.jaci.2012.07.045 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 120QT UT WOS:000317187200034 PM 23014587 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Host-microbial interactions in patients with chronic rhinosinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; REFRACTORY CHRONIC RHINOSINUSITIS; TOLL-LIKE RECEPTORS; BACTERIAL BIOFILMS; EPITHELIAL-CELLS; INNATE IMMUNITY; STAPHYLOCOCCUS-AUREUS; NASAL POLYPOSIS; SINONASAL CAVITY; BINDING-PROTEIN C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org NR 63 TC 6 Z9 6 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2013 VL 131 IS 4 BP 1263 EP + DI 10.1016/j.jaci.2013.02.020 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 120QT UT WOS:000317187200055 PM 23540620 ER PT J AU Carbo, C Yuki, K Demers, M Wagner, DD Shimaoka, M AF Carbo, Carla Yuki, Koichi Demers, Melanie Wagner, Denisa D. Shimaoka, Motomu TI Isoflurane inhibits neutrophil recruitment in the cutaneous Arthus reaction model SO JOURNAL OF ANESTHESIA LA English DT Article DE beta 2 Integrin; Reverse passive Arthus reaction; Skin; Isoflurane; Neutrophil recruitment ID INTERCELLULAR-ADHESION MOLECULE-1; SELECTIN GLYCOPROTEIN LIGAND-1; ANESTHETIC ACTION; INTEGRIN LFA-1; MICE; INFLAMMATION; MECHANISMS; MIGRATION; MAC-1; SURGERY AB Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including beta 2 integrins. The dependency of neutrophil recruitment on beta 2 integrins is variable in different tissues, but has not yet been verified in the cutaneous passive reverse Arthus reaction. We examined this question and also evaluated the impact of isoflurane on neutrophil recruitment to the skin because we previously showed in vitro that isoflurane binds and inhibits beta 2 integrins. The dependency on beta 2 integrins in neutrophil recruitment to the skin in the Arthus reaction was examined using alpha L, alpha M and beta 2 knockout mice. Then, we evaluated the effect of isoflurane on neutrophil recruitment to the skin. In addition, the effects of isoflurane on neutrophil binding to intercellular adhesion molecule-1 (ICAM-1), one of the beta 2 integrin ligands, were studied in vitro using cell adhesion assays. Neutrophil recruitment to the skin in the Arthus reaction model was totally dependent on beta 2 integrins, as beta 2 knockout mice completely abolished it. However, the defect of only one of the beta 2 integrins was not sufficient to abolish neutrophil recruitment. Isoflurane reduced neutrophil recruitment to the skin by approximately 90 %. Also, isoflurane inhibited neutrophil adhesion to beta 2 integrin ligand ICAM-1. We demonstrated that (1) neutrophil recruitment to the skin was totally dependent on beta 2 integrins, and (2) isoflurane significantly impaired neutrophil recruitment. Based on the previous studies on the contribution of other adhesion molecules in neutrophil recruitment, it is likely that isoflurane at least partially affects on beta 2 integrins in this model. C1 [Carbo, Carla; Yuki, Koichi; Demers, Melanie; Wagner, Denisa D.; Shimaoka, Motomu] Immune Dis Inst, Boston, MA USA. [Carbo, Carla; Demers, Melanie; Wagner, Denisa D.; Shimaoka, Motomu] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Carbo, Carla; Demers, Melanie; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Yuki, Koichi] Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Yuki, Koichi; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Shimaoka, Motomu] Mie Univ, Grad Sch Med, Dept Mol Pathobiol & Cell Adhes Biol, Tsu, Mie 5148507, Japan. RP Yuki, K (reprint author), Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM yuki.koichi@gmail.com; shimaoka@doc.medic.mie-u.ac.jp FU National Institute of Health (NIH) [HL041002, K08GM101345]; CHMC Anesthesia Foundation FX In part supported by National Institute of Health (NIH) grants HL041002 (D. W.), K08GM101345 (K.Y.) and CHMC Anesthesia Foundation (K.Y.). Acknowledge Dr. Roderic G. Eckenhoff (University of Pennsylvania) for valuable suggestions. NR 46 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0913-8668 J9 J ANESTH JI J. Anesth. PD APR PY 2013 VL 27 IS 2 BP 261 EP 268 DI 10.1007/s00540-012-1508-1 PG 8 WC Anesthesiology SC Anesthesiology GA 123CR UT WOS:000317366400016 PM 23096126 ER PT J AU Gurubhagavatula, I Fields, BG Morales, CR Hurley, S Pien, GW Wick, LC Staley, BA Townsend, RR Maislin, G AF Gurubhagavatula, Indira Fields, Barry G. Morales, Christian R. Hurley, Sharon Pien, Grace W. Wick, Lindsay C. Staley, Bethany A. Townsend, Raymond R. Maislin, Greg TI Screening for Severe Obstructive Sleep Apnea Syndrome in Hypertensive Outpatients SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID POSITIVE AIRWAY PRESSURE; HIGH BLOOD-PRESSURE; DAYTIME SLEEPINESS; DIAGNOSTIC SYSTEM; CONTROLLED-TRIAL; ASSOCIATION; POLYSOMNOGRAPHY; PREVALENCE; MEN; POPULATION AB The authors attempted to validate a 2-stage strategy to screen for severe obstructive sleep apnea syndrome (s-OSAS) among hypertensive outpatients, with polysomnography (PSG) as the gold standard. Using a prospective design, outpatients with hypertension were recruited from medical outpatient clinics. Interventions included (1) assessment of clinical data; (2) home sleep testing (HST); and (3) 12-channnel, in-laboratory PSG. The authors developed models using clinical or HST data alone (single-stage models) or clinical data in tandem with HST (2-stage models) to predict s-OSAS. For each model, area under receiver operating characteristic curves (AUCs), sensitivity, specificity, negative likelihood ratio, and negative post-test probability (NPTP) were computed. Models were then rank-ordered based on AUC values and NPTP. HST used alone had limited accuracy (AUC=0.727, NPTP=2.9%). However, models that used clinical data in tandem with HST were more accurate in identifying s-OSAS, with lower NPTP: (1) facial morphometrics (AUC=0.816, NPTP=0.6%); (2) neck circumference (AUC=0.803, NPTP=1.7%); and Multivariable Apnea Prediction Score (AUC=0.799, NPTP=1.5%) where sensitivity, specificity, and NPTP were evaluated at optimal thresholds. Therefore, HST combined with clinical data can be useful in identifying s-OSAS in hypertensive outpatients, without incurring greater cost and patient burden associated with in-laboratory PSG. These models were less useful in identifying obstructive sleep apnea syndrome of any severity. C1 [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Pulm & Crit Care & Sleep Sect, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira; Fields, Barry G.; Morales, Christian R.; Hurley, Sharon; Pien, Grace W.; Wick, Lindsay C.; Staley, Bethany A.; Maislin, Greg] Univ Penn, Med Ctr, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira; Fields, Barry G.; Pien, Grace W.] Univ Penn, Med Ctr, Div Sleep Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Fields, BG (reprint author), Ctr Sleep & Circadian Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM barry.fields@uphs.upenn.edu FU National Institutes of Health [K23 RR16068, RO1-OH009149, T32 HL07713]; Veterans Integrated Services Network FX This work was supported by National Institutes of Health grant K23 RR16068, RO1-OH009149, T32 HL07713, and by the Veterans Integrated Services Network 4 Competitive Pilot Project Fund. ResMed, Inc provided an unrestricted loan for use of portable diagnostic sleep study equipment (AutoSet) and had no role in protocol development, data collection, storage, analysis, or manuscript preparation. NR 41 TC 8 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD APR PY 2013 VL 15 IS 4 BP 279 EP 288 DI 10.1111/jch.12073 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 119YK UT WOS:000317135700010 PM 23551728 ER PT J AU Elmer, J Wilcox, SR Raja, AS AF Elmer, Jonathan Wilcox, Susan R. Raja, Ali S. TI MASSIVE TRANSFUSION IN TRAUMATIC SHOCK SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE hemorrhage; coagulopathy; massive transfusion; resuscitation; trauma ID FRESH-FROZEN PLASMA; RED-BLOOD-CELL; LIFE-THREATENING COAGULOPATHY; ACUTE LUNG INJURY; PROTHROMBIN COMPLEX CONCENTRATE; RANDOMIZED CONTROLLED-TRIAL; DAMAGE CONTROL HEMATOLOGY; INDEPENDENT RISK-FACTOR; LAST 60 YEARS; EXSANGUINATION PROTOCOL AB Background: Hemorrhage after trauma is a common cause of death in the United States and globally. The primary goals when managing traumatic shock are the restoration of oxygen delivery to end organs, maintenance of circulatory volume, and prevention of ongoing bleeding through source control and correction of coagulopathy. Achieving these goals may require massive transfusion of blood products. Although use of blood products may be lifesaving, dose-related adverse effects are well described. Discussion: Complications of massive transfusion include interdependent derangements such as coagulopathy, hypothermia, acidosis, and electrolyte abnormalities, as well as infectious and immunomodulatory phenomena. This article explores the pathogenesis, implications, prevention, and treatment of these complications through the use of massive transfusion protocols. Particular attention is given to the optimal ratio of blood products transfused in large volume resuscitation and prevention of secondary coagulopathy. Conclusions: Observational data indicate that the development and use of a massive transfusion protocol may reduce the morbidity and mortality associated with large-volume resuscitation of patients with hemorrhagic shock. Such protocols should include a pre-defined ratio of packed red blood cells, fresh frozen plasma, and platelets transfused; most commonly, the ratio used is 1:1:1. Additionally, such protocols should monitor for and correct hypothermia, hypofibrinogenemia, and electrolyte disturbances such as hypocalcemia and hyperkalemia. (C) 2013 Published Elsevier Inc. C1 [Elmer, Jonathan; Raja, Ali S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Elmer, Jonathan; Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raja, AS (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. OI Wilcox, Susan/0000-0001-7477-7531 NR 119 TC 19 Z9 21 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2013 VL 44 IS 4 BP 829 EP 838 DI 10.1016/j.jemermed.2012.11.025 PG 10 WC Emergency Medicine SC Emergency Medicine GA 121YQ UT WOS:000317282000026 PM 23375220 ER PT J AU Ring, D AF Ring, David TI Benchmarking Changes in Symptom Intensity and Magnitude of Disability SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 0 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2013 VL 38A IS 4 BP 650 EP 651 DI 10.1016/j.jhsa.2012.12.031 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 121LK UT WOS:000317246100002 PM 23537442 ER PT J AU Bolmers, A Luiten, WE Doornberg, JN Brouwer, KM Goslings, JC Ring, D Kloen, P AF Bolmers, Annelies Luiten, Willem E. Doornberg, Job N. Brouwer, Kim M. Goslings, J. Carel Ring, David Kloen, Peter TI A Comparison of the Long-Term Outcome of Partial Articular (AO Type B) and Complete Articular (AO Type C) Distal Radius Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Trauma; distal radius fracture; outcome; wrist function ID DISPLACED INTRAARTICULAR FRACTURES; YOUNG-ADULTS; INTERNAL-FIXATION; OPEN REDUCTION; END AB Purpose A short-term comparison of AO type B (shearing) and type C (compression) articular fractures of the distal radius found no significant differences in functional outcome, but long-term studies would provide important information. We tested the null hypothesis that there is no difference in arm-specific disability between patients with type B and C fractures in long-term follow-up. Methods We evaluated 46 patients (17 with type B fractures and 29 patients with 31 type C fractures of the distal radius) with a mean age of 39 years at the time of injury at a mean of 20 years after operative treatment. We used the Disabilities of the Arm, Shoulder, and Hand questionnaire and 2 physician-based rating systems, the modified Mayo wrist score and the modified Gartland and Werley score. We performed bivariate and multivariable analyses to identify the factors that contributed most to the variation in these scores. Results There were no significant differences between patients with type B and C fractures on the Disabilities of the Arm, Shoulder, and Hand, modified Mayo wrist, or Gartland and Werley scores, or with respect to range of motion, grip strength, and arthrosis. The only statistical difference was in volar tilt of the articular surface on lateral radiographs. Conclusions On average, patients undergoing operative treatment of type B and type C articular fractures of the distal radius have similar impairment, symptoms, and disability in the long-term. (J Hand Surg 2013;38A:753-759. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Univ Amsterdam, Dept Surg, Orthotrauma Res Ctr Amsterdam, Orthopaed Residency Program,Trauma Unit, NL-1100 DD Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Upper Extrem Serv, Boston, MA USA. RP Doornberg, JN (reprint author), Univ Amsterdam, Acad Med Ctr Amsterdam, Orthopaed Residency Program, Orthotrauma Res Ctr Amsterdam,Secretariaat Orthop, G4 Noord,Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. EM jobdoombergortho@gmail.com FU Keuning-Marti-Eckhardt Foundation FX D.R. is a consultant for Biomet. J.N.D. received a Postdoctoral Research Fellowship from the Keuning-Marti-Eckhardt Foundation. There was no external finding source for the preparation of this manuscript. NR 17 TC 6 Z9 6 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2013 VL 38A IS 4 BP 753 EP 759 DI 10.1016/j.jhsa.2012.12.027 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 121LK UT WOS:000317246100018 PM 23453896 ER PT J AU Hartzell, TL Kuo, P Eberlin, KR Winograd, JM Day, CS AF Hartzell, Tristan L. Kuo, Phoebe Eberlin, Kyle R. Winograd, Jonathan M. Day, Charles S. TI The Overutilization of Resources in Patients With Acute Upper Extremity Trauma and Infection SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Emergency; infection; transfer; trauma ID AMERICAN-COLLEGE; FINANCIAL IMPACT; TRIAGE CRITERIA; MAJOR TRAUMA; HEALTH-CARE; EMERGENCY; CENTERS; INJURY; BENEFIT; SYSTEM AB Purpose To compare patients with acute upper extremity injuries and infections presenting initially to the emergency department with patients transferred from outside institutions, and to evaluate triage guidelines for the appropriate transfer of these patients. Methods We reviewed the records of 1,172 consecutive patients with acute upper extremity injuries or infections presenting to 2 level 1 trauma centers over 3-month periods. We analyzed demographics, transfer details, injury characteristics, intervention received, follow-up, and complications. Triage guidelines were established by a board of academic upper extremity and emergency physicians and retrospectively applied to patient data. Results Of 1,172 patients, 155 (13%) arrived via transfer from outside facilities. Transferred patients had more complex injuries by our guidelines, but many did not require level 1 emergent care. The receiving emergency department discharged 26% of the transferred patients without upper extremity specialist evaluation, and 24% of the transferred patients received no procedural intervention at any point. Only 10% went to the operating room emergently. Implementing our guidelines for appropriate triage, we found that 53% of transfers did not require emergent transfer to a level 1 facility. These nonemergent transfers spent an average of 15.2 hours from the time of initial evaluation at the outside facility to discharge from the level 1 emergency department, compared with 3.1 hours in patients who arrived primarily. Retrospectively, our triage guidelines had a 2% undertriage rate and a 3% overtriage rate. Conclusions Over half of the patients transferred with upper extremity injuries and infections for specialized evaluation may be transferred unnecessarily. Guidelines for the care and transfer of patients with acute upper extremity injuries or infections may lead to better use of resources. (J Hand Surg 2013;38A:766-773. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Faith Reg Hlth Serv, Norfolk, NE 68701 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Hartzell, TL (reprint author), Faith Reg Hlth Serv, Dept Surg, 301 N 27th St,Suite 8, Norfolk, NE 68701 USA. EM tristanhartzell@gmail.com NR 25 TC 13 Z9 13 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2013 VL 38A IS 4 BP 766 EP 773 DI 10.1016/j.jhsa.2012.12.016 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 121LK UT WOS:000317246100020 PM 23395105 ER PT J AU Kumar, P Upadhyay, GA Cavaliere-Ogus, C Heist, EK Altman, RK Chatterjee, NA Parks, KA Singh, JP AF Kumar, Prabhat Upadhyay, Gaurav A. Cavaliere-Ogus, Christine Heist, E. Kevin Altman, Robert K. Chatterjee, Neal A. Parks, Kimberly A. Singh, Jagmeet P. TI Right ventricular lead adjustment in cardiac resynchronization therapy and acute hemodynamic response: a pilot study SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Cardiac resynchronization therapy; Right ventricular lead position; Left ventricular lead position; Left ventricular lead electrical delay; Hemodynamic response ID CORONARY VENOUS ANATOMY; CHRONIC HEART-FAILURE; LITHIUM DILUTION; POSITION; SITE; RESYNCHRONISATION; ECHOCARDIOGRAPHY; OPTIMIZATION; VARIABILITY; MORTALITY AB Optimal left ventricular (LV) lead position has emerged as an important determinant of response after cardiac resynchronization therapy (CRT). Comparatively, strategy for right ventricular (RV) lead optimization remains uncertain. Three variations of RV lead position (apex, mid-septal, and high septal) were tested in seven consecutive patients. At each location, intra-procedural measurement of LV lead electrical delay (LVLED) was obtained during intrinsic rhythm and RV pacing (RV-LVLED). Simultaneous cardiac output assessment was performed using the LiDCO (TM) (lithium chloride indicator dilution) system. Final RV lead location was selected based on best-measured cardiac output. Clinical and echocardiographic outcomes were assessed at baseline and 6 months. Adjustment of RV lead position after securing a LV lead site led to an incremental change of 30 +/- 18 % (range, 7-52 %) in the cardiac index (CI). There was substantial variation in acute hemodynamic response (a dagger CI, 14 +/- 13 %; range, 3-41 %) seen with pacing from each patient's worst to best RV lead position; no single RV lead position emerged as optimal across all patients. Paced RV-LVLED was not correlated with percent change in CI (r = 0.18; p = NS). LV ejection fraction (LVEF) increased significantly (28 +/- 4 to 40 +/- 8 %, p = 0.006) at 6 months. LVLED measured during intrinsic rhythm, but not during RV pacing, correlated with percent change in LVEF (r = 0.88, p = 0.02). RV lead position adjustment can be used to enhance acute hemodynamic response during CRT. Measurement of paced RV-LVLED, however, does not reliably predict change in cardiac output. C1 [Kumar, Prabhat; Upadhyay, Gaurav A.; Cavaliere-Ogus, Christine; Heist, E. Kevin; Altman, Robert K.; Chatterjee, Neal A.; Parks, Kimberly A.; Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp,Heart Ctr, Boston, MA 02412 USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561 FU Medtronic Inc.; Medtronic; Biotronik; St. Jude Medical; Boston Scientific; Sorin Group; Boston Scientific Corp.; Guidant Corp FX This study was supported in part by a research grant from Medtronic Inc.; Christine Cavaliere is an employee of and receives salary support from Medtronic. E. Kevin Heist receives honoraria from Biotronik, Boston Scientific, Medtronic, St. Jude Medical, and Sorin group; receives research grants from Biotronik, St. Jude Medical, and Boston Scientific; and is consultant to Boston Scientific, St. Jude Medical, and Sorin group (all modest). Kimberly A. Parks received honoraria from Sorin Group and Research grants from Medtronic, St. Jude Medical, and Sorin Group. Jagmeet P Singh has received research grants from St. Jude Medical, Medtronic Inc., Boston Scientific Corp., and Biotronik; has received honoraria/speaker fees from Medtronic Inc., Biotronik, Guidant Corp, Sorin group, and St. Jude Medical; and has served on advisory Board/Steering Committee and as consultant to Boston Scientific Corp., Biotronik, St. Jude Medical, Medtronic, Sorin Group, Cardioinsight, and Thoratec Inc. All other authors have no potential conflicts of interest. NR 34 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD APR PY 2013 VL 36 IS 3 BP 223 EP 231 DI 10.1007/s10840-012-9759-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 123YX UT WOS:000317430300004 PM 23263893 ER PT J AU Ptaszek, LM Chalhoub, F Perna, F Beinart, R Barrett, CD Danik, SB Heist, EK Ruskin, JN Mansour, M AF Ptaszek, Leon M. Chalhoub, Fadi Perna, Francesco Beinart, Roy Barrett, Conor D. Danik, Stephan B. Heist, E. Kevin Ruskin, Jeremy N. Mansour, Moussa TI Rapid acquisition of high-resolution electroanatomical maps using a novel multielectrode mapping system SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Animal studies; Biomedical engineering; Electroanatomical mapping; Catheter ablation ID RIGHT-VENTRICULAR CARDIOMYOPATHY/DYSPLASIA; OUTFLOW TRACT TACHYCARDIA; FOCAL ATRIAL TACHYCARDIA; CATHETER ABLATION; RADIOFREQUENCY ABLATION; ENDOMYOCARDIAL BIOPSY; FIBRILLATION; SUBSTRATE; ACCURACY; TECHNOLOGY AB Conventional electroanatomical mapping systems employ roving catheters with one or a small number of electrodes. Maps acquired using these systems usually contain a small number of points and take a long time to acquire. Use of a multielectrode catheter could facilitate rapid acquisition of higher-resolution maps through simultaneous collection of data from multiple points in space; however, a large multielectrode array could potentially limit catheter maneuverability. The purpose of this study was to test the feasibility of using a novel, multielectrode catheter to map the right atrium and the left ventricle. Electroanatomical mapping of the right atrium and the left ventricle during both sinus and paced rhythm were performed in five swine using a conventional mapping catheter and a novel, multielectrode catheter. Average map acquisition times for the multielectrode catheter (with continuous data collection) ranged from 5.2 to 9.5 min. These maps contained an average of 2,753 to 3,566 points. Manual data collection with the multielectrode catheter was less rapid (average map completion in 11.4 to 18.1 min with an average of 870 to 1,038 points per map), but the conventional catheter was slower still (average map completion in 28.6 to 32.2 min with an average 120 to 148 points per map). Use of this multielectrode catheter is feasible for mapping the left ventricle as well as the right atrium. The multielectrode catheter facilitates acquisition of electroanatomical data more rapidly than a conventional mapping catheter. This results in shorter map acquisition times and higher-density electroanatomical maps in these chambers. C1 [Ptaszek, Leon M.; Chalhoub, Fadi; Perna, Francesco; Beinart, Roy; Barrett, Conor D.; Danik, Stephan B.; Heist, E. Kevin; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, MGH Heart Ctr, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, MGH Heart Ctr, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM mmansour@partners.org OI Perna, Francesco/0000-0002-9019-9492 FU Deane Institute for Integrative Research Atrial Fibrillation and Stroke at the Massachusetts General Hospital; Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University and its affiliated academic health care centers; Boston Scientific; Biotronik; St. Jude Medical; Biosense Webster; Medtronic; St. JudeMedical; MC 10; Voyage Medical; CardioFocus FX L.M.P. received research support from the Deane Institute for Integrative Research Atrial Fibrillation and Stroke at the Massachusetts General Hospital. Statistical analyses were performed with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH award No. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers).; Leon M. Ptaszek, M. D., Ph.D., Fadi Chalhoub, M. D., Francesco Perna, M. D., Roy Beinart, M. D., Conor D. Barrett, M. D., and Stephan B. Danik, M. D. have no financial disclosures to declare. E. Kevin Heist, M. D., Ph. D. declares no financial support but with potential conflicts of interest from the following: Boston Scientific (research grant and honoraria), Biotronik (research grant and honoraria), Boston Scientific (research grant, consultant, and honoraria), Medtronic (honoraria), Sanofi (consultant), Sorin (consultant and honoraria), and St. Jude Medical (research grant, consultant, and honoraria). Jeremy N. Ruskin, M. D. declares no financial support but with potential conflicts of interest from the following: Atricure (consultant), Biosense Webster (consultant and fellowship support), Boston Scientific (fellowship support), CardioFocus (Clinical Oversight Committee-no compensation), CardioInsight (Scientific Advisory Board), CryoCath (Scientific Steering Committee-no compensation), Medtronic (consultant and fellowship support), St. JudeMedical (fellowship support), and Third Rock Ventures (consultant). Moussa Mansour, M. D. declares the following disclosures: Biosense Webster (consultant and research grant), Boston Scientific (consultant and research grant), St. Jude Medical (consultant and research grant), Medtronic (consultant), MC 10 (research grant), Voyage Medical (research grant), Rhythmia Medical (research grant), and CardioFocus (research grant). NR 30 TC 5 Z9 5 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD APR PY 2013 VL 36 IS 3 BP 233 EP 242 DI 10.1007/s10840-012-9733-y PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 123YX UT WOS:000317430300005 PM 23179916 ER PT J AU Hayakawa, K Miyamoto, N Seo, JH Pham, LDD Kim, KW Lo, EH Arai, K AF Hayakawa, Kazuhide Miyamoto, Nobukazu Seo, Ji Hae Pham, Loc-Duyen D. Kim, Kyu-Won Lo, Eng H. Arai, Ken TI High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE endothelial progenitor cells (EPCs); high-mobility group box 1 (HMGB1); neurovascular unit; reactive astrocytes; white matter injury; white matter remodeling ID GLYCATION END-PRODUCTS; OLIGODENDROCYTE PRECURSOR CELLS; TOLL-LIKE RECEPTORS; EXPERIMENTAL STROKE; ISCHEMIC-STROKE; MOUSE MODEL; IN-VITRO; NEUROVASCULAR UNIT; BRAIN; ACTIVATION AB High-mobility group box 1 (HMGB1) was initially described as a damage-associated-molecular-pattern (DAMP) mediator that worsens acute brain injury after stroke. But, recent findings suggest that HMGB1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell (EPC) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine (LPC) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB1 was up-regulated in GFAP-positive reactive astrocytes, along with the accumulation of Flk1/CD34-double-positive EPCs that expressed pro-recovery mediators such as brain-derived neurotrophic factor and basic fibroblast growth factor. AstrocyteEPC signaling required the HMGB1 receptor RAGE as treatment with RAGE-neutralizing antibody significantly decreased EPC accumulation. Moreover, suppression of HMGB1 with siRNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB1 from reactive astrocytes may attract EPCs to promote recovery after white matter injury. C1 [Hayakawa, Kazuhide; Miyamoto, Nobukazu; Seo, Ji Hae; Pham, Loc-Duyen D.; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. [Hayakawa, Kazuhide; Miyamoto, Nobukazu; Seo, Ji Hae; Pham, Loc-Duyen D.; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. [Hayakawa, Kazuhide; Miyamoto, Nobukazu; Seo, Ji Hae; Pham, Loc-Duyen D.; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Charlestown, MA USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, NeuroVasc Coordinat Res Ctr, Coll Pharm, Seoul, South Korea. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu; karai@partners.org FU Deane Foundation; MGH ECOR Fund for Medical Discovery; American Heart Association; National Institutes of Health; Research Abroad from the Japan Society for the Promotion of Science; National Research Foundation of Korea; World Class University Program; Global Research Laboratory Program FX Supported in part by the Deane Foundation, MGH ECOR Fund for Medical Discovery, American Heart Association, National Institutes of Health, Research Abroad from the Japan Society for the Promotion of Science, National Research Foundation of Korea, the World Class University Program, and the Global Research Laboratory Program. NR 58 TC 15 Z9 15 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2013 VL 125 IS 2 BP 273 EP 280 DI 10.1111/jnc.12120 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 122DV UT WOS:000317297700011 PM 23227954 ER PT J AU Belland, L Handel, D Yadav, K Heard, K Rivera, L Eisenberg, A Noble, M Mekala, S Valley, M Hwang, U AF Belland, L. Handel, D. Yadav, K. Heard, K. Rivera, L. Eisenberg, A. Noble, M. Mekala, S. Valley, M. Hwang, U. TI Disparities in the quality of pain care for geriatric patients in the Emergency Department (ED). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Belland, L.; Rivera, L.; Hwang, U.] Mt Sinai Sch Med, New York, NY USA. [Hwang, U.] James J Peters VAMC, GRECC, Bronx, NY USA. [Heard, K.; Valley, M.] Univ Colorado, Sch Med, Denver, CO USA. [Yadav, K.; Eisenberg, A.] George Washington Univ, Washington, DC USA. [Handel, D.; Noble, M.; Mekala, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S83 EP S83 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600238 ER PT J AU Bowling, B Sharma, P O'Hare, AM Allman, RM Muntner, P AF Bowling, B. Sharma, P. O'Hare, A. M. Allman, R. M. Muntner, P. TI Increasing Prevalence of Reduced Estimated Glomerular Filtration Rate among the Oldest-Old US Adults from 1988-1994 through 2005-2010. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Bowling, B.; Allman, R. M.] Birmingham VA Med Ctr, Birmingham, AL USA. [Sharma, P.; Muntner, P.] UAB, Birmingham, AL USA. [O'Hare, A. M.] VA Puget Sound, Seattle, WA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S116 EP S116 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600330 ER PT J AU Brown, RT Ahalt, C Steinman, MA Williams, BA AF Brown, R. T. Ahalt, C. Steinman, M. A. Williams, B. A. TI Hands on the Hood, Grandpa: Assessing the Need for Geriatrics Health Training among Police. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Brown, R. T.; Ahalt, C.; Steinman, M. A.; Williams, B. A.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S15 EP S15 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600041 ER PT J AU Carrejo, M DeWitt, M Tan, RS AF Carrejo, M. DeWitt, M. Tan, R. S. TI The Collaborative Model of Geriatrics & Mental Health Care for Older Veterans in a Nursing Home. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Carrejo, M.; DeWitt, M.; Tan, R. S.] VA Med Ctr, Houston, TX USA. [DeWitt, M.] Baylor Coll Med, Sect Geriatr, Houston, TX 77030 USA. [Tan, R. S.] Univ Texas Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S112 EP S113 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600320 ER PT J AU Fega, R Motyckova, G Sherman, A DeAngelo, DJ Abel, GA Steensma, D Wadleigh, M Stone, RM Driver, JA AF Fega, R. Motyckova, G. Sherman, A. DeAngelo, D. J. Abel, G. A. Steensma, D. Wadleigh, M. Stone, R. M. Driver, J. A. TI Geriatric Assessment Variables Add Prognostic Value to the International Prognostic Scoring System for Myelodysplastic Syndrome. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Fega, R.] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Motyckova, G.; DeAngelo, D. J.; Abel, G. A.; Steensma, D.; Wadleigh, M.; Stone, R. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sherman, A.] Univ Cincinnati, Cincinnati, OH USA. [Driver, J. A.] VA Boston Med Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Driver, J. A.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S121 EP S121 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600344 ER PT J AU Franco, E Ramadan, F AF Franco, E. Ramadan, F. TI "A MONSTER IN MY STOMACH": A CASE OF ABDOMINAL PAIN. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Franco, E.; Ramadan, F.] Massachusetts Gen Hosp, Boston, MA 02114 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S77 EP S78 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600221 ER PT J AU Fung, CH Martin, J Jouldjian, S Dzierzewski, J Josephson, K Alessi, C AF Fung, C. H. Martin, J. Jouldjian, S. Dzierzewski, J. Josephson, K. Alessi, C. TI Mental health and sleep characteristics among older veterans with untreated obstructive sleep apnea and comorbid insomnia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Fung, C. H.; Martin, J.; Alessi, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fung, C. H.; Martin, J.; Jouldjian, S.; Dzierzewski, J.; Josephson, K.; Alessi, C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S94 EP S94 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600266 ER PT J AU Ghidei, L Simone, M Salow, M Zimmerman, K Paquin, A Skarf, LM Kostas, T Rudolph, JL AF Ghidei, L. Simone, M. Salow, M. Zimmerman, K. Paquin, A. Skarf, L. Michal Kostas, T. Rudolph, J. L. TI Aging, Adherence, and Antiretroviral Therapy: A Systematic Review of Adherence in Older HIV-Infected Individuals. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Ghidei, L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Simone, M.; Kostas, T.; Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Simone, M.; Skarf, L. Michal; Kostas, T.] Harvard Univ, Sch Med, Boston, MA USA. [Salow, M.; Paquin, A.] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Salow, M.; Zimmerman, K.; Paquin, A.; Skarf, L. Michal; Rudolph, J. L.] VA Boston Healthcare Syst, Div Geriatr & Palliat Care, Boston, MA USA. [Zimmerman, K.] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S111 EP S112 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600317 ER PT J AU Grigoryan, K Javedan, H Rudolph, J AF Grigoryan, K. Javedan, H. Rudolph, J. TI Ortho-Geriatric Models and Optimal Outcomes: A Systematic Review and Meta-Analysis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Grigoryan, K.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Javedan, H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rudolph, J.] VA Boston Healthcare Syst, GRECC, Boston, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S8 EP S9 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600023 ER PT J AU Gruenewald, D Virtue, J Hartmann, T Kopf, W Nason, E White, E AF Gruenewald, D. Virtue, J. Hartmann, T. Kopf, W. Nason, E. White, E. TI Outcomes For Outpatient Veterans With Cancer Receiving Care Coordination-Home Telehealth Services. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Gruenewald, D.; Virtue, J.; Hartmann, T.; Kopf, W.; Nason, E.; White, E.] VA Puget Sound Hlth Care Syst, Geriatr Extended Care, Seattle, WA USA. [Gruenewald, D.] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S56 EP S56 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600158 ER PT J AU Hanson, AJ Hernandez, H Bartholomew, LM Gabriel, AK Chapman, D Craft, S AF Hanson, A. J. Hernandez, H. Bartholomew, L. M. Gabriel, A. K. Chapman, D. Craft, S. TI APOE Genotype and Gender Influence Glucose Tolerance in Older Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Hanson, A. J.; Hernandez, H.; Bartholomew, L. M.; Gabriel, A. K.; Chapman, D.; Craft, S.] Univ Washington, Seattle, WA 98195 USA. [Hanson, A. J.] VA Puget Sound HCS, GRECC, Seattle, WA USA. [Craft, S.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S114 EP S114 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600324 ER PT J AU Hernandez, A Ramadan, F AF Hernandez, A. Ramadan, F. TI Is this Aspiration Pneumonia? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Hernandez, A.; Ramadan, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S128 EP S128 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600364 ER PT J AU Hung, WW Ross, JS Siu, AL AF Hung, W. W. Ross, J. S. Siu, A. L. TI Predictors of adverse events during acute medical hospital admission among older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Hung, W. W.; Siu, A. L.] Mt Sinai Sch Med, New York, NY USA. [Hung, W. W.; Siu, A. L.] James J Peters VA Med Ctr, Bronx, NY USA. [Ross, J. S.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S171 EP S171 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600491 ER PT J AU Kelley, E Nguyen, G Anjum, S Lee, S Sanchez-Reilly, S AF Kelley, E. Nguyen, G. Anjum, S. Lee, S. Sanchez-Reilly, S. TI Is PTSD a Geriatric Condition? Caring for Vietnam Era Older Adults Facing Terminal Illness. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Kelley, E.; Anjum, S.; Sanchez-Reilly, S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kelley, E.; Nguyen, G.; Anjum, S.; Lee, S.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, GRECC GEC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S227 EP S227 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600654 ER PT J AU Kinosian, B Mann, E Hammond, J Haggerty, M Feinberg, A Casarett, D AF Kinosian, B. Mann, E. Hammond, J. Haggerty, M. Feinberg, A. Casarett, D. TI Hospital <@> Home as an Inter-agency Collaborative in the VA SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Kinosian, B.; Mann, E.; Casarett, D.] Univ Penn, Philadelphia, PA 19104 USA. [Kinosian, B.; Hammond, J.; Haggerty, M.; Feinberg, A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S9 EP S9 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600024 ER PT J AU Kostas, TR Simone, M Zimmerman, K Salow, M Noto, N Rudolph, JL McMahon, GT AF Kostas, T. R. Simone, M. Zimmerman, K. Salow, M. Noto, N. Rudolph, J. L. McMahon, G. T. TI Improving Medication Management Competency Through an Interdisciplinary Workshop. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Kostas, T. R.; Salow, M.; Noto, N.; Rudolph, J. L.] VA Boston Healthcare Syst, Boston, MA USA. [Kostas, T. R.; Simone, M.; Rudolph, J. L.; McMahon, G. T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Simone, M.; McMahon, G. T.] Harvard Univ, Sch Med, Boston, MA USA. [Zimmerman, K.] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S153 EP S153 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600440 ER PT J AU LaMantia, MA Jhanji, S Maina, M Nazir, A Alder, C Chodosh, J Boustani, M AF LaMantia, M. A. Jhanji, S. Maina, M. Nazir, A. Alder, C. Chodosh, J. Boustani, M. TI Redesigning Acute Care for Cognitively Impaired Older Adults: Optimizing Health Care Services for the 21st Century. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [LaMantia, M. A.; Jhanji, S.; Maina, M.; Boustani, M.] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [LaMantia, M. A.; Jhanji, S.; Maina, M.; Boustani, M.] Regenstrief Inst Inc, Indianapolis, IN USA. [Nazir, A.] Indiana Univ, Geriatr Program, Indianapolis, IN 46204 USA. [Alder, C.] Wishard Hlth Serv, Indianapolis, IN USA. [Chodosh, J.] VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [Chodosh, J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S112 EP S112 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600319 ER PT J AU Levy, C Edes, T Whitfield, E Kinosian, B AF Levy, C. Edes, T. Whitfield, E. Kinosian, B. TI Medical Foster Homes - Is this new model of care an effective substitute for nursing homes? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Levy, C.; Whitfield, E.] Denver VA Med Ctr, Denver, CO USA. [Kinosian, B.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Edes, T.] Vet Affairs Cent Off, Washington, DC 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S109 EP S110 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600311 ER PT J AU Matsuwaka, S Jouldjian, S Martin, J Alessi, C AF Matsuwaka, S. Jouldjian, S. Martin, J. Alessi, C. TI Insomnia in Older Veterans: Prevalence, Self-Rated Health, and Talking to a Doctor about Sleep Problems. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Matsuwaka, S.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Jouldjian, S.; Martin, J.; Alessi, C.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. [Martin, J.; Alessi, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S205 EP S205 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600590 ER PT J AU Methvin, BL Lee, S Sharp, C Sanchez-Reilly, S Ross, J AF Methvin, B. L. Lee, S. Sharp, C. Sanchez-Reilly, S. Ross, J. TI Caregiver Burden Among Family Caregivers Of Homebound Older Veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Methvin, B. L.; Sanchez-Reilly, S.; Ross, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, S.; Sharp, C.; Sanchez-Reilly, S.; Ross, J.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S93 EP S93 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600264 ER PT J AU Methvin, BL Lee, S Ross, J AF Methvin, B. L. Lee, S. Ross, J. TI Analysis of YouTube Resources for Caregivers of Aging Individuals SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Methvin, B. L.; Ross, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, S.; Ross, J.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600019 ER PT J AU Meziab, O Yaffe, K Brach, J Simonsick, EM Harris, TB Barnes, DE AF Meziab, O. Yaffe, K. Brach, J. Simonsick, E. M. Harris, T. B. Barnes, D. E. TI Changes in Physical Activity Before and After Development of Pre-Clinical Cognitive Impairment. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Meziab, O.] Univ Arizona, Coll Med, Tucson, AZ USA. [Yaffe, K.; Barnes, D. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brach, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Simonsick, E. M.; Harris, T. B.] NIA, Baltimore, MD 21224 USA. [Yaffe, K.; Barnes, D. E.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S115 EP S115 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600327 ER PT J AU Moody, S Newsom, EM Covinsky, KE AF Moody, S. Newsom, E. M. Covinsky, K. E. TI Determinants Of Emotional Recovery And Perceived Change In Health Following A Disaster SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Moody, S.; Covinsky, K. E.] Univ Calif San Francisco, Med Div Geriatr, San Francisco, CA 94143 USA. [Moody, S.; Covinsky, K. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Newsom, E. M.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA USA. [Moody, S.] Kameda Med Ctr, Grad Med Educ, Kamogawa City, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S102 EP S102 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600291 ER PT J AU Mori, T Greendale, GA Cauley, JA Han, W Huang, M Karlamangla, AS AF Mori, T. Greendale, G. A. Cauley, J. A. Han, W. Huang, M. Karlamangla, A. S. TI Dietary Phytoestrogens and Femoral Neck Strength: Findings from the Study of Women's Health Across the Nation. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Mori, T.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Mori, T.; Greendale, G. A.; Han, W.; Huang, M.; Karlamangla, A. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S87 EP S88 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600249 ER PT J AU Mulligan, EA Moye, J Schwartzenburg, M Gosian, J Herman, L Naik, AD AF Mulligan, E. A. Moye, J. Schwartzenburg, M. Gosian, J. Herman, L. Naik, A. D. TI Beyond Mortality and Treatment Effects: Cancer Impacts Older Survivors' Social Roles, Emotional States and Relationships. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Mulligan, E. A.; Moye, J.; Gosian, J.] VA Boston Hlth Care Syst, Boston, MA USA. [Mulligan, E. A.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Schwartzenburg, M.] Rice Univ, Houston, TX USA. [Herman, L.; Naik, A. D.] Michael E DeBakey VAMC HSR&D CoE, Houston, TX USA. [Herman, L.; Naik, A. D.] Baylor Coll Med, Houston, TX 77030 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S119 EP S119 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600339 ER PT J AU Nazir, A Lamantia, M Perkins, A Hui, S Campbell, N Khan, B Chodosh, J Boustani, M AF Nazir, A. Lamantia, M. Perkins, A. Hui, S. Campbell, N. Khan, B. Chodosh, J. Boustani, M. TI Impact of Cognitive Impairment on Rehospitalizations SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Nazir, A.] Indiana Univ, Geriatr Program, Indianapolis, IN 46204 USA. [Lamantia, M.; Perkins, A.; Hui, S.; Campbell, N.; Khan, B.; Boustani, M.] Indiana Univ, Ctr Aging Res, Regenstrief Inst Inc, Indianapolis, IN 46204 USA. [Chodosh, J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Chodosh, J.] VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S104 EP S104 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600296 ER PT J AU Northern, J Beckjord, S Rossi, MI Thatcher, T Kendjelic, E AF Northern, J. Beckjord, S. Rossi, M. I. Thatcher, T. Kendjelic, E. TI The Efficacy of a Neuropsychological Test Battery used in a VA Driving Clinic on Assessing Driving Ability amongst Older Veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Northern, J.; Rossi, M. I.; Thatcher, T.; Kendjelic, E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Beckjord, S.] Apex Psychol Care & Memory Ctr, Pittsburgh, PA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S64 EP S64 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600182 ER PT J AU O'Kula, S Gottesman, E Hung, W Boockvar, K AF O'Kula, S. Gottesman, E. Hung, W. Boockvar, K. TI The Spanish-English Language Barrier as a Factor in Veterans' Care Transitions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [O'Kula, S.; Hung, W.; Boockvar, K.] Mt Sinai Sch Med, New York, NY USA. [Gottesman, E.; Hung, W.; Boockvar, K.] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S219 EP S219 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600632 ER PT J AU Qiu, A Ortiz, J Cruz-Oliver, D Sanchez-Reilly, S AF Qiu, A. Ortiz, J. Cruz-Oliver, D. Sanchez-Reilly, S. TI Barriers to End of Life Care among Latino Elders: A Healthcare Provider Perspective. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Qiu, A.; Ortiz, J.; Sanchez-Reilly, S.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Ortiz, J.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. [Cruz-Oliver, D.] St Louis Univ, Dept Internal Med, Div Geriatr, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S211 EP S212 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600609 ER PT J AU Reed, ML AF Reed, M. L. TI A Case of Granuloma Annulare and Malignancy. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Reed, M. L.] VA Puget Sound, Geriatr, Tacoma, WA USA. [Reed, M. L.] Madigan Healthcare Syst, Family Med, Tacoma, WA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S80 EP S80 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600228 ER PT J AU Rothrock, AG Sawyer, P Ford, CR Brown, CJ AF Rothrock, A. G. Sawyer, P. Ford, C. R. Brown, C. J. TI Can a Single Dose of Interprofessional Team Training Influence Medical Student Attitudes Toward Healthcare Teams? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Rothrock, A. G.; Sawyer, P.; Ford, C. R.; Brown, C. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Brown, C. J.] Birmingham VA Med Ctr, Birmingham, AL 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S145 EP S145 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600417 ER PT J AU Sherman, AE Motyckova, G Fega, K DeAngelo, DJ Abel, GA Steensma, D Wadleigh, M Stone, RM Driver, JA AF Sherman, A. E. Motyckova, G. Fega, K. DeAngelo, D. J. Abel, G. A. Steensma, D. Wadleigh, M. Stone, R. M. Driver, J. A. TI Geriatric Assessment in Older Patients with Acute Myeloid Leukemia: A Prospective Study of Associated Treatment and Outcomes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Sherman, A. E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Motyckova, G.; DeAngelo, D. J.; Abel, G. A.; Steensma, D.; Wadleigh, M.; Stone, R. M.; Driver, J. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fega, K.] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Driver, J. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S201 EP S201 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600580 ER PT J AU Siddiqui, A Hwang, UY AF Siddiqui, A. Hwang, U. Y. TI The Effects of Age on the Quality of ED Pain Care and Outcomes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Siddiqui, A.; Hwang, U. Y.] Mt Sinai Sch Med, New York, NY USA. [Hwang, U. Y.] James J Peters VAMC, GRECC, Bronx, NY 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S83 EP S83 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600237 ER PT J AU Smith, GM Block, S Schaefer, K Bernacki, R AF Smith, G. M. Block, S. Schaefer, K. Bernacki, R. TI Serious Illness Communication Checklist: Effects on Clinician Attitude and Confidence. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Smith, G. M.; Block, S.; Schaefer, K.; Bernacki, R.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, G. M.; Block, S.; Schaefer, K.; Bernacki, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S207 EP S208 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600597 ER PT J AU Su, C McMahan, R Sudore, R AF Su, C. McMahan, R. Sudore, R. TI Family Matters: Effects of Birth Order and Family Dynamics on Surrogate Decision Making SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Su, C.] Mt Sinai Sch Med, New York, NY USA. [McMahan, R.; Sudore, R.] San Francisco VA Med Ctr, San Francisco, CA USA. [McMahan, R.; Sudore, R.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S6 EP S6 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600017 ER PT J AU Win, AZ Ceresa, C Allison, TA AF Win, A. Z. Ceresa, C. Allison, T. A. TI The Prevalence of Malnutrition in Frail Older Veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2013 CL Grapevine, TX SP Amer Geriatr Soc C1 [Win, A. Z.; Ceresa, C.; Allison, T. A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Allison, T. A.] Univ San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94117 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2013 VL 61 SU 1 SI SI BP S159 EP S159 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120QW UT WOS:000317187600456 ER PT J AU Hall, RK O'Hare, AM Anderson, RA Colon-Emeric, CS AF Hall, Rasheeda K. O'Hare, Ann M. Anderson, Ruth A. Colon-Emeric, Cathleen S. TI End-Stage Renal Disease in Nursing Homes: A Systematic Review SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE Renal dialysis; skilled nursing facilities; aged ID EXTENDED-CARE FACILITY; LONG-TERM-CARE; PERITONEAL-DIALYSIS; PATIENT CHARACTERISTICS; STARTING DIALYSIS; HEMODIALYSIS; REHABILITATION; MORTALITY; PREVALENCE; EXPERIENCE AB Objectives/Introduction: Demand for nursing home (NH) care by patients with end-stage renal disease (ESRD) is likely to increase with growing numbers of older adults initiating chronic dialysis. We completed a systematic review to summarize the literature on NH residents with ESRD. Methods: MEDLINE, CINAHL, EMBASE, and relevant conference proceedings were searched to identify articles using the following MESH terms or related key words in the title or abstract: "residential facilities", "renal dialysis", "renal replacement therapy", and "chronic kidney failure". We selected case control, cohort studies, and clinical trials that included older adults with ESRD (defined as those receiving chronic dialysis or those with stage 5 chronic kidney disease) living in residential care facilities. We abstracted information on study design, quality, and results. Results: Of 198 unique citations identified by the search strategy, 14 articles met eligibility criteria. Most articles were multicenter studies that were conducted in the 1990s. One study focused on patients with stage 5 chronic kidney disease, and the remaining 13 studies focused on patients receiving chronic dialysis, of which eight studies included only those receiving peritoneal dialysis, four studies included patients receiving both peritoneal dialysis and hemodialysis, and one study included only patients receiving hemodialysis. All studies were observational, no clinical trials were identified, and study design limitations and heterogeneity within study populations were common. Summarizing results across these studies suggests that NH residents with ESRD have limited survival, particularly early after dialysis initiation. Functional impairment is highly prevalent in this population and independently associated with poor outcomes. Conclusions: NH residents with ESRD appear to be a particularly vulnerable population, but current information on their prevalence, characteristics, and outcomes is limited. Further research is needed to provide a better understanding of modifiable predictors of survival and functional decline in this population. Copyright (C) 2013 -American Medical Directors Association, Inc. C1 [Hall, Rasheeda K.] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA. [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, HSR&D Ctr Excellence, Seattle, WA USA. [Anderson, Ruth A.] Duke Univ, Sch Nursing, Durham, NC 27710 USA. [Anderson, Ruth A.; Colon-Emeric, Cathleen S.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. [Colon-Emeric, Cathleen S.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Colon-Emeric, Cathleen S.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP Hall, RK (reprint author), Duke Univ, Med Ctr, Box DUMC 2747,2424 Erwin Rd,Suite 605, Durham, NC 27710 USA. EM rasheeda.stephens@duke.edu OI Anderson, Ruth/0000-0001-6640-644X FU Claude D. Pepper Older Americans Independence Center [NIH P30 AG028716]; Agency for Healthcare Research and Quality [T32HS019490] FX None of the authors report any potential conflicts of interest. This material is the result of work supported with resources and the use of facilities at the Durham VA Medical Center. This study is supported by the Claude D. Pepper Older Americans Independence Center (NIH P30 AG028716) and the Agency for Healthcare Research and Quality (T32HS019490). Some of the data reported here has been supplied by the United States Renal Data System (USRDS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States government. NR 32 TC 4 Z9 4 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD APR PY 2013 VL 14 IS 4 BP 242 EP 247 DI 10.1016/j.jamda.2013.01.004 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 121YI UT WOS:000317281200005 PM 23375523 ER PT J AU Pellikka, PA Douglas, PS Miller, JG Abraham, TP Baumann, R Buxton, DB Byrd, BF Chen, P Cook, NL Gardin, JM Hansen, G Houle, HC Husson, S Kaul, S Klein, AL Lang, RM Leong-Poi, H Lopez, H Mahmoud, TM Maslak, S McCulloch, ML Metz, S Nagueh, SF Pearlman, AS Pibarot, P Picard, MH Porter, TR Prater, D Rodriguez, R Sarano, ME Scherrer-Crosbie, M Shirali, GS Sinusas, A Slosky, JJ Sugeng, L Tatpati, A Villanueva, FS von Ramm, OT Weissman, NJ Zamani, S AF Pellikka, Patricia A. Douglas, Pamela S. Miller, James G. Abraham, Theodore P. Baumann, Rolf Buxton, Denis B. Byrd, Benjamin F., III Chen, Peter Cook, Nakela L. Gardin, Julius M. Hansen, Gunnar Houle, Helene C. Husson, Stefan Kaul, Sanjiv Klein, Allan L. Lang, Roberto M. Leong-Poi, Howard Lopez, Hector Mahmoud, Tamer M. Maslak, Sam McCulloch, Marti L. Metz, Steve Nagueh, Sherif F. Pearlman, Alan S. Pibarot, Philippe Picard, Michael H. Porter, Thomas R. Prater, David Rodriguez, Rudy Sarano, Maurice E. Scherrer-Crosbie, Marielle Shirali, Girish S. Sinusas, Albert Slosky, Jack J. Sugeng, Lissa Tatpati, Anand Villanueva, Flordeliza S. von Ramm, Olaf T. Weissman, Neil J. Zamani, Shaun TI American Society of Echocardiography Cardiovascular Technology and Research Summit: A Roadmap for 2020 SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material DE Echocardiography; Cardiac imaging; Cardiovascular imaging; Cardiovascular technology; Cardiovascular technology development; Research; Clinical Research; Myocardial deformation; Three-dimensional imaging; Doppler; Contrast echocardiography; Valvular heart disease; Therapeutic ultrasound; Research infrastructure; Research training ID VALVULAR HEART-DISEASE; REGIONAL MYOCARDIAL-FUNCTION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; DIAGNOSTIC ULTRASOUND; IN-VIVO; EAE/ASE RECOMMENDATIONS; MICROBUBBLES; STRAIN; QUANTIFICATION; INVESTIGATORS C1 [Pellikka, Patricia A.; Sarano, Maurice E.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Douglas, Pamela S.; von Ramm, Olaf T.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Miller, James G.] Washington Univ, Dept Phys, St Louis, MO 63130 USA. [Abraham, Theodore P.] Johns Hopkins Univ, Baltimore, MD USA. [Baumann, Rolf] TomTec Imaging Syst GmbH, Munich, Germany. [Buxton, Denis B.; Cook, Nakela L.] NHLBI, Bethesda, MD 20892 USA. [Byrd, Benjamin F., III] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Chen, Peter] GE Healthcare Med Diagnost, Chicago, IL USA. [Gardin, Julius M.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Hansen, Gunnar] GE Healthcare, Horten, Norway. [Houle, Helene C.] Siemens Med Solut USA Inc, Mountain View, CA USA. [Husson, Stefan] GE Ultrasound, Milwaukee, WI USA. [Kaul, Sanjiv] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Klein, Allan L.] Cleveland Clin, Cleveland, OH 44106 USA. [Lang, Roberto M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Leong-Poi, Howard] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Lopez, Hector] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Mahmoud, Tamer M.] Abbott Vasc Struct Heart, Menlo Pk, CA USA. [McCulloch, Marti L.; Nagueh, Sherif F.] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Metz, Steve] Philips Healthcare, Seattle, WA USA. [Pearlman, Alan S.] Univ Washington, Seattle, WA 98195 USA. [Pibarot, Philippe] Univ Laval, Quebec Heart Inst, Quebec City, PQ, Canada. [Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Picard, Michael H.; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA. [Porter, Thomas R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Prater, David] Philips Healthcare, Andover, MA USA. [Rodriguez, Rudy; Zamani, Shaun] Edwards Lifesci, Irvine, CA USA. [Shirali, Girish S.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Sinusas, Albert; Sugeng, Lissa] Yale Univ, New Haven, CT USA. [Slosky, Jack J.] Lantheus Med Imaging, North Billerica, MA USA. [Tatpati, Anand] Siemens Med Solut, San Francisco, CA USA. [Villanueva, Flordeliza S.] Univ Pittsburgh, Pittsburgh, PA USA. [Weissman, Neil J.] Washington Hosp Ctr, MedStar Res Inst, Washington, DC 20010 USA. RP Pellikka, PA (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org OI Buxton, Denis/0000-0003-3077-6435; Picard, Michael/0000-0002-9264-3243 NR 37 TC 15 Z9 15 U1 0 U2 15 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 2013 VL 26 IS 4 BP 325 EP 338 DI 10.1016/j.echo.2013.02.003 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122UM UT WOS:000317343600001 PM 23537771 ER PT J AU Bhatia, RS Kumar, V Picard, MH Weiner, RB AF Bhatia, R. Sacha Kumar, Vishesh Picard, Michael H. Weiner, Rory B. TI Comparison of the 2008 and 2011 Appropriate Use Criteria for Stress Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Appropriate use criteria; Stress echocardiography ID AMERICAN-HEART-ASSOCIATION; STATEMENT; CARDIOLOGY; MEDICARE; EXERCISE; OUTCOMES; SOCIETY; DISEASE; KIDNEY AB Background: The 2008 appropriate use criteria (AUC) for stress echocardiographic (SE) examinations were revised in 2011 to cover a wider range of scenarios of use. Data comparing the 2008 and 2011 AUC for SE are limited. Methods: A retrospective chart review of SE studies performed at an academic medical center was conducted, and ordering of SE studies was assessed using the 2008 and 2011 AUC. Results: A total of 252 consecutive SE studies performed in 2011 were reviewed. The 2008 AUC classified 126 SE studies (50%), and the 2011 AUC classified 221 SE studies (88%) (P < .001). Of all SE studies, 106 (42%) were performed as part of evaluations for noncardiac solid-organ transplantation. The majority of these studies (79%) were classified as inappropriate using the 2011 AUC and were not classifiable using the 2008 AUC. Of the 146 SE studies performed for other reasons, 69% were appropriate and 22% were inappropriate using the 2011 AUC. Inappropriate SE studies for both the general nontransplant and noncardiac solid-organ transplantation populations were nearly exclusively ordered for perioperative assessment with normal functional capacity. The SE studies that remained unclassified by the 2011 AUC were related to the assessment of specialized cardiac conditions, including hypertrophic cardiomyopathy and follow-up after heart transplantation. Conclusions: The 2011 AUC classify a significantly greater proportion of SE studies compared with the 2008 AUC. Most of the reclassified SE studies using the 2011 AUC were inappropriate and were ordered for perioperative assessments in patients with normal functional capacity. (J Am Soc Echocardiogr 2013;26:339-43.) C1 [Bhatia, R. Sacha; Kumar, Vishesh; Picard, Michael H.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bhatia, RS (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rsbhatia@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 19 TC 6 Z9 7 U1 1 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 2013 VL 26 IS 4 BP 339 EP 343 DI 10.1016/j.echo.2012.12.001 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122UM UT WOS:000317343600002 PM 23313389 ER PT J AU Tecilazich, F Dinh, T Lyons, TE Guest, J Villafuerte, RA Sampanis, C Gnardellis, C Zuo, CS Veves, A AF Tecilazich, Francesco Thanh Dinh Lyons, Thomas E. Guest, Julie Villafuerte, Rosemond A. Sampanis, Christos Gnardellis, Charalambos Zuo, Chun S. Veves, Aristidis TI Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; ENERGY PHOSPHATE-METABOLISM; SKELETAL-MUSCLE; INSULIN-RESISTANCE; CALF MUSCLE; SKIN MICROCIRCULATION; TASK-FORCE; NEUROPATHY; EXERCISE AB Objective: To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. Methods: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. Results: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-alpha (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-alpha were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. Conclusions: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups. (J Vasc Surg 2013;57:997-1005.) C1 [Tecilazich, Francesco; Thanh Dinh; Lyons, Thomas E.; Guest, Julie; Sampanis, Christos; Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. [Tecilazich, Francesco; Thanh Dinh; Lyons, Thomas E.; Guest, Julie; Sampanis, Christos; Veves, Aristidis] Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. [Tecilazich, Francesco; Thanh Dinh; Lyons, Thomas E.; Guest, Julie; Sampanis, Christos; Veves, Aristidis] Harvard Univ, Sch Med, Boston, MA USA. [Villafuerte, Rosemond A.; Zuo, Chun S.] McLean Hosp, MR Imaging Ctr, Belmont, MA 02178 USA. [Villafuerte, Rosemond A.; Zuo, Chun S.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Gnardellis, Charalambos] Technol Educ Inst Messolonghi, Mesolongion, Greece. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, 1 Deaconess Rd,PA 321A, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU NIH [1R21DK082987, R21MH081076]; Clinical Translational Science Award [UL1RR025758]; Beth Israel Deaconess Medical Center from the National Center for Research Resources FX This work is funded in part by NIH Grant 1R21DK082987 (A. V.) and NIH Grant R21MH081076 (C.S.Z.). The project described was supported by the Clinical Translational Science Award UL1RR025758 to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 37 TC 6 Z9 6 U1 0 U2 4 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 2013 VL 57 IS 4 BP 997 EP 1005 DI 10.1016/j.jvs.2012.10.011 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 120QZ UT WOS:000317187900014 PM 23465172 ER PT J AU Draca, N Lazic, R Simic, P Dumic-Cule, I Luetic, AT Gabric, N AF Draca, Natasa Lazic, Ratimir Simic, Petra Dumic-Cule, Ivo Luetic, Ana Tikvica Gabric, Nikica TI Potential beneficial role of sevelamer hydrochloride in diabetic retinopathy SO MEDICAL HYPOTHESES LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-ARTERY CALCIFICATION; CHRONIC KIDNEY-DISEASE; RETINAL VASCULAR CALIBER; MAINTENANCE HEMODIALYSIS-PATIENTS; URINARY ALBUMIN EXCRETION; CELL-ADHESION MOLECULE-1; STAGE RENAL-DISEASE; ATHEROSCLEROSIS RISK; ENDOTHELIAL DYSFUNCTION AB Patients with chronic kidney disease (CKD) experience co-morbid illnesses, including cardiovascular disease and retinopathy. Sevelamer hydrochloride (Renagel (R)); a non-calcium phosphate binder reduces coronary artery and aortic calcification as compared to calcium containing phosphate binders and additionally effects inflammatory biomarkers such as C-reactive protein (CRP), and lowers LDL cholesterol in patients with CKD. Since retinopathy is proven to be associated with increased coronary calcification, shared pathophysiological processes may contribute to both microvascular and macrovascular disease. We here suggest three different mechanisms of possible sevelamer's influence on the retinopathy: (1) by direct effect on the microvasculature through lowering CRP and LDL, involved in endothelial dysfunction and atherogenesis, (2) indirectly by attenuation of vascular calcification of aorta and carotid internal artery, it reduces ischaemia and improves circulation in the opthalmic artery and hence postponing retinopathy, (3) through hypertension by reducing atherosclerosis and calcification of carotid arteries, sevelamer decreases stiffness and intima-media wall thickness, therefore lowering blood pressure, which is well known to increase progression of diabetic retinopathy. So far no studies have yet been published on the direct influence of sevelamer on the retinopathy which we believe has good theoretical background. With its combined macrovascular and microvascular effect, sevelamer could potentially postpone and/or decrease retinopathy in diabetic patients with hypertension, and that are on hemodialysis or even predialysis patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Draca, Natasa; Lazic, Ratimir; Gabric, Nikica] Univ Rijeka, Eye Specialty Hosp Svjetlost, Sch Med, Zagreb 10000, Croatia. [Simic, Petra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Dumic-Cule, Ivo] Univ Zagreb, Sch Med, Zagreb 41000, Croatia. [Luetic, Ana Tikvica] Univ Zagreb, Dept Obstet & Gynecol, Clin Hosp Sveti Duh, Sch Med, Zagreb 41000, Croatia. RP Draca, N (reprint author), Univ Rijeka, Eye Specialty Hosp Svjetlost, Sch Med, Heinzelova 39, Zagreb 10000, Croatia. EM natasha.draca@gmail.com NR 78 TC 2 Z9 2 U1 0 U2 37 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD APR PY 2013 VL 80 IS 4 BP 431 EP 435 DI 10.1016/j.mehy.2012.12.035 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500021 PM 23357670 ER PT J AU Tanabe, KK Chiocca, EA AF Tanabe, Kenneth K. Chiocca, E. Antonio TI "Infectious" Optimism for Treatment of Hepatocellular Carcinoma SO MOLECULAR THERAPY LA English DT Editorial Material ID CANCER C1 [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7-924, Boston, MA 02114 USA. EM ktanabe@partners.org NR 10 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD APR PY 2013 VL 21 IS 4 BP 721 EP 724 DI 10.1038/mt.2013.47 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 119PR UT WOS:000317110300003 PM 23542566 ER PT J AU Montgomery, EB AF Montgomery, Erwin B., Jr. TI Predictors of Parkinson's disease-not quite sound SO MOVEMENT DISORDERS LA English DT Editorial Material C1 [Montgomery, Erwin B., Jr.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Montgomery, Erwin B., Jr.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Montgomery, EB (reprint author), Univ Alabama Birmingham, Dept Neurol, 1720 7th Ave South, Birmingham, AL 35294 USA. EM emontgom@uab.edu NR 5 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2013 VL 28 IS 4 BP 413 EP 415 DI 10.1002/mds.25432 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 123CO UT WOS:000317366100002 PM 23483647 ER PT J AU Fisher, MB Mauck, RL AF Fisher, Matthew B. Mauck, Robert L. TI Starting with form, emerging with function: nanofibrous scaffolds for tissue engineering of orthopedic tissuesalternatives SO NANOMEDICINE LA English DT Editorial Material DE function; nanofibrous scaffold; orthopedics; structure; tissue engineering ID LIGAMENT AB "This is an exciting time for the tissue engineering and regenerative medicine field as the complexity and usefulness of scaffolds, including nanofibrous scaffolds, continues to increase." C1 [Fisher, Matthew B.; Mauck, Robert L.] Univ Penn, Perelman Sch Med, Dept Orthoped Surg, McKay Orthoped Res Lab, Philadelphia, PA 19104 USA. [Fisher, Matthew B.; Mauck, Robert L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Mauck, Robert L.] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, Perelman Sch Med, Dept Orthoped Surg, McKay Orthoped Res Lab, 36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu RI Fisher, Matthew/M-5809-2016 OI Fisher, Matthew/0000-0002-3212-0870 FU NIAMS NIH HHS [P30AR050950, R01AR056624]; NIBIB NIH HHS [R01EB02425] NR 21 TC 4 Z9 4 U1 0 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD APR PY 2013 VL 8 IS 4 SI SI BP 505 EP 508 DI 10.2217/NNM.13.18 PG 4 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 120NU UT WOS:000317178200002 PM 23560399 ER PT J AU Bellot, G McClintock, MA Chou, JJ Shih, WM AF Bellot, Gaetan McClintock, Mark A. Chou, James J. Shih, William M. TI DNA nanotubes for NMR structure determination of membrane proteins SO NATURE PROTOCOLS LA English DT Article ID LIQUID-CRYSTALLINE MEDIUM; RESIDUAL DIPOLAR COUPLINGS; MOLECULAR ALIGNMENT; BIOLOGICAL MACROMOLECULES; POLYACRYLAMIDE-GELS; DETERGENT MICELLES; NANOSCALE SHAPES; WEAK ALIGNMENT; PROTON CHANNEL; FOLDING DNA AB Finding a way to determine the structures of integral membrane proteins using solution nuclear magnetic resonance (NMR) spectroscopy has proved to be challenging. A residual-dipolar-coupling-based refinement approach can be used to resolve the structure of membrane proteins up to 40 kDa in size, but to do this you need a weak-alignment medium that is detergent-resistant and it has thus far been difficult to obtain such a medium suitable for weak alignment of membrane proteins. We describe here a protocol for robust, large-scale synthesis of detergent-resistant DNA nanotubes that can be assembled into dilute liquid crystals for application as weak-alignment media in solution NMR structure determination of membrane proteins in detergent micelles. The DNA nanotubes are heterodimers of 400-nm-long six-helix bundles, each self-assembled from a M13-based p7308 scaffold strand and >170 short oligonucleotide staple strands. Compatibility with proteins bearing considerable positive charge as well as modulation of molecular alignment, toward collection of linearly independent restraints, can be introduced by reducing the negative charge of DNA nanotubes using counter ions and small DNA-binding molecules. This detergent-resistant liquid-crystal medium offers a number of properties conducive for membrane protein alignment, including high-yield production, thermal stability, buffer compatibility and structural programmability. Production of sufficient nanotubes for four or five NMR experiments can be completed in 1 week by a single individual. C1 [Bellot, Gaetan; Chou, James J.; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bellot, Gaetan; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Bellot, Gaetan; Shih, William M.] Wyss Inst Biol Inspired Engn Harvard, Boston, MA USA. [McClintock, Mark A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM william_shih@dfci.harvard.edu RI Chou, James/N-9840-2013 FU US National Institutes of Health (NIH) [1U54GM094608, 1DP20D004641] FX We thank I. Ayala and J. Boisbouvier (CNRS, Institut de Biologie Structurale) for the gift of the ubiquitin vector and R. Sounier (Harvard Medical School) for helpful discussions. This work was supported by the US National Institutes of Health (NIH) grants 1U54GM094608 to J.J.C., and 1DP20D004641 and 1U54GM094608 to W.M.S. NR 52 TC 18 Z9 18 U1 3 U2 66 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD APR PY 2013 VL 8 IS 4 BP 755 EP 770 DI 10.1038/nprot.2013.037 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 119PY UT WOS:000317111000010 PM 23518667 ER PT J AU DeCaprio, JA Garcea, RL AF DeCaprio, James A. Garcea, Robert L. TI A cornucopia of human polyomaviruses SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID MERKEL-CELL POLYOMAVIRUS; LARGE T-ANTIGEN; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; AFRICAN-GREEN MONKEY; INDUCED DEMYELINATING DISEASE; GLUTATHIONE-S-TRANSFERASE; CAPSID PROTEIN VP1; JC VIRUS; RESPIRATORY-DISEASE; WU POLYOMAVIRUS AB During the past 6 years, focused virus hunting has led to the discovery of nine new human polyomaviruses, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. The discovery of so many new and highly divergent human polyomaviruses raises key questions regarding their evolution, tropism, latency, reactivation, immune evasion and contribution to disease. This Review describes the similarities and differences among the new human polyomaviruses and discusses how these viruses might interact with their human host. C1 [DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [DeCaprio, James A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Garcea, Robert L.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Garcea, Robert L.] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer 440, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu; robert.garcea@colorado.edu FU US Public Health Service [P01CA050661, RO1 CA93804, R01CA63113, RO1CA37667] FX This work was supported in part by US Public Health Service grants P01CA050661, RO1 CA93804 and R01CA63113 to J.A.D. and RO1CA37667 to R.L.G. The authors thank D. McDonald for assistance with the bioinformatics NR 163 TC 101 Z9 105 U1 1 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD APR PY 2013 VL 11 IS 4 BP 264 EP 276 DI 10.1038/nrmicro2992 PG 13 WC Microbiology SC Microbiology GA 114YD UT WOS:000316778000014 PM 23474680 ER PT J AU Walker, DA Liu, JF Kieran, M Jabado, N Picton, S Packer, R St Rose, C AF Walker, David A. Liu, JoFen Kieran, Mark Jabado, Nada Picton, Susan Packer, Roger St Rose, Christian CA CPN Paris 2011 Conference TI A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method SO NEURO-ONCOLOGY LA English DT Article DE low-grade astrocytoma ID OPTIC PATHWAY GLIOMAS; CHILDREN; TUMORS AB A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking 70 agreement from 60 of respondents; where 70 consensus occurred, the statement was modified and resubmitted for voting. Twenty-seven statements meeting consensus criteria are reported. For HCLGG, statements describing overall therapeutic purposeand indications for biopsy, observation, or treatment aimed at limiting the risk of visual damage and the need for on-going clinical trials were made. Primary surgical resection was not recommended. For DIPG, biopsy was recommended to ascertain biological characteristics to enhance understanding and targeting of treatments, especially in clinical trials. For HGG, biopsy is essential, the World Health Organization classification was recommended; selection of surgical strategy to achieve gross total resection in a single or multistep process should be discussed with the PNMDT and integrated with trials based drug strategies for adjuvant therapies. C1 [Walker, David A.; Liu, JoFen] Univ Nottingham, Childrens Brain Tumour Res Ctr, Queens Med Ctr, Nottingham NG7 2UH, England. [Liu, JoFen; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jabado, Nada] McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Res Inst, Montreal, PQ, Canada. [Picton, Susan] St James Univ Hosp, Reg Paediat Oncol Unit, Leeds, W Yorkshire, England. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [St Rose, Christian] Hop Necker Enfants Malad, Serv Neurochirurg, Paris, France. RP Walker, DA (reprint author), Univ Nottingham, Childrens Brain Tumour Res Ctr, Queens Med Ctr, Nottingham NG7 2UH, England. EM david.walker@nottingham.ac.uk RI Hargrave, Darren/H-1066-2014; OI Hargrave, Darren/0000-0001-8219-9807; Depreitere, Bart/0000-0002-7458-0648; Ternier, Jessica/0000-0003-4673-802X; FRASSANITO, PAOLO/0000-0003-0071-3126; Kieran, Mark/0000-0003-2184-7692; Dorfer, Christian/0000-0002-1843-7732; Van Vuurden, Dannis/0000-0002-1364-9007 NR 9 TC 23 Z9 23 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 IS 4 BP 462 EP 468 DI 10.1093/neuonc/nos330 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 117PM UT WOS:000316965600008 PM 23502427 ER PT J AU Peereboom, DM Ahluwalia, MS Ye, XB Supko, JG Hilderbrand, SL Phuphanich, S Nabors, LB Rosenfeld, MR Mikkelsen, T Grossman, SA AF Peereboom, David M. Ahluwalia, Manmeet S. Ye, Xiaobu Supko, Jeffrey G. Hilderbrand, Sarah L. Phuphanich, Surasak Nabors, L. Burt Rosenfeld, Myrna R. Mikkelsen, Tom Grossman, Stuart A. CA New Approaches Brain Tumor Therapy TI NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme SO NEURO-ONCOLOGY LA English DT Article DE EGFR; erlotinib; pharmacokinetics; glioblastoma; Ras signaling; sorafenib; targeted therapy ID GROWTH-FACTOR-RECEPTOR; REFRACTORY SOLID TUMORS; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; HIGH-GRADE GLIOMAS; DAYS ON/7 DAYS; MALIGNANT GLIOMA; RAF KINASE; CLINICAL PHARMACOKINETICS; POSTRADIATION THERAPY AB The signal transduction pathways of epidermal growth factor receptor and Ras are both important in the growth of glioblastoma multiforme (GBM). We hypothesized that inhibition of both pathways would improve the survival time of patients with recurrent GBM. Patients with recurrent/progressive GBM with 02 prior chemotherapy regimens received erlotinib 150 mg once daily and sorafenib 400 mg twice daily until progression. The primary endpoint was overall survival. Pharmacokinetic sampling was performed during cycle 1. The median overall survival was 5.7 months. Progression-free survival at 6 months was 14. Toxicity was manageable. Clearance of erlotinib was markedly enhanced by sorafenib. The study did not meet its objective of a 30 increase in overall survival time compared with historical controls. Erlotinib and sorafenib have significant pharmacokinetic interactions that may negatively impact the efficacy of the combination regimen. C1 [Peereboom, David M.; Ahluwalia, Manmeet S.] Cleveland Clin, Cleveland, OH 44195 USA. [Ye, Xiaobu; Grossman, Stuart A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Supko, Jeffrey G.; Hilderbrand, Sarah L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Phuphanich, Surasak] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Rosenfeld, Myrna R.] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. RP Peereboom, DM (reprint author), Cleveland Clin, Burkhardt Brain Tumor & Neurooncol Ctr, Neurol Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM peerebd@ccf.org OI Rosenfeld, Myrna/0000-0001-5095-2534 FU National Cancer Institute [CA-62475] FX This work was supported by the National Cancer Institute (grant no. CA-62475). NR 53 TC 27 Z9 28 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2013 VL 15 IS 4 BP 490 EP 496 DI 10.1093/neuonc/nos322 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 117PM UT WOS:000316965600011 PM 23328813 ER PT J AU Beloiartsev, A Baron, DM Yu, BL Bloch, KD Zapol, WM AF Beloiartsev, Arkadi Baron, David M. Yu, Binglan Bloch, Kenneth D. Zapol, Warren M. TI Hemoglobin infusion does not alter murine pulmonary vascular tone SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Hemoglobin; Endothelium; Hypoxia; Vasoconstriction; Nitric oxide ID CELL-FREE HEMOGLOBIN; NITRIC-OXIDE SYNTHASE; STROMA-FREE HEMOGLOBIN; ENDOTHELIAL DYSFUNCTION; RELAXING FACTOR; OXYGEN CARRIER; RAT LUNGS; VASOCONSTRICTION; BLOOD; HYPERTENSION AB Plasma hemoglobin (Hb) scavenges endothelium-derived nitric oxide (NO), producing systemic and pulmonary vasoconstriction in many species. We hypothesized that i.v. administration of murine cell-free Hb would produce pulmonary vasoconstriction and enhance hypoxic pulmonary vasoconstriction (HPV) in mice. To assess the impact of plasma Hb on basal pulmonary vascular tone in anesthetized mice we measured left lung pulmonary vascular resistance (LPVRI) before and after infusion of Hb at thoracotomy. To confirm the findings obtained at thoracotomy, measurements of right ventricular systolic pressure (RVSP) and systemic arterial pressure (SAP) were obtained in closed-chest wild-type mice. To elucidate whether pretreatment with Hb augments HPV we assessed the increase in LPVRI before and during regional lung hypoxia produced by left mainstem bronchial occlusion (LMBO) in wild-type mice pretreated with Hb. Infusion of Hb increased SAP but did not change pulmonary arterial pressure (PAP), left lung pulmonary arterial flow (Q(LPA)) or LPVRI in either wild-type or diabetic mice with endothelial dysfunction. Scavenging of NO by plasma Hb did not alter HPV in wild-type mice. Inhibition of NO synthase with L-NAME did not change the basal LPVRI, but augmented HPV during LMBO. Our data suggest that scavenging of NO by plasma Hb does not alter pulmonary vascular tone in mice. Therefore, generation of NO in the pulmonary circulation is unlikely to be responsible for the low basal pulmonary vascular tone of mice. (c) 2013 Elsevier Inc. All rights reserved. C1 [Beloiartsev, Arkadi; Baron, David M.; Yu, Binglan; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Beloiartsev, Arkadi; Baron, David M.; Yu, Binglan; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Sch Med, Boston, MA USA. RP Zapol, WM (reprint author), Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; National Institute of Health, Bethesda, Maryland [HL074352] FX This study was supported by funds of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Dr. Kenneth D. Bloch was supported by a National Institute of Health R01 grant (HL074352), Bethesda, Maryland. NR 54 TC 1 Z9 1 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD APR 1 PY 2013 VL 30 BP 1 EP 8 DI 10.1016/j.niox.2012.12.007 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 122LV UT WOS:000317320500001 PM 23313572 ER PT J AU Loh, AR Joseph, D Keenan, JD Lietman, TM Naseri, A AF Loh, Allison R. Joseph, Damien Keenan, Jeremy D. Lietman, Thomas M. Naseri, Ayman TI Predictors of Matching in an Ophthalmology Residency Program SO OPHTHALMOLOGY LA English DT Article ID SELECTION; DIRECTORS; SCORES AB Purpose: To examine the characteristics of US medical students applying for ophthalmology residency and to determine the predictors of matching. Design: A retrospective case series. Participants: A total of 3435 medical students from the United States who applied to an ophthalmology residency program from 2003 to 2008 were included. Methods: Matched and unmatched applicants were compared and stratified by predictor variables, including United States Medical Licensing Examination (USMLE) Step 1 score, Alpha Omega Alpha (AOA) status, medical school reputation, and medical school geographic region. Differences in proportions were analyzed using the Fisher exact test. Logistic regression was used to determine the predictors of successful matching. Main Outcome Measures: Successful matching to an ophthalmology program. Results: The majority of applicants (72%, 2486/3435) matched in ophthalmology. In multivariate analysis, AOA membership (odds ratio [OR], 2.6, P < 0.0001), USMLE score (OR, 1.6; P < 0.0001), presence of an ophthalmology residency at medical school (OR, 1.4; P = 0.01), top 25 medical school (OR, 1.4; P < 0.03), top 10 medical school (OR, 1.6; P < 0.02), and allopathic degree (OR, 4.0; P < 0.0001) were statistically significant predictors of matching. Approximately 60% (1442/2486) of applicants matched to the same geographic region as their medical school. Applicants were more likely to match at a program in the same geographic region as their medical school than would be predicted by chance alone (P < 0.0001). In multivariate analysis, higher USMLE score (OR, 0.9; P < 0.0001) and top 10 medical school (OR, 0.7; P = 0.027) were statistically significant predictors of matching to outside the geographic region as one's medical school. Conclusions: The majority of applicants applying for an ophthalmology residency position match successfully. Higher performance on quantitative metrics seems to confer an advantage for matching. The majority of applicants match at a residency program within the same geographic region as one's medical school. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:865-870 (C) 2013 by the American Academy of Ophthalmology. C1 [Loh, Allison R.; Keenan, Jeremy D.; Lietman, Thomas M.; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94121 USA. [Joseph, Damien] San Francisco Match Program, San Francisco, CA USA. [Keenan, Jeremy D.; Lietman, Thomas M.; Naseri, Ayman] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94121 USA. [Naseri, Ayman] San Francisco Vet Adm Med Ctr, Dept Ophthalmol, San Francisco, CA USA. RP Naseri, A (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way, San Francisco, CA 94121 USA. EM Ayman.Naseri@va.gov NR 19 TC 5 Z9 5 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2013 VL 120 IS 4 BP 865 EP 870 DI 10.1016/j.ophtha.2012.09.028 PG 6 WC Ophthalmology SC Ophthalmology GA 122UL UT WOS:000317343500033 PM 23260256 ER PT J AU Bassetto, F Turra, G Salmaso, R Lancerotto, L Del Vecchio, DA AF Bassetto, Franco Turra, Giovanni Salmaso, Roberto Lancerotto, Luca Del Vecchio, Daniel A. TI Autologous Injectable Dermis: A Clinical and Histological Study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PROSTHETIC BREAST RECONSTRUCTION; COCKTAIL INJECTION MICROGRAFT; COMPLETE SUBMUSCULAR COVERAGE; MINIGRAFT MIXTURE; FAT; OUTCOMES; ADJUNCTION; SURVIVAL; FASCIA AB Background: No perfect solution yet exists for dermal fillers. The authors hypothesized that autologous dermis can be processed in an operator-friendly manner and adopted in selected patients as a filler, following the principle of replacing "like with like." Methods: The authors designed a prototype "cutting chamber" to morsel dermis into an injectable form. Autologous injectable dermis grafting was performed in 16 patients who underwent lip or labionasal fold correction concomitant with abdominoplasty or cesarean scar correction; patient dermis was used for the donor graft. Furthermore, injectable dermis grafting was performed in the subcutaneous tissue of three patients undergoing multistage reconstructive procedures for obesity. The grafts were harvested and examined histologically at 3, 7, and 12 months. Results: Dermis processing and injection proved feasible with limited effort. All 16 patients presented good volume maintenance by 12 months. Two reported transient palpable firmness for the first 6 months, which subsequently resolved. Histological examination of processed and injected dermis showed volume maintenance over time, effective revascularization of the mass, and structural reorganization with collagen bundles and nested fibroblasts reminiscent of reticular dermis. A transient inflammatory reaction was observed, consistent with the expected healing events. Conclusions: Use of autologous dermis as a filler substance for both aesthetic and reconstructive procedures appears to be a feasible option. It could be advised for patients requiring filler correction who undergo concomitant procedures involving excision of potential donor dermis. (Plast. Reconstr. Surg. 131: 589e, 2013.) C1 Univ Padua, Inst Plast Surg, I-35100 Padua, Italy. Univ Hosp Padova, Dept Pathol, Padua, Italy. Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. [Del Vecchio, Daniel A.] Back Bay Plast Surg, Boston, MA 02116 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Del Vecchio, DA (reprint author), Back Bay Plast Surg, 38 Newbury St, Boston, MA 02116 USA. EM dandelvecchio@aol.com NR 14 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2013 VL 131 IS 4 BP 589E EP 596E DI 10.1097/PRS.0b013e318282770c PG 8 WC Surgery SC Surgery GA 121YW UT WOS:000317282800013 PM 23542277 ER PT J AU Hazani, R Rao, A Ford, R Yaremchuk, MJ Wilhelmi, BJ AF Hazani, Ron Rao, Arun Ford, Rachel Yaremchuk, Michael J. Wilhelmi, Bradon J. TI The Safe Zone for Placement of Chin Implants SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INFERIOR ALVEOLAR NERVE; LOWER LIP POSITION; ESSENTIAL COMPONENT; MENTALIS MUSCLE; AUGMENTATION AB Background: Alloplastic chin augmentation requires the surgeon to predict the location of the mental foramen and the origin of the mentalis muscle to avoid the postoperative sequelae lower lip parasthesia, lower lip incompetence, or chin ptosis. The authors define a safe zone of dissection along the inferior border of the mandible for placement of alloplastic chin implants. Methods: Fourteen fresh cadaveric hemifaces were dissected with the aid of loupe magnification. Previously described anatomic landmarks were used to identify the origin of the mentalis muscle and the location of the mental foramen along the alveolar ridge of the mandible. Vertical distances were then measured from the mandibular border to the inferior aspect of the mentalis muscle origin and the lower edge of the mental foramen to construct the zone of safe dissection. Results: The mentalis was identified as a fan-shaped muscle originating from the alveolar process below the incisors roots and inserting into the chin just below the labiomental sulcus. The mental foramen was located most commonly below the roots of the first and second premolars or in the space between the roots. The mentalis origin and the mental foramen were 1.8 +/- 0.3 cm and 1.5 +/- 0.2 cm cephalad to the inferior edge of the mandible, respectively. These distances define the borders of a safe zone above the mandibular border. Conclusions: A safe zone of dissection for alloplastic chin augmentation is identified. This study is applicable to implant placement through a submental or an intraoral incision. This safe zone is also useful for reconstructive or orthognathic mandible procedures. (Plast. Reconstr. Surg. 131: 869, 2013.) C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. Loma Linda Univ, Sch Med, Loma Linda, CA 92350 USA. RP Hazani, R (reprint author), Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM ronmdsurg@hotmail.com NR 16 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2013 VL 131 IS 4 BP 869 EP 872 DI 10.1097/PRS.0b013e3182818e6c PG 4 WC Surgery SC Surgery GA 121YW UT WOS:000317282800068 PM 23542258 ER PT J AU Eriksson, E Rohrich, RJ Sachs, DH Pomahac, B Delmonico, FL Caterson, EJ Goldwyn, RM AF Eriksson, Elof Rohrich, Rod J. Sachs, David H. Pomahac, Bohdan Delmonico, Francis L. Caterson, E. J. Goldwyn, Robert M. TI The Nobler Angels of Our Nature: A Tribute to Joseph E. Murray, MD, 1919 to 2012 SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Biographical-Item C1 [Eriksson, Elof] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas Southwestern Med Ctr, Dept Plast Surg, Dallas, TX USA. RP Eriksson, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 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 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2013 VL 131 IS 4 BP 912 EP 913 DI 10.1097/PRS.0b013e31828aaf23 PG 2 WC Surgery SC Surgery GA 121YW UT WOS:000317282800074 PM 23542265 ER PT J AU Meyer, F Zhang, BH Gao, X Prigerson, HG AF Meyer, Fremonta Zhang, Baohui Gao, Xin Prigerson, Holly G. TI Associations between cognitive impairment in advanced cancer patients and psychiatric disorders in their caregivers SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; caregiver; cognitive impairment; depression; psychiatric disorder ID MENTAL STATUS QUESTIONNAIRE; GENERALIZED ANXIETY; OF-LIFE; DEMENTIA; DELIRIUM; HEALTH AB Objective This study examined whether cognitive impairment in advanced cancer patients is associated with a heightened frequency of psychiatric disorders in their primary caregivers. Methods Three hundred fifty-six patient-caregiver dyads were interviewed and administered the Short Portable Mental Status Questionnaire and the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition approximately 3.4months before the patient's death. The Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition was administered to caregivers again approximately 6months after the patient's death. Results Forty-six (12.9%) patients displayed signs of mild cognitive impairment at the baseline interview. After adjustment for relevant confounders, patient cognitive impairment was significantly associated with caregiver pre-loss major depressive disorder [OR 6.88 (95% CI 1.3235.92); p=0.02], without associated increases in suicidality. There were no significant associations between patient cognitive impairment and caregiver pre-loss generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or grief. Likewise, there were no significant associations between patient cognitive impairment and caregiver post-loss psychiatric disorders, but caregivers of cognitively impaired patients appeared to be less satisfied with the patient's manner of death (p=0.01). Conclusions Caregivers of cognitively impaired advanced cancer patients appear at heightened risk of major depression that resolves after the patient's death. Further study with a larger sample and more sensitive longitudinal cognitive measures is indicated. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Meyer, Fremonta; Zhang, Baohui; Gao, Xin; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyer, Fremonta; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Meyer, F (reprint author), 450 Brookline Ave,SW411, Boston, MA 02115 USA. EM flmeyer@partners.org FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370, CA 156732]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to Dr Prigerson: MH63892 from the National Institute of Mental Health and CA 106370 and CA 156732 from the National Cancer Institute; and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 14 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD APR PY 2013 VL 22 IS 4 BP 952 EP 955 DI 10.1002/pon.3076 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 122IQ UT WOS:000317312200031 PM 22451155 ER PT J AU Saladin, ME Gray, KM McRae-Clark, AL LaRowe, SD Yeatts, SD Baker, NL Hartwell, KJ Brady, KT AF Saladin, Michael E. Gray, Kevin M. McRae-Clark, Aimee L. LaRowe, Steven D. Yeatts, Sharon D. Baker, Nathaniel L. Hartwell, Karen J. Brady, Kathleen T. TI A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans SO PSYCHOPHARMACOLOGY LA English DT Article DE Reconsolidation; Retrieval; Craving; Cocaine dependence; Cue exposure; Human subjects ID BETA-ADRENERGIC-BLOCKADE; NORADRENERGIC BLOCKADE; RECEPTOR BLOCKADE; ERASING FEAR; DAILY-LIFE; EXTINCTION; CONSOLIDATION; ADDICTION; PREFERENCE; DISRUPTION AB This study examined the effects of propranolol vs. placebo, administered immediately after a "retrieval" session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent "test" session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up. CD participants received either 40 mg propranolol or placebo immediately following a "retrieval" CCE session. The next day, participants received a "test" session of CCE that was identical to the "retrieval" session except no medication was administered. Participants underwent a "follow-up" CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions. Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use. This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted. C1 [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Saladin, Michael E.; Gray, Kevin M.; McRae-Clark, Aimee L.; LaRowe, Steven D.; Yeatts, Sharon D.; Baker, Nathaniel L.; Hartwell, Karen J.; Brady, Kathleen T.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA. [Gray, Kevin M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Youth Div, Charleston, SC 29425 USA. [Yeatts, Sharon D.; Baker, Nathaniel L.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Subst Abuse Treatment Ctr, Charleston, SC USA. [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, Charleston, SC 29425 USA. RP Saladin, ME (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, 77 President St,Room 224,MSC700, Charleston, SC 29425 USA. EM saladinm@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NIDA grant [R21DA025155]; South Carolina Clinical & Translational Research (SCTR) Institute; NIH [UL1 RR029882, UL1 TR000062] FX This research was supported by NIDA grant R21DA025155 (Saladin, PI) and by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH Grant Numbers UL1 RR029882 and UL1 TR000062. The authors report no conflicts of interest pertaining to this study. NR 91 TC 24 Z9 25 U1 3 U2 20 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 2013 VL 226 IS 4 BP 721 EP 737 DI 10.1007/s00213-013-3039-3 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 122GL UT WOS:000317306200009 PM 23460266 ER PT J AU Levitt, JJ Rosow, LK Nestor, PG Pelavin, PE Swisher, TM McCarley, RW Shenton, ME AF Levitt, James J. Rosow, Laura K. Nestor, Paul G. Pelavin, Paula E. Swisher, Talis M. McCarley, Robert W. Shenton, Martha E. TI A volumetric MRI study of limbic, associative and sensorimotor striatal subregions in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Magnetic Resonance Imaging; Striatum; Ventral striatum; Dorsal striatum; Prefrontal cortex ID POSITRON-EMISSION-TOMOGRAPHY; SCHIZOTYPAL PERSONALITY-DISORDER; MESOLIMBIC DOPAMINE TRANSMISSION; FRONTAL-SUBCORTICAL CIRCUITS; CAUDATE NUCLEI VOLUMES; BASAL GANGLIA VOLUMES; NEUROLEPTIC-NAIVE; PREMORBID ADJUSTMENT; ANTIPSYCHOTIC-DRUGS; PREFRONTAL CORTEX AB Introduction: Cognitive and emotional functioning is mediated by frontal-subcortical feedback loops. The striatum, a component of this circuitry, thus is a possible neural substrate of schizophrenia. Striatum volume, however, is believed to be differentially influenced by neuroleptic treatment due to an anterior-posterior D2 receptor density gradient. We thus rigorously parcellated it into subregions in order to assess whether neuroleptic effect on group differences is regionally specific. Methods: 29 chronic, male, schizophrenia patients and 28 male, normal controls (NCs), group-matched for handedness, age, and parental SES, underwent structural brain imaging on a 1.5 Tesla GE system. We manually measured the volume, normalized for intracranial contents, of the striatum parcellated into anatomic subregions and their corresponding limbic, associative and sensorimotor functional subregions and performed clinical correlations. Results: First, we found a localized bilateral enlargement of the posterior putamen in medicated chronic schizophrenia. Second, we showed associative striatal subregion volumes correlated with executive function in schizophrenia subjects and, to a lesser extent, in NCs. Third, we showed associative striatal subregions inversely correlated with negative symptoms but conversely, the ventral/limbic striatum did not correlate with positive or negative clinical symptoms. Discussion: Our novel parcellation strategy, based on rigorous delineation of the ventral striatum, allowed for the demonstration of localized volumetric differences between schizophrenia and NCs. Furthermore, by parcellating the striatum into functional subregions we demonstrated significant positive correlations between the volume of the associative striatum and executive functioning in schizophrenia, adding further support to the importance of its role in the pathophysiology of schizophrenia. Published by Elsevier B.V. C1 [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Dept Psychiat, Clin Neurosci Div,Lab Neurosci, Brockton, MA 02301 USA. [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Levitt, James J.; Rosow, Laura K.; Pelavin, Paula E.; Swisher, Talis M.; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,MRI Div,Dept Radiol, Boston, MA 02215 USA. RP Levitt, JJ (reprint author), Harvard Univ, VA Boston Healthcare Syst, Dept Psychiat 116A, Sch Med, 940 Belmont St, Brockton, MA 02301 USA. EM james_levitt@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veteran Affairs; VA Schizophrenia Center; Department of Veterans Affairs; National Institutes of Health [K05 MH 700047, R01 MH 50747, R01 MH 40799] FX This work was supported in part by the Department of Veteran Affairs Awards (Merits, JJL, MES, RWM; Research Enhancement Award Program, RWM, MES), by a VA Schizophrenia Center grant (RWM, MES), by a Middleton Award (RWM) from the Department of Veterans Affairs, and by grants from the National Institutes of Health (K05 MH 700047 and R01 MH 50747 to MES, R01 MH 40799 to RWM). Our sponsors served no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 74 TC 9 Z9 9 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2013 VL 145 IS 1-3 BP 11 EP 19 DI 10.1016/j.schres.2012.08.032 PG 9 WC Psychiatry SC Psychiatry GA 122RS UT WOS:000317336200002 PM 23380548 ER PT J AU Matos, FM Raemer, DB AF Matos, Francisco M. Raemer, Daniel B. TI Mixed-Realism Simulation of Adverse Event Disclosure An Educational Methodology and Assessment Instrument SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Patient simulation; Adverse events; Disclosure ID MEDICAL ERRORS; RESIDENTS; AGREEMENT; ATTITUDES; SKILLS AB Introduction: Physicians have an ethical duty to disclose adverse events to patients or families. Various strategies have been reported for teaching disclosure, but no instruments have been shown to be reliable for assessing them. The aims of this study were to report a structured method for teaching adverse event disclosure using mixed-realism simulation, develop and begin to validate an instrument for assessing performance, and describe the disclosure practice of anesthesiology trainees. Methods: Forty-two anesthesiology trainees participated in a 2-part exercise with mixed-realism simulation. The first part took place using a mannequin patient in a simulated operating room where trainees became enmeshed in a clinical episode that led to an adverse event and the second part in a simulated postoperative care unit where the learner is asked to disclose to a standardized patient who systematically moves through epochs of grief response. Two raters scored subjects using an assessment instrument we developed that combines a 4-element behaviorally anchored rating scale (BARS) and a 5-stage objective rating scale. Results: The performance scores for elements within the BARS and the 5-stage instrument showed excellent interrater reliability (Cohen's kappa = 0.7), appropriate range (mean range for BARS, 4.20Y4.47; mean range for 5-stage instrument, 3.73-4.46), and high internal consistency (P < 0.05). Conclusions: We have demonstrated a comprehensive methodology using a mixed-realism simulation that engages learners in an adverse event and allows them to practice disclosure to a structured range of patient responses. We have developed a reliable 2-part instrument with strong psychometric properties for assessing disclosure performance. (Sim Healthcare 8:84-90, 2013) C1 [Matos, Francisco M.; Raemer, Daniel B.] Ctr Med Simulat, Charlestown, MA 02129 USA. [Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Raemer, Daniel B.] Harvard Univ, Sch Med, Boston, MA USA. [Matos, Francisco M.] Coimbra Univ Hosp, Dept Anesthesia Crit Care & Pain Med, Coimbra, Portugal. [Matos, Francisco M.] Univ Beira Interior, CICS UBI Hlth Sci Res Ctr, Covilha, Portugal. RP Raemer, DB (reprint author), Ctr Med Simulat, 100 1st Ave,Suite 400, Charlestown, MA 02129 USA. EM draemer@partners.org NR 31 TC 5 Z9 5 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD APR PY 2013 VL 8 IS 2 BP 84 EP 90 DI 10.1097/SIH.0b013e31827cbb27 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 118QE UT WOS:000317039600004 PM 23334365 ER PT J AU Neofytos, D Kobayashi, K Alonso, CD Cady-Reh, J Lepley, D Harris, M Desai, N Kraus, E Subramanian, A Treadway, S Ostrander, D Thompson, C Marr, K AF Neofytos, D. Kobayashi, K. Alonso, C. D. Cady-Reh, J. Lepley, D. Harris, M. Desai, N. Kraus, E. Subramanian, A. Treadway, S. Ostrander, D. Thompson, C. Marr, K. TI Epidemiology, risk factors, and outcomes of Clostridium difficile infection in kidney transplant recipients SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Clostridium difficile; kidney transplant ID CARE FACILITIES; DIARRHEA; COLITIS; TOXIN; COLONIZATION; VANCOMYCIN; MORTALITY; OUTBREAK; ANTIBODY; DISEASE AB Background We sought to describe the epidemiology and risk factors for Clostridium difficile infection (CDI) among kidney transplant recipients (KTR) between 1 January 2008 and 31 December 2010. Methods A single-institution retrospective study was conducted among all adult KTR with CDI, defined as a positive test for C.difficile by a cell cytotoxic assay for C.difficile toxin A or B or polymerase chain reaction test for toxigenic C.difficile. Results Among 603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37 (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs. 25 (of 475; 5.3%, P=0.08) standard-risk patients. The overall rate of CDI increased from 3.7% in 2008 to 9.4% in 2010 (P=0.05). The median time to CDI diagnosis was 9days, with 27 (73.0%) patients developing CDI within the first 30days after their transplant, and 14 (51.8%) developing CDI within 7days. A casecontrol analysis of 37 CDI cases and 74 matched controls demonstrated the following predictors for CDI among KTR: vancomycin-resistant Enterococcus colonization before transplant (odds ratio [OR]: 3.6, P=0.03), receipt of an organ from Centers for Disease Control high-risk donor (OR: 5.9, P=0.006), and administration of high-risk antibiotics within 30days post transplant (OR: 6.6, P=0.001). Conclusions CDI remains a common early complication in KTR, with rates steadily increasing during the study period. Host and transplant-related factors and exposure to antibiotics appeared to significantly impact the risk for CDI among KTR. C1 [Neofytos, D.; Kobayashi, K.; Alonso, C. D.; Harris, M.; Kraus, E.; Subramanian, A.; Treadway, S.; Ostrander, D.; Marr, K.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kobayashi, K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alonso, C. D.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Cady-Reh, J.; Lepley, D.] Johns Hopkins Univ, Qual Improvement Dept, Baltimore, MD USA. [Desai, N.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Thompson, C.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Biostat, Baltimore, MD USA. [Marr, K.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. RP Neofytos, D (reprint author), Johns Hopkins Sch Med, Transplant & Oncol Infect Dis Program, Div Infect Dis, 1830 E Monument St,Suite 421, Baltimore, MD 21205 USA. EM dneofyt1@jhmi.edu FU NIH [K24 AI085118]; National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [101872]; Pfizer; Astellas; Merck FX The study was in part supported by a grant from the NIH: K24 AI085118. Statistical analysis was, in part, supported by a National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health Grant (101872).; D.N. has received research grants from Pfizer. K.M. has received grant support from Astellas, Merck, and Pfizer, and has served on advisory boards or as consultant for Astellas, Merck, Optimer, and Pfizer. All other authors: No conflicts of interest. NR 32 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD APR PY 2013 VL 15 IS 2 BP 134 EP 141 DI 10.1111/tid.12030 PG 8 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 122AT UT WOS:000317287900011 PM 23173772 ER PT J AU Welty, LJ Carter, RE Finkelstein, DM Harrell, FE Lindsell, CJ Macaluso, M Mazumdar, M Nietert, PJ Oster, RA Pollock, BH Roberson, PK Ware, JH AF Welty, Leah J. Carter, Rickey E. Finkelstein, Dianne M. Harrell, Frank E., Jr. Lindsell, Christopher J. Macaluso, Maurizio Mazumdar, Madhu Nietert, Paul J. Oster, Robert A. Pollock, Brad H. Roberson, Paula K. Ware, James H. CA Clinical Translational Sci Award C TI Strategies for Developing Biostatistics Resources in an Academic Health Center SO ACADEMIC MEDICINE LA English DT Article ID MEDICAL-RESEARCH AB Biostatistics-the application of statistics to understanding health and biology-provides powerful tools for developing research questions, designing studies, refining measurements, analyzing data, and interpreting findings. Biostatistics plays an important role in health-related research, yet biostatistics resources are often fragmented, ad hoc, or oversubscribed within academic health centers (AHCs). Given the increasing complexity and quantity of health-related data, the emphasis on accelerating clinical and translational science, and the importance of conducting reproducible research, the need for the thoughtful development of biostatistics resources within AHCs is growing. In this article, the authors identify strategies for developing biostatistics resources in three areas: (1) recruiting and retaining biostatisticians, (2) efficiently using biostatistics resources, and (3) improving biostatistical contributions to science. AHCs should consider these three domains in building strong biostatistics resources, which they can leverage to support a broad spectrum of research. For each of the three domains, the authors describe the advantages and disadvantages of AHCs creating centralized biostatistics units rather than dispersing such resources across clinical departments or other research units. They also address the challenges that biostatisticians face in contributing to research without sacrificing their individual professional growth or the trajectory of their research teams. The authors ultimately recommend that AHCs create centralized biostatistics units because this approach offers distinct advantages both to investigators who collaborate with biostatisticians as well as to the biostatisticians themselves, and it is better suited to accomplish the research and education missions of AHCs. C1 [Welty, Leah J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Carter, Rickey E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Carter, Rickey E.] Mayo Clin, Ctr Translat Sci Awards, Rochester, MN USA. [Finkelstein, Dianne M.] Harvard Univ, Sch Med, Boston, MA USA. [Finkelstein, Dianne M.; Ware, James H.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. [Harrell, Frank E., Jr.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Harrell, Frank E., Jr.] Vanderbilt Inst Clin & Translat Res, Design Biostat & Res Eth Program, Nashville, TN USA. [Lindsell, Christopher J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Lindsell, Christopher J.; Macaluso, Maurizio] Univ Cincinnati, Ctr Clin & Translat Sci & Training, Cincinnati, OH USA. [Macaluso, Maurizio] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH USA. [Mazumdar, Madhu] Cornell Univ, Weill Cornell Med Coll, Div Biostat & Epidemiol, Dept Publ Hlth, New York, NY 10021 USA. [Mazumdar, Madhu] Cornell Univ, Weill Cornell Med Coll, Res Design & Biostat Core, Clin & Translat Sci Ctr, New York, NY 10021 USA. [Nietert, Paul J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Nietert, Paul J.] South Carolina Clin & Translat Sci Inst, Biostat Epidemiol & Res Design Program, Charleston, SC USA. [Oster, Robert A.] Univ Alabama Birmingham, Sch Med, Dept Med, Div Prevent Med, Birmingham, AL USA. [Oster, Robert A.] Univ Alabama Birmingham, Sch Med, Ctr Clin & Translat Sci, Biostat Epidemiol & Res Design Program, Birmingham, AL USA. [Pollock, Brad H.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pollock, Brad H.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Biostat Epidemiol & Res Design Core, Inst Integrat Med & Sci, San Antonio, TX 78229 USA. [Roberson, Paula K.] Univ Arkansas Med Sci, Coll Med, Dept Biostat, Little Rock, AR 72205 USA. [Roberson, Paula K.] Univ Arkansas Med Sci, Coll Med, Biostat & Res Design Component Translat Res Inst, Little Rock, AR 72205 USA. [Ware, James H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Welty, LJ (reprint author), Dept Prevent Med, Suite 1400,680 N Lake Shore Dr, Chicago, IL 60611 USA. EM lwelty@northwestern.edu RI Macaluso, Maurizio/J-2076-2015; OI Macaluso, Maurizio/0000-0002-2977-9690; Lindsell, Christopher/0000-0002-3297-2811; Nietert, Paul/0000-0002-3933-4986 FU National Center for Research Resources; NCATS, National Institutes of Health (NIH), through the CTSA Program; NIH CTSA [UL1 TR000135, UL1 RR025741, UL1 RR024150, UL1 TR000170, UL1 RR025758, UL1 TR000445, UL1 RR024975]; NIH CTSA. [UL1 TR000077, UL1 RR026314, UL1 TR000457, UL1 RR024996, UL1 TR000062, UL1 RR029882, UL1 TR000165, UL1 RR025777, UL1 TR000149, UL1 RR025767, UL1 TR000039, UL1 RR029884, UL1 TR000150] FX This project was funded in whole or in part with federal funds from the National Center for Research Resources and NCATS, National Institutes of Health (NIH), through the CTSA Program, which is part of the Roadmap Initiative, Re-Engineering the Clinical Research Enterprise (award numbers listed below in order of NCATS, NCRR). This article was approved by the CTSA Consortium Publications Committee.; The NIH CTSA funding was awarded to Northwestern University Feinberg School of Medicine (UL1 TR000150, UL1 RR025741), Mayo Clinic (UL1 TR000135, UL1 RR024150), Harvard University School of Medicine (UL1 TR000170, UL1 RR025758), Vanderbilt University (UL1 TR000445, UL1 RR024975), University of Cincinnati (UL1 TR000077, UL1 RR026314), Weill Cornell Medical College (UL1 TR000457, UL1 RR024996), Medical University of South Carolina (UL1 TR000062, UL1 RR029882), University of Alabama at Birmingham (UL1 TR000165, UL1 RR025777), University of Texas Health Science Center at San Antonio (UL1 TR000149, UL1 RR025767), and University of Arkansas for Medical Sciences (UL1 TR000039, UL1 RR029884). NR 16 TC 8 Z9 8 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2013 VL 88 IS 4 BP 454 EP 460 DI 10.1097/ACM.0b013e31828578ed PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 116AD UT WOS:000316853100012 PM 23425984 ER PT J AU Theobald, CN Stover, DG Choma, NN Hathaway, J Green, JK Peterson, NB Sponsler, KC Vasilevskis, EE Kripalani, S Sergent, J Brown, NJ Denny, JC AF Theobald, Cecelia N. Stover, Daniel G. Choma, Neesha N. Hathaway, Jacob Green, Jennifer K. Peterson, Neeraja B. Sponsler, Kelly C. Vasilevskis, Eduard E. Kripalani, Sunil Sergent, John Brown, Nancy J. Denny, Joshua C. TI The Effect of Reducing Maximum Shift Lengths to 16 Hours on Internal Medicine Interns' Educational Opportunities SO ACADEMIC MEDICINE LA English DT Article ID SURGICAL RESIDENT EDUCATION; PATIENT-CARE; ACCREDITATION-COUNCIL; SCHOOL CURRICULUM; 80-HOUR WORKWEEK; DUTY HOURS; IMPACT; EXPERIENCE; PROGRAM; RESTRICTIONS AB Purpose To evaluate educational experiences of internal medicine interns before and after maximum shift lengths were decreased from 30 hours to 16 hours. Method The authors compared educational experiences of internal medicine interns at Vanderbilt University Medical Center before (2010; 47 interns) and after (2011; 50 interns) duty hours restrictions were implemented in July 2011. The authors compared number of inpatient encounters, breadth of concepts in notes, exposure to five common presenting problems, procedural experience, and attendance at teaching conferences. Results Following the duty hours restrictions, interns cared for more unique patients (mean 118 versus 140 patients per intern, P = .005) and wrote more history and physicals (mean 73 versus 88, P = .005). Documentation included more total concepts after the 16-hour maximum shift implementation, with a 14% increase for history and physicals (338 versus 387, P < .001) and a 10% increase for progress notes (316 versus 349, P < .001). There was no difference in the median number of selected procedures performed (6 versus 6, P = 0.94). Attendance was higher at the weekly chief resident conference (60% versus 68% of expected attendees, P < .001) but unchanged at morning report conferences (79% versus 78%, P = .49). Conclusions Intern clinical exposure did not decrease after implementation of the 16-hour shift length restriction. In fact, interns saw more patients, produced more detailed notes, and attended more conferences following duty hours restrictions. C1 [Theobald, Cecelia N.; Choma, Neesha N.; Hathaway, Jacob; Green, Jennifer K.; Peterson, Neeraja B.; Sponsler, Kelly C.; Vasilevskis, Eduard E.; Kripalani, Sunil; Sergent, John; Brown, Nancy J.; Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Theobald, Cecelia N.] VA Tennessee Valley Healthcare Syst, VA Qual Scholars, Nashville, TN 37212 USA. [Stover, Daniel G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stover, Daniel G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hathaway, Jacob] VA Tennessee Valley Healthcare Syst, Primary Care Serv, Nashville, TN 37212 USA. [Green, Jennifer K.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Peterson, Neeraja B.; Sergent, John] Vanderbilt Univ, Sch Med, Internal Med Residency Program, Nashville, TN 37212 USA. [Sponsler, Kelly C.] VA Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. RP Theobald, CN (reprint author), VA Tennessee Valley Healthcare Syst, GRECC, 1310 24th Ave S, Nashville, TN 37212 USA. EM cecelia.theobald@vanderbilt.edu OI Vasilevskis, Eduard/0000-0001-8165-5321; Stover, Daniel/0000-0001-9003-8165 FU Office of Academic Affiliations, Department of Veterans Affairs, VA National Quality Scholars Program; National Institutes of Health [K23AG040157]; VA Tennessee Valley Geriatric Research, Education, and Clinical Center FX This material is based on work supported by the Office of Academic Affiliations, Department of Veterans Affairs, VA National Quality Scholars Program, and was made possible by the use of the facilities at VA Tennessee Valley Healthcare System, Nashville, Tennessee.; Funding for Dr. Vasilevskis was provided by the National Institutes of Health (K23AG040157) and the VA Tennessee Valley Geriatric Research, Education, and Clinical Center. NR 39 TC 12 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2013 VL 88 IS 4 BP 512 EP 518 DI 10.1097/ACM.0b013e318285800f PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 116AD UT WOS:000316853100023 PM 23425987 ER PT J AU Sarwar, A Ding, A Slanetz, PJ AF Sarwar, Ammar Ding, Alexander Slanetz, Priscilla J. TI Getting Involved in Organized Medicine-A Remedy for the Current Health Care Crisis? SO ACADEMIC RADIOLOGY LA English DT Letter C1 [Sarwar, Ammar; Slanetz, Priscilla J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Ding, Alexander] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sarwar, Ammar; Ding, Alexander; Slanetz, Priscilla J.] Harvard Univ, Sch Med, Boston, MA USA. RP Sarwar, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02115 USA. OI Slanetz, Priscilla/0000-0003-1248-5116 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2013 VL 20 IS 4 BP 519 EP 520 DI 10.1016/j.acra.2012.10.001 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118MF UT WOS:000317028900020 PM 23498996 ER PT J AU Cubeddu, RJ Palacios, IF Blankenship, JC Horvath, SA Xu, K Kovacic, JC Dangas, GD Witzenbichler, B Guagliumi, G Kornowski, R Dudek, D Stone, GW Mehran, R AF Cubeddu, Roberto J. Palacios, Igor F. Blankenship, James C. Horvath, Sofia A. Xu, Ke Kovacic, Jason C. Dangas, George D. Witzenbichler, Bernhard Guagliumi, Giulio Kornowski, Ran Dudek, Dariusz Stone, Gregg W. Mehran, Roxana TI Outcome of Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. During On- Versus Off-hours (A Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial Substudy) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRIMARY ANGIOPLASTY; HOSPITAL MORTALITY; REPERFUSION; TIME; DELAY; IMPACT AB Patients with ST-segment elevation myocardial infarction (STEMI) admitted during nonregular working hours (off-hours) have been reported to have greater mortality than those admitted during regular working hours (on-hours), perhaps because of the lower availability of catheterization laboratory services and longer door-to-balloon times. This might not be the case, however, for hospital centers in which primary percutaneous coronary intervention (PCI) is invariably performed. We conducted a substudy using the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction study data to determine whether the STEMI arrival time was associated with differing clinical outcomes. We identified all patients with STEMI admitted to a PCI-capable hospital who underwent primary PCI. Patients presenting during on-hours were compared to those presenting during off-hours. The primary outcome of death, major adverse cardiovascular events, and net adverse clinical events was examined. We identified 2,440 patients (1,205 [49%] on-hours and 1,235 [51%] off-hours). Similar baseline characteristics were observed. The off-hour patients had a significantly longer door-to-balloon time (92 vs 75 minutes; p < 0.0001) and total ischemic time (209 vs 194 minutes; p < 0.0001). Despite these differences, the risk-adjusted all-cause mortality, major adverse cardiovascular events, and net adverse clinical events rates were similar for both groups during the in-hospital, 1-year, and 3-year follow-up. In conclusion, patients with STEMI presenting to primary PCI hospitals during off-hours might have slightly longer delays to revascularization; however, they experienced similar short- and long-term survival and clinical outcomes as those arriving during on-hours. 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:946-954) C1 [Cubeddu, Roberto J.; Horvath, Sofia A.] Aventura Hosp Med Ctr, Miami, FL USA. [Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Blankenship, James C.] Geisinger Med Ctr, Danville, PA 17822 USA. [Xu, Ke; Dangas, George D.; Stone, Gregg W.; Mehran, Roxana] Cardiovasc Res Fdn, New York, NY USA. [Kovacic, Jason C.; Dangas, George D.; Mehran, Roxana] Mt Sinai Sch Med, New York, NY USA. [Witzenbichler, Bernhard] Charite Campus Benjamin Franklin, Berlin, Germany. [Guagliumi, Giulio] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Kornowski, Ran] Rabin Med Ctr, Petah Tiqwa, Israel. [Kornowski, Ran] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Dudek, Dariusz] Jagiellonian Univ, Krakow, Poland. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. RP Mehran, R (reprint author), Cardiovasc Res Fdn, New York, NY USA. EM roxana.mehran@mountsinai.org FU National Institutes of Health (Bethesda, Maryland) [1K08HL111330-01]; Medicines Company (Parsippany, New Jersey); Bristol-Myers Squibb/Sanofi (New York, New York); Bristol-Myers Squibb/Sanofi (Paris, France); Eli Lilly and Company/Daiichi Sankyo Co. (Indianapolis, Indiana); Eli Lilly and Company/Daiichi Sankyo Co. (Tokyo, Japan); Boston Scientific (Natick, Massachusetts); Medicines Company; Abbott Vascular; Medtronic (Minneapolis, Minnesota); LightLab Imaging (Westford, Massachusetts); Boston Scientific; St. Jude Medical; Volcano Corporation; BMS/Sanofi; Lilly/Daiichi Sankyo; Cardiovascular Research Foundation FX Dr. Kovacic is supported by National Institutes of Health grant 1K08HL111330-01 (Bethesda, Maryland); Dr. Dangas has received research grants (institutional) from The Medicines Company (Parsippany, New Jersey), Bristol-Myers Squibb/Sanofi (New York, New York and Paris, France), and Eli Lilly and Company/Daiichi Sankyo Co. (Indianapolis, Indiana and Tokyo, Japan), and is a consultant to Abbott Vascular (Santa Clara, California), AstraZeneca (Wilmington, Delaware), Janssen Pharmaceuticals (Titusville, New Jersey), Regado Biosciences (Basking Ridge, New Jersey), The Medicines Company, Merck & Co. (Whitehouse Station, New Jersey), and BMS/Sanofi; Dr. Witzenbichler has received lecture fees (modest) from Boston Scientific (Natick, Massachusetts) and The Medicines Company; Dr. Guagliumi is a consultant to Boston Scientific, St. Jude Medical (St. Paul, Minnesota), Volcano Corporation (San Diego, California), and Cordis (Bridgewater Township, New Jersey) and has received research grants from Abbott Vascular, Medtronic (Minneapolis, Minnesota), Boston Scientific (Natick, Massachusetts), and LightLab Imaging (Westford, Massachusetts); Dr. Dudek has received grant support from Boston Scientific, St. Jude Medical, and Volcano Corporation and is a consultant for Boston Scientific and St. Jude Medical; Dr. Stone is a consultant to Boston Scientific; Dr. Mehran has received research grants (institutional) from The Medicines Company (Parsippany, New Jersey), BMS/Sanofi, and Lilly/Daiichi Sankyo, and is a consultant to Abbott Vascular, AstraZeneca, Janssen Pharmaceuticals, Regado Biosciences, The Medicines Company, Merck, and BMS/Sanofi;; The HORIZONS-AMI trial was sponsored by the Cardiovascular Research Foundation with research grant support from Boston Scientific (Natick, Massachusetts) and The Medicines Company (Parsippany, New Jersey). NR 26 TC 11 Z9 11 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2013 VL 111 IS 7 BP 946 EP 954 DI 10.1016/j.amjcard.2012.11.062 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 117AE UT WOS:000316923700005 PM 23340031 ER PT J AU Schiros, CG Ahmed, MI Sanagala, T Zha, W McGiffin, DC Bamman, MM Gupta, H Lloyd, SG Denney, TS Dell'Italia, LJ AF Schiros, Chun G. Ahmed, Mustafa I. Sanagala, Thriveni Zha, Wei McGiffin, David C. Bamman, Marcas M. Gupta, Himanshu Lloyd, Steven G. Denney, Thomas S., Jr. Dell'Italia, Louis J. TI Importance of Three-Dimensional Geometric Analysis in the Assessment of the Athlete's Heart SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ISOLATED MITRAL REGURGITATION; LEFT-VENTRICULAR TORSION; BETA-BLOCKADE; EXERCISE; VOLUME AB How the left ventricle remodels in response to a high-volume stimulus is important in evaluating the endurance athlete's heart. Marathoners and patients with isolated, moderate chronic compensated mitral regurgitation (MR) represent physiologic and pathologic forms of eccentric left ventricular (LV) remodeling in response to intermittent and chronic volume overload, respectively. Thus, in this study, magnetic resonance imaging with tissue tagging and 3-dimensional data analysis at rest were performed in 19 marathoners (mean age 39 +/- 10 years, 47% women), 17 patients with isolated MR without coronary artery disease or medical therapy (mean age 46 +/- 5 years, 53% women), and 24 controls (mean age 45 +/- 8 years, 50% women). Marathoners and patients with MR had approximately 35% greater LV end-diastolic volume indexes, approximately 50% greater end-systolic volume indexes, and approximately 34% greater LV stroke volume indexes (p < 0.0001) compared to controls. However, marathoners' hearts had increased long-axis length, while those of patients with MR did not differ from the hearts of controls. The hearts of patients with MR had greater LV global and apex sphericity compared to those of marathoners and controls (p < 0.0001). Marathoners had normal LV mass/volume ratios and wall thicknesses, whereas these were significantly decreased in the MR group. In marathoners, the baseline LV work rate was similar to that in controls and higher in patients with MR compared to controls. In conclusion, marathoners' hearts achieve elevated stroke volume at rest with adherence to an elliptical shape defined by 3-dimensional geometry and mass/volume ratio. Thus, a comprehensive evaluation of LV geometry and mass/volume ratio may be important in the evaluation of the athlete's heart. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:1067-1072) C1 [Schiros, Chun G.; Ahmed, Mustafa I.; McGiffin, David C.; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Med, Ctr Heart Failure Res, Birmingham, AL 35233 USA. [Bamman, Marcas M.] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham, AL USA. [Sanagala, Thriveni] Loyola Univ Chicago, Div Cardiol, Dept Med, Stritch Sch Med, Maywood, IL USA. [Zha, Wei; Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Samuel Ginn Coll Engn, Auburn, AL 36849 USA. [Bamman, Marcas M.; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Dell'Italia, LJ (reprint author), Univ Alabama Birmingham, Dept Med, Ctr Heart Failure Res, Birmingham, AL 35233 USA. EM dell'italia@physiology.uab.edu FU National Heart, Lung, and Blood Institute Specialized Center for Clinically Oriented Research in Cardiac Dysfunction, Bethesda, Maryland [P50HL077100] FX This study was funded by Grant P50HL077100 from the National Heart, Lung, and Blood Institute Specialized Center for Clinically Oriented Research in Cardiac Dysfunction, Bethesda, Maryland. NR 22 TC 6 Z9 6 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2013 VL 111 IS 7 BP 1067 EP 1072 DI 10.1016/j.amjcard.2012.12.027 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 117AE UT WOS:000316923700024 PM 23332597 ER PT J AU Salinardi, TC Batra, P Roberts, SB Urban, LE Robinson, LM Pittas, AG Lichtenstein, AH Deckersbach, T Saltzman, E Das, SK AF Salinardi, Taylor C. Batra, Payal Roberts, Susan B. Urban, Lorien E. Robinson, Lisa M. Pittas, Anastassios G. Lichtenstein, Alice H. Deckersbach, Thilo Saltzman, Edward Das, Sai Krupa TI Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LOW-GLYCEMIC LOAD; DIABETES-PREVENTION; PHYSICAL-ACTIVITY; OBESITY; PROGRAM; DIET; OVERWEIGHT; EMPLOYEES; EPIDEMIC AB Background: Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. Objective: We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). Design: Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. Results: The mean +/- SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 +/- 0.7 compared with +0.9 +/- 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P <= 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 +/- 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 +/- 0.5 compared with +0.7 +/- 0.2 kg, respectively; P = 0.02). Conclusion: Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222. Am J Clin Nutr 2013;97:667-76. C1 [Salinardi, Taylor C.; Batra, Payal; Roberts, Susan B.; Urban, Lorien E.; Robinson, Lisa M.; Lichtenstein, Alice H.; Saltzman, Edward; Das, Sai Krupa] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Pittas, Anastassios G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Das, SK (reprint author), Jean Mayer USDA Human Nutr Res Ctr Aging, Energy Metab Lab, 711 Washington St, Boston, MA 02111 USA. EM sai.das@tufts.edu FU USDA [58-1950-0-0014]; Tufts University; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University [H15001-DAX023]; National Heart, Lung and Blood Institute [T32 HL 069772] FX Supported by the USDA (agreement 58-1950-0-0014 with Tufts University); the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University (pilot grant H15001-DAX023); and the National Heart, Lung and Blood Institute (grant T32 HL 069772; to TCS). NR 40 TC 16 Z9 17 U1 2 U2 40 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2013 VL 97 IS 4 BP 667 EP 676 DI 10.3945/ajcn.112.046995 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 113CQ UT WOS:000316644200003 PM 23426035 ER PT J AU Kong, FM Lally, BE Chang, JY Chetty, IJ Decker, RH Ginsburg, ME Kestin, LL Langer, CJ Movsas, B Videtic, GMM Willers, H Rosenzweig, KE AF Kong, Feng-Ming (Spring) Lally, Brian E. Chang, Joe Yujiao Chetty, Indrin J. Decker, Roy H. Ginsburg, Mark E. Kestin, Larry L. Langer, Corey J. Movsas, Benjamin Videtic, Gregory M. M. Willers, Henning Rosenzweig, Kenneth E. CA Expert Panel Radiation TI ACR Appropriateness Criterias (R) Radiation Therapy for Small-Cell Lung Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE small cell lung cancer; radiation therapy; appropriateness criteria ID PROPHYLACTIC CRANIAL IRRADIATION; COMBINED-MODALITY TREATMENT; RANDOMIZED CLINICAL-TRIAL; LEUKEMIA GROUP-B; PHASE-III TRIAL; COUNCIL COMPARATIVE TRIAL; CISPLATIN PLUS ETOPOSIDE; THORACIC RADIOTHERAPY; COMPLETE REMISSION; COMBINATION CHEMOTHERAPY AB The current standard of care for small cell lung cancer is combined-modality therapy, including the use of chemotherapy, surgery (in selected cases of limited stage of disease), and radiation therapy. This review will focus on the role, dose fractionation, technology and timing of thoracic radiation, and the role and dose regimen of prophylactic cranial irradiation for both limited and extensive stage of diseases. Consensus recommendation from experts is summarized in the tables for 2 typical case scenarios. 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 [Kong, Feng-Ming (Spring)] Univ Michigan, Ann Arbor Veteran Affairs Med Ctr, Ann Arbor, MI 48109 USA. [Chetty, Indrin J.; Movsas, Benjamin] Henry Ford Hlth Syst, Detroit, MI USA. [Kestin, Larry L.] 21st Century Oncol Michigan, Farmington Hills, MI USA. [Lally, Brian E.] Univ Miami, Dept Radiat Oncol, Miami, FL USA. [Chang, Joe Yujiao] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Decker, Roy H.] Yale Univ, Sch Med, New Haven, CT USA. [Ginsburg, Mark E.] Columbia Univ, Soc Thorac Surg, New York, NY USA. [Rosenzweig, Kenneth E.] Mt Sinai Sch Med, New York, NY USA. [Langer, Corey J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Videtic, Gregory M. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Willers, Henning] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kong, FM (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM fengkong@med.umich.edu FU Henry Ford Health System Radiation Oncology Department from Varian Inc.; Philips Inc.; Resonant Inc. FX B.M. provides research support to Henry Ford Health System Radiation Oncology Department from Varian Inc.; Philips Inc.; and Resonant Inc. NR 63 TC 6 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2013 VL 36 IS 2 BP 206 EP 213 DI 10.1097/COC.0b013e31827e5523 PG 8 WC Oncology SC Oncology GA 114KP UT WOS:000316740100018 PM 23511336 ER PT J AU Tse, JY Pawlak, AC Boussahmain, C Routhier, CA Dias-Santagata, D Kalomiris, D Hoang, MP AF Tse, Julie Y. Pawlak, Amanda C. Boussahmain, Chakib Routhier, Caitlin Ann Dias-Santagata, Dora Kalomiris, Dimitrios Hoang, Mai P. TI Basal Cell Carcinoma With Osteosarcomatous Component SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE basal cell carcinoma; osteosarcomatous carcinoma; TP53; carcinosarcoma ID PRIMARY CUTANEOUS CARCINOSARCOMA; ANALYSIS SHOWS; GIANT-CELLS; SKIN; TUMORS; BREAST AB Sarcomatoid carcinoma or carcinosarcomas of the skin are rare. Basal cell carcinoma (BCC) with osteosarcomatous differentiation is the second most common sarcomatoid carcinoma of the skin, following squamous cell carcinoma with heterologous mesenchymal differentiation. There are only 11 cases of BCC with osteosarcomatous component reported in the literature, with limited documented molecular analyses. The authors report the clinical and histological features of 2 cases with molecular analyses for recurrent mutations in 17 cancer genes. In both cases, the epithelial or BCC component was positive for BerEP4 and high-molecular weight cytokeratin, whereas the sarcomatous component was negative for both markers. Mutational analyses revealed TP53 mutation in 1 case with p53 expression noted in both components. The other case was negative for both p53 expression and TP53 mutation. C1 [Tse, Julie Y.; Pawlak, Amanda C.; Boussahmain, Chakib; Routhier, Caitlin Ann; Dias-Santagata, Dora; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. [Tse, Julie Y.; Pawlak, Amanda C.; Boussahmain, Chakib; Routhier, Caitlin Ann; Dias-Santagata, Dora; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kalomiris, Dimitrios] Adv Dermatol, Dermatopathol, Delray Beach, FL USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 26 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 2013 VL 35 IS 2 BP 261 EP 265 DI 10.1097/DAD.0b013e31826b352b PG 5 WC Dermatology SC Dermatology GA 117GJ UT WOS:000316941200024 PM 23221485 ER PT J AU Pham, CM Syed, AA Siddiqui, HA Keller, RA Kowalewski, C AF Pham, Catherine M. Syed, Almas A. Siddiqui, Huma A. Keller, Richard A. Kowalewski, Catherine TI Case of Metastatic Basal Cell Carcinoma to Bone Marrow, Resulting in Myelophthisic Anemia SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE metastatic; non-melanoma skin cancer; basal cell carcinoma ID CYTOTOXIC THERAPY; SKIN AB Background: While basal cell carcinoma (BCC) remains the most common skin cancer, the incidence of metastasis is rare. Most cases of metastatic BCC have been to regional lymph nodes. Metastasis to bone marrow with myelophthisic anemia is especially rare. To our knowledge, there have been only 5 reported cases in literature. We report a sixth case. Observations: A 46-year-old male patient presented with an 8 x 7-cm ulcerated plaque on his chest, found to be morpheaform basal cell on pathology. Laboratory findings were notable for normocytic anemia, thrombocytopenia, and elevated LDH. Further work up with bone marrow biopsy revealed tumor cells staining positive for CK AE1/AE3, BerEP4, CK7, CD56, and PIN-4. This confirmed the diagnosis of metastatic BCC (MBCC) to bone marrow. Conclusions: Although the rate of metastasis for BCC is rare, once it occurs, prognosis is poor. MBCC remains a challenge to treat. Therefore, it is critical to resolve the primary BCC and obtain vigilant follow-up, especially in patients with multiple risk factors for MBCC. C1 [Pham, Catherine M.; Syed, Almas A.] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, San Antonio, TX 78229 USA. [Siddiqui, Huma A.] Audie L Murphy Mem Vet Adm Med Ctr, Dept Pathol, San Antonio, TX 78229 USA. [Keller, Richard A.; Kowalewski, Catherine] Audie L Murphy Mem Vet Adm Med Ctr, Div Dermatol, San Antonio, TX 78229 USA. RP Kowalewski, C (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Hlth Care Serv, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. NR 19 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 2013 VL 35 IS 2 BP E34 EP E36 DI 10.1097/DAD.0b013e3182761362 PG 3 WC Dermatology SC Dermatology GA 117GJ UT WOS:000316941200004 PM 23147353 ER PT J AU Schulman, S Awad, MM Kuter, DJ AF Schulman, Sol Awad, Mark M. Kuter, David J. TI Neutrophil-erythrocyte rosettes in autoimmune hemolytic anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID RED-CELLS; MONOCYTES; BINDING C1 [Schulman, Sol; Kuter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schulman, Sol; Awad, Mark M.; Kuter, David J.] Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. [Awad, Mark M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schulman, S (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM sol.schulman@gmail.com OI schulman, sol/0000-0002-5229-3592 NR 7 TC 1 Z9 1 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2013 VL 88 IS 4 BP 333 EP 334 DI 10.1002/ajh.23277 PG 2 WC Hematology SC Hematology GA 115JQ UT WOS:000316808800016 PM 22886729 ER PT J AU Brierley, CK Morgan, EA Sprague, JR Odejide, OO DeAngelo, DJ Steensma, DP AF Brierley, Charlotte K. Morgan, Elizabeth A. Sprague, Julian R. Odejide, Oreofe O. DeAngelo, Daniel J. Steensma, David P. TI An extreme example of focal bone marrow involvement in acute myeloid leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID HODGKINS-LYMPHOMA; SPECIMENS; DYSPLASIA C1 [Brierley, Charlotte K.] Univ Oxford, Christ Church, Oxford, England. [Morgan, Elizabeth A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sprague, Julian R.] Univ Vermont, Vermont Canc Ctr, Fletcher Allen Hlth Care, Burlington, VT USA. [Odejide, Oreofe O.; DeAngelo, Daniel J.; Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Suite D1B30 Mayer 1B21, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284; Morgan, Elizabeth/0000-0001-5880-9337 NR 16 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2013 VL 88 IS 4 BP 335 EP 336 DI 10.1002/ajh.23350 PG 2 WC Hematology SC Hematology GA 115JQ UT WOS:000316808800017 PM 23115117 ER PT J AU Dietz, PM Kuklina, EV Bateman, BT Callaghan, WM AF Dietz, Patricia M. Kuklina, Elena V. Bateman, Brian T. Callaghan, William M. TI Assessing Cardiovascular Disease Risk among Young Women with a History of Delivering a Low-Birth-Weight Infant SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE low birth weight; fetal growth; cardiovascular disease; preterm ID FETAL-GROWTH RESTRICTION; ISCHEMIC-HEART-DISEASE; PREGNANCY COMPLICATIONS; RETROSPECTIVE COHORT; PRETERM DELIVERY; SERUM COTININE; UNITED-STATES; MORTALITY; MOTHERS; PREECLAMPSIA AB Objective To assess the prevalence and risk factors of cardiovascular disease (CVD) among younger women by pregnancy history. Methods Cross-sectional study using 1999 to 2006 National Health and Nutrition Examination Survey including women aged 20 to 64 years who had delivered at least one infant (n = 4820). Women self-reported pregnancy history and a clinician diagnosed CVD; CVD risk factors included hypertension (mean systolic blood pressure [BP] >= 140 mm Hg or mean diastolic BP >= 90 mm Hg, or currently treated), high cholesterol (total cholesterol >= 240 mg/dL or currently treated), diabetes (self-report or hemoglobin A1c >= 6.5), and smoking (self-report or cotinine-verified). Multivariable logistic regression was used to assess the association between pregnancy history and CVD. Results Of the women we studied, 4.6% had CVD; 3.1% had delivered a term low-birth-weight infant (TLBWI). Women with a history of TLBWI had an adjusted odds ratio (AOR) of 2.07 (95% confidence intervals [CI] 1.08 to 3.99) for CVD compared with women without a history of LBWI. Adjustment for hypertension and high cholesterol mildly attenuated the association (AOR 1.85, 95% CI 0.89 to 3.83). Among women without CVD (n = 4555), 23.11 with a history of TLBWI had two risk factors compared with 14.0% of those without a history of LBWI (p = 0.0016). Conclusion Women with a history of TLBWI should be informed of a possible increased risk of CVD and encouraged to receive screenings as recommended. C1 [Dietz, Patricia M.; Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Dietz, PM (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, 4770 Buford Hwy NE,MS K-23, Atlanta, GA 30341 USA. EM PDietz@cdc.gov NR 37 TC 4 Z9 4 U1 1 U2 9 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD APR PY 2013 VL 30 IS 4 BP 267 EP 273 DI 10.1055/s-0032-1323589 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 115SF UT WOS:000316831500003 PM 22875656 ER PT J AU Ahmad, FS Tsang, T AF Ahmad, Faraz S. Tsang, Thomas TI Diabetes Prevention, Health Information Technology, and Meaningful Use Challenges and Opportunities SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PHYSICIAN ORDER ENTRY; RANDOMIZED CONTROLLED-TRIAL; CLINICAL DECISION-SUPPORT; CENTERED MEDICAL HOME; OF-THE-LITERATURE; HEART-FAILURE; RECORD USE; CARE; MANAGEMENT; QUALITY AB The U.S. health system has historically been poorly equipped to confront the growing impact of diabetes on the nation's health. The Affordable Care Act legislates a number of new strategies-such as innovative payment and delivery models and increased public health funding-intended to improve diabetes prevention and care quality. Health information technology (IT) is often cited as a critical part of these strategies. Through the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009, the federal government has been supporting the rapid adoption of health IT, and more specifically of electronic health records (EHRs) through the Centers for Medicare and Medicaid Services (CMS) EHR Incentive Program. Health IT has the potential to contribute to diabetes prevention and improved quality of care, but the evidence supporting its benefits is mixed. This article provides a brief overview of the CMS EHR Incentive Program and meaningful-use criteria. Then it examines health IT strategies for diabetes prevention in the context of current evidence and identifies areas of needed research and innovation. (Am J Prev Med 2013;44(4S4):S357-S363) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Ahmad, Faraz S.] Univ Penn, Perelman Sch Med, Ctr Therapeut Effectiveness Res, Ctr Healthcare Improvement & Patient Safety, Philadelphia, PA 19104 USA. [Ahmad, Faraz S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Tsang, Thomas] Dupont Merck Pharmaceut Co, Strategy & Business Dev, Boston, MA USA. RP Ahmad, FS (reprint author), Hosp Univ Penn, 3400 Spruce St,100 Centrex, Philadelphia, PA 19104 USA. EM faraz.ahmad@uphs.upenn.edu FU Joslin Diabetes Center; Novo Nordisk FX Publication of this supplement was supported by Joslin Diabetes Center and Novo Nordisk. NR 61 TC 8 Z9 8 U1 5 U2 39 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2013 VL 44 IS 4 SU 4 BP S357 EP S363 DI 10.1016/j.amepre.2012.12.020 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 113NH UT WOS:000316674200011 PM 23498299 ER PT J AU Beaser, RS Brown, JA AF Beaser, Richard S. Brown, Julie A. TI Preventive Intervention in Diabetes A New Model for Continuing Medical Education SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BLOOD-GLUCOSE CONTROL; LIFE-STYLE INTERVENTION; SELF-ASSESSMENT; CLINICAL-PRACTICE; GLYCEMIC CONTROL; US ADULTS; TYPE-2; PROGRAM; MELLITUS; PERFORMANCE AB Competence and skills in overcoming clinical inertia for diabetes treatment, and actually supporting and assisting the patient through adherence and compliance (as opposed to just reiterating what they "should" be doing and then assigning them the blame if they fail) is a key component to success in addressing diabetes, and to date it is a component that has received little formal attention. To improve and systematize diabetes care, it is critical to move beyond the "traditional" continuing medical education (CME) model of imparting knowledge as the entirety of the educational effort, and move toward a focus on Performance Improvement CME. This new approach does not just teach new information but also provides support for improvements where needed most within practice systems based on targeted data-based on self-assessments for the entire system of care. Joslin data conclude that this new approach will benefit support, clinical, and office teams as well as the specialist. In short, the Performance Improvement CME structure reflects the needed components of the successful practice today, particularly for chronic conditions such as diabetes, including the focus on interdisciplinary team care and on quality improvement, which is becoming more and more aligned with reimbursement schemes, public and private, in the U.S. (Am J Prev Med 2013;44(4S4):S394-S399) (C) 2013 American Journal of Preventive Medicine C1 [Beaser, Richard S.; Brown, Julie A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Brown, Julie A.] Harvard Univ, Sch Med, Boston, MA USA. RP Beaser, RS (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Richard.beaser@joslin.harvard.edu FU Joslin Diabetes Center; Novo Nordisk FX Publication of this supplement was supported by Joslin Diabetes Center and Novo Nordisk. NR 48 TC 2 Z9 2 U1 1 U2 13 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 2013 VL 44 IS 4 SU 4 BP S394 EP S399 DI 10.1016/j.amepre.2013.01.003 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 113NH UT WOS:000316674200017 PM 23498305 ER PT J AU Brooks, JL AF Brooks, John L., III TI Diabetes Prevention The Joslin Diabetes Center SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Brooks, JL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM john.brooks@joslin.harvard.edu 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 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2013 VL 44 IS 4 SU 4 BP S299 EP S300 DI 10.1016/j.amepre.2013.01.005 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 113NH UT WOS:000316674200002 PM 23498290 ER PT J AU Miller, SC Baktash, SH Webb, TS Whitehead, CR Maynard, C Wells, TS Otte, CN Gore, RK AF Miller, Shannon C. Baktash, Suzanne H. Webb, Timothy S. Whitehead, Casserly R. Maynard, Charles Wells, Timothy S. Otte, Clifford N. Gore, Russel K. TI Risk for Addiction-Related Disorders Following Mild Traumatic Brain Injury in a Large Cohort of Active-Duty US Airmen SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ALCOHOL-USE; SUBSTANCE-ABUSE; HEAD-INJURY; DRUG-USE; AFGHANISTAN; DEPRESSION; IRAQ; POPULATION; PATTERNS; CARE AB Objective: Military personnel are at increased risk for traumatic brain injury (TBI) from combat and noncombat exposures. The sequelae of moderate to severe TBI are well described, but little is known regarding long-term performance decrements associated with mild TBI. Furthermore, while alcohol and drug use are well known to increase risk for TBI, little is known regarding the reverse pattern. The authors sought to assess possible associations between mild TBI and addiction-related disorders in active-duty U.S. military personnel. Method: A historical prospective study was conducted using electronically recorded demographic, medical, and military data for more than a half million active-duty U.S. Air Force service members. Cases were identified by ICD-9-CM codes considered by an expert panel to be indicative of mild TBI. Outcomes included ICD-9-CM diagnoses of selected addiction-related disorders. Cox proportional hazards modeling was used to calculate hazard ratios while controlling for varying lengths of follow-up and potential confounding variables. Results: Airmen with mild TBI were at increased risk for certain addiction-related disorders compared with a similarly injured non-mild TBI comparison group. Hazards for alcohol dependence, nicotine dependence, and nondependent abuse of drugs or alcohol were significantly elevated, with a consistent decrease over time. Conclusions: A novel finding of this study was the initial increased risk for addiction-related disorders that decreased with time, thus eroding war fighter performance in a military population. Moreover, these results suggest that mild TBI is distinguished from moderate to severe TBI in terms of timing of the risk, indicating that there is a need for screening and prevention of addiction-related disorders in mild TBI. Screening may be warranted in military troops as well as civilians at both short- and long-term milestones following mild TBI. (Am J Psychiatry 2013; 170:383-390) C1 [Whitehead, Casserly R.] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Psychiat & Behav Neurosci, Ctr Treatment Res & Educ Addict Disorders, Cincinnati, OH USA. Univ Tennessee, Dept Elect Engn & Comp Sci, Knoxville, TN USA. USAF, Res Lab, Vulnerabil Anal Branch, AFMC Human Performance Wing 711, Wright Patterson AFB, OH 45433 USA. Infoscitex Corp, Waltham, MA USA. VA Puget Sound, Epidemiol Res & Informat Ctr, Seattle, WA USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Whitehead, CR (reprint author), Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. EM casserly.whitehead.ctr@wpafb.af.mil RI Maynard, Charles/N-3906-2015; Gore, Russell/N-8988-2016 OI Maynard, Charles/0000-0002-1644-7814; Gore, Russell/0000-0002-8012-1579 NR 37 TC 15 Z9 17 U1 1 U2 19 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2013 VL 170 IS 4 BP 383 EP 390 DI 10.1176/appi.ajp.2012.12010126 PG 8 WC Psychiatry SC Psychiatry GA 117AW UT WOS:000316925500008 PM 23429886 ER PT J AU Melcher, ML Blosser, CD Baxter-Lowe, LA Delmonico, FL Gentry, SE Leishman, R Knoll, GA Leffell, MS Leichtman, AB Mast, DA Nickerson, PW Reed, EF Rees, MA Rodrigue, JR Segev, DL Serur, D Tullius, SG Zavala, EY Feng, S AF Melcher, M. L. Blosser, C. D. Baxter-Lowe, L. A. Delmonico, F. L. Gentry, S. E. Leishman, R. Knoll, G. A. Leffell, M. S. Leichtman, A. B. Mast, D. A. Nickerson, P. W. Reed, E. F. Rees, M. A. Rodrigue, J. R. Segev, D. L. Serur, D. Tullius, S. G. Zavala, E. Y. Feng, S. TI Dynamic Challenges Inhibiting Optimal Adoption of Kidney Paired Donation: Findings of a Consensus Conference SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allocation; donor evaluation; finances; histocompatibility testing; kidney paired donation; nondirected donors; paired kidney exchange; transport ID CLINICAL-RELEVANCE; EXCHANGE PROGRAMS; CROSS-MATCHES; DONOR KIDNEYS; TRANSPLANTATION; CHAIN; PARTICIPATION; EXPERIENCE; TRANSPORT; OUTCOMES AB While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 2930, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document. C1 [Melcher, M. L.] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Blosser, C. D.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Baxter-Lowe, L. A.; Feng, S.] UCSF, Dept Surg, San Francisco, CA USA. [Delmonico, F. L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Delmonico, F. L.] New England Organ Bank Inc, Boston, MA USA. [Gentry, S. E.] USN Acad, Dept Math, Annapolis, MD 21402 USA. [Leishman, R.] United Network Organ Sharing, Richmond, VA USA. [Knoll, G. A.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada. [Leffell, M. S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Leichtman, A. B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Mast, D. A.] Stanford Hosp & Clin, Palo Alto, CA USA. [Nickerson, P. W.] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada. [Reed, E. F.] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Rees, M. A.] Univ Toledo, Med Ctr, Dept Urol & Pathol, Toledo, OH 43606 USA. [Rodrigue, J. R.] Beth Israel Deaconess Med Sch, Transplant Inst, Boston, MA USA. [Segev, D. L.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Serur, D.] Cornell Univ, Dept Surg, New York, NY 10021 USA. [Tullius, S. G.] Harvard Univ, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Zavala, E. Y.] Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37240 USA. RP Feng, S (reprint author), UCSF, Dept Surg, San Francisco, CA USA. EM sandy.feng@ucsfmedctr.org OI Nickerson, Peter/0000-0002-7393-7799; Melcher, Marc/0000-0002-7185-4383 FU AHRQ HHS [R18 HS020610] NR 37 TC 19 Z9 19 U1 1 U2 6 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 2013 VL 13 IS 4 BP 851 EP 860 DI 10.1111/ajt.12140 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 116VT UT WOS:000316911900008 PM 23398969 ER PT J AU Malinoski, DJ Patel, MS Ahmed, O Daly, MC Mooney, S Graybill, CO Foster, CE Salim, A AF Malinoski, D. J. Patel, M. S. Ahmed, O. Daly, M. C. Mooney, S. Graybill, C. O. Foster, C. E. Salim, A. CA United Network Organ Sharing UNOS TI The Impact of Meeting Donor Management Goals on the Development of Delayed Graft Function in Kidney Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Catastrophic brain injury guidelines; critical care; delayed graft function ID DECEASED ORGAN DONORS; RENAL-FUNCTION; RISK-FACTORS; SURVIVAL; RESUSCITATION; DONATION; NUMBER AB Many organ procurement organizations (OPOs) utilize preset critical care endpoints as donor management goals (DMGs) in order to standardize care and improve outcomes. The objective of this study was to determine the impact of meeting DMGs on delayed graft function (DGF) in renal transplant recipients. All eight OPOs of the United Network for Organ Sharing Region 5 prospectively implemented nine DMGs in every donor after neurologic determination of death (DNDD). DMGs met was defined a priori as achieving any seven of the nine DMGs and this was recorded at the time of consent for donation to reflect donor hospital ICU management, 1218 h later, and prior to organ recovery. Multivariable analyses were performed to identify independent predictors of DGF (dialysis in the first week after transplantation) with a p < 0.05. A total of 722 transplanted kidneys from 492 DNDDs were included. A total of 28% developed DGF. DMGs were met at consent in 14%, 1218 h in 32% and prior to recovery in 38%. DGF was less common when DMGs were met at consent (17% vs. 30%, p = 0.007). Independent predictors of DGF were age, Cr and cold ischemia time, while meeting DMGs at consent was significantly protective. The management of potential organ donors prior to consent affects outcomes and should remain a priority in the intensive care unit. C1 [Malinoski, D. J.] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA. [Patel, M. S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ahmed, O.; Daly, M. C.; Mooney, S.; Foster, C. E.] Univ Calif Irvine, Div Transplantat Surg, Orange, CA 92668 USA. [Graybill, C. O.] United Network Organ Sharing, Richmond, VA USA. [Salim, A.] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. RP Malinoski, DJ (reprint author), Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA. EM malinosk@ohsu.edu FU Health Resources and Services Administration [234-2005-37011C] FX Additionally, this work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 26 TC 16 Z9 18 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 IS 4 BP 993 EP 1000 DI 10.1111/ajt.12090 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 116VT UT WOS:000316911900023 PM 23406284 ER PT J AU Chung, RT Gordon, FD Curry, MP Schiano, TD Emre, S Corey, K Markmann, JF Hertl, M Pomposelli, JJ Pomfret, EA Florman, S Schilsky, M Broering, TJ Finberg, RW Szabo, G Zamore, PD Khettry, U Babcock, GJ Ambrosino, DM Leav, B Leney, M Smith, HL Molrine, DC AF Chung, R. T. Gordon, F. D. Curry, M. P. Schiano, T. D. Emre, S. Corey, K. Markmann, J. F. Hertl, M. Pomposelli, J. J. Pomfret, E. A. Florman, S. Schilsky, M. Broering, T. J. Finberg, R. W. Szabo, G. Zamore, P. D. Khettry, U. Babcock, G. J. Ambrosino, D. M. Leav, B. Leney, M. Smith, H. L. Molrine, D. C. TI Human Monoclonal Antibody MBL-HCV1 Delays HCV Viral Rebound Following Liver Transplantation: A Randomized Controlled Study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE HCV RNA titer; hepatitis C virus; liver transplantation; monoclonal antibody ID HEPATITIS-C VIRUS; IMMUNE GLOBULIN; NEUTRALIZING ANTIBODIES; GAMMA-GLOBULIN; OPEN-LABEL; PROPHYLAXIS; RECURRENCE; PREVENTION; KINETICS; IMMUNOGLOBULINS AB Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon- and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n = 6) or placebo (n = 5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p = 0.02) for the antibody-treated group (range 3.07 to 3.34) compared to placebo group (range 0.331 to 1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p < 0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway. C1 [Chung, R. T.; Corey, K.; Markmann, J. F.; Hertl, M.] Massachusetts Gen Hosp, Dept Transplant Surg, Boston, MA 02114 USA. [Gordon, F. D.; Pomposelli, J. J.; Pomfret, E. A.; Khettry, U.] Lahey Clin Med Ctr, Dept Transplantat, Burlington, MA 01803 USA. [Curry, M. P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schiano, T. D.; Florman, S.] Mt Sinai Med Ctr, Dept Surg, New York, NY 10029 USA. [Emre, S.; Schilsky, M.] Yale New Haven Med Ctr, Dept Med, New Haven, CT 06504 USA. [Broering, T. J.; Babcock, G. J.; Ambrosino, D. M.; Leav, B.; Leney, M.; Smith, H. L.; Molrine, D. C.] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02125 USA. [Finberg, R. W.; Szabo, G.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Zamore, P. D.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Zamore, P. D.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA USA. RP Molrine, DC (reprint author), Univ Massachusetts, Sch Med, MassBiol, Harbor Campus, Boston, MA 02125 USA. EM deborah.molrine@umassmed.edu RI sebastianovitsch, stepan/G-8507-2013 FU MassBiologics, University of Massachusetts, Boston, MA; CTSA grant [UL1TR000067]; NIH [DK078772]; MassBiologics; Merck; Gilead; Pfizer; Romark FX This study was funded by MassBiologics, University of Massachusetts, Boston, MA. CTSA grant (UL1TR000067) awarded to Mt. Sinai School of Medicine for CRC research support. RTC was supported in part by NIH DK078772.; The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. DMA, TJB and GJB are co-inventors on relevant patents with all rights and royalties assigned to MassBiologics; GJB, TJB, DMA, BL ML, HLS, DCM are current or former employees of MassBiologics; RTC, FDG, MPC, TDS, SE received research support from MassBiologics; RTC (Grant: Merck, Gilead, Pfizer, Romark); FDG (Consulting: Merck, Vertex; Grant: Merck; Speaking and Teaching: Merck); TDS (Advisory Committees or Review Panels: Vertex, Salix, Merck, Gilead); DMA spouse is stockholder, Merck. NR 30 TC 35 Z9 36 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 IS 4 BP 1047 EP 1054 DI 10.1111/ajt.12083 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 116VT UT WOS:000316911900030 PM 23356386 ER PT J AU Vagefi, PA Kelsey, PB Hochberg, EP Kotton, CN AF Vagefi, Parsia A. Kelsey, Peter B. Hochberg, Ephraim P. Kotton, Camille N. TI Jaundice Six Months Following Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 [Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg, Boston, MA 02115 USA. [Kelsey, Peter B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Hochberg, Ephraim P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol, Boston, MA USA. [Kotton, Camille N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Vagefi, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg, Boston, MA 02115 USA. EM pvagefi@partners.org NR 0 TC 1 Z9 1 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 2013 VL 13 IS 4 BP 1106 EP 1108 DI 10.1111/ajt.12052 PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 116VT UT WOS:000316911900040 PM 23551633 ER PT J AU Berry, JD Miller, R Moore, DH Cudkowicz, ME Van den Berg, LH Kerr, DA Dong, YW Ingersoll, EW Archibald, D AF Berry, James D. Miller, Robert Moore, Dan H. Cudkowicz, Merit E. Van den Berg, Leonard H. Kerr, Douglas A. Dong, Yingwen Ingersoll, Evan W. Archibald, Donald TI The Combined Assessment of Function and Survival (CAFS): A new endpoint for ALS clinical trials SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Amyotrophic lateral sclerosis; clinical trials; study design; ALS survival; ALS function; primary endpoint ID AMYOTROPHIC-LATERAL-SCLEROSIS; COMPOSITE OUTCOMES; JOINT ANALYSIS; MORTALITY; TIME AB Our objective was to describe a new endpoint for amyotrophic lateral sclerosis (ALS), the Combined Assessment of Function and Survival (CAFS). CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome. Historically, ALS clinical trials have assessed survival and function as independent endpoints. Combined endpoints have been used in other diseases to decrease the confounding effect of mortality on analysis of functional outcomes. We explored the application of a similar approach in ALS, the CAFS endpoint, which was used as a pre-specified secondary analysis in a phase II study of dexpramipexole. Those results and some hypothetical examples based on modeling exercises are presented here. CAFS is the primary endpoint of a dexpramipexole phase III study in ALS. In conclusion, the CAFS is a robust statistical tool for ALS clinical trials and appropriately accounts for and weights mortality in the analysis of function. C1 [Berry, James D.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA. [Miller, Robert; Moore, Dan H.] Calif Pacific Med Ctr, San Francisco, CA USA. [Van den Berg, Leonard H.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Kerr, Douglas A.; Dong, Yingwen] Biogen Idec Inc, Cambridge, MA USA. [Ingersoll, Evan W.; Archibald, Donald] Knopp Biosci, Pittsburgh, PA USA. RP Berry, JD (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, Bigelow 1256, Boston, MA 02114 USA. EM jdberry@partners.org FU Biogen Idec, Inc.; Muscular Dystrophy Association; ALS Therapy Alliance; Baxter FX Medical writing assistance was provided by Aruna Seth of UBC Scientific Solutions and funded by Biogen Idec, Inc.; J. D. Berry has served as a consultant to Biogen Idec, Inc. and as a paid speaker for Oakstone Publishing. He is a site co-investigator for the EMPOWER study. He receives research support from the Muscular Dystrophy Association and the ALS Therapy Alliance. R. Miller served on a Biogen Idec advisory board. M. E. Cudkowicz is the principal investigator of the ongoing EMPOWER study and receives a grant from Biogen Idec, Inc. for this role. In the past 2 years, she has served as a consultant for Teva Pharmaceuticals, Millenium, and Trophos (Data and Safety Monitoring Board) and has served on an advisory board for Biogen Idec, Inc. L. H. van den Berg has served on a Biogen Idec, Inc. advisory board and has received travel grants from Baxter. D. A. Kerr and Y. Dong are employees of Biogen Idec, Inc. E. Ingersoll and D. Archibald are employees of Knopp Biosciences LLC. NR 25 TC 19 Z9 19 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD APR PY 2013 VL 14 IS 3 BP 162 EP 168 DI 10.3109/21678421.2012.762930 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 117KT UT WOS:000316952900002 PM 23323713 ER PT J AU Cotten, JF AF Cotten, Joseph F. TI TASK-1 (KCNK3) and TASK-3 (KCNK9) Tandem Pore Potassium Channel Antagonists Stimulate Breathing in Isoflurane-Anesthetized Rats SO ANESTHESIA AND ANALGESIA LA English DT Article ID UPPER ABDOMINAL-SURGERY; BACKGROUND K+ CHANNEL; CAROTID-BODY; CHEMORECEPTOR CELLS; RESPIRATORY NEURONS; DOXAPRAM; ANESTHESIA; PH; CONTRIBUTE; CURRENTS AB BACKGROUND: TASK-1 and TASK-3 tandem pore potassium channel subunits provide a constitutive acidic pH- and hypoxia-inhibited potassium conductance. TASK channels are expressed in a number of tissues involved in regulation of breathing, and the TASK-1/TASK-3 heterodimer provides the predominant hypoxia-sensitive potassium conductance in carotid body type 1 glomus chemosensing cells. The carotid bodies have an important role in regulation of breathing. Doxapram is a potent TASK-1 and TASK-3 potassium channel antagonist and a carotid body and breathing stimulant. PK-THPP and A1899 are potent and selective TASK-1 and TASK-3 antagonists. I hypothesized PK-THPP and A1899 are, like doxapram, breathing stimulants. METHODS: I studied rat TASK-3 potassium channel function by Ussing chamber using Fischer rat thyroid monolayers. To quantify breathing effects, I studied male Sprague Dawley rats spontaneously breathing 1.5% isoflurane in room air by noninvasive plethysmography and by arterial blood gas analysis. RESULTS: PK-THPP, A1899, and doxapram inhibit rat TASK-3 potassium channel function with IC(50)s of 42 nM (33-52), 1.6 mu M (0.8-3.3), and 22 mu M (18-28) (n = 4-6; 95% confidence limits). IV PK-THPP, A1899, and doxapram stimulated breathing by plethysmography with a peak change in minute ventilation relative to baseline of 84% +/- 19% and 226% +/- 56% (for PK-THPP at 0.5 and 5 mg/kg; mean +/- SEM; n = 3-4; P < 0.05 and P < 0.001, respectively, relative to vehicle); 46% +/- 2% and 236% +/- 48% (for A1899 at 5 and 25 mg/kg; n = 3-4; P > 0.05 and P < 0.001, respectively); 103% +/- 20% (for doxapram at 25 mg/kg; n = 4), and 33% +/- 9% (for dimethylsulfoxide vehicle at 1 mL/kg; n = 4). PK-THPP and A1899, unlike doxapram, induced a profound and lasting respiratory alkalosis by arterial blood gas analysis. Thirty minutes after IV drug administration, I observed an arterial pH and carbon dioxide partial pressure of 7.62 +/- 0.02 and 23 +/- 0.8 mm Hg (for PK-THPP after 5 mg/kg; n = 4; P < 0.001 for both relative to vehicle), 7.49 +/- 0.02 and 31 +/- 2 mm Hg (for A1899 at 25 mg/kg; n = 6; P < 0.05 and 0.001, respectively), 7.43 +/- 0.03 and 39 +/- 4 mm Hg (for doxapram after 25 mg/kg; n = 4; P > 0.05 for both), and 7.38 +/- 0.03 and 48 +/- 4 mm Hg (for dimethylsulfoxide vehicle after 1 mL/kg; n = 3). CONCLUSIONS: PK-THPP and A1899 are potent rat TASK-3 antagonists and effective breathing stimulants. PK-THPP and A1899 effects on breathing were of greater magnitude and/or duration relative to that of doxapram. PK-THPP and A1899 or related compounds may have therapeutic potential for treating breathing disorders..(Anesth Analg 2013;116:810-6) C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cotten, JF (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, GRB 444,55 Fruit St, Boston, MA 02114 USA. EM jcotten@partners.org FU NIH/NIGMS [GM083216]; Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine FX This work was supported by NIH/NIGMS GM083216 and Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine. NR 44 TC 11 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2013 VL 116 IS 4 BP 810 EP 816 DI 10.1213/ANE.0b013e318284469d PG 7 WC Anesthesiology SC Anesthesiology GA 113EA UT WOS:000316648100011 PM 23460565 ER PT J AU Forman, SA AF Forman, Stuart A. TI The Expanding Genetic Toolkit for Exploring Mechanisms of General Anesthesia SO ANESTHESIOLOGY LA English DT Editorial Material ID RECEPTOR BETA-3 SUBUNIT; A RECEPTOR; KNOCKOUT MICE; ETOMIDATE C1 [Forman, Stuart A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Forman, SA (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM saforman@partners.org FU NIGMS NIH HHS [P01 GM058448, GM089745, R01 GM089745, GM58448] NR 14 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2013 VL 118 IS 4 BP 769 EP 771 DI 10.1097/ALN.0b013e318287b7e4 PG 3 WC Anesthesiology SC Anesthesiology GA 109GR UT WOS:000316355000002 PM 23364596 ER PT J AU Sasaki, N Meyer, MJ Eikermann, M AF Sasaki, Nobuo Meyer, Matthew J. Eikermann, Matthias TI Postoperative Respiratory Muscle Dysfunction Pathophysiology and Preventive Strategies SO ANESTHESIOLOGY LA English DT Review ID OBSTRUCTIVE SLEEP-APNEA; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; RESIDUAL NEUROMUSCULAR BLOCKADE; UPPER AIRWAY COLLAPSIBILITY; UPPER ABDOMINAL-SURGERY; TUMOR-NECROSIS-FACTOR; INDUCED DIAPHRAGMATIC DYSFUNCTION; POSITIVE-PRESSURE VENTILATION; NEGATIVE PHARYNGEAL PRESSURE AB Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible. C1 [Sasaki, Nobuo; Meyer, Matthew J.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org NR 235 TC 23 Z9 24 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2013 VL 118 IS 4 BP 961 EP 978 DI 10.1097/ALN.0b013e318288834f PG 18 WC Anesthesiology SC Anesthesiology GA 109GR UT WOS:000316355000028 PM 23429163 ER PT J AU Forman, SA AF Forman, Stuart A. TI A Paradigm Shift from Biophysical to Neurobiological: The Fading Influence of Claude Bernard's Ideas about General Anesthesia SO ANESTHESIOLOGY LA English DT Letter ID CONSCIOUSNESS C1 [Forman, Stuart A.] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Forman, Stuart A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Forman, SA (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM saforman@partners.org FU NIGMS NIH HHS [P01 GM058448, R01 GM089745] NR 12 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2013 VL 118 IS 4 BP 984 EP 985 DI 10.1097/ALN.0b013e3182860777 PG 2 WC Anesthesiology SC Anesthesiology GA 109GR UT WOS:000316355000032 PM 23511525 ER PT J AU Scemama, PH Hull, JW AF Scemama, Pascal H. Hull, Jeffrey W. TI Case Scenario Consistent with Lack of Knowledge and Psychological Bias Reply SO ANESTHESIOLOGY LA English DT Letter C1 [Scemama, Pascal H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scemama, PH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pscemamadegialluly@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2013 VL 118 IS 4 BP 991 EP 991 DI 10.1097/ALN.0b013e3182862f4a PG 1 WC Anesthesiology SC Anesthesiology GA 109GR UT WOS:000316355000039 PM 23511532 ER PT J AU Shindoh, J Andreou, A Aloia, TA Zimmitti, G Lauwers, GY Laurent, A Nagorney, DM Belghiti, J Cherqui, D Poon, RTP Kokudo, N Vauthey, JN AF Shindoh, Junichi Andreou, Andreas Aloia, Thomas A. Zimmitti, Giuseppe Lauwers, Gregory Y. Laurent, Alexis Nagorney, David M. Belghiti, Jacques Cherqui, Daniel Poon, Ronnie Tung-Ping Kokudo, Norihiro Vauthey, Jean-Nicolas TI Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID AMERICAN-JOINT-COMMITTEE; LIVER-TRANSPLANTATION; CIRRHOSIS; RESECTION; CLASSIFICATION; PROGRESSION; VALIDATION; PATHOLOGY; JAPAN AB Excellent long-term outcomes have been reported recently for patients with small (a parts per thousand currency sign2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm. In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (a parts per thousand currency sign2 cm) and patients with tumors larger than 2 cm was analyzed. In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27-1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11-1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01-1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups-HCC a parts per thousand currency sign2, > 2 cm without MVI, and HCC > 2 cm with MVI-significant between-group survival difference was observed (p < 0.0001). Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (a parts per thousand currency sign2 vs. > 2 cm). C1 [Shindoh, Junichi; Andreou, Andreas; Aloia, Thomas A.; Zimmitti, Giuseppe; Vauthey, Jean-Nicolas] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX 77030 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Laurent, Alexis; Cherqui, Daniel] Hop Henri Mondor, Dept Digest & Hepatobiliary Surg & Liver Transpla, F-94010 Creteil, France. [Nagorney, David M.] Mayo Clin, Dept Gastroenterol & Gen Surg, Rochester, MI USA. [Belghiti, Jacques] Beaujon Hosp, AP HP, Dept Hepatopancreatobiliary & Transplantat Surg, Clichy, France. [Poon, Ronnie Tung-Ping] Univ Hong Kong, Dept Surg, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Kokudo, Norihiro] Univ Tokyo, Dept Surg, Hepatobiliary Pancreat Surg Div, Tokyo, Japan. RP Shindoh, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX 77030 USA. EM jvauthey@mdanderson.org FU National Institutes of Health through Cancer Center Support Grant [CA016672] FX The authors thank Ms. Stephanie Deming and Ms. Ruth Haynes for their contribution to our manuscript. The University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through Cancer Center Support Grant CA016672. NR 35 TC 16 Z9 18 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 IS 4 BP 1223 EP 1229 DI 10.1245/s10434-012-2739-y PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 109TV UT WOS:000316392600025 PM 23179993 ER PT J AU Coopey, SB Specht, MC Warren, L Smith, BL Winograd, JM Fleischmann, K AF Coopey, Suzanne B. Specht, Michelle C. Warren, Lisa Smith, Barbara L. Winograd, Jonathan M. Fleischmann, Katharine TI Use of Preoperative Paravertebral Block Decreases Length of Stay in Patients Undergoing Mastectomy Plus Immediate Reconstruction SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID BREAST-CANCER SURGERY; 20-YEAR FOLLOW-UP; GENERAL-ANESTHESIA; RADICAL-MASTECTOMY; UNITED-STATES; CARCINOMA AB A prior study in patients undergoing breast surgery with and without the use of paravertebral blocks (PVB) found no significant difference in patient length of stay (LOS). However, patients undergoing bilateral procedures and those undergoing immediate reconstructions were excluded. We sought to determine if the use of PVB in patients undergoing unilateral or bilateral mastectomy plus immediate reconstruction decreases patient LOS. We undertook a retrospective review of patients who had mastectomies with immediate reconstructions with and without the use of preoperative PVB. Outcomes including LOS, postoperative nausea and vomiting, and time to oral narcotics were compared between groups. Mean LOS for the PVB group was 42 h. This was significantly less than the mean LOS of 47 h for the nonblock group (p = .0015). The significantly lower LOS for the PVB group was true for patients undergoing bilateral procedures (p = .045), unilateral procedures (p = .0031), tissue expander placement (p = .0114), and immediate implant placement (p = .037). Mean time to conversion to oral narcotics was significantly shorter in the PVB group (15 h) compared with the nonblock group (20 h) (p < .001). The incidence of postoperative nausea in the PVB group (42.8 %) was also significantly less than in the nonblock group (54.7 %) (p = .031). The routine use of preoperative PVB in patients undergoing mastectomy plus immediate reconstruction significantly decreased patient LOS. In addition to improved pain control from the block itself, quicker conversion to oral narcotics because of less postoperative nausea likely contributed to a decreased LOS. C1 [Coopey, Suzanne B.; Specht, Michelle C.; Warren, Lisa; Smith, Barbara L.; Winograd, Jonathan M.; Fleischmann, Katharine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Coopey, SB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM scoopey@partners.org NR 19 TC 12 Z9 12 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 IS 4 BP 1282 EP 1286 DI 10.1245/s10434-012-2678-7 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 109TV UT WOS:000316392600033 PM 23064793 ER PT J AU Santamaria-Barria, JA Boland, GM Yeap, BY Nardi, V Dias-Santagata, D Cusack, JC AF Santamaria-Barria, Juan A. Boland, Genevieve M. Yeap, Beow Y. Nardi, Valentina Dias-Santagata, Dora Cusack, James C., Jr. TI Merkel Cell Carcinoma: 30-Year Experience from a Single Institution SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SENTINEL LYMPH-NODE; TRABECULAR CARCINOMA; RADIATION-THERAPY; CASE SERIES; SYNCHRONOUS CARBOPLATIN/ETOPOSIDE; MULTIMODALITY MANAGEMENT; ADJUVANT RADIOTHERAPY; CYTOKERATIN 20; SKIN; POLYOMAVIRUS AB Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Few single-institution series have been reported. Review of MCC patients treated at our institution between 1980 and 2010. Patient, tumor, and treatment variables were analyzed to determine MCC-specific outcomes. We identified 161 patients with MCC. There was a 2.5-fold increase in cases over the last decade. Median length of follow-up was 36 months. Stage at diagnosis was I in 35 %, II in 21 %, IIIa in 12 %, IIIb in 23 %, and IV in 9 %. The 5-year MCC-specific survival rates were 87, 63, 42, and 0 % for stages I, II, III, and IV, respectively. Death from the disease occurred in 10 % of patients with T1 and in 50 % with larger lesions. One-third of patients presented with nodal disease. Sentinel lymph node biopsy (SLNB) identified micrometastases in 9 out of 27 (33 %) early-stage patients. Recurrence developed in 56 % of SLNB-positive and 39 % of SLNB-negative patients. Half of patients recurred after a median time of 9 months. Proportions of first recurrence location were distant (52 %), nodal (27 %), and local (21 %). Adjuvant treatments did not improve recurrence or survival rates. One-third of patients died of the disease. SLNB identifies micrometastasis in one-third of early-stage patients. Negative SLNB may predict for improved but not necessarily favorable outcome. Initial tumor size and clinical nodal disease predict for poor outcome. High recurrence rates warrant the development of more effective adjuvant therapies, and better markers of recurrence and treatment response for MCC are needed. C1 [Santamaria-Barria, Juan A.; Boland, Genevieve M.; Cusack, James C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Nardi, Valentina; Dias-Santagata, Dora] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Santamaria-Barria, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. EM jcusack@partners.org NR 63 TC 24 Z9 24 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2013 VL 20 IS 4 BP 1365 EP 1373 DI 10.1245/s10434-012-2779-3 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 109TV UT WOS:000316392600046 PM 23208132 ER PT J AU Lima, XT Alora-Palli, MB Kimball, AB Kay, J AF Lima, Xinaida Taligare Alora-Palli, Maria Beatrice Kimball, Alexandra Boer Kay, Jonathan TI Validation of a Screening Instrument for Nephrogenic Systemic Fibrosis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID CONTRAST AGENT; RENAL-FAILURE; GADOLINIUM; DERMOPATHY; ASSOCIATION; DEPOSITION; SKIN AB Objective To develop and pilot test a screening tool to identify cases of nephrogenic systemic fibrosis (NSF) among patients exposed to gadolinium-containing contrast agents. Methods Sixty English-speaking subjects were enrolled: 10 subjects diagnosed as having NSF, 10 subjects with other fibrosing skin diseases, 20 subjects with nonfibrosing skin diseases, and 20 subjects without a skin disease. Subjects answered a questionnaire with 8 closed-ended (yes/no) questions focusing on cutaneous and musculoskeletal manifestations of NSF. The subjects were evaluated by a dermatologist for the presence of clinical signs of NSF. We compared the number of affirmative responses in the NSF group to those in the other groups, and the optimal cutoff that would differentiate groups was calculated. Discrimination, positive and negative predictive values, and internal consistency were also assessed. Results Subjects in the NSF group tended to provide more affirmative answers. Using a cutoff of 3 affirmative responses yields a sensitivity of 90% and a specificity of 70%, with an area under the curve of 0.85, indicating good discrimination. Sensitivity analysis using modified control group or weighted scores exhibited only slightly better discriminatory power. The positive predictive value of the questionnaire ranged from 0.3% to 39.7%, and its negative predictive values ranged from 97% to >99% with the different proposed prevalence estimates. The instrument had high internal consistency. Conclusion This pilot study demonstrates that this questionnaire has both high internal consistency and good discriminatory ability. Thus, it may be used to screen populations for NSF. C1 [Lima, Xinaida Taligare; Alora-Palli, Maria Beatrice; Kimball, Alexandra Boer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kay, Jonathan] UMass Mem Med Ctr, Worcester, MA 01605 USA. [Kay, Jonathan] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Kay, J (reprint author), UMass Mem Med Ctr, Rheumatol Ctr, 119 Belmont St, Worcester, MA 01605 USA. EM jonathan.kay@umassmemorial.org OI Kay, Jonathan/0000-0002-8970-4260 NR 26 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2013 VL 65 IS 4 BP 637 EP 642 DI 10.1002/acr.21877 PG 6 WC Rheumatology SC Rheumatology GA 116UI UT WOS:000316908100020 PM 23097320 ER PT J AU Conway, KL Kuballa, P Khor, B Zhang, M Shi, HN Virgin, HW Xavier, RJ AF Conway, Kara L. Kuballa, Petric Khor, Bernard Zhang, Mei Shi, Hai Ning Virgin, Herbert W. Xavier, Ramnik J. TI ATG5 regulates plasma cell differentiation SO AUTOPHAGY LA English DT Article DE ATG5; B lymphocytes; antibody secretion; immunity; plasma cell differentiation ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; UNFOLDED PROTEIN RESPONSE; INTESTINAL PANETH CELLS; AUTOPHAGY GENE ATG5; TRANSCRIPTION FACTOR; CROHN-DISEASE; B-CELLS; INFLAMMATION; EXPRESSION; BLIMP-1 AB Autophagy is a conserved homeostatic process in which cytoplasmic contents are degraded and recycled. Two ubiquitin-like conjugation pathways are required for the generation of autophagosomes, and ATG5 is necessary for both of these processes. Studies of mice deficient in ATG5 reveal a key role for autophagy in T lymphocyte function, as well as in B cell development and B-1a B cell maintenance. However, the role of autophagy genes in B cell function and antibody production has not been described. Using mice in which Atg5 is conditionally deleted in B lymphocytes, we showed here that this autophagy gene is essential for plasma cell homeostasis. In the absence of B cell ATG5 expression, antibody responses were significantly diminished during antigen-specific immunization, parasitic infection and mucosal inflammation. Atg5-deficient B cells maintained the ability to produce immunoglobulin and undergo class-switch recombination, yet had impaired SDC1 expression, significantly decreased antibody secretion in response to toll-like receptor ligands, and an inability to upregulate plasma cell transcription factors. These results build upon previous data demonstrating a role for ATG5 in early B cell development, illustrating its importance in late B cell activation and subsequent plasma cell differentiation. C1 [Conway, Kara L.; Kuballa, Petric; Khor, Bernard; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Conway, Kara L.; Kuballa, Petric; Khor, Bernard; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Conway, Kara L.; Kuballa, Petric; Khor, Bernard; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Conway, Kara L.; Kuballa, Petric; Khor, Bernard; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Khor, Bernard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv, Boston, MA USA. [Zhang, Mei; Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Zhang, Mei; Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. EM xavier@molbio.mgh.harvard.edu OI Khor, Bernard/0000-0003-4689-5092 FU National Institutes of Health [DK043351, DK083756, DK086502, DK060049]; CCFA Genetics Initiative Grant FX We acknowledge Noboru Mizushima (Tokyo Medical and Dental University, Tokyo, Japan) for providing Atg5flox/flox mice and WT and atg5-/- MEFs. We also acknowledge Natalia Nedelsky for review of the manuscript and helpful discussions. This work was supported by the National Institutes of Health Grants DK043351, DK083756, DK086502 and DK060049 (to R.J.X.), and CCFA Genetics Initiative Grant (to R.J.X./H.W.V.). NR 47 TC 44 Z9 45 U1 3 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR PY 2013 VL 9 IS 4 BP 528 EP 537 DI 10.4161/auto.23484 PG 10 WC Cell Biology SC Cell Biology GA 114HR UT WOS:000316732200007 PM 23327930 ER PT J AU Nunes, P Ernandez, T Roth, I Qiao, XM Strebel, D Bouley, R Charollais, A Ramadori, P Foti, M Meda, P Feraille, E Brown, D Hasler, U AF Nunes, Paula Ernandez, Thomas Roth, Isabelle Qiao, Xiaomu Strebel, Deborah Bouley, Richard Charollais, Anne Ramadori, Pierluigi Foti, Michelangelo Meda, Paolo Feraille, Eric Brown, Dennis Hasler, Udo TI Hypertonic stress promotes autophagy and microtubule-dependent autophagosomal clusters SO AUTOPHAGY LA English DT Article DE ATG12; Golgi apparatus; MAP1LC3/LC3; MAPRE1/EB1; MTOC; SQSTM1/p62; apoptosis; autophagy; dynein; lysosome; microtubule; osmotic stress; proteasome; rapamycin; tubulin; ubiquitin ID DUCT PRINCIPAL CELLS; COATED PIT FORMATION; PROTEIN AGGREGATION; ENDOPLASMIC-RETICULUM; POTASSIUM-DEPLETION; SELECTIVE AUTOPHAGY; MAMMALIAN AUTOPHAGY; ACTIN CYTOSKELETON; EPITHELIAL-CELLS; GOLGI-APPARATUS AB Osmotic homeostasis is fundamental for most cells, which face recurrent alterations of environmental osmolality that challenge cell viability. Protein damage is a consequence of hypertonic stress, but whether autophagy contributes to the osmoprotective response is unknown. Here, we investigated the possible implications of autophagy and microtubule organization on the response to hypertonic stress. We show that hypertonicity rapidly induced long-lived protein degradation, LC3-II generation and Ptdlns3K-dependent formation of LC3- and ATG12-positive puncta. Lysosomotropic agents chloroquine and bafilomycin A 1, but not nutrient deprivation or rapamycin treatment, further increased LC3-II generation, as well as ATG12-positive puncta, indicating that hypertonic stress increases autophagic flux. Autophagy induction upon hypertonic stress enhanced cell survival since cell death was increased by ATG12 siRNA-mediated knockdown and reduced by rapamycin. We additionally showed that hypertonicity induces fast reorganization of microtubule networks, which is associated with strong reorganization of microtubules at centrosomes and fragmentation of Golgi ribbons. Microtubule remodeling was associated with pericentrosomal clustering of ATG12-positive autolysosomes that colocalized with SQSTM1/p62 and ubiquitin, indicating that autophagy induced by hypertonic stress is at least partly selective. Efficient autophagy by hypertonic stress required microtubule remodeling and was DYNC/dynein-dependent as autophagosome clustering was enhanced by paclitaxel-induced microtubule stabilization and was reduced by nocodazole- induced tubulin depolymerization as well as chemical (EHNA) or genetic [DCTN2/dynactin 2 (p50) overexpression] interference of DYNC activity. The data document a general and hitherto overlooked mechanism, where autophagy and microtubule remodeling play prominent roles in the osmoprotective response. C1 [Nunes, Paula; Ernandez, Thomas; Roth, Isabelle; Qiao, Xiaomu; Strebel, Deborah; Charollais, Anne; Ramadori, Pierluigi; Foti, Michelangelo; Meda, Paolo; Feraille, Eric; Hasler, Udo] Univ Geneva, Dept Cellular Physiol & Metab, Geneva, Switzerland. [Ernandez, Thomas; Roth, Isabelle; Qiao, Xiaomu; Strebel, Deborah; Feraille, Eric; Hasler, Udo] Univ Geneva, Dept Med Specialties, Serv Nephrol, Geneva, Switzerland. [Nunes, Paula; Bouley, Richard; Brown, Dennis; Hasler, Udo] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Nunes, Paula; Bouley, Richard; Brown, Dennis; Hasler, Udo] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Hasler, U (reprint author), Univ Geneva, Dept Cellular Physiol & Metab, Geneva, Switzerland. EM Udo.Hasler@unige.ch RI Nunes-Hasler, Paula/N-4337-2015 OI Nunes-Hasler, Paula/0000-0002-4598-685X FU Swiss National Science Foundation [3100A0_122559/1, 31003A_138408/1, IZ73ZO-127935, 310030_141162, CR3213_129987, 310000-120280/1]; Foundation Novartis pour la Recherche en Sciences Medico-Biologique; Fondation Ernest Boninchi; Fondation Schmidheiny; Amgen; Juvenile Diabetes Research Foundation [40-2011-11, 5-2012281]; European Union [BETAIMAGE 222980, BETATRAIN 289932, IMIDIA C2008-T7]; Fondation Schmidheiny grant; National Institutes of Health Grant [DK38452]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43351] FX This work was supported by a Swiss National Science Foundation Grants 3100A0_122559/1 and 31003A_138408/1 and grants from the Foundation Novartis pour la Recherche en Sciences Medico-Biologique, Fondation Ernest Boninchi, Fondation Schmidheiny and Amgen to U.H.; Swiss National Science Foundation Grants IZ73ZO-127935, 310030_141162, CR3213_129987, grants from the Juvenile Diabetes Research Foundation (40-2011-11, 5-2012281) and grants from the European Union (BETAIMAGE 222980, BETATRAIN 289932 and IMIDIA C2008-T7) to P.M.; a Swiss National Science Foundation Grant 310000-120280/1 to M.F.; a Fondation Schmidheiny grant to T.E. and a National Institutes of Health Grant DK38452 to R.B. and D.B. The microscopy core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43351). NR 94 TC 16 Z9 18 U1 3 U2 28 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR PY 2013 VL 9 IS 4 BP 550 EP 567 DI 10.4161/auto.23662 PG 18 WC Cell Biology SC Cell Biology GA 114HR UT WOS:000316732200009 PM 23380587 ER PT J AU Steele, JW Gandy, S AF Steele, John W. Gandy, Sam TI Latrepirdine (Dimebon (R)), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model SO AUTOPHAGY LA English DT Editorial Material DE Alzheimer; therapeutics; latrepirdine; dimebon; synuclein; macroautophagy; amyloid; lysosome; presenilin; neurodegeneration AB Alzheimer disease (AD) is a form of neurodegeneration that develops over the course of multiple decades and as a result of the accumulation of the pathogenic amyloid-beta (A beta) peptide, also known as A4. In late-stage AD, failure of autophagic clearance results in neuronal cell bodies that are almost entirely consumed by autophagic vacuoles (AVs). Previously, we have shown that the potential AD drug latrepirdine (aka Dimebon (R)), a Russian antihistamine that has shown mixed results in phase II clinical trials in AD, regulates metabolism of the amyloid-beta/A4 precursor protein (APP). In two Molecular Psychiatry papers in 2012, we sought to determine the mechanism through which latrepirdine regulates APP metabolism and to determine, using an Alzheimer mouse model, whether latrepirdine provides protection from the toxicity associated with the accumulation of A beta. In cultured cells, we provided evidence that latrepirdine stimulates MTOR- and ATG5-dependent autophagy, leading to the reduction of intracellular levels of APP metabolites, including A beta. Consistent with this finding, we found that chronic latrepirdine administration resulted in increased levels of the biomarkers thought to correlate with autophagy activation in the brains of TgCRND8 (APP K670M, N671L, V717F) or wild-type mice, and that treatment was associated with abrogation of behavioral deficit, reduction in A beta neuropathology, and prevention of autophagic failure among TgCRND8 mice. C1 [Steele, John W.] Rockefeller Univ, Elizabeth & Zachary Fisher Ctr Alzheimers Dis Res, New York, NY 10021 USA. [Steele, John W.] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, Ctr Cognit Hlth, New York, NY USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, Ctr Cognit Hlth, New York, NY 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, Bronx, NY USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, Ctr Cognit Hlth, New York, NY USA. EM samuel.gandy@mssm.edu NR 0 TC 39 Z9 42 U1 1 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR PY 2013 VL 9 IS 4 BP 617 EP 618 DI 10.4161/auto.23487 PG 2 WC Cell Biology SC Cell Biology GA 114HR UT WOS:000316732200018 PM 23380933 ER PT J AU Purcell, SM AF Purcell, Shaun M. TI Antidepressant Response and Polygenes SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 [Purcell, Shaun M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Purcell, Shaun M.] Broad Inst, Cambridge, MA USA. RP Purcell, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM shaun.purcell@mssm.edu NR 6 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2013 VL 73 IS 7 BP 600 EP 601 DI 10.1016/j.biopsych.2013.01.023 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 113RL UT WOS:000316685400004 PM 23497743 ER PT J AU Hek, K Demirkan, A Lahti, J Terracciano, A Teumer, A Cornelis, MC Amin, N Bakshis, E Baumert, J Ding, JZ Liu, YM Marciante, K Meirelles, O Nalls, MA Sun, YV Vogelzangs, N Yu, L Bandinelli, S Benjamin, EJ Bennett, DA Boomsma, D Cannas, A Coker, LH de Geus, E De Jager, PL Diez-Roux, AV Purcell, S Hu, FB Rimm, EB Hunter, DJ Jensen, MK Curhan, G Rice, K Penman, AD Rotter, JI Sotoodehnia, N Emeny, R Eriksson, JG Evans, DA Ferrucci, L Fornage, M Gudnason, V Hofman, A Illig, T Kardia, S Kelly-Hayes, M Koenen, K Kraft, P Kuningas, M Massaro, JM Melzer, D Mulas, A Mulder, CL Murray, A Oostra, BA Palotie, A Penninx, B Petersmann, A Pilling, LC Psaty, B Rawal, R Reiman, EM Schulz, A Shulman, JM Singleton, AB Smith, AV Sutin, AR Uitterlinden, AG Volzke, H Widen, E Yaffe, K Zonderman, AB Cucca, F Harris, T Ladwig, KH Llewellyn, DJ Raikkonen, K Tanaka, T van Duijn, CM Grabe, HJ Launer, LJ Lunetta, KL Mosley, TH Newman, AB Tiemeier, H Murabito, J AF Hek, Karin Demirkan, Ayse Lahti, Jari Terracciano, Antonio Teumer, Alexander Cornelis, Marilyn C. Amin, Najaf Bakshis, Erin Baumert, Jens Ding, Jingzhong Liu, Yongmei Marciante, Kristin Meirelles, Osorio Nalls, Michael A. Sun, Yan V. Vogelzangs, Nicole Yu, Lei Bandinelli, Stefania Benjamin, Emelia J. Bennett, David A. Boomsma, Dorret Cannas, Alessandra Coker, Laura H. de Geus, Eco De Jager, Philip L. Diez-Roux, Ana V. Purcell, Shaun Hu, Frank B. Rimm, Eric B. Hunter, David J. Jensen, Majken K. Curhan, Gary Rice, Kenneth Penman, Alan D. Rotter, Jerome I. Sotoodehnia, Nona Emeny, Rebecca Eriksson, Johan G. Evans, Denis A. Ferrucci, Luigi Fornage, Myriam Gudnason, Vilmundur Hofman, Albert Illig, Thomas Kardia, Sharon Kelly-Hayes, Margaret Koenen, Karestan Kraft, Peter Kuningas, Maris Massaro, Joseph M. Melzer, David Mulas, Antonella Mulder, Cornelis L. Murray, Anna Oostra, Ben A. Palotie, Aarno Penninx, Brenda Petersmann, Astrid Pilling, Luke C. Psaty, Bruce Rawal, Rajesh Reiman, Eric M. Schulz, Andrea Shulman, Joshua M. Singleton, Andrew B. Smith, Albert V. Sutin, Angelina R. Uitterlinden, Andre G. Voelzke, Henry Widen, Elisabeth Yaffe, Kristine Zonderman, Alan B. Cucca, Francesco Harris, Tamara Ladwig, Karl-Heinz Llewellyn, David J. Raikkonen, Katri Tanaka, Toshiko van Duijn, Cornelia M. Grabe, Hans J. Launer, Lenore J. Lunetta, Kathryn L. Mosley, Thomas H., Jr. Newman, Anne B. Tiemeier, Henning Murabito, Joanne TI A Genome-Wide Association Study of Depressive Symptoms SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Center for Epidemiologic Studies Depression Scale; CHARGE consortium; depression; depressive symptoms; genetics; genome-wide association study; meta-analysis ID MAJOR DEPRESSION; CES-D; ATHEROSCLEROSIS RISK; VITAL EXHAUSTION; LIFE EVENTS; POPULATION; DISORDER; GENE; METAANALYSIS; LINKAGE AB Background: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 x 10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 x 10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 x 10(-3)). This 5q21 region reached genome-wide significance (p = 4.78 x 10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. C1 [Hek, Karin; Mulder, Cornelis L.; Tiemeier, Henning] Erasmus MC, Res Ctr O3, Dept Psychiat, NL-3000 CA Rotterdam, Netherlands. [Hek, Karin; Hofman, Albert; Kuningas, Maris; Uitterlinden, Andre G.; Tiemeier, Henning] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Teumer, Alexander] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Cornelis, Marilyn C.; Hu, Frank B.; Rimm, Eric B.; Jensen, Majken K.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Bakshis, Erin; Diez-Roux, Ana V.; Kardia, Sharon] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Baumert, Jens; Emeny, Rebecca; Ladwig, Karl-Heinz] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Ding, Jingzhong] Wake Forest Univ, Dept Internal Med, Div Geriatr, Winston Salem, NC 27109 USA. [Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Marciante, Kristin] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Terracciano, Antonio; Meirelles, Osorio; Sutin, Angelina R.] NIA, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Sun, Yan V.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Vogelzangs, Nicole; Penninx, Brenda] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Vogelzangs, Nicole; Penninx, Brenda] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Bandinelli, Stefania] Geriatr Unit Azienda Sanitaria Firenze, Florence, Italy. [Benjamin, Emelia J.; Kelly-Hayes, Margaret; Massaro, Joseph M.; Lunetta, Kathryn L.; Murabito, Joanne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med & Publ Hlth, Sect Cardiol & Prevent Med, Dept Med, Boston, MA 02215 USA. [Boomsma, Dorret; de Geus, Eco] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Cannas, Alessandra; Mulas, Antonella] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Coker, Laura H.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp,Program Translat NeuroPsych, Boston, MA 02115 USA. [Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Broad Inst, Cambridge, MA USA. [Hu, Frank B.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Penman, Alan D.] Univ Mississippi, Med Ctr, Ctr Biostat, Jackson, MS 39216 USA. [Penman, Alan D.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Eriksson, Johan G.] Univ Helsinki, Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Dept Internal Med, Chicago, IL 60612 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA. [Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Tiemeier, Henning] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands. [Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Kelly-Hayes, Margaret] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Koenen, Karestan] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA. [Melzer, David; Pilling, Luke C.; Llewellyn, David J.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [Murray, Anna] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter, Devon, England. [Mulder, Cornelis L.] Erasmus MC, Mental Hlth Ctr BavoEuropoort, NL-3000 CA Rotterdam, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. [Palotie, Aarno] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge, England. [Palotie, Aarno; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. Univ Cent Hosp, Helsinki, Finland. [Palotie, Aarno] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA. [Penninx, Brenda] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Penninx, Brenda] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Petersmann, Astrid] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Psaty, Bruce] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rawal, Rajesh] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Reiman, Eric M.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Schulz, Andrea; Grabe, Hans J.] Univ Med Greifswald, Helios Hosp, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, Kopavogur, Iceland. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Harris, Tamara; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Murabito, Joanne] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Curhan, Gary] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Dept Med, Reykjavik, Iceland. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Terracciano, Antonio; Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA. [Demirkan, Ayse; Amin, Najaf; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Demirkan, Ayse; Amin, Najaf; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Genet Epidemiol Unit, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. [Shulman, Joshua M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Shulman, Joshua M.] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA. RP Tiemeier, H (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM h.tiemeier@erasmusmc.nl RI Smith, Albert/K-5150-2015; Pilling, Luke/E-4917-2013; terracciano, antonio/B-1884-2008; Singleton, Andrew/C-3010-2009; Ladwig, Karl-Heinz/B-5351-2014; Newman, Anne/C-6408-2013; Emeny, Rebecca/I-1100-2014; Gudnason, Vilmundur/K-6885-2015; de Geus, Eco/M-9318-2015; OI Zonderman, Alan B/0000-0002-6523-4778; Ware, Erin/0000-0003-4731-8158; Lahti, Jari/0000-0002-4310-5297; Raikkonen, Katri/0000-0003-3124-3470; Murray, Anna/0000-0002-2351-2522; Melzer, David/0000-0002-0170-3838; Tiemeier, Henning/0000-0002-4395-1397; Benjamin, Emelia/0000-0003-4076-2336; Eriksson, Johan/0000-0002-2516-2060; Smith, Albert/0000-0003-1942-5845; Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812; Lunetta, Kathryn/0000-0002-9268-810X; Pilling, Luke/0000-0002-3332-8454; Ladwig, Karl-Heinz/0000-0003-0710-1720; Newman, Anne/0000-0002-0106-1150; Emeny, Rebecca/0000-0002-8780-5439; Gudnason, Vilmundur/0000-0001-5696-0084; de Geus, Eco/0000-0001-6022-2666; Mulas, Antonella/0000-0002-6856-1483 FU Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium; National Institutes of Health (NIH) [N01-AG-12100, HHSN268200625226C, UL1RR025005, HHSN268200782096C, R01 MH086498, CA65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233]; NIA; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL087641, R01-HL093029, R01-HL70825]; National Human Genome Research Institute [U01-HG004402]; NIH Roadmap for Medical Research; NIH, National Institute on Aging [NO1-AG-1-2109]; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756, N01-HC-25195, N02-HL-6-4278, N01-HC-65226]; NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, R01AG15819, R01AG17917, K08AG34290, P30AG10161, R01AG30146]; Clinical and Translational Science Institute [UL1RR033176]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; European Community; European Network for Genetic and Genomic Epidemiology Consortium [HEALTHF-4-2007- 201413]; European Special Populations Research Network; European Commission [018947, LSHG-CT-2006-01947]; Netherlands Organisation for Scientific Research, Erasmus MC; Centre for Medical Systems Biology; Netherlands Brain Foundation (HersenStichting Nederland); Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; Academy of Finland; Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of Helsinki; European Science Foundation (EUROSTRESS); Ministry of Education; Ahokas Foundation; Emil Aaltonen Foundation; Juho Vainio Foundation; Wellcome Trust [WT098051]; Italian Ministry of Health [ICS 110.1RS97.71]; U.S. National Institute on Aging [N01]AG]916413, N01]AG]821336, 263 MD 9164 13, 263 MD 821336]; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research; Munich Center of Health Sciences as part of Ludwig-Maximilians-University; Netherlands Organisation of Scientific Research Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research [050-060-810]; Erasmus MC; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (Directorate-General XII); Municipality of Rotterdam; Vidi Grant of Netherlands Organization for the Health Research and Development [2009-017.106.370]; BavoEuropoort; German Bundesministerium fur Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; Translational Genomics Research Institute; Burroughs Wellcome Fund; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; German Research Foundation (DFG) [GR 1912/5-1]; Federal Ministry of Education and Research Germany; Humboldt Foundation; German Research Foundation; Lundbeck; Janssen-Cilag; Eli Lilly; Novartis; AstraZeneca; SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health; Sanofi-Aventis; Biotronik; [R01-AG29451]; [N01-HC-95159]; [N01-HC-95169]; [UL1-RR-024156]; [R01 HL101161] FX We acknowledge the essential role of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium in development and support of this manuscript. Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium members include the Netherland's Rotterdam Study, the National Heart, Lung, and Blood Institute's (NHLBI) Framingham Heart Study, Cardiovascular Health Study, the NHLBI's Atherosclerosis Risk in Communities Study, and the National Institute on Aging's (NIA) Iceland Age, Gene/Environment Susceptibility Study.; The Age, Gene/Environment Susceptibility Reykjavik Study has been funded by National Institutes of Health (NIH) contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament).; The Atherosclerosis Risk in Communities Study research is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 and Grants R01-HL087641, R01-HL093029, and R01-HL70825; National Human Genome Research Institute contract U01-HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the Atherosclerosis Risk in Communities Study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; The Baltimore Longitudinal Study of Aging research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.; This Cardiovascular Health Study research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI Grants HL080295, HL075366, HL087652, and HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported, in part, by Clinical and Translational Science Institute Grant UL1RR033176 to the Cedars-Sinai General Clinical Research Center Genotyping core, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK063491 to the Southern California Diabetes Endocrinology Research Center, and the Governors' Chair in Medical Genetics (JIR).; The Erasmus Rucphen Family (ERF) research was supported through funds from The European Community's Seventh Framework Programme (FP7/2007-2013), European Network for Genetic and Genomic Epidemiology Consortium, Grant agreement HEALTHF-4-2007- 201413.; The genotyping for the ERF study was supported by European Special Populations Research Network and the European Commission FP6 STRP Grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by Grants from the Netherlands Organisation for Scientific Research, Erasmus MC, the Centre for Medical Systems Biology, and the Netherlands Brain Foundation (HersenStichting Nederland). We are grateful to all participating individuals and their relatives, general practitioners, and neurologists for their contributions and to P. Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and P. Snijders for his help in data collection.; Framingham Heart Study: The phenotype-genotype association analyses were supported by R01-AG29451. "This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center.''; Helsinki Birth Cohort Study has been supported by Grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, European Science Foundation (EUROSTRESS), Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation, and Wellcome Trust (Grant number WT098051). We thank all study participants, as well as everybody involved in the Helsinki Birth Cohort Study.; The Health, Aging and Body Composition research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA Grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research. Center for Inherited Disease Research is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported, in part, by the Intramural Research Program of the NIH, National Institute on Aging. Dr. Yaffe is supported by NIH Grant R01 MH086498.; The Invechhiare in Chianti Study was supported as a targeted project (ICS 110.1RS97.71) by the Italian Ministry of Health, by the U.S. National Institute on Aging (Contracts N01]AG]916413, N01] AG] 821336, 263 MD 9164 13, and 263 MD 821336), and, in part, by the Intramural Research Program, National Institute on Aging, National Institutes of Health.; The Multi-Ethnic Study of Atherosclerosis (MESA) SNP Health Association Resource project is conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159 through N01-HC-95169 and UL1-RR-024156. Funding for genotyping was provided by NHLBI Contract N02-HL-6-4278 and N01-HC-65226. Funding for this project was also provided by #R01 HL101161.; The Monitoring of Trends and Determinants of Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by Grants from the German Federal Ministry of Education and Research. Furthermore, the research was supported within the Munich Center of Health Sciences as part of Ludwig-Maximilians-University.; The Nurses' Health Studies are supported by NIH Grants CA 65725, CA87969 (National Cancer Institute), CA49449, CA67262, CA50385, and 5UO1CA098233.; The generation and management of genome-wide association study genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research Investments (number 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015), the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research project number 050-060-810. The Rotterdam Study is funded by Erasmus MC and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (Directorate-General XII), and the Municipality of Rotterdam. Henning Tiemeier was supported by the Vidi Grant of Netherlands Organization for the Health Research and Development (2009-017.106.370). Karin Hek was supported by a Grant from BavoEuropoort. We are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, and Marjolein Peters for their help in creating the genome-wide association study database, and Dr. Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data. We thank Dr. Karol Estrada, Dr. Fernando Rivadeneira, Dr. Tobias A. Knoch, Anis Abuseiris, Luc V. de Zeeuw, and Rob de Graaf (Erasmus MC Rotterdam, The Netherlands) for their help in creating GRIMP and BigGRID, MediGRID, and Services@MediGRID/D-Grid (funded by the German Bundesministerium fur Forschung und Technology; Grants 01 AK 803 A-H, 01 IG 07015 G) for access to their grid computing resources.; The Rush Memory and Aging Project is supported by NIA Grants R01AG15819, R01AG17917, and K08AG34290 and the Translational Genomics Research Institute. The Rush Religious Orders Study is supported by NIA Grants P30AG10161, R01AG15819, R01AG30146, and K08AG34290 and the Translational Genomics Research Institute. We thank the study participants and the staff of the Rush Alzheimer's Disease Center. Joshua Shulman was additionally supported by a Career Award for Medical Scientists from Burroughs Wellcome Fund.; The SardiNIA research was supported, in part, by the Intramural Research Program of the NIH, National Institute on Aging. Funding was also provided through contract NO1-AG-1-2109 from the NIA-NIH.; Study of Health in Pomerania is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grant no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (Grant no. 03ZIK012) and a joint Grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the Center of Knowledge Interchange program of the Siemens AG. This work was also funded by the German Research Foundation (DFG: GR 1912/5-1), Federal Ministry of Education and Research Germany, the Humboldt Foundation, and the German Research Foundation.; Study of Health in Pomerania: To HJG German Research Foundation; Federal Ministry of Education and Research Germany; speakers honoraria from Bristol-Myers Squibb, Eli Lilly, Novartis, Eisai, Wyeth, Pfizer, Boehringer Ingelheim, and Servier; and travel funds from Lundbeck, Janssen-Cilag, Eli Lilly, Novartis, AstraZeneca, and SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health. To HV research grants by Sanofi-Aventis, Biotronik, the Humboldt Foundation, the Federal Ministry of Education and Research (Germany), and the German Research Foundation. All other authors reported no biomedical financial interests or potential conflicts of interest. NR 75 TC 60 Z9 61 U1 1 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2013 VL 73 IS 7 BP 667 EP 678 DI 10.1016/j.biopsych.2012.09.033 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 113RL UT WOS:000316685400013 PM 23290196 ER PT J AU Leussis, MP Berry-Scott, EM Saito, M Jhuang, H de Haan, G Alkan, O Luce, CJ Madison, JM Sklar, P Serre, T Root, DE Petryshen, TL AF Leussis, Melanie P. Berry-Scott, Erin M. Saito, Mai Jhuang, Hueihan de Haan, Georgius Alkan, Ozan Luce, Catherine J. Madison, Jon M. Sklar, Pamela Serre, Thomas Root, David E. Petryshen, Tracey L. TI The ANK3 Bipolar Disorder Gene Regulates Psychiatric-Related Behaviors That Are Modulated by Lithium and Stress SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Ankyrin G; dentate gyrus; GWAS; mouse; RNA interference; schizophrenia ID DENTATE GYRUS; SYNAPTIC PLASTICITY; ANXIETY; ABNORMALITIES; HIPPOCAMPAL; ANKYRIN(G); DEPRESSION; SEGMENTS; CHANNELS; CACNA1C AB Background: Ankyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown. Methods: To gain insight into the potential disease relevance of ANK3, we examined the function of mouse Ank3 in the regulation of psychiatric-related behaviors using genetic, neurobiological, pharmacological, and gene-environment interaction (G x E) approaches. Ank3 expression was reduced in mouse brain either by viral-mediated RNA interference or through disruption of brain-specific Ank3 in a heterozygous knockout mouse. Results: RNA interference of Ank3 in hippocampus dentate gyrus induced a highly specific and consistent phenotype marked by decreased anxiety-related behaviors and increased activity during the light phase, which were attenuated by chronic treatment with the mood stabilizer lithium. Similar behavioral alterations of reduced anxiety and increased motivation for reward were also exhibited by Ank3+/- heterozygous mice compared with wild-type Ank3+/+ mice. Remarkably, the behavioral traits of Ank3+/- mice transitioned to depression-related features after chronic stress, a trigger of mood episodes in BD. Ank3+/- mice also exhibited elevated serum corticosterone, suggesting that reduced Ank3 expression is associated with elevated stress reactivity. Conclusions: This study defines a new role for Ank3 in the regulation of psychiatric-related behaviors and stress reactivity that lends support for its involvement in BD and establishes a general framework for determining the disease relevance of genes implicated by patient genome-wide association studies. C1 [Leussis, Melanie P.; Berry-Scott, Erin M.; Saito, Mai; de Haan, Georgius; Madison, Jon M.; Petryshen, Tracey L.] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Leussis, Melanie P.; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Leussis, Melanie P.; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Leussis, Melanie P.; Berry-Scott, Erin M.; Saito, Mai; de Haan, Georgius; Luce, Catherine J.; Madison, Jon M.; Petryshen, Tracey L.] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Jhuang, Hueihan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Alkan, Ozan; Root, David E.] Broad Inst Harvard & Massachusetts Inst Technol, RNA Interference Platform, Cambridge, MA USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Serre, Thomas] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. RP Petryshen, TL (reprint author), Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM petryshen@chgr.mgh.harvard.edu FU Stanley Medical Research Institute; RNAi Consortium; Massachusetts General Hospital Executive Committee on Research; McGovern Institute Neurotechnology Program; Robert J. and Nancy D. Carney Fund for Scientific Innovation; Bristol Myers Squibb; Pfizer FX Funding was provided by the Stanley Medical Research Institute (to JM, PS, TLP), The RNAi Consortium (to DER), the Massachusetts General Hospital Executive Committee on Research (to MPL), the McGovern Institute Neurotechnology Program (to TS), and the Robert J. and Nancy D. Carney Fund for Scientific Innovation (to TS).; Dr. Serre reports receiving research funding from Bristol Myers Squibb. Dr. Sklar reports having received a consultant fee from Pfizer and reports a patent on brain-derived neurotrophic factor and bipolar disorder. The other authors report no biomedical financial interests or potential conflicts of interest. NR 44 TC 26 Z9 27 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 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2013 VL 73 IS 7 BP 683 EP 690 DI 10.1016/j.biopsych.2012.10.016 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 113RL UT WOS:000316685400015 PM 23237312 ER PT J AU Lee, IS Spector, M AF Lee, In-Seop Spector, Myron TI Biomedical materials and 2013 SO BIOMEDICAL MATERIALS LA English DT Editorial Material C1 [Lee, In-Seop] Yonsei Univ, Seoul 120749, South Korea. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Lee, IS (reprint author), Yonsei Univ, Seoul 120749, South Korea. NR 3 TC 0 Z9 0 U1 1 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD APR PY 2013 VL 8 IS 2 AR 020201 DI 10.1088/1748-6041/8/2/020201 PG 1 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 114MS UT WOS:000316746100001 ER PT J AU Wang, TY Halaney, D Ho, D Feldman, MD Milner, TE AF Wang, Tianyi Halaney, David Ho, Derek Feldman, Marc D. Milner, Thomas E. TI Two-photon luminescence properties of gold nanorods SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID EXCITATION CROSS-SECTIONS; ASPECT RATIO; METAL NANOPARTICLES; CORONARY PLAQUE; IN-VITRO; PHOTOLUMINESCENCE; ABSORPTION; FIELD; ENHANCEMENT; SIMULATION AB Gold nanorods can be internalized by macrophages (an important early cellular marker in atherosclerosis and cancer) and used as an imaging contrast agent for macrophage targeting. Objective of this study is to compare two-photon luminescence (TPL) properties of four aspect ratios of gold nanorods with surface plasmon resonance at 700, 756, 844 and 1060 nm respectively. TPL from single nanorods and Rhodamine 6G particles was measured using a laser-scanning TPL microscope. Nanorod TPL emission spectrum was recorded by a spectrometer. Quadratic dependence of luminescence intensity on excitation power (confirming a TPL process) was observed below a threshold (e. g., <1.6 mW), followed by photobleaching at higher power levels. Dependence of nanorod TPL intensity on excitation wavelength indicated that the two-photon action cross section (TPACS) is plasmon-enhanced. Largest TPACS of a single nanorod (12271 GM) was substantially larger than a single Rhodamine 6G particle (25 GM) at 760 nm excitation. Characteristics of nanorod TPL emission spectrum can be explained by plasmon-enhanced interband transition of gold. Comparison results of TPL brightness, TPACS and emission spectrum of nanorods can guide selection of optimal contrast agent for selected imaging applications. (C) 2013 Optical Society of America C1 [Wang, Tianyi; Ho, Derek; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Halaney, David; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Halaney, David; Feldman, Marc D.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Wang, TY (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn C0800, Austin, TX 78712 USA. EM Tianyi.Wang@utexas.edu OI Halaney, David/0000-0003-4437-0516 FU VA Merit grant; Clayton Foundation for Biomedical Research; Janey and Dolph Briscoe Center for Cardiovascular Research; Cigarrora Endowed Professorship; Marion E. Forsman Professorship in Engineering; American Society for Laser Medicine and Surgery FX The authors would like to acknowledge the technical support from Nanopartz, Inc, Mr. John Alford from Andor Technology, PLC, and kind supply of the objective patent and model by Drs. Fabian F. Voigt and Fritjof Helmchen from University of Zurich. This work is supported by a VA Merit grant, the Clayton Foundation for Biomedical Research, Janey and Dolph Briscoe Center for Cardiovascular Research, a Cigarrora Endowed Professorship (M. D. F.), a Marion E. Forsman Professorship in Engineering (T. E. M.), and a travel grant from the American Society for Laser Medicine and Surgery (T. W.). NR 53 TC 23 Z9 25 U1 4 U2 94 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 2013 VL 4 IS 4 BP 584 EP 595 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 117GW UT WOS:000316942500011 PM 23577293 ER PT J AU Chung, A Bachmann, A Sancha, FG Collins, E Tabatabaei, S Muir, G Woo, H AF Chung, A. Bachmann, A. Gomez Sancha, F. Collins, E. Tabatabaei, S. Muir, G. Woo, H. TI Photoselective vaporisation of the prostate using the 180 W lithium triborate laser in the treatment of benign prostatic obstruction: an international multicenter experience SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the Urological-Society-of-Australia-and-New Zealand CY APR 13-16, 2013 CL Melbourne, AUSTRALIA SP Urol Soc Australia & New Zealand DE Prostatic hyperplasia; lasers; prostatectomy; transurethral resection of prostate; lower urinary tract symptoms C1 [Chung, A.; Woo, H.] Univ Sydney, Sydney Adventist Hosp Clin Sch, Sydney, NSW 2006, Australia. [Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Gomez Sancha, F.] ICUA Clin CEMTRO, Dept Urol, Madrid, Spain. [Collins, E.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Tabatabaei, S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Muir, G.] Kings Coll Hosp, Dept Urol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2013 VL 111 SU 1 SI SI MA 4 BP 14 EP 15 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 116XQ UT WOS:000316917000004 ER PT J AU Wong, S Miller, K Smith, MR Dearnaley, D Dogliott, L Egerdie, B Fizazi, K Kueppers, F De Oca, LM Morote, J Pavlik, I Sieber, P Tammel, TJ Van Poppel, H Wirth, M Ye, Z Braun, A AF Wong, S. Miller, K. Smith, M. R. Dearnaley, D. Dogliott, L. Egerdie, B. Fizazi, K. Kueppers, F. Montes De Oca, L. Morote, J. Pavlik, I. Sieber, P. Tammel, T. J. Van Poppel, H. Wirth, M. Ye, Z. Braun, A. TI Denosumab in men with non-metastatic castration-resistant prostate cancer (CRPC) and PSA doubling time (PSADT) <= 6 months - a post-hoc analysis of a randomised trial SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the Urological-Society-of-Australia-and-New Zealand CY APR 13-16, 2013 CL Melbourne, AUSTRALIA SP Urol Soc Australia & New Zealand C1 [Wong, S.] Western Hosp, Footscray, Vic, Australia. [Miller, K.] Charite, Berlin, Germany. [Smith, M. R.] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Dearnaley, D.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. [Dogliott, L.] Osped San Luigi Gonzaga, Orbassano, TO, Italy. [Egerdie, B.] Urol Associates, Urol Med Res, Kitchener, ON, Canada. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. [Kueppers, F.] Canterbury Urol Res Trust, Christchurch, New Zealand. [Montes De Oca, L.] Ctr Diagnost Urol, Buenos Aires, DF, Argentina. [Morote, J.] Hosp Valle De Hebron, Barcelona, Spain. [Pavlik, I.] Gen Teaching Hosp, Urol Clin, Prague, Czech Republic. [Pavlik, I.] Fac Med 1, Prague, Czech Republic. [Sieber, P.] Urol Associates Lancaster, Lancaster, PA USA. [Tammel, T. J.] Tampere Univ Hosp, Tampere, Finland. [Van Poppel, H.] Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. [Wirth, M.] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Ye, Z.; Braun, A.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2013 VL 111 SU 1 SI SI MA 51 BP 37 EP 38 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 116XQ UT WOS:000316917000047 ER PT J AU Saad, F Patrick, DJ Smith, M Cleeland, C Fallowfield, L Tombal, B Oudard, S Shore, N Marx, G Coleman, R Gomez-Veiga, F Damiao, R Zhou, Y Arellano, J Braun, A Qian, Y AF Saad, F. Patrick, D. J. Smith, M. Cleeland, C. Fallowfield, L. Tombal, B. Oudard, S. Shore, N. Marx, G. Coleman, R. Gomez-Veiga, F. Damiao, R. Zhou, Y. Arellano, J. Braun, A. Qian, Y. TI The impact of bone metastases on pain: post-hoc analysis of a phase III study of denosumab in men with non-metastatic Castration-Resistant Prostate Cancer (CRPC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the Urological-Society-of-Australia-and-New Zealand CY APR 13-16, 2013 CL Melbourne, AUSTRALIA SP Urol Soc Australia & New Zealand C1 [Saad, F.] Univ Montreal Hosp Ctr, CRCHUM, Montreal, PQ, Canada. [Patrick, D. J.] Univ Washington, Seattle, WA 98195 USA. [Smith, M.] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Cleeland, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Tombal, B.] Univ Sussex, SHORE C, Brighton, E Sussex, England. [Tombal, B.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. [Oudard, S.] Georges Pompidou Hosp, Paris, France. [Shore, N.] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Marx, G.] Sydney Adventist Hosp, Wahroonga, NSW, Australia. [Marx, G.] Univ Sydney, Sydney, NSW 2006, Australia. [Coleman, R.] Univ Sheffield, Weston Pk Hosp, Sheffield, S Yorkshire, England. [Gomez-Veiga, F.] Hosp Juan Canalejo, La Coruna, Spain. [Damiao, R.] Univ Estado Rio De Janeiro, Rio De Janeiro, Brazil. [Zhou, Y.; Arellano, J.; Braun, A.; Qian, Y.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2013 VL 111 SU 1 SI SI MA 52 BP 38 EP 38 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 116XQ UT WOS:000316917000048 ER PT J AU Glotzbecker, B Ho, VT Aldridge, J Kim, HT Horowitz, G Ritz, J Soiffer, R Avigan, D Rosenblatt, J AF Glotzbecker, B. Ho, V. T. Aldridge, J. Kim, H. T. Horowitz, G. Ritz, J. Soiffer, R. Avigan, D. Rosenblatt, J. TI Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD SO BONE MARROW TRANSPLANTATION LA English DT Article DE Vitamin D; GVHD; hematopoietic SCT ID BONE-MINERAL DENSITY; VITAMIN-D STATUS; VERSUS-HOST-DISEASE; LONG-TERM SURVIVORS; 1,25-DIHYDROXYVITAMIN D-3; DENDRITIC CELLS; MULTIPLE-SCLEROSIS; D DEFICIENCY; MARROW TRANSPLANTATION; LIVER-TRANSPLANTATION AB Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to have potent immunomodulatory effects. We performed a retrospective cohort analysis to evaluate whether monohydroxyvitamin D levels before allogeneic hematopoietic SCT (HSCT) correlate with the risk of GVHD. Fifty-three patients who underwent myeloablative HSCT were studied. Vitamin D levels were measured in serum samples obtained before HSCT. The median 25-hydroxyvitamin vitamin D level was 21.9 ng/mL (7.8-45.7). The cumulative incidence (CI) of grades II-IV acute GVHD at 100 days was 53.1% in patients with vitamin D<25, versus 33.3% in patients with vitamin D >= 25 ng/mL (P=0.13). The CI of chronic GVHD (cGVHD) at 2 years in patients with vitamin D<25 was 63.8%, compared with 23.8% in patients with vitamin D >= 25 ng/mL (P=0.009). Similarly, the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin D<25 compared with those with vitamin D >= 25 ng/mL (54.5% versus 14.3%, P=0.005). In a multivariable competing risk model, low pre-transplant vitamin D levels remained a significant factor associated with cGVHD (hazard ratio=5.26, P=0.02). Our results demonstrate that vitamin D deficiency before HSCT is associated with an increased risk of cGVHD. Bone Marrow Transplantation (2013) 48, 593-597; doi: 10.1038/bmt.2012.177; published online 24 September 2012 C1 [Glotzbecker, B.; Ho, V. T.; Aldridge, J.; Kim, H. T.; Ritz, J.; Soiffer, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Horowitz, G.] Beth Israel Deaconess Med Ctr, Dept Clin Chem, Boston, MA 02215 USA. [Avigan, D.; Rosenblatt, J.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Glotzbecker, B (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM brett_glotzbecker@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU Pasquarello Tissue Bank; NIH [CA142106, AI29530] FX This work was supported in part by the Pasquarello Tissue Bank and NIH grants CA142106 and AI29530. NR 50 TC 8 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2013 VL 48 IS 4 BP 593 EP 597 DI 10.1038/bmt.2012.177 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 118NP UT WOS:000317032500019 PM 23000654 ER PT J AU Chen, YB McDonough, S Chen, H Kennedy, J Illiano, C Attar, EC Ballen, KK Dey, BR McAfee, SL Jagasia, M Soiffer, R Spitzer, TR Ritz, J AF Chen, Y-B McDonough, S. Chen, H. Kennedy, J. Illiano, C. Attar, E. C. Ballen, K. K. Dey, B. R. McAfee, S. L. Jagasia, M. Soiffer, R. Spitzer, T. R. Ritz, J. TI Expression of alpha 4 beta 7 integrin on memory CD8(+) T cells at the presentation of acute intestinal GVHD SO BONE MARROW TRANSPLANTATION LA English DT Article DE intestinal GVHD; alpha 4 beta 7 integrin; lymphocyte trafficking ID VERSUS-HOST-DISEASE; L-SELECTIN; PEYERS PATCH; NATALIZUMAB; MIGRATION; THERAPY; COLITIS; NAIVE; SITE AB Acute intestinal GVHD remains a major source of morbidity after allogeneic hematopoietic cell transplantation (HCT). alpha 4 beta 7 integrin is a cell surface molecule that mediates lymphocyte trafficking to intestinal tissue. In this analysis, peripheral blood was collected at the time of presentation of symptoms of acute GVHD and before any treatment. In all, 45 samples were collected and divided into three groups on the basis of subsequent evaluation: intestinal GVHD (n = 15), skin GVHD (n = 20) and no GVHD (n = 10). Two patients developed intestinal GVHD after DLI. The no-GVHD group comprised 10 patients who presented with suspicious symptoms, but evaluation yielded other etiologies. Analysis by flow cytometry showed that intestinal GVHD patients had a significantly higher percentage of alpha 4 beta 7 integrin-expressing memory CD8(+) T cells (median 7.69%; lower and upper quartiles, 1.06% and 11.64%, respectively) compared with patients with skin GVHD (1.26%; 0.57% and 2.49%) and no GVHD (0.96%; 0.44% and 1.85%), P = 0.03. No differences were found in alpha 4 beta 7 expression in any CD4(+) T-cell subsets or naive CD8(+) T cells. This study adds to the evidence that alpha 4 beta 7 integrin is involved in lymphocyte trafficking in acute intestinal GVHD. Bone Marrow Transplantation (2013) 48, 598-603; doi: 10.1038/bmt.2012.191; published online 8 October 2012 C1 [Chen, Y-B; Kennedy, J.; Illiano, C.; Attar, E. C.; Ballen, K. K.; Dey, B. R.; McAfee, S. L.; Spitzer, T. R.; Ritz, J.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Div Bone Marrow Transplantat, Boston, MA 02114 USA. [McDonough, S.; Soiffer, R.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Chen, H.; Jagasia, M.] Vanderbilt Univ, Dept Biostat, Nashville, TN USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Dept Hematol & Oncol, Div Bone Marrow Transplantat, Cox 106,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU NIH [AI29530, HL070149]; Ted and Ellen Pasquarello Research Fund; Wernick Family Fund for Cancer Care; Rogers Family Foundation; Leukemia & Lymphoma Society; Millennium Pharmaceuticals, Inc. FX This research was supported in part by NIH grants AI29530 and HL070149, the Ted and Ellen Pasquarello Research Fund, the Wernick Family Fund for Cancer Care, the Rogers Family Foundation and the Leukemia & Lymphoma Society. This research was presented in abstract form at the American Society for Bone Marrow Transplantation (ASBMT) Tandem Meetings in San Diego, CA from 1 to 5 February 2012.; Dr Chen receives funding to conduct clinical research from Millennium Pharmaceuticals, Inc. The other authors declare no conflict of interest. NR 25 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2013 VL 48 IS 4 BP 598 EP 603 DI 10.1038/bmt.2012.191 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 118NP UT WOS:000317032500020 PM 23042495 ER PT J AU Park, ER Gareen, IF Jain, A Ostroff, JS Duan, FH Sicks, JD Rakowski, W Diefenbach, M Rigotti, NA AF Park, Elyse R. Gareen, Ilana F. Jain, Amanda Ostroff, Jamie S. Duan, Fenghai Sicks, JoRean D. Rakowski, William Diefenbach, Michael Rigotti, Nancy A. TI Examining whether lung screening changes risk perceptions: National Lung Screening Trial participants at 1-year follow-up SO CANCER LA English DT Article DE cancer; lung screening; risk perception; smoking ID COMPUTED-TOMOGRAPHY; SMOKING-CESSATION; UNITED-STATES; CIGARETTE-SMOKING; TEACHABLE MOMENT; CANCER-PATIENTS; PERCEIVED RISK; BEHAVIOR; SMOKERS; BLAME AB BACKGROUND: The National Lung Screening Trial (NLST) research team reported reduced lung cancer mortality among current and former smokers with a minimum 30 pack-year history who were screened with spiral computed tomography scans compared with chest x-rays. The objectives of the current study were to examine, at 1-year follow-up: 1) risk perceptions of lung cancer and smoking-related diseases and behavior change determinants, 2) whether changes in risk perceptions differed by baseline screening result; and 3) whether changes in risk perceptions affected smoking behavior. METHODS: A 25-item risk perception questionnaire was administered to a subset of participants at 8 American College of Radiology Imaging Network/NLST sites before initial and 1-year follow-up screens. Items assessed risk perceptions of lung cancer and smoking-related diseases, cognitive and emotional determinants of behavior change, and knowledge of smoking risks. RESULTS: Among 430 NLST participants (mean age, 61.0 years; 55.6% men; 91.9% white), half were current smokers at baseline. Overall, risk perceptions and associated cognitive and emotional determinants of behavior change did not change significantly from prescreen trial enrollment to 1-year follow-up and did not differ significantly by screening test result. Changes in risk perceptions were not associated with changes in smoking status (9.7% of participants quit, and 6.6% relapsed) at 1-year follow-up. CONCLUSIONS: Lung screening did not change participants' risk perceptions of lung cancer or smoking-related disease. A negative screening test, which was the most common screening result, did not appear to decrease risk perceptions nor provide false reassurance to smokers. Cancer 2013. (c) 2012 American Cancer Society. C1 [Park, Elyse R.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Park, Elyse R.; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Dept Med, Boston, MA USA. [Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gareen, Ilana F.; Jain, Amanda; Duan, Fenghai; Sicks, JoRean D.] Brown Univ, Sch Med, Ctr Stat Sci, Providence, RI 02912 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rakowski, William] Brown Univ, Dept Behav & Social Sci, Publ Hlth Program, Providence, RI 02912 USA. [Diefenbach, Michael] Mt Sinai Sch Med, Dept Urol, New York, NY USA. [Diefenbach, Michael] Mt Sinai Sch Med, Div Internal Med, New York, NY USA. RP Park, ER (reprint author), Mongan Inst Hlth Policy, 50 Staniford St,Room 907, Boston, MA 02114 USA. EM epark@partners.org RI Gareen, Ilana/I-2816-2014; Duan, Fenghai/J-3709-2014; OI Gareen, Ilana/0000-0002-0457-5595; Duan, Fenghai/0000-0002-5084-0070; Ostroff, Jamie/0000-0003-2671-5680 FU American Cancer Society's Mentored Research Scholar Award [MRSG-005-05-CPPB]; ACRIN/NLST Trial [U01 CA79778 S2]; NHLBI Midcareer Investigator Award in Patient-Oriented Research [K24-HL04440]; Nabi Biopharmaceuticals FX This project was funded by a grant from the American Cancer Society's Mentored Research Scholar Award (MRSG-005-05-CPPB), the ACRIN/NLST Trial (U01 CA79778 S2), and a NHLBI Midcareer Investigator Award in Patient-Oriented Research (#K24-HL04440).; Dr. Rigotti works as an unpaid consultant for Pfizer and Alere Wellbeing. She previously received funding from Nabi Biopharmaceuticals and royalties from work published in UptoDate. NR 35 TC 7 Z9 7 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2013 VL 119 IS 7 BP 1306 EP 1313 DI 10.1002/cncr.27925 PG 8 WC Oncology SC Oncology GA 115KU UT WOS:000316811900004 PM 23280348 ER PT J AU Merkow, RP Kmiecik, TE Bentrem, DJ Winchester, DP Stewart, AK Ko, CY Bilimoria, KY AF Merkow, Ryan P. Kmiecik, Thomas E. Bentrem, David J. Winchester, David P. Stewart, Andrew K. Ko, Clifford Y. Bilimoria, Karl Y. TI Effect of including cancer-specific variables on models examining short-term outcomes SO CANCER LA English DT Article DE colorectal cancer; outcomes; risk-adjustment; outcomes; American College of Surgeons National Surgical Quality Improvement Program; National Cancer Data Base; cancer stage; neoadjuvant therapy ID SURGICAL QUALITY IMPROVEMENT; RISK PREDICTION MODELS; RECTAL-CANCER; ABDOMINOPERINEAL RESECTION; PREOPERATIVE RADIOTHERAPY; SURGERY; SAFETY; CARE; COMPLICATIONS; PROGRAM AB BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) generally has not collected cancer-specific variables. Because increasing numbers of studies are using ACS NSQIP data to study cancer surgery, the objectives of the current study were 1) to examine differences between existing ACS NSQIP variables and cancer registry variables, and 2) to determine whether the addition of cancer-specific variables improves modeling of short-term outcomes. METHODS: Data from patients in the ACS NSQIP and National Cancer Data Base (NCDB) who underwent colorectal resection for cancer were linked (2006-2008). By using regression methods, the relative importance of cancer staging and neoadjuvant therapy variables were assessed along with their effects on morbidity, serious morbidity, and mortality. RESULTS: From 146 hospitals, 11,405 patients were identified who underwent surgery for colorectal cancer (colon, 85%; rectum, 15%). The NCDB metastatic cancer variable and the ACS NSQIP disseminated cancer variables agreed marginally (Cohen kappa coefficient, 0.454). For mortality, only the ACS NSQIP disseminated cancer variable and the NCDB stage IV variable were identified as important predictors; whereas the variables stage I through III, tumor (T)-classification, and lymph node (N)-classification were not selected. Cancer stage variables were inconsistently important for serious morbidity (stage IV, T-classification), superficial surgical site infection (N-classification), venous thromboembolism (metastatic cancer), and pneumonia (T-classification). With respect to neoadjuvant therapy, ACS NSQIP and NCDB variables agreed moderately (kappa, 0.570) and predicted superficial surgical site infection, serious morbidity, and organ space surgical site infection. The model fit was similar regardless of the inclusion of stage and neoadjuvant therapy variables. CONCLUSIONS: Although advanced disease stage and neoadjuvant therapy variables were predictors of short-term outcomes, their inclusion did not improve the models. Cancer 2013. (c) 2012 American Cancer Society. C1 [Merkow, Ryan P.; Winchester, David P.; Stewart, Andrew K.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Kmiecik, Thomas E.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.; Kmiecik, Thomas E.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Northwestern Inst Comparat Effectiveness Res Onco, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado Denver, Dept Surg, Aurora, CO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 North St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU American Cancer Society; Agency for Healthcare Research and Quality; Northwestern Institute for Comparative Effectiveness Research in Oncology FX This study was supported by the American Cancer Society, the Agency for Healthcare Research and Quality, and the Northwestern Institute for Comparative Effectiveness Research in Oncology. NR 36 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2013 VL 119 IS 7 BP 1412 EP 1419 DI 10.1002/cncr.27891 PG 8 WC Oncology SC Oncology GA 115KU UT WOS:000316811900018 PM 23184472 ER PT J AU Armstrong, EJ Kwa, AT Yeo, KK Mahmud, E Javed, U Patel, M Shunk, KA MacGregor, JS Low, RI Rogers, JH AF Armstrong, Ehrin J. Kwa, Andrew T. Yeo, Khung Keong Mahmud, Ehtisham Javed, Usman Patel, Mitul Shunk, Kendrick A. MacGregor, John S. Low, Reginald I. Rogers, Jason H. TI Angiographically confirmed stent thrombosis in contemporary practice: Insights from intravascular ultrasound SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stent thrombosis; intravascular ultrasound; acute coronary syndrome (ACS); intravascular ultrasound (IVUS); thrombosis (THRM) ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; DRUG-ELUTING STENTS; IMPLANTATION; PREDICTORS; MALAPPOSITION; FRACTURE; IMPACT; DEPLOYMENT; OUTCOMES AB Objective: We hypothesized that patients presenting with stent thrombosis (ST) have a high prevalence of stent underexpansion and malapposition when assessed by intravascular ultrasound (IVUS). Background: IVUS can provide mechanistic insight into mechanical factors, including stent underexpansion, malapposition, and fracture that may predispose to ST. Methods: All consecutive cases of angiographically confirmed ST from a multicenter registry (from 2005 to 2010) were reviewed. All IVUS images were reviewed off-line for the presence of stent underexpansion, malapposition, and fracture. KaplanMeier analysis was used to determine whether use of IVUS at the time of ST was associated with long-term mortality and major adverse cardiovascular events. Results: IVUS was performed in 32 of 173 subjects with ST (18%). Stent underexpansion was present in 82% of cases and in all cases of early ST, with a mean stent expansion of 0.7 +/- 0.23 by MUSIC criteria. Stent malapposition was most frequently observed in very late ST (40%). In-hospital mortality was similar between subjects who had IVUS performed at the time of ST when compared with the non-IVUS group (3.2% vs. 4.3%, P = 0.8). Subjects who had IVUS performed at the time of ST had lower rates of mortality (HR 0.4, 95% CI 0.1-1.6, P =0.2) and major adverse cardiovascular events (HR 0.5, 95% CI 0.21.4, P =0.2) at follow-up, but these values were not statistically significant. Conclusions: There is a high prevalence of stent underexpansion in early ST, while the prevalence of malapposition is higher in very late ST. Use of IVUS during treatment for ST may identify mechanisms underlying the development of ST. (c) 2012 Wiley Periodicals, Inc. C1 [Armstrong, Ehrin J.; Kwa, Andrew T.; Yeo, Khung Keong; Javed, Usman; Low, Reginald I.; Rogers, Jason H.] Calif State Univ Sacramento, Davis Med Ctr, Sacramento, CA 95819 USA. [Mahmud, Ehtisham; Patel, Mitul] Univ Calif San Diego, San Diego Med Ctr, San Diego, CA 92103 USA. [Shunk, Kendrick A.] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, San Francisco, CA USA. [MacGregor, John S.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Rogers, JH (reprint author), 4860 Y St,Suite 2820, Sacramento, CA 95817 USA. EM jason.rogers@ucdmc.ucdavis.edu FU Boston Scientific; Abbott Vascular; Sanofi Aventis FX Drs. Armstrong, Kwa, Javed, Patel, Shunk, and MacGregor have no disclosures. Dr Low is on the advisory board of Abbott Vascular and Boston Scientific. Dr Rogers is a consultant for Volcano, Medtronic, Cordis, and Boston Scientific. Dr Mahmud is on the Speakers Bureau for Medtronic and Eli Lilly; is a consultant for Eli Lilly; and has research support from Boston Scientific, Abbott Vascular and Sanofi Aventis. NR 31 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 2013 VL 81 IS 5 BP 782 EP 790 DI 10.1002/ccd.24460 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 113TL UT WOS:000316691300010 PM 22511567 ER PT J AU Chen, BB Mallampalli, RK AF Chen, Bill B. Mallampalli, Rama K. TI F-box protein substrate recognition A new insight SO CELL CYCLE LA English DT Editorial Material ID IDENTIFICATION; DEGRADATION; ARREST; FBXL2 C1 [Chen, Bill B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Chen, BB (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM chenb@upmc.edu; mallampallirk@upmc.edu FU BLRD VA [I01 BX002200]; NHLBI NIH HHS [R01 HL098174, R01 HL116472, R01 HL096376] NR 10 TC 5 Z9 5 U1 1 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2013 VL 12 IS 7 BP 1009 EP 1010 DI 10.4161/cc.23071 PG 2 WC Cell Biology SC Cell Biology GA 117HJ UT WOS:000316943900001 PM 23255120 ER PT J AU Ghosh, SK Pantazopoulos, P Medarova, Z Moore, A AF Ghosh, Subrata K. Pantazopoulos, Pamela Medarova, Zdravka Moore, Anna TI Expression of Underglycosylated MUC1 Antigen in Cancerous and Adjacent Normal Breast Tissues SO CLINICAL BREAST CANCER LA English DT Article DE Cancer biomarker; Glucosylation; Malignant transformation; Sialation; Tumor grade ID GENE-EXPRESSION; CELL-LINES; TUMOR CHARACTERISTICS; CARCINOMA CELLS; SERIAL ANALYSIS; EPISIALIN MUC1; OVARIAN-CANCER; LUNG-CANCER; THERAPY; ADHESION AB Underglycosylated mucin 1 antigen (uMUC1) is aberrantly expressed in breast cancer. Using tissue microarray (TMA) and fresh-frozen breast cancer tissues, we analyzed its expression and found changes associated with higher tumor grade. We also observed changes in tissues adjacent to tumor but identified as normal on pathology reports. These findings suggest that uMUC1 can indeed serve as an early diagnostic marker. Introduction: Mucin 1 antigen (MUC1) is a high-molecular-weight transmembrane glycoprotein with an aberrant expression profile in various malignancies, including breast cancer. Its increased overexpression and underglycosylation in breast cancer is associated with tumor invasiveness and metastatic potential. In this study, we took the next step toward establishing MUC1 as a potential diagnostic, prognostic, and therapeutic target by investigating its expression and posttranslational modification (glycosylation/sialylation). Patients and Methods: In these studies we used a breast cancer tissue microarray (TMA) and fresh-frozen multistage breast cancer tissues. We analyzed in detail the expression of normal and underglycosylated/sialated MUC1 by immunohistochemical techniques, real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and various analytic techniques. Results: We found that changes in cellular localization as well as in upregulation and/or underglycosylation of MUC1 were associated with higher tumor grade. A key finding in this study was that underglycosylated MUC1 (uMUC1) overexpression and sialation were observed in tissues adjacent to tumor but identified as normal on pathology reports. Conclusions: These findings suggest that uMUC1 can indeed be used as an early diagnostic marker and provide additional insights into breast cancer management. Clinical Breast Cancer, Vol. 13, No. 2, 109-18 (C) 2013 Elsevier Inc. All rights reserved. C1 [Ghosh, Subrata K.; Pantazopoulos, Pamela; Medarova, Zdravka; Moore, Anna] Harvard Univ, Sch Med, Dept Radiol,Massachusetts Gen Hosp, Mol Imaging Lab,MGH HST Athinoula A Martinos Ctr, Boston, MA 02115 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Bldg 75, Charlestown, MA 02129 USA. EM zmedarova@partners.org; amoore@helix.mgh.harvard.edu FU NIH [1RO1CA135650] FX This study was supported in part by the NIH grant award 1RO1CA135650 to A.M and Z.M. NR 61 TC 13 Z9 15 U1 0 U2 12 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD APR PY 2013 VL 13 IS 2 BP 109 EP 118 DI 10.1016/j.clbc.2012.09.016 PG 10 WC Oncology SC Oncology GA 115RK UT WOS:000316829400005 PM 23122537 ER PT J AU Oxnard, GR Janne, PA AF Oxnard, Geoffrey R. Jaenne, Pasi A. TI Power in Numbers: Meta-analysis to Identify Inhibitor-Sensitive Tumor Genotypes SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CELL LUNG-CANCER; MUTATIONS; EGFR; GEFITINIB AB Widespread tumor genotyping has increased the complexity of lung cancer care, often identifying mutations of uncertain clinical significance. In the accompanying article, the authors carried out a meta-analysis of the published literature on EGF receptor (EGFR) genotype and erlotinib/gefitinib sensitivity to develop a publicly accessible database to inform patient care. Clin Cancer Res; 19(7); 1634-6. (C) 2013 AACR. C1 [Oxnard, Geoffrey R.; Jaenne, Pasi A.] Lowe Ctr Thorac Oncol, Boston, MA USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Oxnard, Geoffrey R.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM 223, Boston, MA 02215 USA. EM pjanne@partners.org FU NCI NIH HHS [P50 CA090578, P50CA090578, R01 CA114465, R01CA114465] NR 12 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2013 VL 19 IS 7 BP 1634 EP 1636 DI 10.1158/1078-0432.CCR-13-0169 PG 3 WC Oncology SC Oncology GA 118BH UT WOS:000316996900002 PM 23403632 ER PT J AU Tothova, Z Steensma, DP Ebert, BL AF Tothova, Zuzana Steensma, David P. Ebert, Benjamin L. TI New Strategies in Myelodysplastic Syndromes: Application of Molecular Diagnostics to Clinical Practice SO CLINICAL CANCER RESEARCH LA English DT Article ID PROGNOSTIC SCORING SYSTEM; ACUTE MYELOID-LEUKEMIA; FLOW-CYTOMETRY; WORKING CONFERENCE; EPIGENETIC CHANGES; POINT MUTATIONS; TET2 MUTATIONS; GENE; FREQUENT; IMPACT AB An increasingly complete compendium of recurrently mutated genes in myelodysplastic syndromes (MDS) has been defined, and the application of massively parallel sequencing to identify mutations in clinical practice now promises to improve the care of patients with this disease. More than 25 recurrent MDS-associated somatic mutations have been identified, involving biologic pathways as diverse as chromatin remodeling and pre-mRNA splicing. Several of these mutations have been shown to have prognostic implications that are independent of existing risk stratification systems based on clinical and pathologic parameters. Application of these recent discoveries to diagnosis, prognosis, risk stratification, and treatment selection for patients with MDS has the potential to improve patient outcomes. Here, we review recent advances in MDS and discuss potential applications of these discoveries to clinical practice. Clin Cancer Res; 19(7); 1637-43. (C) 2013 AACR. C1 [Tothova, Zuzana; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Tothova, Zuzana; Steensma, David P.; Ebert, Benjamin L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Karp Family Res Labs, 5-211,1 Blackfan Circle, Boston, MA 02115 USA. EM Benjamin_Ebert@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 FU NIH [R01 HL082945, P01 CA108631]; Leukemia and Lymphoma Society; Burroughs-Wellcome Fund FX This work was funded by the NIH (grants R01 HL082945 and P01 CA108631), the Leukemia and Lymphoma Society, and the Burroughs-Wellcome Fund. NR 49 TC 9 Z9 13 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2013 VL 19 IS 7 BP 1637 EP 1643 DI 10.1158/1078-0432.CCR-12-1251 PG 7 WC Oncology SC Oncology GA 118BH UT WOS:000316996900003 PM 23329810 ER PT J AU Pinto, EM Morton, C Rodriguez-Galindo, C McGregor, L Davidoff, AM Mercer, K Debelenko, LV Billups, C Ribeiro, RC Zambetti, GP AF Pinto, Emilia M. Morton, Christopher Rodriguez-Galindo, Carlos McGregor, Lisa Davidoff, Andrew M. Mercer, Kimberly Debelenko, Larisa V. Billups, Catherine Ribeiro, Raul C. Zambetti, Gerard P. TI Establishment and Characterization of the First Pediatric Adrenocortical Carcinoma Xenograft Model Identifies Topotecan as a Potential Chemotherapeutic Agent SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II; CANCER-PATIENTS; HIGH-RISK; ETOPOSIDE; CISPLATIN; TUMORS; DOXORUBICIN; CHILDREN; MITOTANE; P53 AB Purpose: Pediatric adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Conventional chemotherapeutic agents have shown limited utility and are largely ineffective in treating children with advanced ACC. The lack of cell lines and animal models of pediatric ACC has hampered the development of new therapies. Here we report the establishment of the first pediatric ACC xenograft model and the characterization of its sensitivity to selected chemotherapeutic agents. Experimental Design: A tumor from an 11-year-old boy with previously untreated ACC was established as a subcutaneous xenograft in immunocompromised CB17 scid(-/-) mice. The patient harbored a germline TP53 G245C mutation, and the primary tumor showed loss of heterozygosity with retention of the mutated TP53 allele. Histopathology, DNA fingerprinting, gene expression profiling, and biochemical analyses of the xenograft were conducted and compared with the primary tumor and normal adrenal cortex. The second endpoint was to assess the preliminary antitumor activity of selected chemotherapeutic agents. Results: The xenograft maintained the histopathologic and molecular features of the primary tumor. Screening the xenograft for drug responsiveness showed that cisplatin had a potent antitumor effect. However, etoposide, doxorubicin, and a panel of other common cancer drugs had little or no antitumor activity, with the exception of topotecan, which was found to significantly inhibit tumor growth. Consistent with these preclinical findings, topotecan as a single agent in a child with relapsed ACC resulted in disease stabilization. Conclusion: Our study established a novel TP53-associated pediatric ACC xenograft and identified topotecan as a potentially effective agent for treating children with this disease. Clin Cancer Res; 19(7); 1740-7. (C)2013 AACR. C1 [Pinto, Emilia M.; Ribeiro, Raul C.] St Jude Childrens Res Hosp, Int Outreach Program, Memphis, TN 38105 USA. [Pinto, Emilia M.; Zambetti, Gerard P.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. [Morton, Christopher; Davidoff, Andrew M.; Mercer, Kimberly] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA. [McGregor, Lisa; Ribeiro, Raul C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Debelenko, Larisa V.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Billups, Catherine] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Zambetti, GP (reprint author), St Jude Childrens Res Hosp, Dept Biochem, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM gerard.zambetti@stjude.org FU National Institutes of Health/National Cancer Institute [CA021765, CA023099]; Johnson & Johnson Pharmaceutical Research and Development; American Lebanese Syrian Associated Charities (ALSAC) FX National Institutes of Health/National Cancer Institute (CA021765, CA023099), Johnson & Johnson Pharmaceutical Research and Development, and the American Lebanese Syrian Associated Charities (ALSAC). NR 32 TC 7 Z9 7 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2013 VL 19 IS 7 BP 1740 EP 1747 DI 10.1158/1078-0432.CCR-12-3354 PG 8 WC Oncology SC Oncology GA 118BH UT WOS:000316996900013 PM 23406775 ER PT J AU Holkova, B Supko, JG Ames, MM Reid, JM Shapiro, GI Perkins, EB Ramakrishnan, V Tombes, MB Honeycutt, C McGovern, RM Kmieciak, M Shrader, E Wellons, MD Sankala, H Doyle, A Wright, J Roberts, JD Grant, S AF Holkova, Beata Supko, Jeffrey G. Ames, Matthew M. Reid, Joel M. Shapiro, Geoffrey I. Perkins, Edward Brent Ramakrishnan, Viswanathan Tombes, Mary Beth Honeycutt, Connie McGovern, Renee M. Kmieciak, Maciej Shrader, Ellen Wellons, Martha D. Sankala, Heidi Doyle, Austin Wright, John Roberts, John D. Grant, Steven TI A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2 SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; DEPENDENT KINASE INHIBITOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; FLAVOPIRIDOL INDUCES APOPTOSIS; BREAST-CARCINOMA CELLS; ACUTE MYELOID-LEUKEMIA; HYDROXAMIC ACID SAHA; DOWN-REGULATION; TRANSCRIPTIONAL REPRESSION; MYELODYSPLASTIC SYNDROMES AB Purpose: This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Experimental Design: Patients received vorinostat (200mgorally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily x 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly x 2. The alvocidib dose was escalated using a standard 3+3 design. Results: Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Conclusions: Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. Clin Cancer Res; 19(7); 1873-83. (C)2013 AACR. C1 [Holkova, Beata; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D.; Sankala, Heidi; Roberts, John D.; Grant, Steven] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Holkova, Beata; Perkins, Edward Brent; Roberts, John D.; Grant, Steven] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. [Ramakrishnan, Viswanathan] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Inst Mol Med, Richmond, VA 23298 USA. [Supko, Jeffrey G.; Shapiro, Geoffrey I.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Ames, Matthew M.; Reid, Joel M.; McGovern, Renee M.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA. [Doyle, Austin; Wright, John] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Grant, S (reprint author), Virginia Commonwealth Univ, POB 980035,401 Coll St, Richmond, VA 23298 USA. EM bholkova@mcvh-vcu.edu; stgrant@vcu.edu FU NIH [R21 CA115260, R01 CA93738, P30 CA016059, M01RR00065, U01 CA69912, 23XS026, P30 CA15083, P30 CA60516] FX This study was supported by NIH grants R21 CA115260, R01 CA93738, P30 CA016059, M01RR00065, U01 CA69912, 23XS026, P30 CA15083, and P30 CA60516. NR 50 TC 12 Z9 13 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2013 VL 19 IS 7 BP 1873 EP 1883 DI 10.1158/1078-0432.CCR-12-2926 PG 11 WC Oncology SC Oncology GA 118BH UT WOS:000316996900025 PM 23515411 ER PT J AU Rhee, CM Alexander, EK Bhan, I Brunelli, SM AF Rhee, Connie M. Alexander, Erik K. Bhan, Ishir Brunelli, Steven M. TI Hypothyroidism and Mortality among Dialysis Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SUBCLINICAL THYROID-DISEASE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; CORONARY-HEART-DISEASE; HEMODIALYSIS-PATIENTS; LOW TRIIODOTHYRONINE; PERITONEAL-DIALYSIS; HORMONE METABOLISM; ARTERIAL STIFFNESS; PREVALENCE AB Background and objectives Hypothyroidism is highly prevalent among ESRD patients, but its clinical significance and the benefits of thyroid hormone replacement in this context remain unclear. Design, setting, participants, & measurements This study examined the association between hypothyroidism and all-cause mortality among 2715 adult dialysis patients with baseline thyrotropin levels measured between April. of 2005 and April of 2011. Mortality was ascertained from Social Security Death Master Index and local registration systems. The association between hypothyroidism (thyrotropin greater than assay upper limit normal) and mortality was estimated using Cox proportional hazards models. To reduce the risk of observing reverse-causal associations, models included a 30-day lag between thyrotropin measurement and at-risk time. Results Among 350 (12.9%) hypothyroid and 2365 (87.1%) euthyroid (assay within referent range) patients, 917 deaths were observed during 5352 patient-years of at-risk time. Hypothyroidism was associated with higher mortality. Compared with thyrotropin in the low-normal range (0.4-2.9 mIU/L), subclinical hypothyroidism (thyrotropin >upper limit normal and <= 10.0 mIU/L) was associated with higher mortality; high-normal thyrotropin (>= 3.0 mIU/L and <= upper limit normal) and overt hypothyroidism (thyrotropin >10.0 mIU/L) were associated with numerically greater risk, but estimates were not statistically significant. Compared with spontaneously euthyroid controls, patients who were euthyroid while on exogenous thyroid replacement were not at higher mortality risk, whereas patients who were hypothyroid were at higher mortality risk. Sensitivity analyses indicated that effects on cardiovascular risk factors may mediate the observed association between hypothyroidism and death. Conclusions These data suggest that hypothyroidism is associated with higher mortality in dialysis patients, which may be ameliorated by thyroid hormone replacement therapy. Clin J Am Soc Nephrol 8: 593-601, 2013. doi: 10.2215/CJN.06920712 C1 [Rhee, Connie M.; Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Alexander, Erik K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Brunelli, Steven M.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. [Rhee, Connie M.; Alexander, Erik K.; Bhan, Ishir; Brunelli, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. [Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02114 USA. RP Brunelli, SM (reprint author), Brigham & Womens Hosp, 75 Francis St,MRB 4, Boston, MA 02115 USA. EM sbrunelli@partners.org FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants [DK007527-26, DK093201, DK079056]; Veracyte, Inc.; Asuragen, Inc FX This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants DK007527-26 (to C.M.R.), DK093201 (to C.M.R.), and DK079056 (to S.M.B.).; E.K.A. receives research support from Veracyte, Inc. and Asuragen, Inc. Since completing work on this study, S.M.B. has become a full-time employee of DaVita Clinical Research. None of the other authors declare any relevant conflicts of interest. NR 49 TC 17 Z9 20 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2013 VL 8 IS 4 BP 593 EP 601 DI 10.2215/CJN.06920712 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 118KB UT WOS:000317023300014 PM 23258793 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Introduction: Perspectives on Integrated Nephrology Care SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Mail Stop 111 F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2013 VL 8 IS 4 BP 681 EP 681 DI 10.2215/CJN.00230113 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 118KB UT WOS:000317023300024 PM 23564886 ER PT J AU Ginat, DT Kelly, HR Schaefer, PW Davidson, CJ Curry, W AF Ginat, Daniel T. Kelly, Hillary R. Schaefer, Pamela W. Davidson, Christian J. Curry, William TI Recurrent scalp metastasis from glioblastoma following resection SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Glioblastoma; Metastasis; Recurrence; Scalp; MRI ID MULTIFORME C1 [Ginat, Daniel T.; Kelly, Hillary R.; Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Davidson, Christian J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Curry, William] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 5 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD APR PY 2013 VL 115 IS 4 BP 461 EP 463 DI 10.1016/j.clineuro.2012.05.038 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 117TN UT WOS:000316976100015 PM 22727368 ER PT J AU Benes, CH AF Benes, C. H. TI Functionalizing Genomic Data for Personalization of Medicine SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; DRUG-SENSITIVITY; CANCER AB The wealth of genomic information currently available to researchers and clinicians has dramatically changed the way some diseases are defined. However, leveraging this information is a major challenge, in part because previously established concepts and tools used for research and development are largely inadequate. Using the example of cancer genomics, this article focuses on systems-biology approaches to inform the development of personalized medicine. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. RP Benes, CH (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. EM cbenes@partners.org FU Wellcome Trust [086357]; National Institutes of Health [1U54 HG006097-01] FX This study was supported by Wellcome Trust grant 086357 and National Institutes of Health grant 1U54 HG006097-01. NR 5 TC 3 Z9 3 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2013 VL 93 IS 4 BP 309 EP 311 DI 10.1038/clpt.2012.219 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 115YI UT WOS:000316847400009 PM 23321554 ER PT J AU Horner, MD Mintzer, JE Turner, TH Edmiston, KR Brawman-Mintzer, O AF Horner, Michael David Mintzer, Jacobo E. Turner, Travis H. Edmiston, Keith R. Brawman-Mintzer, Olga TI Attentional functioning in patients with posttraumatic stress disorder: a preliminary study SO CNS SPECTRUMS LA English DT Article DE PTSD; neuropsychology; attention; cognition ID INTIMATE PARTNER VIOLENCE; COMBAT VETERANS; MEMORY FUNCTION; PTSD; SYMPTOMS; SURVIVORS; DEFICITS; WAR AB Objective. To compare patients with posttraumatic stress disorder (PTSD) to patients without psychiatric or cognitive disorders on neuropsychological measures of attention. Methods. The sample included 19 patients with PTSD and 22 participants with no cognitive or psychiatric diagnosis. All had been referred for clinical neuropsychological evaluation at a VA Medical Center. None were diagnosed with dementia, delirium, or current substance dependence except nicotine or caffeine, and none had a history of stroke or of traumatic brain injury with loss of consciousness. Patients were excluded if they failed to exert adequate effort on testing. Results. PTSD patients performed significantly more poorly than patients without psychiatric diagnoses on Digit Span. Conclusion. PTSD patients were impaired relative to participants without psychiatric diagnoses on a measure of focused attention. Several factors, including the small sample size, suggest that the results should be considered preliminary. C1 [Horner, Michael David; Mintzer, Jacobo E.; Turner, Travis H.; Brawman-Mintzer, Olga] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Horner, Michael David; Mintzer, Jacobo E.; Turner, Travis H.; Brawman-Mintzer, Olga] Med Univ S Carolina, Charleston, SC 29425 USA. [Edmiston, Keith R.] Coll Charleston, Charleston, SC 29401 USA. RP Horner, MD (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM hornermd@musc.edu RI Kilic, Cengiz/I-9145-2013 FU Department of Veterans Affairs; Pfizer; NIH/NIA; Genentech; University of San Diego; Novartis, Inc.; Janssen; Wyeth, Inc.; Lilly Research Labs; Eli Lilly Company; CSP [545]; Elan Pharmaceuticals; BioPharma Connex; Takeda; Shire; Novartis FX This study was supported in part by the Department of Veterans Affairs.; Jacobo Mintzer has the following disclosures: Pfizer: research support (grant); NIH/NIA: research support (grant); Genentech: research support (grant); University of San Diego: research support (grant); Novartis, Inc.: research support (grant); Janssen: research support (grant); Wyeth, Inc.: research support (grant); Lilly Research Labs: research support (grant); Eli Lilly & Company: research support (grant); CSP #545: research support (grant); Elan Pharmaceuticals: research support (grant); BioPharma Connex: founder and chair (salary); NeuroQuest: consultant. Olga Brawman-Mintzer has the following disclosures: Takeda: research support (grant); Shire: research support (grant); Novartis: research support (grant). The remaining authors have nothing to disclose. NR 30 TC 4 Z9 4 U1 0 U2 14 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2013 VL 18 IS 2 BP 90 EP 94 DI 10.1017/S1092852912000909 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 119WO UT WOS:000317130200006 PM 23298713 ER PT J AU Delahanty, DL Gabert-Quillen, C Ostrowski, SA Nugent, NR Fischer, B Morris, A Pitman, RK Bon, J Fallon, W AF Delahanty, Douglas L. Gabert-Quillen, Crystal Ostrowski, Sarah A. Nugent, Nicole R. Fischer, Beth Morris, Adam Pitman, Roger K. Bon, John Fallon, William, Jr. TI The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: a randomized trial SO CNS SPECTRUMS LA English DT Article ID QUALITY-OF-LIFE; GLUCOCORTICOID-INDUCED IMPAIRMENT; MOTOR-VEHICLE ACCIDENTS; STRESS-DISORDER; DECLARATIVE MEMORY; PERITRAUMATIC DISSOCIATION; MAJOR DEPRESSION; SEPTIC SHOCK; PTSD; VICTIMS AB Objective/Introduction. Secondary pharmacological interventions have shown promise at reducing the development of posttraumatic stress disorder symptoms (PTSS) in preclinical studies. The present study examined the preliminary efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing PTSS in traumatic injury victims. Methods. Sixty-four traumatic injury patients (34% female) were randomly assigned in a double-blind protocol to receive either a 10-day course of hydrocortisone or placebo initiated within 12 hours of the trauma. One-month and 3-months posttrauma participants completed an interview to assess PTSS and self-report measures of depression and health-related quality of life. Results. Hydrocortisone recipients reported fewer PTSD and depression symptoms, and had greater improvements in health-related quality of life during the first 3 months posttrauma than did placebo recipients. Hydrocortisone recipients who had never received prior mental health treatment had the lowest PTSD scores. Conclusion. Low-dose hydrocortisone may be a promising approach to the prevention of PTSD in acutely injured trauma patients, and may be particularly efficacious in acutely injured trauma victims without a history of significant psychopathology. C1 [Delahanty, Douglas L.; Gabert-Quillen, Crystal; Morris, Adam] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Ostrowski, Sarah A.] Akron Childrens Hosp, NeuroDev Sci Ctr, Akron, OH USA. [Nugent, Nicole R.] RIH Bradley Hasbro Childrens Res Ctr, Alpert Brown Med Sch, Providence, RI USA. [Fischer, Beth] Ctr Family Safety & Healing, Columbus, OH USA. [Pitman, Roger K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bon, John] Summa Hlth Syst, Dept Pharm, Akron, OH USA. [Delahanty, Douglas L.; Fallon, William, Jr.] Dept Trauma Serv, Akron, OH USA. RP Delahanty, DL (reprint author), Kent State Univ, Dept Psychol, 144 Kent Hall, Kent, OH 44242 USA. EM ddelahan@kent.edu FU National Institute of Mental Health [R34 MH73014]; Ohio Board of Regents FX Funding for this study was provided by the National Institute of Mental Health (R34 MH73014) and the Ohio Board of Regents. NR 55 TC 28 Z9 29 U1 5 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2013 VL 18 IS 2 BP 103 EP 111 DI 10.1017/S1092852913000096 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 119WO UT WOS:000317130200008 PM 23557627 ER PT J AU Mayaud, L Lai, PS Clifford, GD Tarassenko, L Celi, LA Annane, D AF Mayaud, Louis Lai, Peggy S. Clifford, Gari D. Tarassenko, Lionel Celi, Leo Anthony Annane, Djillali TI Dynamic Data During Hypotensive Episode Improves Mortality Predictions Among Patients With Sepsis and Hypotension SO CRITICAL CARE MEDICINE LA English DT Article DE data mining; hospital mortality; physiologic reserve; sepsis; Severity of Illness Index ID INTENSIVE-CARE-UNIT; SEPTIC SHOCK; HOSPITAL MORTALITY; CRITICALLY-ILL; PROGNOSTIC MODEL; SCORING SYSTEMS; ROC CURVE; THERAPY; INDEX; ICU AB Objectives: To determine if a prediction rule for hospital mortality using dynamic variables in response to treatment of hypotension in patients with sepsis performs better than current models. Design: Retrospective cohort study. Setting: All ICUs at a tertiary care hospital. Patients: Adult patients admitted to ICUs between 2001 and 2007 of whom 2,113 met inclusion criteria and had sufficient data. Interventions: None. Measurements and Main Results: We developed a prediction algorithm for hospital mortality in patients with sepsis and hypotension requiring medical intervention using data from the Multiparameter Intelligent Monitoring in Intensive Care II. We extracted 189 candidate variables, including treatments, physiologic variables and laboratory values collected before, during, and after a hypotensive episode. Thirty predictors were identified using a genetic algorithm on a training set (n = 1500) and validated with a logistic regression model on an independent validation set (n = 613). The final prediction algorithm used included dynamic information and had good discrimination (area under the receiver operating curve = 82.0%) and calibration (Hosmer-Lemeshow C statistic = 10.43, p = 0.06). This model was compared with Acute Physiology and Chronic Health Evaluation IV using reclassification indices and was found to be superior with an Net Reclassification Improvement of 0.19 (p < 0.001) and an Integrated Discrimination Improvement of 0.09 (p < 0.001). Conclusions: Hospital mortality predictions based on dynamic variables surrounding a hypotensive event is a new approach to predicting prognosis. A model using these variables has good discrimination and calibration and offers additional predictive prognostic information beyond established ones. (Crit Care Med 2013; 41: 954-962) C1 [Mayaud, Louis; Clifford, Gari D.; Tarassenko, Lionel] Univ Oxford, Inst Biomed Engn, Oxford OX3 7DQ, England. [Mayaud, Louis] Ctr Invest Clin & Innovat Technol, INSERM, Garches, France. [Mayaud, Louis] Univ Versailles St Quentin, Hop Raymond Poincare, APHP, Intens Care Unit, Garches, France. [Mayaud, Louis] Univ Versailles St Quentin, Versailles, France. [Annane, Djillali] Paris Hosp Trust, Raymond Poincare Hosp, APHP, Intens Care Unit, Paris, France. [Lai, Peggy S.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Celi, Leo Anthony] Harvard Massachusetts Inst Technol, Lab Computat Physiol Hlth Sci & Technol, Cambridge, MA USA. [Celi, Leo Anthony] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. RP Mayaud, L (reprint author), Univ Oxford, Dept Engn Sci, Inst Biomed Engn IBME, ORCRB,Roosevelt Dr, Oxford OX3 7DQ, England. EM louis.mayaud@eng.ox.ac.uk FU RCUK Digital Economy Programme (Centre for Doctoral Training in Healthcare Innovation) [EP/G036861/1]; National Institute of Health (NIH); National Institute of Biomedical Imaging and Bioengineering (NIBIB) [2R01 EB001659] FX Supported, in part, by the RCUK Digital Economy Programme (Centre for Doctoral Training in Healthcare Innovation) grant (EP/G036861/1) to L. M. The National Institute of Health (NIH) and its National Institute of Biomedical Imaging and Bioengineering (NIBIB) under grant (2R01 EB001659) funded the MIMIC II database. NR 49 TC 9 Z9 10 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2013 VL 41 IS 4 BP 954 EP 962 DI 10.1097/CCM.0b013e3182772adb PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 114HN UT WOS:000316731800013 PM 23385106 ER PT J AU Melo, MFV Bates, JHT AF Melo, Marcos F. Vidal Bates, Jason H. T. TI Pleural Effusion in Acute Respiratory Distress Syndrome: Water, Water, Everywhere, Nor Any Drop to Drain SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute lung injury; acute respiratory distress syndrome; computed tomography; lung imaging; pleural effusion; respiratory physiology ID END-EXPIRATORY PRESSURE; MECHANICS; DOGS C1 [Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bates, Jason H. T.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Bates, Jason H. T.] Univ Vermont, Coll Med, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2013 VL 41 IS 4 BP 1133 EP 1134 DI 10.1097/CCM.0b013e31827c02cb PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 114HN UT WOS:000316731800031 PM 23528756 ER PT J AU Higgins, MJ Liedke, PER Goss, PE AF Higgins, Michaela J. Liedke, Pedro E. R. Goss, Paul E. TI Extended adjuvant endocrine therapy in hormone dependent breast cancer: The paradigm of the NCIC-CTG MA.17/BIG 1-97 trial SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Extended adjuvant endocrine therapy; MA.17 ID CARDIOVASCULAR RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; 2-GENE EXPRESSION RATIO; MOLECULAR GRADE INDEX; TO-TREAT ANALYSIS; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; RANDOMIZED-TRIAL; COST-EFFECTIVENESS AB Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Higgins, Michaela J.; Liedke, Pedro E. R.; Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Liedke, Pedro E. R.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. RP Goss, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Lawrence House 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 58 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD APR PY 2013 VL 86 IS 1 BP 23 EP 32 DI 10.1016/j.critrevonc.2012.09.013 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 118MD UT WOS:000317028700003 PM 23116626 ER PT J AU Krmpotich, TD Tregellas, JR Thompson, LL Banich, MT Klenk, AM Tanabe, JL AF Krmpotich, Theodore D. Tregellas, Jason R. Thompson, Laetitia L. Banich, Marie T. Klenk, Amanda M. Tanabe, Jody L. TI Resting-state activity in the left executive control network is associated with behavioral approach and is increased in substance dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Substance dependence; Approach; Avoidance; Resting-state; Executive control network; Laterality ID INTRINSIC CONNECTIVITY NETWORKS; DEFAULT-MODE; FUNCTIONAL CONNECTIVITY; ACTIVATION SYSTEMS; INHIBITION SYSTEM; HEALTHY-SUBJECTS; DECISION-MAKING; USE DISORDERS; ADDICTION; REWARD AB Background: Individuals with drug addictions report increased willingness to approach rewards. Approach behaviors are thought to involve executive control processes and are more strongly represented in the left compared to right prefrontal cortex. A direct link between approach tendencies and left hemisphere activity has not been shown in the resting brain. We hypothesized that compared to controls, substance dependent individuals (SDI) would have greater left hemisphere activity in the left executive control network (ECN) at rest. Methods: Twenty-five SDI and 25 controls completed a Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) questionnaire and underwent a resting-state fMRI scan. Group independent component analysis was performed. We used template matching to identify the left and right ECN separately and compared the corresponding components across groups. Across group, BAS scores were correlated with signal fluctuations in the left ECN and BIS scores with right ECN. Results: BAS scores were higher in SDI compared to controls (p < .003) and correlated with signal fluctuation in the left ECN. SDI showed significantly more activity than controls in the left prefrontal cortex of the left ECN. Conversely, SDI showed less activity than controls in the right prefrontal cortex of the right ECN. Conclusions: Results from this study suggest that approach tendencies are related to the left ECN, even during rest. Higher resting-state signal in the left ECN may play a role in heightened approach tendencies that contribute to drug-seeking behavior. Published by Elsevier Ireland Ltd. C1 [Krmpotich, Theodore D.; Klenk, Amanda M.; Tanabe, Jody L.] Univ Colorado Denver, Dept Radiol, Denver, CO USA. [Tregellas, Jason R.; Thompson, Laetitia L.; Banich, Marie T.; Tanabe, Jody L.] Univ Colorado Denver, Dept Psychiat, Denver, CO USA. [Banich, Marie T.] Univ Colorado Boulder, Inst Cognit Sci, Boulder, CO USA. [Tregellas, Jason R.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO USA. RP Tanabe, JL (reprint author), 12700 E 17th Ave,C278, Aurora, CO 80045 USA. EM Jody.Tanabe@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU NIDA [R01 DA024104, DA027748] FX Funding for this study was provided by NIDA grants R01 DA024104 and DA027748; NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 45 TC 15 Z9 16 U1 0 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2013 VL 129 IS 1-2 BP 1 EP 7 DI 10.1016/j.drugalcdep.2013.01.021 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 115QS UT WOS:000316827600001 PM 23428318 ER PT J AU Shen, XYY Kosten, TA Lopez, AY Kinsey, BM Kosten, TR Orson, FM AF Shen, Xiaoyun Y. Kosten, Therese A. Lopez, Angel Y. Kinsey, Berma M. Kosten, Thomas R. Orson, Frank M. TI A vaccine against methamphetamine attenuates its behavioral effects in mice SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Conjugate vaccine; Keyhole limpet hemocyanin; Monophosphoryl lipid A; Serum antibody titers; Locomotor activity; Conditioned place preference ID CONDITIONED PLACE PREFERENCE; ACTIVE IMMUNIZATION; MONOCLONAL-ANTIBODIES; COCAINE; RATS; AMPHETAMINE; (+)-METHAMPHETAMINE; NICOTINE; IMMUNOGENICITY; NEUROTOXICITY AB Background: Vaccines have treatment potential for methamphetamine (MA) addiction. We tested whether a conjugate vaccine against MA (succinyl-methamphetamine-keyhole limpet hemocyanin carrier protein; SMA-KLH) would generate MA antibodies and alter MA-induced behaviors. Methods: Mice were injected with SMA-KLH and received booster administrations 3 and 20 weeks later. Serum antibody titers reached peak levels by 4-6 weeks, remained at a modest level through 18 weeks, peaked again at 22 weeks after the second boost, and were still elevated at 35 weeks. At 7 weeks, groups of vaccinated and non-vaccinated mice were administered one of three MA doses (1, 2 or 3 mg/kg) to assess locomotor activity. Results: Non-vaccinated mice showed dose-dependent effects of MA with hypolocomotion at the lowest dose and elevated activity levels at the highest dose. Both dose effects were reduced in SMA-KLH groups, particularly low dose-induced hypolocomotion at later times post MA administration. Separate groups of vaccinated and non-vaccinated mice were trained in MA place conditioning at 30 weeks with either 0 (vehicle) or 0.5 mg/kg MA. Although times spent in the MA-paired side did not differ between groups on test vs. baseline sessions, SMA-KLH mice conditioned with MA showed reduced conditioned approach behaviors and decreased conditioned activity levels compared to control groups. Conclusion: These data suggest SMA-KLH attenuates the ability of MA to support place conditioning and reduces or delays its locomotor effects. Overall, results support SMA-KLH as a candidate MA vaccine. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Shen, Xiaoyun Y.; Lopez, Angel Y.; Kinsey, Berma M.; Orson, Frank M.] Michael E Debakey Vet Med Affairs Ctr, Dept Med, Houston, TX 77030 USA. [Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Michael E Debakey Vet Med Affairs Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Kosten, TA (reprint author), Michael E Debakey VAMC, Res Serv Line 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu FU National Institute on Drug Abuse (NIDA) [DP1DA033502, U01023898]; NIH; Department of Veterans Affairs FX This research was supported by grants DP1DA033502 and U01023898 from The National Institute on Drug Abuse (NIDA). NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Drs. T.A. Kosten, T.R. Kosten, and Orson have received funding from the NIH and the Department of Veterans Affairs. NR 41 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2013 VL 129 IS 1-2 BP 41 EP 48 DI 10.1016/j.drugalcdep.2012.09.007 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 115QS UT WOS:000316827600006 PM 23022610 ER PT J AU Kelly, JF Stout, RL Slaymaker, V AF Kelly, John F. Stout, Robert L. Slaymaker, Valerie TI Emerging adults' treatment outcomes in relation to 12-step mutual-help attendance and active involvement SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcoholics Anonymous; Narcotics Anonymous; 12-Step; Young adults; Emerging adults; Addiction treatment ID LEEDS-DEPENDENCE-QUESTIONNAIRE; UNTREATED INDIVIDUALS; GROUP PARTICIPATION; SUBSTANCE-ABUSE; BEHAVIOR-CHANGE; USE DISORDERS; ALCOHOL; MECHANISMS; ASSOCIATION; ADOLESCENTS AB Background: Participation in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) during and following treatment has been found to confer recovery-related benefit among adults and adolescents, but little is known about emerging adults (18-24years). This transitional life-stage is distinctive for greater distress, higher density of psychopathology, and poorer treatment and continuing care compliance. Greater knowledge would inform the utility of treatment referrals to 12-step organizations for this age-group. Methods: Emerging adults (N=303; 18-24years; 26% female; 95% White; 51% comorbid [SCID-derived] axis I disorders) enrolled in a naturalistic study of residential treatment effectiveness assessed at intake, 3,6, and 12 months on 12-step attendance and involvement and treatment outcomes (percent days abstinent [PDA]; percent days heavy drinking [PDHD]). Lagged hierarchical linear models (HLMs) tested whether attendance and involvement conferred recovery benefits, controlling for a variety of confounds. Results: The percentage attending 12-step meetings prior to treatment (36%) rose sharply at 3 months (89%), was maintained at 6 months (82%), but declined at 12 months (76%). Average attendance peaked at about 3 times per week at 3 months dropping to just over once per week at 12 months. Initially high, but similarly diminishing, levels of active 12-step involvement were also observed. Lagged HLMs found beneficial effects for attendance, but stronger effects, which increased overtime, for active involvement. Several active 12-step involvement indices were associated individually with outcome benefits. Conclusions: Ubiquitous 12-step organizations may provide a supportive recovery context for this high-risk population at a developmental stage where non-using/sober peers are at a premium. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Stout, Robert L.] Decis Sci Inst Providence, Providence, RI USA. [Slaymaker, Valerie] Hazelden Fdn, Ctr City, MN USA. RP Kelly, JF (reprint author), MGH Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org OI Stout, Robert/0000-0003-2596-241X FU National Institute of Alcohol Abuse and Alcoholism [NIAAA R21AA018185-01A2] FX This research was supported by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA R21AA018185-01A2; Mechanisms and Moderators of Behavior Change among young adults treated for Alcohol use disorder). NIAAA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 62 TC 19 Z9 19 U1 3 U2 40 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 2013 VL 129 IS 1-2 BP 151 EP 157 DI 10.1016/j.drugalcdep.2012.10.005 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 115QS UT WOS:000316827600020 PM 23122600 ER PT J AU Mentz, RJ Hernandez, AF Stebbins, A Ezekowitz, JA Felker, GM Heizer, GM Atar, D Teerlink, JR Califf, RM Massie, BM Hasselblad, V Starling, RC O'Connor, CM Ponikowski, P AF Mentz, Robert J. Hernandez, Adrian F. Stebbins, Amanda Ezekowitz, Justin A. Felker, G. Michael Heizer, Gretchen M. Atar, Dan Teerlink, John R. Califf, Robert M. Massie, Barry M. Hasselblad, Vic Starling, Randall C. O'Connor, Christopher M. Ponikowski, Piotr TI Predictors of early dyspnoea relief in acute heart failure and the association with 30-day outcomes: findings from ASCEND-HF SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Dyspnoea relief; Prognosis; Outcomes ID EUROPEAN-SOCIETY; NESIRITIDE; NITROGLYCERIN; REGISTRY; PROTECT; UPDATE; TRIAL AB To examine the characteristics associated with early dyspnoea relief during acute heart failure (HF) hospitalization, and its association with 30-day outcomes. ASCEND-HF was a randomized trial of nesiritide vs. placebo in 7141 patients hospitalized with acute HF in which dyspnoea relief at 6 h was measured on a 7-point Likert scale. Patients were classified as having early dyspnoea relief if they experienced moderate or marked dyspnoea improvement at 6 h. We analysed the clinical characteristics, geographical variation, and outcomes (mortality, mortality/HF hospitalization, and mortality/hospitalization at 30 days) associated with early dyspnoea relief. Early dyspnoea relief occurred in 2984 patients (43). In multivariable analyses, predictors of dyspnoea relief included older age and oedema on chest radiograph; higher systolic blood pressure, respiratory rate, and natriuretic peptide level; and lower serum blood urea nitrogen (BUN), sodium, and haemoglobin (model mean C index 0.590). Dyspnoea relief varied markedly across countries, with patients enrolled from Central Europe having the lowest risk-adjusted likelihood of improvement. Early dyspnoea relief was associated with lower risk-adjusted 30-day mortality/HF hospitalization [hazard ratio (HR) 0.81; 95 confidence interval (CI) 0.680.96] and mortality/hospitalization (HR 0.85; 95 CI 0.740.99), but similar mortality. Clinical characteristics such as respiratory rate, pulmonary oedema, renal function, and natriuretic peptide levels are associated with early dyspnoea relief, and moderate or marked improvement in dyspnoea was associated with a lower risk for 30-day outcomes. C1 [Mentz, Robert J.; Hernandez, Adrian F.; Felker, G. Michael; Califf, Robert M.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Hernandez, Adrian F.; Stebbins, Amanda; Felker, G. Michael; Heizer, Gretchen M.; Califf, Robert M.; Hasselblad, Vic; O'Connor, Christopher M.] Duke Clin Res Inst, Durham, NC 27715 USA. [Ezekowitz, Justin A.] Univ Alberta, Edmonton, AB, Canada. [Atar, Dan] Oslo Univ Hosp, Oslo, Norway. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Starling, Randall C.; Ponikowski, Piotr] Cleveland Clin, Cleveland, OH 44106 USA. [Starling, Randall C.; Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. RP Hernandez, AF (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM adrian.hernandez@duke.edu RI Ezekowitz, Justin/C-4579-2013; Ponikowski, Piotr/O-6454-2015; Hernandez, Adrian F./A-7818-2016 OI Ezekowitz, Justin/0000-0002-2724-4086; Ponikowski, Piotr/0000-0002-3391-7064; Hernandez, Adrian F./0000-0003-3387-9616 FU Johnson and Johnson; Scios Inc.; Amgen; Bayer; Corthera; Cytokinetics; Novartis; Trevena; Johnson Johnson; DCRI; Otsuka; Roche Diagnostics; Merck; BG Medicine; NIH FX Johnson and Johnson provided funding for the overall ASCEND-HF trial.; J.R.T. has received research grants for his role as a Steering committee member in ASCEND-HF from Scios Inc., the sponsor of this trial. He received research support and/or consultation fees from Amgen, Bayer, Corthera, Cytokinetics, Novartis, and Trevena. R. C. has received research grants and consulting fees from Johnson & Johnson. All other industry relations are publicly displayed at www.dcri.org/about-us. J.E. is currently conducting research sponsored by Johnson & Johnson. B. M. has received consulting fees/honoraria from DCRI. G. M. F. has received consulting fees from Amgen, Trevena, Otsuka, Roche Diagnostics, Novartis, Merck, and BG Medicine, and research funding from NIH, Amgen, Otsuka, and Roche Diagnostics. P. P. has received fees in respect of consultancy and speaker's bureau from Scios Inc., Corthera, Novartis, Johnson & Johnson, and Bayer. All other authors declare no conflict of interest. NR 24 TC 18 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD APR PY 2013 VL 15 IS 4 BP 456 EP 464 DI 10.1093/eurjhf/hfs188 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 117LR UT WOS:000316955400014 PM 23159547 ER PT J AU Lauritzen, HPMM AF Lauritzen, Hans P. M. M. TI Insulin- and Contraction-Induced Glucose Transporter 4 Traffic in Muscle: Insights From a Novel Imaging Approach SO EXERCISE AND SPORT SCIENCES REVIEWS LA English DT Review DE living mice; intravital; in vivo; PI3 kinase; AMP kinase; LKB1 ID RAT SKELETAL-MUSCLE; STIMULATED GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; LIVING MICE; TRANSVERSE TUBULES; T-TUBULES; IN-VIVO; PROTEIN; FIBERS; AS160 AB LAURITZEN, H. P. M. M. Insulin- and contraction-induced glucose transporter 4 traffic in muscle: insights from a novel imaging approach. Exerc. Sport Sci. Rev., Vol. 41, No. 2, pp. 77-86, 2013. Insulin- and contraction-mediated glucose transporter 4 (GLUT4) trafficking have different kinetics in mature skeletal muscle. Intravital imaging indicates that insulin-stimulated GLUT4 trafficking differs between t-tubules and sarcolemma. In contrast, contraction-induced GLUT4 trafficking does not differ between membrane surfaces. This distinction likely is caused by differences in the underlying signaling pathways regulating GLUT4 vesicle depletion, GLUT4 membrane fusion, and GLUT4 reinternalization. C1 Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Lauritzen, HPMM (reprint author), Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Room 525, Boston, MA 02215 USA. EM Hans.Lauritzen@joslin.harvard.edu FU Weimann Foundation; DERC (Diabetes and Endocrinology Research Center) at the Joslin Diabetes Center [P30DK036836] FX This project was supported by funding from the Weimann Foundation and the DERC (Diabetes and Endocrinology Research Center) P30DK036836 at the Joslin Diabetes Center. NR 40 TC 3 Z9 3 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-6331 J9 EXERC SPORT SCI REV JI Exerc. Sport Sci. Rev. PD APR PY 2013 VL 41 IS 2 BP 77 EP 86 DI 10.1097/JES.0b013e318275574c PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 114IA UT WOS:000316733100003 PM 23072821 ER PT J AU Pistilli, EE Quinn, LS AF Pistilli, Emidio E. Quinn, LeBris S. TI From Anabolic to Oxidative: Reconsidering the Roles of IL-15 and IL-15R alpha in Skeletal Muscle SO EXERCISE AND SPORT SCIENCES REVIEWS LA English DT Review DE cytokines; myokines; fatigue; oxidative muscle; atrophy; hypertrophy ID TUMOR-BEARING RATS; INTERLEUKIN-15 RECEPTOR; CARBOHYDRATE INGESTION; CYTOKINE; EXERCISE; PROTEIN; ALPHA; DIFFERENTIATION; EXPRESSION; ELEVATION AB PISTILLI, E. E. and L. S. QUINN. From anabolic to oxidative: reconsidering the roles of IL-15 and IL-15R alpha in skeletal muscle. Exerc. Sport Sci. Rev., Vol. 41, No. 2, pp. 100-106, 2013. Interleukin 15 (IL-15) and its receptor IL-15 receptor-alpha (IL-15R alpha) are suggested to function in the determination of skeletal muscle phenotypes, with IL-15 originally proposed as an anabolic cytokine. This review will focus on recent work demonstrating that manipulation of IL-15 and IL-15R alpha in vivo promotes changes in exercise capacity, muscle fatigue, and gene expression indicative of a more oxidative skeletal muscle phenotype. C1 [Pistilli, Emidio E.] W Virginia Univ, Div Exercise Physiol, Sch Med, Morgantown, WV 26506 USA. [Pistilli, Emidio E.] W Virginia Univ, Ctr Cardiovasc & Resp Sci, Sch Med, Morgantown, WV 26506 USA. [Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Quinn, LeBris S.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Pistilli, EE (reprint author), W Virginia Univ, Div Exercise Physiol, Sch Med, Morgantown, WV 26506 USA. EM epistilli2@hsc.wvu.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [5T32AR053461]; Department of Veterans Affairs [BX001026] FX This work was supported by a Ruth L. Kirschstein National Research Service Award (5T32AR053461) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to E. E. Pistilli) and Merit Review BX001026 from the Department of Veterans Affairs (to L. S. Quinn), with resources from the VA Puget Sound Health Care System. NR 35 TC 8 Z9 8 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-6331 J9 EXERC SPORT SCI REV JI Exerc. Sport Sci. Rev. PD APR PY 2013 VL 41 IS 2 BP 100 EP 106 DI 10.1097/JES.0b013e318275d230 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 114IA UT WOS:000316733100006 PM 23072822 ER PT J AU Hartmann, M Furrer, S Herzog, MH Merfeld, DM Mast, FW AF Hartmann, Matthias Furrer, Sarah Herzog, Michael H. Merfeld, Daniel M. Mast, Fred W. TI Self-motion perception training: thresholds improve in the light but not in the dark SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Self-motion thresholds; Whole-body motion; Perceptual learning; Vestibular thresholds; Vestibular learning ID QUALITATIVELY DIFFERENT MECHANISMS; HUMAN VESTIBULAR CORTEX; EARTH-VERTICAL AXIS; WHOLE-BODY; VESTIBULOOCULAR REFLEX; CONTRAST DISCRIMINATION; VELOCITY STORAGE; VISUAL-SYSTEM; ORIENTATION; ROTATION AB We investigated perceptual learning in self-motion perception. Blindfolded participants were displaced leftward or rightward by means of a motion platform and asked to indicate the direction of motion. A total of eleven participants underwent 3,360 practice trials, distributed over twelve (Experiment 1) or 6 days (Experiment 2). We found no improvement in motion discrimination in both experiments. These results are surprising since perceptual learning has been demonstrated for visual, auditory, and somatosensory discrimination. Improvements in the same task were found when visual input was provided (Experiment 3). The multisensory nature of vestibular information is discussed as a possible explanation of the absence of perceptual learning in darkness. C1 [Hartmann, Matthias; Furrer, Sarah; Mast, Fred W.] Univ Bern, Dept Psychol, CH-3000 Bern, Switzerland. [Hartmann, Matthias; Mast, Fred W.] Univ Bern, Ctr Cognit Learning & Memory, CH-3000 Bern, Switzerland. [Herzog, Michael H.] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Psychophys, Lausanne, Switzerland. [Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA. RP Hartmann, M (reprint author), Univ Bern, Dept Psychol, Muesmattstr 45, CH-3000 Bern, Switzerland. EM matthias.hartmann@psy.unibe.ch RI Hartmann, Matthias/D-8586-2014; OI Herzog, Michael/0000-0001-5433-1030 FU Swiss National Science Foundation [PDFMP1_127238, CRSII1-125135/1] FX This study was funded by the Swiss National Science Foundation (Pro*Doc grant PDFMP1_127238 and Sinergia grant CRSII1-125135/1). We thank Cora Bobst, Wilhelm Klatt, and Antje Stahnke for assistance in data collection. NR 79 TC 7 Z9 7 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2013 VL 226 IS 2 BP 231 EP 240 DI 10.1007/s00221-013-3428-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 115QA UT WOS:000316825800008 PM 23392475 ER PT J AU Deepa, SS Pulliam, D Hill, S Shi, Y Walsh, ME Salmon, A Sloane, L Zhang, N Zeviani, M Viscomi, C Musi, N Van Remmen, H AF Deepa, Sathyaseelan S. Pulliam, Daniel Hill, Shauna Shi, Yun Walsh, Michael E. Salmon, Adam Sloane, Lauren Zhang, Ning Zeviani, Massimo Viscomi, Carlo Musi, Nicolas Van Remmen, Holly TI Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity SO FASEB JOURNAL LA English DT Article DE fatty acid oxidation; PGC-1 alpha; longevity; Surf1 ID CYTOCHROME-C-OXIDASE; ACTIVATED RECEPTOR-ALPHA; FATTY-ACID OXIDATION; ADIPOSE-TISSUE; LIFE-SPAN; GLUCOSE-METABOLISM; SKELETAL-MUSCLE; GROWTH-HORMONE; KNOCKOUT MICE; UP-REGULATION AB Mice lacking Surf1, a complex IV assembly protein, have similar to 50-70% reduction in cytochrome c oxidase activity in all tissues yet a paradoxical increase in lifespan. Here we report that Surf1(-/-) mice have lower body (15%) and fat (20%) mass, in association with reduced lipid storage, smaller adipocytes, and elevated indicators of fatty acid oxidation in white adipose tissue (WAT) compared with control mice. The respiratory quotient in the Surf1(-/-) mice was significantly lower than in the control animals (0.83-0.93 vs. 0.90-0.98), consistent with enhanced fat utilization in Surf1(-/-) mice. Elevated fat utilization was associated with increased insulin sensitivity measured as insulin-stimulated glucose uptake, as well as an increase in insulin receptor levels (similar to 2-fold) and glucose transporter type 4 (GLUT4; similar to 1.3-fold) levels in WAT in the Surf1(-/-) mice. The expression of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1 alpha) mRNA and protein was up-regulated by 2.5- and 1.9-fold, respectively, in WAT from Surf1(-/-) mice, and the expression of PGC-1 alpha target genes and markers of mitochondrial biogenesis was elevated. Together, these findings point to a novel and unexpected link between reduced mitochondrial complex IV activity, enhanced insulin sensitivity, and increased mitochondrial biogenesis that may contribute to the increased longevity in the Surf1(-/-) mice.-Deepa, S. S., Pulliam, D., Hill, S., Shi, Y., Walsh, M. E., Salmon, A., Sloane, L., Zhang, N., Zeviani, M., Viscomi, C., Musi, N., Van Remmen, H. Improved insulin sensitivity associated with reduced mitochondrial complex IV assembly and activity. FASEB J. 27, 1371-1380 (2013). www.fasebj.org C1 [Deepa, Sathyaseelan S.; Pulliam, Daniel; Hill, Shauna; Shi, Yun; Walsh, Michael E.; Salmon, Adam; Sloane, Lauren; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Deepa, Sathyaseelan S.; Pulliam, Daniel; Hill, Shauna; Walsh, Michael E.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Zhang, Ning; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78245 USA. [Salmon, Adam; Musi, Nicolas; Van Remmen, Holly] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Zeviani, Massimo; Viscomi, Carlo] Ist Ricovero & Cura Carattere Sci, Fdn Ist Neurol Carlo Besta, Unit Mol Neurogenet, Milan, Italy. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr,Mail Code 5566, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu RI Zeviani, Massimo/K-2891-2014; Viscomi, Carlo/R-1940-2016 FU Ellison Medical Foundation; Telethon grant [GPP10005]; Italian Ministry of Health [GR2010-2306756] FX The authors thank Yuhong Liu, Li Yan, Marian Sabia, Amanda Jernigan, and Barbara Hunter for technical support. This work was supported by an Ellison Medical Foundation Senior Scholar award to H. V. R. Telethon grant GPP10005 to M.Z. and Italian Ministry of Health grant GR2010-2306756 to C.V. are also acknowledged. The authors report no conflicts of interest. NR 47 TC 14 Z9 14 U1 0 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 IS 4 BP 1371 EP 1380 DI 10.1096/fj.12-221879 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 117GF UT WOS:000316940800010 PM 23241310 ER PT J AU Oh, HC Brugge, WR AF Oh, Hyoung-Chul Brugge, William R. TI EUS-guided pancreatic cyst ablation: a critical review SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID SIMPLE RENAL CYSTS; HEPATIC CYSTS; ETHANOL INJECTION; PERCUTANEOUS ASPIRATION; ALCOHOL SCLEROTHERAPY; SINGLE INSTITUTION; PORCINE PANCREAS; THYROID CYSTS; FOLLOW-UP; LESIONS C1 [Oh, Hyoung-Chul] Chung Ang Univ, Coll Med, Div Gastroenterol, Seoul 156756, South Korea. [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. FU ASGE Cook Medical Don Wilson Award FX The authors disclosed no financial relationships relevant to this publication. Dr Oh was supported by the 2012 ASGE Cook Medical Don Wilson Award. NR 47 TC 16 Z9 18 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2013 VL 77 IS 4 BP 526 EP 533 DI 10.1016/j.gie.2012.10.033 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 115CP UT WOS:000316790300002 PM 23321339 ER PT J AU Shao, DD Tsherniak, A Gopal, S Weir, BA Tamayo, P Stransky, N Schumacher, SE Zack, TI Beroukhim, R Garraway, LA Margolin, AA Root, DE Hahn, WC Mesirov, JP AF Shao, Diane D. Tsherniak, Aviad Gopal, Shuba Weir, Barbara A. Tamayo, Pablo Stransky, Nicolas Schumacher, Steven E. Zack, Travis I. Beroukhim, Rameen Garraway, Levi A. Margolin, Adam A. Root, David E. Hahn, William C. Mesirov, Jill P. TI ATARiS: Computational quantification of gene suppression phenotypes from multisample RNAi screens SO GENOME RESEARCH LA English DT Article ID CANCER-CELL LINES; HEPATOCYTE NUCLEAR FACTOR-1-BETA; GENOME-WIDE ASSOCIATION; OVARIAN-CANCER; BREAST-CANCER; HIT SELECTION; TARGET GENE; COPY-NUMBER; INTERFERENCE; IDENTIFICATION AB Genome-scale RNAi libraries enable the systematic interrogation of gene function. However, the interpretation of RNAi screens is complicated by the observation that RNAi reagents designed to suppress the mRNA transcripts of the same gene often produce a spectrum of phenotypic outcomes due to differential on-target gene suppression or perturbation of off-target transcripts. Here we present a computational method, Analytic Technique for Assessment of RNAi by Similarity (ATARiS), that takes advantage of patterns in RNAi data across multiple samples in order to enrich for RNAi reagents whose phenotypic effects relate to suppression of their intended targets. By summarizing only such reagent effects for each gene, ATARiS produces quantitative, gene-level phenotype values, which provide an intuitive measure of the effect of gene suppression in each sample. This method is robust for data sets that contain as few as 10 samples and can be used to analyze screens of any number of targeted genes. We used this analytic approach to interrogate RNAi data derived from screening more than 100 human cancer cell lines and identified HNF1B as a transforming oncogene required for the survival of cancer cells that harbor HNF1B amplifications. ATARiS is publicly available at http://broadinstitute.org/ataris. C1 [Shao, Diane D.; Tsherniak, Aviad; Gopal, Shuba; Weir, Barbara A.; Tamayo, Pablo; Stransky, Nicolas; Schumacher, Steven E.; Zack, Travis I.; Beroukhim, Rameen; Garraway, Levi A.; Margolin, Adam A.; Root, David E.; Hahn, William C.; Mesirov, Jill P.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Shao, Diane D.; Beroukhim, Rameen; Garraway, Levi A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Schumacher, Steven E.; Zack, Travis I.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Zack, Travis I.] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Beroukhim, Rameen; Garraway, Levi A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Garraway, Levi A.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM William_Hahn@dfci.harvard.edu; mesirov@broad.mit.edu RI Schumacher, Steven/E-9821-2013 OI Schumacher, Steven/0000-0002-6819-5647 FU NIH/NCI [RC2 CA148268, P01 CA050661, U54 CA112962, R01 CA109467]; H.L. Snyder Medical Foundation; Ivy Research Foundation FX We thank the Broad Institute Project Achilles investigators for the data from RNAi pooled screening, and the Broad-Novartis Cancer Cell Line Encyclopedia investigators for providing cell lines for validation. We thank D. Nijhawan, J. Rosenbluh, D. Barbie, and F. Verdeguer for helpful discussions. We thank L. Solomon and L. Gaffney for assistance with figure design. This work was supported by grants from the NIH/NCI (RC2 CA148268, P01 CA050661, U54 CA112962, R01 CA109467), the H.L. Snyder Medical Foundation, and the Ivy Research Foundation. NR 58 TC 39 Z9 40 U1 0 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2013 VL 23 IS 4 BP 665 EP 678 DI 10.1101/gr.143586.112 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 116YY UT WOS:000316920500008 PM 23269662 ER PT J AU Kutner, N Zhang, R Johansen, K Bliwise, D AF Kutner, Nancy Zhang, Rebecca Johansen, Kirsten Bliwise, Donald TI Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US Renal Data System special study data SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Sleep; sleep quality; sleepiness; hemodialysis; mortality risk ID QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; NAP HABITS; LONG-SLEEP; DIALYSIS; DURATION; SIESTA; POPULATION; HEALTH; DEPRESSION AB Fragmented nocturnal sleep is commonly reported by patients undergoing daytime conventional hemodialysis (CHD) and may be associated with higher mortality risk. Subjective sleepiness during CHD is also frequently observed. We examined the association of reported sleep fragmentation and nocturnal and daytime (intradialytic) sleep durations with survival in a national cohort of 1440 CHD patients who were interviewed in 20052007 in a phone survey conducted by the US Renal Data System. Patient survival was followed through September 30, 2010 in the US Renal Data System. A total of 76% of patients reported that they typically dozed off or slept during their treatment, and intradialytic dozing was especially common among patients whose treatment shift started before 1000 hours. There was a trend for patients who reported dozing during CHD to report nocturnal sleep fragmentation (60.4% vs. 55.1%; P=0.07). With adjustment for intradialytic sleep and other covariates, nocturnal sleep fragmentation was not associated with survival. Mortality risk was higher for patients who reported sleeping 9 or more hours/night compared with the referent category of nocturnal sleep equal to 67 hours (hazard ratio: 1.50 [95% confidence interval: 1.042.17]; P=0.03). Continued investigation of the association of timing and duration of sleep with hemodialysis patient outcomes is warranted. C1 [Kutner, Nancy; Zhang, Rebecca; Johansen, Kirsten; Bliwise, Donald] Emory Univ, US Renal Data Syst, Rehabil Qual Life Special Studies Ctr, Atlanta, GA 30322 USA. [Bliwise, Donald] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Johansen, Kirsten] Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Johansen, Kirsten] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Kutner, N (reprint author), Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. EM nkutner@emory.edu FU National Institutes of Health [HHSN267200715004C]; ADB [N01-DK-7-5004] FX This study was supported by National Institutes of Health contract HHSN267200715004C, ADB No. N01-DK-7-5004 (Dr. Kutner). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. NR 28 TC 5 Z9 5 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD APR PY 2013 VL 17 IS 2 BP 223 EP 229 DI 10.1111/hdi.12005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 117PX UT WOS:000316966700004 PM 23216956 ER PT J AU Race, E Keane, MM Verfaellie, M AF Race, Elizabeth Keane, Margaret M. Verfaellie, Mieke TI Losing sight of the future: Impaired semantic prospection following medial temporal lobe lesions SO HIPPOCAMPUS LA English DT Article DE semantic memory; episodic memory; hippocampus; amnesia; imagination ID MENTAL TIME-TRAVEL; CONSTRUCTIVE EPISODIC SIMULATION; AUTOBIOGRAPHICAL MEMORY; RELATIONAL MEMORY; RETRIEVAL; THINKING; EVENTS; HIPPOCAMPUS; AMNESIA; BRAIN AB The ability to imagine the future (prospection) relies on many of the same brain regions that support memory for the past. To date, scientific research has primarily focused on the neural substrates of episodic forms of prospection (mental simulation of spatiotemporally specific future events); however, little is known about the neural substrates of semantic prospection (mental simulation of future nonpersonal facts). Of particular interest is the role of the medial temporal lobes (MTLs), and specifically the hippocampus. Although the hippocampus has been proposed to play a key role in episodic prospection, recent evidence suggests that it may not play a similar role in semantic prospection. To examine this possibility, amnesic patients with MTL lesions were asked to imagine future issues occurring in the public domain. The results showed that patients could list general semantic facts about the future, but when probed to elaborate, patients produced impoverished descriptions that lacked semantic detail. This impairment occurred despite intact performance on standard neuropsychological tests of semantic processing and did not simply reflect deficits in narrative construction. The performance of a patient with damage limited to the hippocampus was similar to that of the remaining patients with MTL lesions and amnesic patients' impaired elaboration of the semantic future correlated with their impaired elaboration of the semantic past. Together, these results provide novel evidence from MTL amnesia that memory and prospection are linked in the semantic domain and reveal that the MTLs play a critical role in the construction of detailed, multi-element semantic simulations. (c) 2012 Wiley Periodicals, Inc. C1 [Race, Elizabeth; Keane, Margaret M.; Verfaellie, Mieke] Boston Univ, VA Boston Healthcare Syst, Memory Disorders Res Ctr, Sch Med, Boston, MA 02130 USA. [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. RP Race, E (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave 151-A, Boston, MA 02130 USA. EM race@bu.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIH (NIMH and NINDS) [R01MH093431, F32NS073212]; Clinical Science Research and Development Service, Department of Veterans Affairs FX Grant sponsor: NIH (NIMH and NINDS); Grant numbers: R01MH093431, F32NS073212; Grant sponsor: Clinical Science Research and Development Service, Department of Veterans Affairs. NR 65 TC 32 Z9 33 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PD APR PY 2013 VL 23 IS 4 BP 268 EP 277 DI 10.1002/hipo.22084 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 113PF UT WOS:000316679300004 PM 23197413 ER PT J AU Ferrone, S AF Ferrone, Soldano TI A tribute to Edgardo Carosella on the occasion of the 6th International Conference on HLA-G held in Paris, France, July 9-11, 2012 SO HUMAN IMMUNOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Ferrone, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. EM SFerrone@Partners.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR PY 2013 VL 74 IS 4 SI SI BP 405 EP 405 DI 10.1016/j.humimm.2012.11.029 PG 1 WC Immunology SC Immunology GA 118KT UT WOS:000317025100003 PM 23232062 ER PT J AU Wong, KFK Gong, JJ Cotten, JF Solt, K Brown, EN AF Wong, Kin Foon Kevin Gong, Jen J. Cotten, Joseph F. Solt, Ken Brown, Emery N. TI Assessing the Effects of Pharmacological Agents on Respiratory Dynamics Using Time-Series Modeling SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Bootstrap; general anesthesia; respiratory rate; serial correlation ID FUNCTIONAL MRI; DEPRESSION; NALOXONE; VARIABILITY; ANTAGONISM; ANESTHESIA; THERAPY; CAT AB Developing quantitative descriptions of how stimulant and depressant drugs affect the respiratory system is an important focus in medical research. Respiratory variables-respiratory rate, tidal volume, and end tidal carbon dioxide-have prominent temporal dynamics that make it inappropriate to use standard hypothesis-testing methods that assume independent observations to assess the effects of these pharmacological agents. We present a polynomial signal plus autoregressive noise model for analysis of continuously recorded respiratory variables. We use a cyclic descent algorithm to maximize the conditional log likelihood of the parameters and the corrected Akaike's information criterion to choose simultaneously the orders of the polynomial and the autoregressive models. In an analysis of respiratory rates recorded from anesthetized rats before and after administration of the respiratory stimulant methylphenidate, we use the model to construct within-animal z-tests of the drug effect that take account of the time-varying nature of the mean respiratory rate and the serial dependence in rate measurements. We correct for the effect of model lack-of-fit on our inferences by also computing bootstrap confidence intervals for the average difference in respiratory rate pre- and postmethylphenidate treatment. Our time-series modeling quantifies within each animal the substantial increase in mean respiratory rate and respiratory dynamics following methylphenidate administration. This paradigm can be readily adapted to analyze the dynamics of other respiratory variables before and after pharmacologic treatments. C1 [Wong, Kin Foon Kevin; Solt, Ken] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02129 USA. [Gong, Jen J.] MIT, Cambridge, MA 02129 USA. [Gong, Jen J.; Cotten, Joseph F.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cotten, Joseph F.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02129 USA. [Solt, Ken; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Solt, Ken; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. EM kfwong@partners.org; jengong@mit.edu; jcotten@partners.org; KSOLT@partners.org; enb@neurostat.mit.edu RI Wong, Kin Foon Kevin/C-7896-2014; OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health [DP1-OD003646, K08-GM094394, K08-GM083216] FX This research was supported by National Institutes of Health Grant DP1-OD003646, Grant K08-GM094394, and Grant K08-GM083216. Asterisk indicates corresponding author. NR 28 TC 0 Z9 0 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD APR PY 2013 VL 60 IS 4 BP 1118 EP 1125 DI 10.1109/TBME.2012.2225834 PG 8 WC Engineering, Biomedical SC Engineering GA 115KX UT WOS:000316812200029 PM 23193230 ER PT J AU Tu, GW Hwabejire, JO Ju, MJ Yang, YF Zhang, GJ Xu, JW Xue, ZG Jiang, C Luo, Z AF Tu, Guo-Wei Hwabejire, J. O. Ju, Min-Jie Yang, Yuan-Feng Zhang, Guang-Jian Xu, Jian-Wei Xue, Zhang-Gang Jiang, C. Luo, Z. TI Multidisciplinary intensive care in extensive necrotizing fasciitis SO INFECTION LA English DT Article DE Necrotizing fasciitis; Soft tissue infection; Klebsiella pneumoniae ID SOFT-TISSUE INFECTIONS; MANAGEMENT; MORTALITY; DETERMINANTS; DIAGNOSIS AB This is a case report of extensive necrotizing fasciitis (NF). A 65-year-old man presented with high fever, pain, swelling, and redness of the perineum, scrotum, and right lower limb. Based on the clinical symptoms and an imaging examination, a diagnosis of NF was made. The patient underwent an extensive exploration followed by daily bedside debridement. A diversion colostomy and six additional debridement procedures on the right thigh and perineum were subsequently performed. Although the patient had an eventful course, he recovered well under a multidisciplinary treatment regimen. The treatment and hospital course of the patient are described. C1 [Tu, Guo-Wei; Ju, Min-Jie; Xue, Zhang-Gang; Luo, Z.] Fudan Univ, Zhongshan Hosp, Dept Anesthesiol, Shanghai 200032, Peoples R China. [Tu, Guo-Wei; Ju, Min-Jie; Xue, Zhang-Gang; Luo, Z.] Fudan Univ, Zhongshan Hosp, Surg Intens Care Unit, Shanghai 200032, Peoples R China. [Hwabejire, J. O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Yang, Yuan-Feng] Fudan Univ, Dept Urol, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Zhang, Guang-Jian; Jiang, C.] Fudan Univ, Dept Orthoped, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Xu, Jian-Wei] Fudan Univ, Dept Plast & Reconstruct Surg, Zhongshan Hosp, Shanghai 200433, Peoples R China. RP Luo, Z (reprint author), Fudan Univ, Zhongshan Hosp, Dept Anesthesiol, 180 Fenglin Rd, Shanghai 200032, Peoples R China. EM jcyh01@sina.com; luo-zhe@zshospital.sh.cn NR 17 TC 6 Z9 6 U1 0 U2 13 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD APR PY 2013 VL 41 IS 2 BP 583 EP 587 DI 10.1007/s15010-012-0346-2 PG 5 WC Infectious Diseases SC Infectious Diseases GA 113BO UT WOS:000316641000040 PM 23104255 ER PT J AU Okike, K Lee, OC Makanji, H Harris, MB Vrahas, MS AF Okike, Kanu Lee, Olivia C. Makanji, Heeren Harris, Mitchel B. Vrahas, Mark S. TI Factors associated with the decision for operative versus non-operative treatment of displaced proximal humerus fractures in the elderly SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Proximal humerus fractures; Orthopaedics; Trauma; Surgical decision-making; Surgery ID RANDOMIZED CONTROLLED-TRIAL; LOCKING-PLATE FIXATION; INTERNAL-FIXATION; SURGICAL-TREATMENT; OPEN REDUCTION; PHILOS PLATE; CONSERVATIVE TREATMENT; EARLY COMPLICATIONS; LOCKED PLATE; EPIDEMIOLOGY AB Background: In the management of displaced proximal humerus fractures in the elderly, wide variation has been documented. However, no prior study has investigated the factors that currently lead surgeons to treat patients with surgical fixation, arthroplasty or non-operative management. The purpose of this study was to identify the factors associated with treatment selection in the management of displaced proximal humerus fractures in individuals over the age of 60 years. To this end, we conducted a retrospective review of all such injuries that presented to our two level-I trauma centres between 2006 and 2009. Patients and methods: From our prospectively collected trauma database, we identified 229 displaced proximal humerus fractures that met all inclusion and exclusion criteria. Data were collected on patient-, fracture-and surgeon-related characteristics that were plausibly related to the decision for treatment. The choice of management was recorded, and logistic regression was used to identify factors associated with the decision for treatment. Results: In the multivariate analysis, the predictors of operative intervention as opposed to non-operative treatment were younger patient age (p = 0.038), associated orthopaedic injuries requiring surgery (p = 0.012), higher Arbeitsgemeinschaft fur Osteosynthesefragen (AO) classification (p = 0.012), translation-type displacement (p = 0.0012) and associated glenohumeral dislocation (p = 0.0006). In addition, shoulder and upper extremity specialists were found to choose operative intervention significantly more frequently than orthopaedic trauma specialists (49.1% vs. 26.1%, adjusted relative risk (RR) 1.96, p = 0.012). Factors associated with the decision for arthroplasty as opposed to fixation were higher Charlson score (p = 0.045), higher Neer classification (p = 0.012), and higher AO classification (p = 0.0097). Conclusions: In this study of displaced proximal humerus fractures in the elderly, the decision for surgery was influenced by the patient's age, the presence of associated orthopaedic injuries, the severity of the fracture and the presence of an associated glenohumeral dislocation. In addition, treatment by a shoulder or upper extremity specialist (as opposed to an orthopaedic trauma specialist) was associated with a higher likelihood of operative intervention. Further investigation into the resultant clinical outcomes is required to determine whether the use of these characteristics to select operative candidates is appropriate and beneficial for patients. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Okike, Kanu; Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Okike, Kanu; Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Lee, Olivia C.] Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 USA. [Makanji, Heeren] Harvard Univ, Sch Med, Boston, MA USA. RP Okike, K (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM okike@post.harvard.edu OI Okike, Kanu/0000-0001-9310-9969 FU Orthopaedic Research and Education Foundation; Depuy Orthopaedics; AO Foundation; OREF/DePuy Orthopaedic Resident Educational Grant; Massachusetts General Hospital Academic Enrichment Fund FX Dr. Okike reports grant support from the Orthopaedic Research and Education Foundation and Depuy Orthopaedics. Dr. Vrahas reports grant support from the AO Foundation, and serving as a consultant for Pioneer Medical. Drs. Lee, Makanji and Harris did not receive any financial payments or other benefits from any commercial entity related to the subject of this article.; This research was supported by an OREF/DePuy Orthopaedic Resident Educational Grant, as well as a grant from the Massachusetts General Hospital Academic Enrichment Fund. Neither entity was involved in the study design; collection, analysis and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. NR 46 TC 12 Z9 12 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD APR PY 2013 VL 44 IS 4 BP 448 EP 455 DI 10.1016/j.injury.2012.09.002 PG 8 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 114GO UT WOS:000316729300010 PM 23022082 ER PT J AU Villar, J Perez-Mendez, L Blanco, J Anon, JM Blanch, L Belda, J Santos-Bouza, A Fernandez, RL Kacmarek, RM AF Villar, Jesus Perez-Mendez, Lina Blanco, Jesus Manuel Anon, Jose Blanch, Lluis Belda, Javier Santos-Bouza, Antonio Lidia Fernandez, Rosa Kacmarek, Robert M. CA Spanish Initiative Epidemiology TI A universal definition of ARDS: the PaO2/FiO(2) ratio under a standard ventilatory setting-a prospective, multicenter validation study SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute respiratory distress syndrome; Protective mechanical ventilation; Standard ventilatory settings; Lung injury severity; Phenotype classification; Definition; Prognosis ID ACUTE RESPIRATORY-DISTRESS; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; CLINICAL-TRIAL; GAS-EXCHANGE; STRATEGY; FAILURE; ADULTS AB The PaO2/FiO(2) is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO2/FiO(2) calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification. We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO(2) a parts per thousand currency sign 200. In the derivation cohort (n = 170), we measured PaO2/FiO(2) with two levels of positive end-expiratory pressure (PEEP) (a parts per thousand yen5 and a parts per thousand yen10 cmH(2)O) and two levels of FiO(2) (a parts per thousand yen0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO(2) > 200), moderate (PaO2/FiO(2) 101-200), and severe (PaO2/FiO(2) a parts per thousand currency sign 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO(2) risk categories in the derivation cohort was PEEP a parts per thousand yen 10 cmH(2)O and FiO(2) a parts per thousand yen 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Our method for assessing PaO2/FiO(2) greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials. C1 [Villar, Jesus; Perez-Mendez, Lina; Blanco, Jesus; Blanch, Lluis; Lidia Fernandez, Rosa] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Lidia Fernandez, Rosa] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. [Perez-Mendez, Lina] Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain. [Blanco, Jesus] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [Manuel Anon, Jose] Hosp Virgen La Luz, Intens Care Unit, Cuenca, Spain. [Blanch, Lluis] Corp Sanitaria & Univ, Crit Care Ctr, Sabadell, Spain. [Belda, Javier] Hosp Clin Valencia, Dept Anesthesia, Valencia, Spain. [Santos-Bouza, Antonio] Complejo Hosp Univ Santiago, Intens Care Unit, Santiago De Compostela, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 01460 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria 35010, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St, Boston, MA 01460 USA. EM jesus.villar54@gmail.com; rkacmarek@partners.org FU Instituto de Salud Carlos III [PI 07/0113, PI 10/0393]; Asociacion Cientifica Pulmon y Ventilacion Mecanica; Hamilton; Maquet FX This work was supported by the Instituto de Salud Carlos III (PI 07/0113, PI 10/0393) and by the Asociacion Cientifica Pulmon y Ventilacion Mecanica. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We have the following competing interests: RMK has received research grants from Hamilton, honorarium for lecturing from Maquet and Hamilton, and is a consultant for Newport, KCL, and Bayer. JV has received research grants from Maquet. The rest of the authors declared that no competing interests exist in relation to the content of this study and manuscript. NR 30 TC 55 Z9 62 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2013 VL 39 IS 4 BP 583 EP 592 DI 10.1007/s00134-012-2803-x PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 114RI UT WOS:000316759500007 PM 23370826 ER PT J AU Sulemanji, DS Marchese, A Wysocki, M Kacmarek, RM AF Sulemanji, Demet S. Marchese, Andrew Wysocki, Marc Kacmarek, Robert M. TI Adaptive support ventilation with and without end-tidal CO2 closed loop control versus conventional ventilation SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Adaptive support ventilation; Closed loop control; ARDS; COPD; Brain injury ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; BREATHING PATTERN; GAS-EXCHANGE; FAILURE; MORTALITY; STRATEGY; VOLUMES AB Our aim was to compare adaptive support ventilation with and without closed loop control by end tidal CO2 (ASVCO(2), ASV) with pressure (PC) and volume control ventilation (VC) during simulated clinical scenarios [normal lungs (N), COPD, ARDS, brain injury (BI)]. A lung model was used to simulate representative compliance (mL/cmH(2)O): resistance (cmH(2)O/L/s) combinations, 45:5 for N and BI, 60:7.7 for COPD, 15:7.7 and 35:7.7 for ARDS. Two levels of PEEP (cmH(2)O) were used for each scenario, 12/16 for ARDS, and 5/10 for others. The CO2 productions of 2, 3, 4 and 5 mL/kg predicted body weight/min were simulated. Tidal volume was set to 6 mL/kg during VC and PC. Outcomes of interest were end tidal CO2 (etCO(2)) and plateau pressure (P (Plat)). EtCO2 levels in N and BI and COPD were similar for all modes. In ARDS, etCO(2) was higher in ASVCO(2) than in other modes (p < 0.001). Under all mechanical conditions ASVCO(2) revealed a narrower range of etCO(2). P (Plat) was similar for all modes in all scenarios but ARDS where P (Plat) in ASV and ASVCO(2) were lower than in VC (p = 0.001). When P (Plat) was a parts per thousand yen28 cmH(2)O, P (plat) in ASV and ASVCO(2) were lower than in VC and PC (p = 0.024). All modes performed similarly in most cases. Minor differences observed were in favor of the closed loop modes. Overall, ASVCO(2) maintained tighter CO2 control. The ASVCO(2) had the greatest impact during ARDS allowing etCO(2) to increase and protecting against hypocapnia evident with other modes while ensuring lower P (plat) and tidal volumes. C1 [Sulemanji, Demet S.; Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Sulemanji, Demet S.; Marchese, Andrew; Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Wysocki, Marc] Hamilton Med, Bonaduz, Switzerland. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St Warren 1225, Boston, MA 02114 USA. EM dsulemanji@partners.org; rkacmarek@partners.org FU Hamilton Medical; Covidien FX Funding in part for this study was provided by Hamilton Medical.; Dr. Kacmarek has received research grants from Covidien and Hamilton Medical, an honorarium for lecturing from Maquet and Hamilton, and is a consultant for Newport Medical, KCI and Bayer. Dr. Wysocki is a full time employee of Hamilton Medical. NR 23 TC 4 Z9 5 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2013 VL 39 IS 4 BP 703 EP 710 DI 10.1007/s00134-012-2742-6 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 114RI UT WOS:000316759500020 PM 23151992 ER PT J AU Ranieri, VM Rubenfeld, GD Thompson, BT AF Ranieri, V. Marco Rubenfeld, Gordon D. Thompson, B. Taylor TI Defining ARDS: do we need a mandatory waiting period? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; EUROPEAN CONSENSUS CONFERENCE; ACUTE LUNG INJURY; CLINICAL-TRIAL COORDINATION; BERLIN DEFINITION; SUPPORTIVE THERAPY; DESIGN STRATEGIES; RELEVANT OUTCOMES; PART 2; ISSUES C1 [Ranieri, V. Marco] Univ Turin, Dipartimento Anestesia & Med Stati Critici, Azienda Osped S Giovanni Battista Molinette, I-10126 Turin, Italy. [Rubenfeld, Gordon D.] Univ Toronto, Program Trauma Emergency & Crit Care, Interdept Div Crit Care Med, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit,Dept Med, Boston, MA USA. RP Ranieri, VM (reprint author), Univ Turin, Dipartimento Anestesia & Med Stati Critici, Azienda Osped S Giovanni Battista Molinette, Corso Dogliotti 14, I-10126 Turin, Italy. EM marco.ranieri@unito.it NR 25 TC 1 Z9 2 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2013 VL 39 IS 4 BP 775 EP 778 DI 10.1007/s00134-013-2834-y PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 114RI UT WOS:000316759500032 PM 23370830 ER PT J AU Williams, AB Wang, HH Burgess, J Li, XH Danvers, K AF Williams, Ann B. Wang, Honghong Burgess, Jane Li, Xianhong Danvers, Karina TI Cultural adaptation of an evidence-based nursing intervention to improve medication adherence among people living with HIV/AIDS (PLWHA) in China SO INTERNATIONAL JOURNAL OF NURSING STUDIES LA English DT Article DE Cultural adaptation; Nursing intervention; Medication adherence; HIV/AIDS; China ID ACTIVE ANTIRETROVIRAL THERAPY; SELF-REPORTED ADHERENCE; HOME VISITS; HIV; DISSEMINATION; CHALLENGES; ISSUES AB Background: Adapting nursing interventions to suit the needs and culture of a new population (cultural adaptation) is an important early step in the process of implementation and dissemination. While the need for cultural adaptation is widely accepted, research-based strategies for doing so are not well articulated. Non-adherence to medications for chronic disease is a global problem and cultural adaptation of existing evidence-based interventions could be useful. Objectives: This paper aims to describe the cultural adaptation of an evidence-based nursing intervention to improve medication adherence among people living with HIV/AIDS and to offer recommendations for adaptation of interventions across cultures and borders. Site: The intervention, which demonstrated efficacy in a randomized controlled trial in North America, was adapted for the cultural and social context of Hunan Province, in south central China. Sources of data: The adaptation process was undertaken by intervention stakeholders including the original intervention study team, the proposed adaptation team, and members of a Community Advisory Board, including people living with HIV/AIDS, family members, and health care workers at the target clinical sites. Procedures: The adaptation process was driven by quantitative and qualitative data describing the new population and context and was guided by principles for cultural adaptation drawn from prevention science research. Results: The primary adaptation to the intervention was the inclusion of family members in intervention activities, in response to the cultural and social importance of the family in rural China. In a pilot test of the adapted intervention, self-reported medication adherence improved significantly in the group receiving the intervention compared to the control group (p = 0.01). Recommendations for cultural adaptation of nursing interventions include (1) involve stakeholders from the beginning; (2) assess the population, need, and context; (3) evaluate the intervention to be adapted with attention to details of the original studies that demonstrated efficacy; (4) compare important elements of the original intervention with those of the proposed new population and context to identify primary points for adaptation; (5) explicitly identify sources of tension between intervention fidelity and cultural adaptive needs; (6) document the process of adaptation, pilot the adapted intervention, and evaluate its effectiveness before moving to dissemination and implementation on a large scale. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Williams, Ann B.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Wang, Honghong; Li, Xianhong] Cent S Univ, Sch Nursing, Changsha, Hunan, Peoples R China. [Burgess, Jane] VA Greater Los Angeles Healthcare Syst, QUERI HIV Hepatitis, Los Angeles, CA 90024 USA. [Danvers, Karina] Yale Univ, Connecticut AIDS Educ & Training Ctr, Sch Nursing, New Haven, CT 06610 USA. RP Williams, AB (reprint author), Univ Calif Los Angeles, Sch Nursing, 10880 Wilshire Blvd,Suite 550, Los Angeles, CA 90024 USA. EM awilliams@sonnet.ucla.edu; Honghong_wang@tom.com; Jane.Burgess@VA.gov; Xianhong_li228@hotmail.com; Karina.Danvers@yale.edu FU National Institute of Mental Health, USA FX Partial funding provided by the National Institute of Mental Health, USA, which had no role in the conduct of the work. NR 26 TC 3 Z9 5 U1 4 U2 38 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7489 J9 INT J NURS STUD JI Int. J. Nurs. Stud. PD APR PY 2013 VL 50 IS 4 SI SI BP 487 EP 494 DI 10.1015/j.ijnurstu.2012.08.018 PG 8 WC Nursing SC Nursing GA 117UC UT WOS:000316977600006 PM 22981372 ER PT J AU Poorvu, PD Sadow, CA Townamchai, K Damato, AL Viswanathan, AN AF Poorvu, Philip D. Sadow, Cheryl A. Townamchai, Kanokpis Damato, Antonio L. Viswanathan, Akila N. TI Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; CISPLATIN CHEMOTHERAPY; SMALL-BOWEL; GUIDED IMRT; CARCINOMA; RADIOTHERAPY; IRRADIATION; GUIDELINES; VOLUME; BRACHYTHERAPY AB Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade >= 3 acute (< 90 day) and late (>= 90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade >= 3 GI toxicity and 3/46 patients (6.5%) experienced late grade >= 3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy. (C) 2013 Elsevier Inc. C1 [Poorvu, Philip D.; Townamchai, Kanokpis; Damato, Antonio L.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Poorvu, Philip D.; Townamchai, Kanokpis; Damato, Antonio L.; Viswanathan, Akila N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sadow, Cheryl A.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Sadow, Cheryl A.] Harvard Univ, Sch Med, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1 L-2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Viswanathan, Akila/0000-0002-2003-0392 NR 20 TC 20 Z9 23 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 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2013 VL 85 IS 5 BP 1262 EP 1268 DI 10.1016/j.ijrobp.2012.10.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115CR UT WOS:000316790500032 PM 23182395 ER PT J AU Nanda, A Chen, MH Moran, BJ Braccioforte, MH D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. D'Amico, Anthony V. TI Cardiovascular Comorbidity and Mortality in Men With Prostate Cancer Treated With Brachytherapy-Based Radiation With or Without Hormonal Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID STATISTICS AB Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P <. 001) and in men with diabetes mellitus (AHR 1.60, P = .03) and hypertension (AHR 1.25, P = .04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P = .17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P < .001), prostate-specific antigen level (AHR 1.25, P = .008), and Gleason score 8-10 disease (AHR 1.71, P = .003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual. (C) 2013 Elsevier Inc. C1 [Nanda, Akash] MD Anderson Canc Ctr Orlando, Dept Radiat Oncol, Orlando, FL USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Nanda, A (reprint author), Anderson Canc Ctr Orlando, Dept Radiat Oncol, 1400 S Orange Ave,MP 760, Orlando, FL 32806 USA. EM akash.nanda@orlandohealth.com NR 20 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2013 VL 85 IS 5 BP E209 EP E215 DI 10.1016/j.ijrobp.2012.11.039 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115CR UT WOS:000316790500002 PM 23332383 ER PT J AU Oreskovic, NM Goodman, E AF Oreskovic, Nicolas M. Goodman, Elizabeth TI Association of Optimism With Cardiometabolic Risk in Adolescents SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Optimism; Biomarkers; Cardiometabolic risk; Adolescents; Disparities ID CORONARY-HEART-DISEASE; LIFE ORIENTATION TEST; DISPOSITIONAL OPTIMISM; CARDIOVASCULAR HEALTH; SOCIOECONOMIC-STATUS; NATIONAL-HEALTH; SOCIAL-STATUS; SELF-ESTEEM; INFLAMMATION; BIOMARKERS AB Purpose: Dispositional optimism is a psychological trait associated with cardiovascular disease outcomes in adults. However, it is not known whether these associations are present in adolescents. We attempted to determine whether an association exits between optimism and 9 biomarkers of cardiometabolic risk during adolescence. Because cardiometabolic risk differs by race and ethnicity, we also explored whether race and ethnicity moderated the optimism-cardiometabolic risk relationship. Methods: This was a cross-sectional study of 529 non-Hispanic white and 421 non-Hispanic black seventh through 12th graders living in greater Cincinnati in 2001-2002. We measured dispositional optimism with the Life-Orientation Test-Revised as a single continuum and as separate optimism and pessimism dimensions. Multivariable regression analyses tested for associations between optimism and nine biomarkers of risk (interleukin-6, tumor necrosis factor-alpha, lipids, insulin, glucose, and fibrinogen), adjusting for age, gender, parent education, body mass index, smoking, and pubertal stage. Results: Dispositional optimism with the Life-Orientation Test-Revised as a single continuum was inversely associated with two risks (interleukin-6, beta = -.03, p = .02; insulin, beta = -.02, p = .01), but only among blacks. Optimism and pessimism were inversely related (R = -.27, p < .001) and both were higher in blacks than whites (p < .001). Optimism was directly associated with high-density lipoprotein among all subjects (beta = .42, p = .03), and among blacks (beta = .74, p = .02) but not whites. Among blacks, optimism was also inversely associated with interleukin-6 (beta = - .07, p = .001) and triglycerides (beta = -.02, p = .04). Pessimism was inversely associated with glucose, but only in whites (beta = -.38, p = .03). Conclusions: Associations between dispositional optimism and cardiometabolic risks are present in adolescence and vary by race and ethnicity. A better understanding of the natural history of these associations over the lifespan may help decrease disparities and prevent cardiometabolic disease. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Oreskovic, Nicolas M.; Goodman, Elizabeth] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM noreskovic@partners.org OI Goodman, Elizabeth/0000-0002-9640-9884; Oreskovic, Nicolas/0000-0001-8702-8636 FU National Institutes of Health [R01HD041527, R01DK59183, K23HL103841] FX This research was supported by National Institutes of Health Grants R01HD041527, R01DK59183, and K23HL103841. NR 36 TC 4 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 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 2013 VL 52 IS 4 BP 407 EP 412 DI 10.1016/j.jadohealth.2012.09.011 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 114HE UT WOS:000316730900005 PM 23298981 ER PT J AU Feruglio, PF Vinegoni, C Fexon, L Thurber, G Sbarbati, A Weissleder, R AF Feruglio, Paolo Fumene Vinegoni, Claudio Fexon, Lioubov Thurber, Greg Sbarbati, Andrea Weissleder, Ralph TI Noise suppressed, multifocus image fusion for enhanced intraoperative navigation SO JOURNAL OF BIOPHOTONICS LA English DT Article DE intraoperative imaging; image processing; fluorescence microscopy; intravital microscopy ID CANCER; A33 AB Current intraoperative imaging systems are typically not able to provide sharp' images over entire large areas or entire organs. Distinct structures such as tissue margins or groups of malignant cells are therefore often difficult to detect, especially under low signal-to-noise-ratio conditions. In this report, we introduce a noise suppressed multifocus image fusion algorithm, that provides detailed reconstructions even when images are acquired under sub-optimal conditions, such is the case for real time fluorescence intraoperative surgery. The algorithm makes use of the Anscombe transform combined with a multi-level stationary wavelet transform with individual threshold-based shrinkage. While the imaging system is integrated with a respiratory monitor triggering system, it can be easily adapted to any commercial imaging system. The developed algorithm is made available as a plugin for Osirix. ((c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) C1 [Feruglio, Paolo Fumene; Vinegoni, Claudio; Fexon, Lioubov; Thurber, Greg; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Feruglio, Paolo Fumene; Vinegoni, Claudio; Fexon, Lioubov; Thurber, Greg; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Feruglio, Paolo Fumene; Sbarbati, Andrea] Univ Verona, Dept Neurol Neuropsychol Morphol & Movement Sci, I-37134 Verona, Italy. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Thurber, Greg/0000-0001-7570-2080 FU [T32CA79443-11]; [2P50CA086355-12]; [2RO1EB006432]; [2U24CA092782] FX This project was funded in part by funds from grants Nr. T32CA79443-11, 2P50CA086355-12, 2RO1EB006432, 2U24CA092782. NR 24 TC 2 Z9 2 U1 0 U2 16 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X J9 J BIOPHOTONICS JI J. Biophotonics PD APR PY 2013 VL 6 IS 4 BP 363 EP 370 DI 10.1002/jbio.201200086 PG 8 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 117ND UT WOS:000316959300012 PM 22887724 ER PT J AU Spatz, JM Ellman, R Cloutier, AM Louis, L van Vliet, M Suva, LJ Dwyer, D Stolina, M Ke, HZ Bouxsein, ML AF Spatz, Jordan M. Ellman, Rachel Cloutier, Alison M. Louis, Leeann van Vliet, Miranda Suva, Larry J. Dwyer, Denise Stolina, Marina Ke, Hua Zhu Bouxsein, Mary L. TI Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE LOSS; HINDLIMB UNLOADING; SCLEROSTIN ANTIBODY; BONE; MOUSE; BONE DENSITY ID INCREASES BONE-FORMATION; ADIPOCYTE DIFFERENTIATION; RAT MODEL; MASS; ADIPOGENESIS; MICE; WNT; IMMOBILIZATION; EXPRESSION; STRENGTH AB Sclerostin, a product of the SOST gene produced mainly by osteocytes, is a potent negative regulator of bone formation that appears to be responsive to mechanical loading, with SOST expression increasing following mechanical unloading. We tested the ability of a murine sclerostin antibody (SclAbII) to prevent bone loss in adult mice subjected to hindlimb unloading (HLU) via tail suspension for 21 days. Mice (n=1117/group) were assigned to control (CON, normal weight bearing) or HLU and injected with either SclAbII (subcutaneously, 25mg/kg) or vehicle (VEH) twice weekly. SclAbII completely inhibited the bone deterioration due to disuse, and induced bone formation such that bone properties in HLU-SclAbII were at or above values of CON-VEH mice. For example, hindlimb bone mineral density (BMD) decreased 9.2%+/- 1.0% in HLU-VEH, whereas it increased 4.2%+/- 0.7%, 13.1%+/- 1.0%, and 30.6%+/- 3.0% in CON-VEH, HLU-SclAbII, and CON-SclAbII, respectively (p<0.0001). Trabecular bone volume, assessed by microcomputed tomography (mu CT) imaging of the distal femur, was lower in HLU-VEH versus CON-VEH (p<0.05), and was 2- to 3-fold higher in SclAbII groups versus VEH (p<0.001). Midshaft femoral strength, assessed by three-point bending, and distal femoral strength, assessed by microfinite element analysis (mu FEA), were significantly higher in SclAbII versus VEH-groups in both loading conditions. Serum sclerostin was higher in HLU-VEH (134 +/- 5pg/mL) compared to CON-VEH (116 +/- 6pg/mL, p<0.05). Serum osteocalcin was decreased by hindlimb suspension and increased by SclAbII treatment. Interestingly, the anabolic effects of sclerostin inhibition on some bone outcomes appeared to be enhanced by normal mechanical loading. Altogether, these results confirm the ability of SclAbII to abrogate disuse-induced bone loss and demonstrate that sclerostin antibody treatment increases bone mass by increasing bone formation in both normally loaded and underloaded environments. (c) 2013 American Society for Bone and Mineral Research. C1 [Spatz, Jordan M.; Ellman, Rachel] Harvard Massachusetts Inst Technol MIT Div Hlth S, Bioastronaut Program, Cambridge, MA USA. [Spatz, Jordan M.; Ellman, Rachel; Cloutier, Alison M.; Louis, Leeann; van Vliet, Miranda; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Spatz, Jordan M.; Bouxsein, Mary L.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. [Suva, Larry J.] Univ Arkansas, Dept Orthoped Surg, Ctr Orthopaed Res, Sch Med, Little Rock, AR 72204 USA. [Dwyer, Denise; Stolina, Marina; Ke, Hua Zhu] Amgen Inc, Thousand Oaks, CA 91320 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. RP Bouxsein, ML (reprint author), Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, 330 Brookline Ave, Boston, MA 02215 USA. EM mbouxsei@bidmc.harvard.edu FU NIH [R21 AR057522]; NASA [NNX10AE39G]; National Space Biomedical Research Institute through NASA [NCC 9-58]; Amgen; NASA; Northrop Grumman Aerospace Systems PhD Training Fellowship FX This work was funded by NIH R21 AR057522, NASA NNX10AE39G, the National Space Biomedical Research Institute through NASA NCC 9-58, and a research grant from Amgen. RE was supported by a NASA-Jenkins predoctoral fellowship. JMS was supported by a Northrop Grumman Aerospace Systems PhD Training Fellowship. NR 31 TC 50 Z9 51 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2013 VL 28 IS 4 BP 865 EP 874 DI 10.1002/jbmr.1807 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112EB UT WOS:000316573900018 PM 23109229 ER PT J AU Ellman, R Spatz, J Cloutier, A Palme, R Christiansen, BA Bouxsein, ML AF Ellman, Rachel Spatz, Jordan Cloutier, Alison Palme, Rupert Christiansen, Blaine A. Bouxsein, Mary L. TI Partial reductions in mechanical loading yield proportional changes in bone density, bone architecture, and muscle mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MECHANICAL LOADING; DISUSE; MECHANOSTAT; FUNCTIONAL ADAPTATION; WEIGHT BEARING ID STRAIN MAGNITUDE; MURINE MODEL; MICE; RATS; IMMOBILIZATION; CORTICOSTERONE; MECHANOSTAT AB Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days. A hindlimb unloaded (HLU) group was included for comparison in addition to age-matched controls in normal housing. Gait kinematics was measured across the full range of weight bearing, and some minor alterations in gait from PWS were identified. With PWS, bone and muscle changes were generally proportional to the degree of unloading. Specifically, total body and hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the distal femur, and cortical area of the femur midshaft were all linearly related to the degree of unloading. Even a load reduction to 70% of normal weight bearing was associated with significant bone deterioration and muscle atrophy. Weight bearing at 20% did not lead to better bone outcomes than HLU despite less muscle atrophy and presumably greater mechanical stimulus, requiring further investigation. These data confirm that the PWS model is highly effective in applying controllable, reduced, long-term loading that produces predictable, discrete adaptive changes in muscle and bone of the hindlimb. (c) 2012 American Society for Bone and Mineral Research (c) 2013 American Society for Bone and Mineral Research C1 [Ellman, Rachel; Spatz, Jordan] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Christiansen, Blaine A.; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Christiansen, Blaine A.; Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA USA. [Spatz, Jordan; Bouxsein, Mary L.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Palme, Rupert] Univ Vet Med, Dept Biomed Sci Biochem, Vienna, Austria. [Christiansen, Blaine A.] Univ Calif Davis, Med Ctr, Dept Orthopaed Surg, Sacramento, CA 95817 USA. RP Ellman, R (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN115, Boston, MA 02215 USA. EM rellman@bidmc.harvard.edu RI Palme, Rupert/A-3499-2008; Christiansen, Blaine/F-9021-2010 OI Palme, Rupert/0000-0001-9466-3662; FU NIH [R21 AR057522]; NASA [NNX10AE39G]; National Space Biomedical Research Institute through NASA [NCC 9-58]; NASA; Northrop Grumman Aerospace Systems Ph.D. Training Fellowship FX This work was supported by NIH R21 AR057522, NASA NNX10AE39G, and the National Space Biomedical Research Institute through NASA NCC 9-58. RE was supported by a NASA-Jenkins predoctoral fellowship. JMS was supported by a Northrop Grumman Aerospace Systems Ph.D. Training Fellowship. We thank Erika Wagner for consultation on the use of the PWS system. We thank Timothy O'Shea for his assistance with the processing of fecal samples. NR 29 TC 23 Z9 23 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2013 VL 28 IS 4 BP 875 EP 885 DI 10.1002/jbmr.1814 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112EB UT WOS:000316573900019 PM 23165526 ER PT J AU Copin, JC da Silva, RF Fraga-Silva, RA Capettini, L Quintao, S Lenglet, S Pelli, G Galan, K Burger, F Braunersreuther, V Schaller, K Deruaz, M Proudfoot, AE Dallegri, F Stergiopulos, N Santos, RAS Gasche, Y Mach, F Montecucco, F AF Copin, Jean-Christophe da Silva, Rafaela F. Fraga-Silva, Rodrigo A. Capettini, Luciano Quintao, Silvia Lenglet, Sebastien Pelli, Graziano Galan, Katia Burger, Fabienne Braunersreuther, Vincent Schaller, Karl Deruaz, Maud Proudfoot, Amanda E. Dallegri, Franco Stergiopulos, Nikolaos Santos, Robson A. S. Gasche, Yvan Mach, Francois Montecucco, Fabrizio TI Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; atherosclerosis; brain ischemia; carotid artery; inflammation ID CEREBRAL-ARTERY OCCLUSION; SHEAR-STRESS; MODEL; HYPERCHOLESTEROLEMIA; CHEMOKINES; MEDIATORS; DISEASE; SINGLE; RATS; DIET AB Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a 'cast' carotid device. In the second model, acute Evasin-3 treatment (5 minutes after cerebral ischemia onset) was assessed in mice subjected to transient left middle cerebral artery occlusion. Although CXCL1 and CXCL2 were upregulated in both atherosclerotic plaques and infarcted brain, only CXCL1 was detectable in serum. In carotid atherosclerosis, treatment with Evasin-3 was associated with reduction in intraplaque neutrophil and matrix metalloproteinase-9 content and weak increase in collagen as compared with Vehicle. In ischemic stroke, treatment with Evasin-3 was associated with reduction in ischemic brain neutrophil infiltration and protective oxidants. No other effects in clinical and histological outcomes were observed. We concluded that Evasin-3 treatment was associated with reduction in neutrophilic inflammation in both mouse models. However, Evasin-3 administration after cerebral ischemia onset failed to improve poststroke outcomes. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 490-498; doi:10.1038/jcbfm.2012.198; published online 19 December 2012 C1 [Copin, Jean-Christophe] Univ Hosp Geneva, Div Neurosurg, Geneva, Switzerland. [Copin, Jean-Christophe; Schaller, Karl; Gasche, Yvan] Univ Geneva, Geneva Neurosci Ctr, CH-1211 Geneva, Switzerland. [da Silva, Rafaela F.; Fraga-Silva, Rodrigo A.; Capettini, Luciano; Quintao, Silvia; Stergiopulos, Nikolaos] Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland. [da Silva, Rafaela F.; Fraga-Silva, Rodrigo A.; Capettini, Luciano; Quintao, Silvia; Santos, Robson A. S.] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil. [Lenglet, Sebastien; Pelli, Graziano; Galan, Katia; Burger, Fabienne; Braunersreuther, Vincent; Mach, Francois; Montecucco, Fabrizio] Univ Geneva, Fdn Med Res, Div Cardiol, CH-1211 Geneva, Switzerland. [Deruaz, Maud] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Proudfoot, Amanda E.] Merck Serono Geneva Res Ctr, Geneva, Switzerland. [Dallegri, Franco; Montecucco, Fabrizio] Univ Genoa, Dept Internal Med, Sch Med, Clin Internal Med 1, I-16126 Genoa, Italy. [Gasche, Yvan] Univ Hosp Geneva, Div Intens Care Med, Geneva, Switzerland. RP Montecucco, F (reprint author), Univ Geneva, Dept Internal Med, Div Cardiol, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland. EM fabrizio.montecucco@unige.ch RI Nbiofar, Inct/J-9539-2013; LENGLET, Sebastien/N-8923-2013; Santos, Robson/C-9336-2011; Montecucco, Fabrizio/K-8543-2016; OI LENGLET, Sebastien/0000-0002-4853-8163; Santos, Robson/0000-0001-8738-5852; Montecucco, Fabrizio/0000-0003-0823-8729; DALLEGRI, FRANCO/0000-0001-9537-4547; Capettini, Luciano/0000-0002-6487-9558 FU Brazilian Swiss Joint Research Program (BSJRP); EU [201668]; Swiss National Science Foundation [310030-118245, 32003B-134963/1]; Novartis Foundation FX This research was funded by the Brazilian Swiss Joint Research Program (BSJRP) to Dr F Mach, Dr N Stergiopulos, and AS Robson. This research was funded by EU FP7, Grant number 201668, AtheroRemo to Dr F Mach. This work was also supported by the Swiss National Science Foundation Grants to Dr F Mach (#310030-118245) and Dr F Montecucco (#32003B-134963/1). This work was also supported by a Grant from Novartis Foundation to Dr F Montecucco. NR 35 TC 25 Z9 25 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2013 VL 33 IS 4 BP 490 EP 498 DI 10.1038/jcbfm.2012.198 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 117CR UT WOS:000316930200004 PM 23250107 ER PT J AU Yun, X Maximov, VD Yu, J Zhu, H Vertegel, AA Kindy, MS AF Yun, Xiang Maximov, Victor D. Yu, Jin Zhu, Hong Vertegel, Alexey A. Kindy, Mark S. TI Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anti-oxidants; antibody; cerebral ischemia; nanoparticles; superoxide dismutase ID CONJUGATED SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; OXYGEN RADICALS; LIPID-PEROXIDATION; FOREBRAIN ISCHEMIA; EDEMA FORMATION; FOCAL ISCHEMIA; IN-VIVO; RATS; BARRIER AB Stroke is one of the major causes of death and disability in the United States. After cerebral ischemia and reperfusion injury, the generation of reactive oxygen species (ROS) and reactive nitrogen species may contribute to the disease process through alterations in the structure of DNA, RNA, proteins, and lipids. We generated various nanoparticles (liposomes, polybutylcyanoacrylate (PBCA), or poly(lactide-co-glycolide) (PLGA)) that contained active superoxide dismutase (SOD) enzyme (4,000 to 20,000 U/kg) in the mouse model of cerebral ischemia and reperfusion injury to determine the impact of these molecules. In addition, the nanoparticles were untagged or tagged with nonselective antibodies or antibodies directed against the N-methyl-D-aspartate (NMDA) receptor 1. The nanoparticles containing SOD protected primary neurons in vitro from oxygen-glucose deprivation (OGD) and limited the extent of apoptosis. The nanoparticles showed protection against ischemia and reperfusion injury when applied after injury with a 50% to 60% reduction in infarct volume, reduced inflammatory markers, and improved behavior in vivo. The targeted nanoparticles not only showed enhanced protection but also showed localization to the CA regions of the hippocampus. Nanoparticles alone were not effective in reducing infarct volume. These studies show that targeted nanoparticles containing protective factors may be viable candidates for the treatment of stroke. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 583-592; doi:10.1038/jcbfm.2012.209; published online 6 February 2013 C1 [Yun, Xiang; Maximov, Victor D.; Vertegel, Alexey A.; Kindy, Mark S.] Clemson Univ, Dept Bioengn, Clemson, SC USA. [Yu, Jin; Zhu, Hong; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kindy, Mark S.] CU MUSC Bioengn Res Program, Charleston, SC USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. EM kindyms@musc.edu RI Maximov, Victor/G-2991-2013 FU National Institutes of Health [R01 ES016774-01, 5 P20 RR016461, 8P20GM103444-04, 5P20RR021949-03]; VA Merit Award; National Science Foundation [IIP-917987] FX This work was partially supported by grants from the National Institutes of Health (R01 ES016774-01, 5 P20 RR016461, 8P20GM103444-04, and 5P20RR021949-03), VA Merit Award, and a grant from the National Science Foundation (IIP-917987). Dr Kindy is a Research Career Scientist in the VA. NR 49 TC 31 Z9 32 U1 5 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2013 VL 33 IS 4 BP 583 EP 592 DI 10.1038/jcbfm.2012.209 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 117CR UT WOS:000316930200015 PM 23385198 ER PT J AU Roccaro, AM Sacco, A Maiso, P Azab, AK Tai, YT Reagan, M Azab, F Flores, LM Campigotto, F Weller, E Anderson, KC Scadden, DT Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Maiso, Patricia Azab, Abdel-Kareem Tai, Yu-Tzu Reagan, Michaela Azab, Feda Flores, Ludmila M. Campigotto, Federico Weller, Edie Anderson, Kenneth C. Scadden, David T. Ghobrial, Irene M. TI BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROMOTE TUMOR-GROWTH; IN-VITRO; PROTEOMIC ANALYSIS; MICROARRAY DATA; KAPPA-B; EXPRESSION; VIVO; MICRORNAS; VESICLES; MICROVESICLES AB BM mesenchymal stromal cells (BM-MSCs) support multiple myeloma (MM) cell growth, but little is known about the putative mechanisms by which the BM microenvironment plays an oncogenic role in this disease. Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR) content differed between MM and normal BM-MSCs, with a lower content of the tumor suppressor miR-15a. In addition, MM BM-MSC-derived exosomes had higher levels of oncogenic proteins, cytokines, and adhesion molecules compared with exosomes from the cells of origin. Importantly, whereas MM BM-MSC-derived exosomes promoted MM tumor growth, normal BM-MSC exosomes inhibited the growth of MM cells. In summary, these in vitro and in vivo studies demonstrated that exosome transfer from BM-MSCs to clonal plasma cells represents a previously undescribed and unique mechanism that highlights the contribution of BM-MSCs to MM disease progression. C1 [Roccaro, Aldo M.; Sacco, Antonio; Maiso, Patricia; Azab, Abdel-Kareem; Tai, Yu-Tzu; Reagan, Michaela; Azab, Feda; Flores, Ludmila M.; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Campigotto, Federico; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 225, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; Reagan, Michaela/E-3549-2017; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Maiso, Patricia/0000-0003-3745-1924; Reagan, Michaela/0000-0003-2884-6481 FU Noxxon; Bristol-Myers Squibb; GlaxoSmithKline; NIH [R01CA154648, R01CA133799, R01CA125690]; Accademia Nazionale dei Lincei (Rome, Italy) FX Irene M. Ghobrial serves on advisory boards for Bristol-Myers Squibb, Millennium, Novartis, and Noxxon and receives research support from Noxxon and Bristol-Myers Squibb. Kenneth C. Anderson serves on the board of directors and/or advisory committees for Celgene, Millennium, Bristol-Myers Squibb, and Onyx and is a scientific founder of Acetylon and Oncopep. David T. Scadden is a stock owner and consultant for Fate Therapeutics, serves as a consultant for GlaxoSmithKline and Bone Therapeutics, and receives research support from GlaxoSmithKline.; The authors thank Lisa Cameron (Confocal and Light Microscopy Core Facility, Dana-Farber Cancer Institute) and Maria Ericcson (Electron Microscopy Facility, Harvard Medical School) for technical help; Riccardo Dalla-Favera for providing C57BL/6 miR-15a/16-1-/- mice; and Siobhan Glavey for editing the manuscript. This work was supported by NIH grants R01CA154648, R01CA133799, and R01CA125690 and by Accademia Nazionale dei Lincei (Rome, Italy). NR 54 TC 184 Z9 191 U1 13 U2 66 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2013 VL 123 IS 4 BP 1542 EP 1555 DI 10.1172/JCI66517 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118JM UT WOS:000317021800017 PM 23454749 ER PT J AU Wang, C Yi, T Qin, LF Maldonado, RA von Andrian, UH Kulkarni, S Tellides, G Pober, JS AF Wang, Chen Yi, Tai Qin, Lingfeng Maldonado, Roberto A. von Andrian, Ulrich H. Kulkarni, Sanjay Tellides, George Pober, Jordan S. TI Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPONSES IN-VIVO; DENDRITIC CELLS; ALLOGRAFT-REJECTION; TRANSPLANTATION TOLERANCE; TRANSENDOTHELIAL MIGRATION; CORNEAL ALLOGRAFTS; IMMUNE PRIVILEGE; GRAFT-REJECTION; EFFECTOR-CELLS; CUTTING EDGE AB Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloiummunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4(+) memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4(+) memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4(+)CD25(hi)CD127(lo)FoxP3(+) cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection. C1 [Wang, Chen; Yi, Tai; Pober, Jordan S.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Qin, Lingfeng; Kulkarni, Sanjay; Tellides, George] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. [Maldonado, Roberto A.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Pober, JS (reprint author), Yale Univ, Sch Med, 10 Amistad St,Room 401D, New Haven, CT 06520 USA. EM jordan.pober@yale.edu FU NIH [P01-HL070295, R01-HL109455, AI06925, AI095261]; NIH Medical Scientist Training Program grant [T32-GM007205]; NIH National Research Service Award (NRSA) predoctoral fellowship [F30HL114253] FX We thank L. Benson and G. Davis for expert assistance in EC culture and animal care. This work is supported by NIH grants P01-HL070295 to J.S. Pober and G. Tellides, R01-HL109455 to J.S. Pober, and AI06925 and AI095261 to U.H. von Andrian. C. Wang was supported by an NIH Medical Scientist Training Program grant (T32-GM007205) and is currently supported by an NIH National Research Service Award (NRSA) predoctoral fellowship (F30HL114253). NR 85 TC 27 Z9 27 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2013 VL 123 IS 4 BP 1677 EP 1693 DI 10.1172/JCI66204 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118JM UT WOS:000317021800028 PM 23478407 ER PT J AU Roth, AJ Ooi, JD Hess, JJ van Timmeren, MM Berg, EA Poulton, CE McGregor, J Burkart, M Hogan, SL Hu, YC Winnik, W Nachman, PH Stegeman, CA Niles, J Heeringa, P Kitching, AR Holdsworth, S Jennette, JC Preston, GA Falk, RJ AF Roth, Aleeza J. Ooi, Joshua D. Hess, Jacob J. van Timmeren, Mirjan M. Berg, Elisabeth A. Poulton, Caroline E. McGregor, JulieAnne Burkart, Madelyn Hogan, Susan L. Hu, Yichun Winnik, Witold Nachman, Patrick H. Stegeman, Coen A. Niles, John Heeringa, Peter Kitching, A. Richard Holdsworth, Stephen Jennette, J. Charles Preston, Gloria A. Falk, Ronald J. TI Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; SMALL-VESSEL VASCULITIS; MPO-ANCA; MICROSCOPIC POLYANGIITIS; WEGENERS-GRANULOMATOSIS; NATURAL AUTOANTIBODIES; BASEMENT-MEMBRANE; MYELOPEROXIDASE; GLOMERULONEPHRITIS; CERULOPLASMIN AB Anti-neutrophil cytoplasmic antibody-associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). This multicenter study sought to determine whether differences in ANCA epitope specificity explain why, in some cases, conventional serologic assays do not correlate with disease activity, why naturally occurring anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are undetected in patients with ANCA-negative disease. Autoantibodies from human and murine samples were epitope mapped using a highly sensitive epitope excision/mass spectrometry approach. Data indicated that MPO autoantibodies from healthy individuals had epitope specificities different from those present in ANCA disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA-negative disease that reacted against a sole linear sequence. Autoantibodies against this epitope had pathogenic properties, as demonstrated by their capacity to activate neutrophils in vitro and to induce nephritis in mice. The confounder for serological detection of these autoantibodies was the presence of a fragment of ceruloplasmin in serum, which was eliminated in purified IgG, allowing detection. These findings implicate immunodominant epitopes in the pathology of ANCA-associated vasculitis and suggest that autoantibody diversity may be common to other autoimmune diseases. C1 [Roth, Aleeza J.; Hess, Jacob J.; Berg, Elisabeth A.; Poulton, Caroline E.; McGregor, JulieAnne; Burkart, Madelyn; Hogan, Susan L.; Hu, Yichun; Nachman, Patrick H.; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.] Univ N Carolina, Dept Med, Div Nephrol & Hypertens, UNC Kidney Ctr, Chapel Hill, NC USA. [Ooi, Joshua D.; Kitching, A. Richard; Holdsworth, Stephen] Monash Univ, Dept Med, Clayton, Vic, Australia. [van Timmeren, Mirjan M.; Stegeman, Coen A.; Heeringa, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands. [Winnik, Witold] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Niles, John] Massachusetts Gen Hosp, Renal Div, Boston, MA 02114 USA. RP Falk, RJ (reprint author), UNC Kidney Ctr, CB 7155,5009 Burnett Womack Bldg, Chapel Hill, NC 27599 USA. EM Ronald_Falk@med.unc.edu RI Heeringa, Peter/A-6008-2009; OI Heeringa, Peter/0000-0001-8684-763X; Kitching, Arthur Richard/0000-0002-2713-2391; Ooi, Joshua/0000-0003-3328-2561 FU NIH/NIDDK [P01 DK058335-06]; NHMRC Australia [1008849] FX This work as supported by federal grant P01 DK058335-06 (NIH/NIDDK) and the NHMRC Australia Project Grant 1008849. The authors acknowledge the UNC Michael Hooker Proteomic Center for training and access to the 4800 MALDI-TOF/TOF mass spectrometer under the expert guidance of Nely Dicheva. We would like to thank Gary Hess for his programming assistance of the compilation of epitope profiles. Anna Fisher and Gary Hatch, U.S. Environmental Protection Agency, are acknowledged for their excellent internal review of the manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 31 TC 65 Z9 70 U1 1 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2013 VL 123 IS 4 BP 1773 EP 1783 DI 10.1172/JCI65292 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118JM UT WOS:000317021800036 PM 23549081 ER PT J AU Westover, MB Bianchi, MT Shafi, M Hoch, DB Cole, AJ Chiappa, K Cash, SS AF Westover, M. Brandon Bianchi, Matt T. Shafi, Mouhsin Hoch, Daniel B. Cole, Andrew J. Chiappa, Keith Cash, Sydney S. TI Inferring Seizure Frequency From Brief EEG Recordings SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Bayes rule; Seizure frequency; Statistical inference; EEG AB Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG. C1 [Westover, M. Brandon; Shafi, Mouhsin; Hoch, Daniel B.; Cole, Andrew J.; Cash, Sydney S.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. [Westover, M. Brandon; Bianchi, Matt T.; Shafi, Mouhsin; Hoch, Daniel B.; Cole, Andrew J.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. [Bianchi, Matt T.] Massachusetts Gen Hosp, Sleep Div, Dept Neurol, Boston, MA 02114 USA. [Chiappa, Keith] King Edward VII Mem Hosp, Paget, Bermuda. [Chiappa, Keith] Dept Internal Med, Paget, Bermuda. RP Westover, MB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WACC 827, Boston, MA 02114 USA. EM mwestover@partners.org OI Hoch, Daniel/0000-0002-4294-024X FU National Institute of Neurological Disorders and Stroke (NINDS) [NS062092] FX S. S. Cash, A. J. Cole, D. B. Hoch, and M. B. Westover receive support from National Institute of Neurological Disorders and Stroke (NINDS) (NS062092). NR 9 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD APR PY 2013 VL 30 IS 2 BP 174 EP 177 DI 10.1097/WNP.0b013e3182767c35 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 117HE UT WOS:000316943400010 PM 23545768 ER PT J AU Stone, RM AF Stone, Richard M. TI Acute Myeloid Leukemia in First Remission: To Choose Transplantation or Not? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; POSTREMISSION THERAPY; INTENSIVE CHEMOTHERAPY; METAANALYSIS; MUTATIONS; ADULTS AB A42-year-oldwomanpresented with bruising and fatigue. HerWBCcount was 10,370/mu L, with a differential showing 5% polys, 5% monos, 10% lymphocytes, and 80% myeloid-appearing blasts, some of which contained Auer rods (Fig 1). Bonemarrow examination revealed90% infiltration with myeloid-appearing blasts, and flow cytometry analysis confirmed the diagnosis of acute myeloid leukemia (AML) with expression of CD33, CD13, and CD117. Cytogenetics revealed a normal female karyotype; molecular testing for NPM1, FLT3-ITD, and CEBP alpha mutations revealed wild-type status for each gene. The patient received induction therapy with daunorubicin 90 mg/m(2) per day for 3 days and continuous-infusion cytarabine 100 mg/m(2) per day for 7 days. After an induction course complicated by Gram-negative bacterial sepsis, her counts recovered by day 32, and bone marrow examination 6 weeks after diagnosis showed a complete remission. One week later she feels well and has normal physical and laboratory examinations. She is an only child (but has a common HLA type) and presents for discussion of postremission therapy options. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 14 TC 12 Z9 13 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2013 VL 31 IS 10 BP 1262 EP 1266 DI 10.1200/JCO.2012.43.4258 PG 5 WC Oncology SC Oncology GA 118DP UT WOS:000317003300011 PM 23439752 ER PT J AU Domchek, SM Bradbury, A Garber, JE Offit, K Robson, ME AF Domchek, Susan M. Bradbury, Angela Garber, Judy E. Offit, Kenneth Robson, Mark E. TI Multiplex Genetic Testing for Cancer Susceptibility: Out on the High Wire Without a Net? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID AMINO-ACID SUBSTITUTIONS; POLICY STATEMENT UPDATE; LI-FRAUMENI SYNDROME; AMERICAN-SOCIETY; MUTATION CARRIERS; BRCA2 MUTATION; OVARIAN-CANCER; BREAST-CANCER; RISK; ONCOLOGY C1 [Domchek, Susan M.; Bradbury, Angela] Univ Penn, Philadelphia, PA 19104 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Offit, Kenneth; Robson, Mark E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Offit, Kenneth; Robson, Mark E.] Weill Cornell Med Coll, New York, NY USA. RP Domchek, SM (reprint author), Univ Penn, Philadelphia, PA 19104 USA. OI Robson, Mark/0000-0002-3109-1692 NR 26 TC 88 Z9 88 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2013 VL 31 IS 10 BP 1267 EP 1270 DI 10.1200/JCO.2012.46.9403 PG 4 WC Oncology SC Oncology GA 118DP UT WOS:000317003300012 PM 23460708 ER PT J AU Schiffer, CA Mangu, PB Wade, JC Camp-Sorrell, D Cope, DG El-Rayes, BF Gorman, M Ligibel, J Mansfield, P Levine, M AF Schiffer, Charles A. Mangu, Pamela B. Wade, James C. Camp-Sorrell, Dawn Cope, Diane G. El-Rayes, Bassel F. Gorman, Mark Ligibel, Jennifer Mansfield, Paul Levine, Mark TI Central Venous Catheter Care for the Patient With Cancer: American Society of Clinical Oncology Clinical Practice Guideline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BLOOD-STREAM INFECTION; PROSPECTIVE RANDOMIZED-TRIAL; DOUBLE-BLIND TRIAL; LOW-DOSE WARFARIN; SUBCLAVIAN-VEIN CATHETERIZATION; ACCESS DEVICES; NEUTROPENIC PATIENTS; HEMATOLOGICAL MALIGNANCIES; THROMBOTIC COMPLICATIONS; HICKMAN CATHETERS AB Purpose To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. Methods A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. Results The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. Recommendations There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low-molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy. J Clin Oncol 31:1357-1370. (C) 2013 by American Society of Clinical Oncology C1 [Schiffer, Charles A.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Schiffer, Charles A.; Mangu, Pamela B.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Wade, James C.] Geisinger Canc Inst, Danville, PA USA. [Camp-Sorrell, Dawn] Univ Alabama Birmingham, Birmingham, AL USA. [Cope, Diane G.] Florida Canc Specialists & Res Inst, Ft Myers, FL USA. [El-Rayes, Bassel F.] Emory Univ, Atlanta, GA 30322 USA. [Ligibel, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mansfield, Paul] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Levine, Mark] Henderson Hosp, Hamilton, ON, Canada. RP Schiffer, CA (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org NR 145 TC 63 Z9 65 U1 1 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2013 VL 31 IS 10 BP 1357 EP 1370 DI 10.1200/JCO.2012.45.5733 PG 14 WC Oncology SC Oncology GA 118DP UT WOS:000317003300025 PM 23460705 ER PT J AU Lepage, KQ Ching, SN Kramer, MA AF Lepage, Kyle Q. Ching, ShiNung Kramer, Mark A. TI Inferring evoked brain connectivity through adaptive perturbation SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Perturbative; Network; Estimation; Functional connectivity; Adaptive ID PULSE ELECTRICAL-STIMULATION; FUNCTIONAL CONNECTIVITY; LANGUAGE SYSTEM; EPILEPSY; SEIZURES; NETWORK; PRINCIPLES; PATTERNS; ONSET AB Inference of functional networks-representing the statistical associations between time series recorded from multiple sensors-has found important applications in neuroscience. However, networksexhibiting time-locked activity between physically independent elements can bias functional connectivity estimates employing passive measurements. Here, a perturbative and adaptive method of inferring network connectivity based on measurement and stimulation-so called "evoked network connectivity" is introduced. This procedure, employing a recursive Bayesian update scheme, allows principled network stimulation given a current network estimate inferred from all previous stimulations and recordings. The method decouples stimulus and detector design from network inference and can be suitably applied to a wide range of clinical and basic neuroscience related problems. The proposed method demonstrates improved accuracy compared to network inference based on passive observation of node dynamics and an increased rate of convergence relative to network estimation employing a na < ve stimulation strategy. C1 [Lepage, Kyle Q.; Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ching, ShiNung] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lepage, KQ (reprint author), Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. EM lepage@math.bu.edu; shinung@neurostat.mit.edu; mak@bu.edu RI Kramer, Mark/A-1291-2014 FU Cognitive Rhythms Collaborative, NSF [DMS-1042134]; NIH [DP1-OD003646]; Burroughs Wellcome Fund FX K.Q.L. acknowledges support for this research from the Cognitive Rhythms Collaborative, NSF grant DMS-1042134 S.C. acknowledges support from NIH DP1-OD003646. S.C. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. M.A.K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. NR 44 TC 5 Z9 5 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD APR PY 2013 VL 34 IS 2 BP 303 EP 318 DI 10.1007/s10827-012-0422-8 PG 16 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 113SS UT WOS:000316689300008 PM 22990598 ER PT J AU Ironson, G O'Cleirigh, C Leserman, J Stuetzle, R Fordiani, J Fletcher, M Schneiderman, N AF Ironson, Gail O'Cleirigh, Conall Leserman, Jane Stuetzle, Rick Fordiani, Joanne Fletcher, MaryAnn Schneiderman, Neil TI Gender-Specific Effects of an Augmented Written Emotional Disclosure Intervention on Posttraumatic, Depressive, and HIV-Disease-Related Outcomes: A Randomized, Controlled Trial SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE expressive writing; emotional disclosure; HIV; trauma; PTSD ID COGNITIVE-PROCESSING THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; CHILDHOOD SEXUAL-ABUSE; STRESS-DISORDER; GAY MEN; RHEUMATOID-ARTHRITIS; HEALTH-STATUS; SEROPOSITIVE WOMEN; INFECTED PATIENTS; IMMUNE FUNCTION AB Objective: Trauma histories and symptoms of PTSD occur at very high rates in people with HIV and are associated with poor disease management and accelerated disease progression. The authors of this study examined the efficacy of a brief written trauma disclosure intervention on posttraumatic stress, depression, HIV-related physical symptoms, and biological markers of HIV disease progression. Method: HIV-infected men and women were randomized to four 30-min expressive writing sessions in either a treatment (trauma writing) or an attention control (daily events writing) condition. The disclosure intervention augmented the traditional emotional disclosure paradigm with probes to increase processing by focusing on trauma appraisals, self-worth, and problem solving. Outcomes were assessed at baseline, 1-, 6-, and 12-month follow-up. Results: Hierarchical linear modeling (N = 244, intent-to-treat analyses) revealed no significant treatment effects for the group as a whole. Gender by treatment group interactions were significant such that women in the trauma-writing group had significantly reduced posttraumatic stress disorder (PTSD) symptoms (p = .017), depression (p = .009), and HIV-related symptoms (p = .022) compared with their controls. In contrast, men in the trauma-treatment condition did not improve more than controls on any outcome variables. Unexpectedly, men in the daily-event-writing control group had significantly greater reductions in depression then men in the trauma-writing group. Treatment effects were magnified in women when the analysis was restricted to those with elevated PTSD symptoms at baseline. Conclusions: A brief (4-session) guided written emotional disclosure intervention resulted in significant and meaningful reductions in PTSD, depression, and physical symptoms for women with HIV, but not for men. C1 [Ironson, Gail; Stuetzle, Rick; Fletcher, MaryAnn; Schneiderman, Neil] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [O'Cleirigh, Conall] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Leserman, Jane] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Fordiani, Joanne] VA Boston Healthcare Syst, Boston, MA USA. [Fordiani, Joanne] Boston VA Res Inst, Boston, MA USA. RP Ironson, G (reprint author), Univ Miami, Dept Psychol, 412 Flipse Bldg,5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA. EM gironson@aol.com FU NCCIH NIH HHS [R01 AT002035]; NIMH NIH HHS [T32 MH018917] NR 89 TC 15 Z9 15 U1 3 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2013 VL 81 IS 2 SI SI BP 284 EP 298 DI 10.1037/a0030814 PG 15 WC Psychology, Clinical SC Psychology GA 116UM UT WOS:000316908500009 PM 23244367 ER PT J AU Mondolfi, AEP Cressey, BD Ahmad, A Tapia-Centola, B Cohen, LM Mahmoodi, M AF Paniz Mondolfi, A. E. Cressey, B. D. Ahmad, A. Tapia-Centola, B. Cohen, L. M. Mahmoodi, M. TI Granulomatous Alopecia: A Variant of Alopecia Areata? SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE alopecia; alopecia areata; granulomatous alopecia; non-scarring ID PRIVILEGE C1 [Paniz Mondolfi, A. E.; Cressey, B. D.; Tapia-Centola, B.; Mahmoodi, M.] Tufts Med Ctr, Miraca Life Sci Res Inst, Dept Dermatol, Boston, MA 02111 USA. [Paniz Mondolfi, A. E.; Tapia-Centola, B.] MSDS UCV IVSS, Inst Biomed, Caracas, Venezuela. [Ahmad, A.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Cohen, L. M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cohen, L. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Mondolfi, AEP (reprint author), Tufts Med Ctr, Miraca Life Sci Res Inst, Dept Dermatol, 800 Washington St,Box 114, Boston, MA 02111 USA. EM Alberto.PanizMondolfi@bcm.edu NR 10 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2013 VL 40 IS 4 BP 358 EP 360 DI 10.1111/cup.12126 PG 3 WC Dermatology; Pathology SC Dermatology; Pathology GA 115KS UT WOS:000316811700002 ER PT J AU Smits, MM Ioannou, GN Boyko, EJ Utzschneider, KM AF Smits, Mark M. Ioannou, George N. Boyko, Edward J. Utzschneider, Kristina M. TI Non-alcoholic fatty liver disease as an independent manifestation of the metabolic syndrome: Results of a US national survey in three ethnic groups SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE factor analysis; insulin resistance; NAFLD; obesity ID INSULIN-RESISTANCE ATHEROSCLEROSIS; CONFIRMATORY FACTOR-ANALYSIS; NUTRITION EXAMINATION SURVEY; HEPATIC STEATOSIS; POPULATION; PREVALENCE; HEALTH; RISK; PATHOPHYSIOLOGY; STEATOHEPATITIS AB Background and Aim The metabolic syndrome (MetS) and each of its components are strongly associated with non-alcoholic fatty liver disease (NAFLD). This has led many investigators to suggest that NAFLD is an independent component of the MetS. We formally tested this hypothesis using confirmatory factor analysis, which allows comparison of different models, with or without including NAFLD as a component of the MetS. Methods We analyzed data from 3846 subjects of the Third National Health and Nutrition Examination Survey (19881994). NAFLD was defined by increased liver fat measured by ultrasonography. Results MetS by Adult Treatment Panel III criteria was present in 20.5%, and 30.2% had NAFLD, defined as mild, moderate, or severe ultrasonographic steatosis. Using confirmatory factor analysis, a basic model representing the MetS using its currently accepted components (glucose, waist, triglyceride/high-density lipoprotein ratio, and mean arterial pressure) showed excellent goodness-of-fit statistics. Addition of NAFLD to the model as a fifth independent variable decreased model fit, suggesting that NAFLD is not an additional independent component of the MetS. Analysis by ethnicity showed that addition of NAFLD decreased model fit in Whites but resulted in minor improvements in non-Hispanic Blacks and Mexican Americans. Conclusions The MetS is strongly associated with NAFLD. However, we found no evidence that NAFLD is an independent component or manifestation of the MetS. Interestingly, ethnic differences might be important in this relationship and require further study. C1 [Smits, Mark M.; Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Ioannou, George N.] VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA. [Smits, Mark M.] Vrije Univ Amsterdam, Med Ctr, Ctr Diabet, Dept Internal Med, Amsterdam, Netherlands. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu RI Smits, Mark/E-6573-2014 OI Smits, Mark/0000-0001-8236-8842 FU Department of Veterans Affairs FX The Department of Veterans Affairs provided support in part for the involvement of Drs Utzschneider, Ioannou, and Boyko in this research. NR 41 TC 42 Z9 42 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD APR PY 2013 VL 28 IS 4 BP 664 EP 670 DI 10.1111/jgh.12106 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 115MV UT WOS:000316817300013 PM 23286209 ER PT J AU Deng, M Soltesz, E Hsich, E Naka, Y Mancini, D Esmailian, F Kobashigawa, J Camacho, M Baran, D Madsen, J LePrince, P Ardehali, A AF Deng, M. Soltesz, E. Hsich, E. Naka, Y. Mancini, D. Esmailian, F. Kobashigawa, J. Camacho, M. Baran, D. Madsen, J. LePrince, P. Ardehali, A. TI Is Lactate Level during Warm Perfusion a Predictor for Post Transplant Outcomes? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Ardehali, A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. [Deng, M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Soltesz, E.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Hsich, E.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Naka, Y.; Mancini, D.] New York Presbyterian Hosp, Columbia Med Ctr, Dept Surg, New York, NY USA. [Esmailian, F.; Kobashigawa, J.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Camacho, M.] Newark Beth Isreal Med Ctr, Barnabas Hlth Heart Ctr, Dept Cardiothorac Surg, Newark, NJ USA. [Baran, D.] Newark Beth Isreal Med Ctr, Barnabas Hlth Heart Ctr, Dept Heart Failure & Transplant, Newark, NJ USA. [Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Grp Hosp Pitie Salpetriere, Dept Surg, F-75634 Paris, France. 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 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 411 BP S156 EP S157 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100408 ER PT J AU Deng, M Soltesz, E Hsich, E Naka, Y Mancini, D Esmailian, F Kobashigawa, J Camacho, M Baran, D Madsen, J LePrince, P Ardehali, A AF Deng, M. Soltesz, E. Hsich, E. Naka, Y. Mancini, D. Esmailian, F. Kobashigawa, J. Camacho, M. Baran, D. Madsen, J. LePrince, P. Ardehali, A. TI Ex-Vivo Perfusion of Human Donor Hearts Reduces Cold Ischemia Time SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Ardehali, A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. [Deng, M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Soltesz, E.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Hsich, E.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Naka, Y.; Mancini, D.] New York Presbyterian Hosp, Columbia Med Ctr, Dept Surg, New York, NY USA. [Esmailian, F.; Kobashigawa, J.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Camacho, M.] Newark Beth Isreal Med Ctr, Barnabas Hlth Heart Ctr, Dept Cardiothorac Surg, Newark, NJ USA. [Baran, D.] Newark Beth Isreal Med Ctr, Barnabas Hlth Heart Ctr, Dept Heart Failure & Transplant, Newark, NJ USA. [Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [LePrince, P.] Grp Hosp Pitie Salpetriere, Dept Surg, F-75634 Paris, France. 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 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 410 BP S156 EP S156 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100407 ER PT J AU Esmailian, F Kobashigawa, JA Naka, Y Mancini, D Soltesz, E Hsich, E Camacho, M Baran, D Madsen, J LePrince, P Deng, M Ardehali, A AF Esmailian, F. Kobashigawa, J. A. Naka, Y. Mancini, D. Soltesz, E. Hsich, E. Camacho, M. Baran, D. Madsen, J. LePrince, P. Deng, M. Ardehali, A. TI The PROCEED II International Heart Transplant Trial with the Organ Care System Technology (OCS) SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Esmailian, F.; Kobashigawa, J. A.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Naka, Y.; Mancini, D.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, Dept Surg, New York, NY USA. [Soltesz, E.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Hsich, E.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Camacho, M.] Beth Israel Deaconess Med Ctr, Barnabas Hlth Heart Ctr Newark, Dept Cardiothorac Surg, Newark, NJ USA. [Baran, D.] Beth Israel Deaconess Med Ctr, Barnabas Hlth Heart Ctr Newark, Dept Heart Failure & Transplant, Newark, NJ USA. [Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [LePrince, P.] Grp Hosp Pitie Salpetriere, Dept Surg, F-75634 Paris, France. [Deng, M.] UCLA Med Ctr, David Geffen Sch Med, Dept Cardiothorac Med, Los Angeles, CA USA. [Ardehali, A.] UCLA Med, David Geffen Sch Med, Div Cardiothor Surg, Dept Surg, Los Angeles, CA USA. NR 0 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 238 BP S95 EP S96 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100238 ER PT J AU Gilpin, SE Guyette, JP Ren, X Gonzalez, G Xiong, L Song, JJ Vacanti, J Ott, HC AF Gilpin, S. E. Guyette, J. P. Ren, X. Gonzalez, G. Xiong, L. Song, J. J. Vacanti, J. Ott, H. C. TI Up-Scaling Decellularization and Whole Organ Culture for Human Lung Regeneration SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Gilpin, S. E.; Guyette, J. P.; Ren, X.; Gonzalez, G.; Xiong, L.; Song, J. J.; Vacanti, J.; Ott, H. C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 169 BP S69 EP S70 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100170 ER PT J AU Guyette, JP Song, JJ Chuang, W Ng, R Charest, JM Gaudette, GR Vacanti, JP Ott, HC AF Guyette, J. P. Song, J. J. Chuang, W. Ng, R. Charest, J. M. Gaudette, G. R. Vacanti, J. P. Ott, H. C. TI Decellularizing Human Hearts: Characterizing Native Cardiac Matrix for Clinical Translation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Guyette, J. P.; Song, J. J.; Chuang, W.; Ng, R.; Charest, J. M.; Vacanti, J. P.; Ott, H. C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Gaudette, G. R.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. NR 0 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 100 BP S45 EP S45 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100101 ER PT J AU Madariaga, MLL Sihag, S Gottschall, JD Farkash, EA Haas, MS Carroll, MC Allan, JS AF Madariaga, M. L. L. Sihag, S. Gottschall, J. D. Farkash, E. A. Haas, M. S. Carroll, M. C. Allan, J. S. TI Mitigating Lung Ischemia-Reperfusion Injury in Miniature Swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Madariaga, M. L. L.; Sihag, S.; Gottschall, J. D.; Allan, J. S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cardiothorac Transplantat Lab, Boston, MA 02114 USA. [Madariaga, M. L. L.; Sihag, S.; Gottschall, J. D.; Farkash, E. A.; Allan, J. S.] Harvard Univ, Sch Med, Boston, MA USA. [Farkash, E. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Carroll, M. C.] Harvard Univ, Sch Med, Dept Immunol, 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 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 832 BP S298 EP S298 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100827 ER PT J AU Michel, SG Madariaga, MLL Tasaki, M Villani, V LaMuraglia, GM Farkash, EA Allan, JS Sachs, DH Yamada, K Madsen, JC AF Michel, S. G. Madariaga, M. L. L. Tasaki, M. Villani, V. LaMuraglia, G. M., II Farkash, E. A. Allan, J. S. Sachs, D. H. Yamada, K. Madsen, J. C. TI Kidney-Induced Cardiac Allograft Tolerance across a Full MHC-Barrier in Miniature Swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Michel, S. G.; Madariaga, M. L. L.; Tasaki, M.; Villani, V.; LaMuraglia, G. M., II; Allan, J. S.; Sachs, D. H.; Yamada, K.; Madsen, J. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Farkash, E. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 164 BP S68 EP S68 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100165 ER PT J AU Morell, E Wolfe, J Ziniel, S Thiagarajan, R Lang, P Cheng, H Kulik, T Smoot, L Blume, ED AF Morell, E. Wolfe, J. Ziniel, S. Thiagarajan, R. Lang, P. Cheng, H. Kulik, T. Smoot, L. Blume, E. D. TI Physician and Parent Perceptions of End-of-Life Experience in Children with Advanced Heart Disease SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Morell, E.] Harvard Univ, Sch Med, Boston, MA USA. [Wolfe, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ziniel, S.; Thiagarajan, R.; Lang, P.; Cheng, H.; Kulik, T.; Smoot, L.; Blume, E. D.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 1 BP S10 EP S10 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100002 ER PT J AU Wang, L Gidea, CG Baran, DA Pieretti, J Guerrero-Miranda, CY Weiss, JA Camacho, M Chen, C Martin, T Zucker, MJ AF Wang, L. Gidea, C. G. Baran, D. A. Pieretti, J. Guerrero-Miranda, C. Y. Weiss, J. A. Camacho, M. Chen, C. Martin, T. Zucker, M. J. TI Pre-Operative Velocity Vector Imaging To Predict the Need for Right Ventricular Support in Patients Undergoing Left Ventricular Assist Device Implantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 24-27, 2013 CL Montreal, CANADA SP Int Soc Heart & Lung Transplantat C1 [Wang, L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gidea, C. G.; Baran, D. A.; Pieretti, J.; Guerrero-Miranda, C. Y.; Weiss, J. A.; Camacho, M.; Martin, T.; Zucker, M. J.] Newark Beth Israel Med Ctr, Heart Failure & Transplant Program, Newark, NJ USA. [Chen, C.] Newark Beth Israel Med Ctr, Div Cardiol, Newark, NJ 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 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2013 VL 32 IS 4 SU S MA 760 BP S273 EP S274 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 114AM UT WOS:000316712100755 ER PT J AU Fitzgerald, DC Fonseca-Kelly, Z Cullimore, ML Safabakhsh, P Saris, CJM Zhang, GX Rostami, A AF Fitzgerald, Denise C. Fonseca-Kelly, Zoe Cullimore, Melissa L. Safabakhsh, Pegah Saris, Christiaan J. M. Zhang, Guang-Xian Rostami, Abdolmohamad TI Independent and Interdependent Immunoregulatory Effects of IL-27, IFN-beta, and IL-10 in the Suppression of Human Th17 Cells and Murine Experimental Autoimmune Encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; CENTRAL-NERVOUS-SYSTEM; HUMAN DENDRITIC CELLS; INTERFERON-BETA; MULTIPLE-SCLEROSIS; KEY REGULATOR; CYTOKINE; INTERLEUKIN-27; INFLAMMATION; WSX-1 AB IFN-beta, IL-27, and IL-10 have been shown to exert a range of similar immunoregulatory effects in murine and human experimental systems, particularly in Th1- and Th17-mediated models of autoimmune inflammatory disease. In this study we sought to translate some of our previous findings in murine systems to human in vitro models and delineate the interdependence of these different cytokines in their immunoregulatory effects. We demonstrate that human IL-27 upregulates IL-10 in T cell-activated PBMC cultures and that IFN-beta drives IL-27 production in activated monocytes. IFN-beta-driven IL-27 is responsible for the upregulation of IL-10, but not IL-17 suppression, by IFN-beta in human PBMCs. Surprisingly, IL-10 is not required for the suppression of IL-17 by either IL-27 or IFN-beta in this model or in de novo differentiating Th17 cells, nor is IL-27 signaling required for the suppression of experimental autoimmune encephalomyelitis (EAE) by IFN-beta in vivo. Furthermore, and even more surprisingly, IL-10 is not required for the suppression of Th17-biased EAE by IL-27, in sharp contrast to Th1-biased EAE. In conclusion, IFN-beta and IL-27 both induce human IL-10, both suppress human Th17 responses, and both suppress murine EAE. However, IL-27 signaling is not required for the therapeutic effect of IFN-beta in EAE. Suppression of Th17-biased EAE by IL-27 is IL-10-independent, in contrast to its mechanism of action in Th1-biased EAE. Taken together, these findings delineate a complex set of interdependent and independent immunoregulatory mechanisms of IFN-beta, IL-27, and IL-10 in human experimental models and in murine Th1- and Th17-driven autoimmunity. The Journal of Immunology, 2013, 190: 3225-3234. C1 [Fitzgerald, Denise C.] Queens Univ Belfast, Ctr Infect & Immun, Belfast BT9 7AE, Antrim, North Ireland. [Fonseca-Kelly, Zoe] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Cullimore, Melissa L.; Safabakhsh, Pegah; Zhang, Guang-Xian; Rostami, Abdolmohamad] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. [Saris, Christiaan J. M.] Amgen Inc, Dept Inflammat Res, Thousand Oaks, CA 91320 USA. RP Fitzgerald, DC (reprint author), Queens Univ Belfast, Hlth Sci Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. EM d.fitzgerald@qub.ac.uk; a.m.rostami@jefferson.edu OI Fonseca-Kelly, Zoe/0000-0002-3960-7796 FU National Institutes of Health [1U19A1082726, 2R01NS046782]; Department of Employment and Learning (Northern Ireland) FX This work was funded by National Institutes of Health Grants 1U19A1082726 and 2R01NS046782 and by the Department of Employment and Learning (Northern Ireland). NR 44 TC 18 Z9 22 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2013 VL 190 IS 7 BP 3225 EP 3234 DI 10.4049/jimmunol.1200141 PG 10 WC Immunology SC Immunology GA 112RO UT WOS:000316610700024 PM 23455508 ER PT J AU Chen, YZ Liu, WC Sun, T Huang, Y Wang, YL Deb, DK Yoon, D Kong, J Thadhani, R Li, YC AF Chen, Yunzi Liu, Weicheng Sun, Tao Huang, Yong Wang, Youli Deb, Dilip K. Yoon, Dosuk Kong, Juan Thadhani, Ravi Li, Yan Chun TI 1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; INFLAMMATORY-BOWEL-DISEASE; KAPPA-B ACTIVATION; T-CELLS; IMMUNE-SYSTEM; LETHAL INFLAMMATION; DENDRITIC CELLS; MICRORNAS; D-3; INHIBITION AB The negative feedback mechanism is essential to maintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH](2)D-3) modulates innate immune response, but the mechanism remains poorly understood. In this article, we report that vitamin D receptor signaling attenuates TLR-mediated inflammation by enhancing the negative feedback inhibition. Vitamin D receptor inactivation leads to hyperinflammatory response in mice and macrophage cultures when challenged with LPS, because of microRNA-155 (miR-155) overproduction that excessively suppresses suppressor of cytokine signaling 1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)(2)D-3 stimulates suppressor of cytokine signaling 1 by downregulating miR-155. 1,25(OH)(2)D-3 downregulates bic transcription by inhibiting NF-kappa B activation, which is mediated by a kappa B cis-DNA element located within the first intron of the bic gene. Together, these data identify a novel regulatory mechanism for vitamin D to control innate immunity. The Journal of Immunology, 2013, 190: 3687-3695. C1 [Chen, Yunzi; Liu, Weicheng; Sun, Tao; Huang, Yong; Wang, Youli; Deb, Dilip K.; Yoon, Dosuk; Kong, Juan; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. [Chen, Yunzi; Kong, Juan; Li, Yan Chun] China Med Univ, Lab Metab Dis Res & Drug Dev, Shenyang 110000, Peoples R China. [Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02115 USA. [Li, Yan Chun] Univ Chicago, Comm Mol Metab & Nutr, Div Biol Sci, Chicago, IL 60637 USA. RP Li, YC (reprint author), China Med Univ, Lab Metab Dis Res & Drug Dev, Shenyang 110000, Peoples R China. EM cyan@medicine.bsd.uchicago.edu FU National Institutes of Health [R01HL085793, R01DK092143]; Clinical and Translational Science Award from National Center for Research Resources [UL1 RR024999] FX This work was supported by National Institutes of Health Grants R01HL085793 and R01DK092143 and Clinical and Translational Science Award Grant UL1 RR024999 from National Center for Research Resources. NR 58 TC 63 Z9 69 U1 2 U2 21 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2013 VL 190 IS 7 BP 3687 EP 3695 DI 10.4049/jimmunol.1203273 PG 9 WC Immunology SC Immunology GA 112RO UT WOS:000316610700072 PM 23436936 ER PT J AU Liew, C Liew, C Windmueller, R Hollister-Lock, J Weir, G Kulkarni, RN Ho, J Qi, J Park, PJ Maas, R Chick, J Gygi, S AF Liew, C. Liew, C. Windmueller, R. Hollister-Lock, J. Weir, G. Kulkarni, R. N. Ho, J. Qi, J. Park, P. J. Maas, R. Chick, J. Gygi, S. TI COMPUTATIONALLY INFORMED IDENTIFICATION OF PANCREATIC ISLET MATURATION PATHWAYS 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 25-26, 2013 CL Chicago, IL SP Cent Soc Clinl & Translat Res (CSCTR), Midwestern Sect Amer Federat Med Res (MWAFMR) C1 [Liew, C.] Univ IL Chicago, Chicago, IL USA. [Liew, C.; Windmueller, R.; Hollister-Lock, J.; Weir, G.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ho, J.; Qi, J.; Park, P. J.; Maas, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chick, J.; Gygi, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2013 VL 61 IS 4 BP 768 EP 768 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 114FB UT WOS:000316725300019 ER PT J AU Zhang, W O-Sullivan, I Unterman, T Bu, S Mashek, M Mashek, D Kahn, C AF Zhang, W. O-Sullivan, I. Unterman, T. Bu, S. Mashek, M. Mashek, D. Kahn, C. TI ADIPOSE TRIACYGLYCEROL LIPASE (ATGL) AND G0S2 MEDIATE EFFECTS OF FOXO1 ON HEPATIC TRIACYLGLYCEROL TURNOVER, LIPOGENIC GENE EXPRESSION AND VLDL SECRETION 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 25-26, 2013 CL Chicago, IL SP Cent Soc Clinl & Translat Res (CSCTR), Midwestern Sect Amer Federat Med Res (MWAFMR) C1 [Zhang, W.; O-Sullivan, I.; Unterman, T.] Univ IL, Chicago, IL USA. [Zhang, W.; O-Sullivan, I.; Unterman, T.] JBVAMC, Chicago, IL USA. [Bu, S.; Mashek, M.; Mashek, D.] Univ Minnesota, St Paul, MN 55108 USA. [Kahn, C.] Joslin Diabet Ctr, Boston, MA 02215 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 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2013 VL 61 IS 4 BP 768 EP 769 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 114FB UT WOS:000316725300020 ER PT J AU Liew, C Liew, C Assmann, A Hu, J Goldfine, A Kulkarni, RN Lipson, KL Urano, F Sindhu, R Philipson, L Lindberg, I Templin, AT Mirmira, RG Sonenberg, N Urano, F AF Liew, C. Liew, C. Assmann, A. Hu, J. Goldfine, A. Kulkarni, R. N. Lipson, K. L. Urano, F. Sindhu, R. Philipson, L. Lindberg, I. Templin, A. T. Mirmira, R. G. Sonenberg, N. Urano, F. TI INSULIN SIGNALING MODULATES PROINSULIN PROCESSING BY REGULATING TRANSLATION INITIATION IN PANCREATIC beta-CELLS 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 25-26, 2013 CL Chicago, IL SP Cent Soc Clinl & Translat Res (CSCTR), Midwestern Sect Amer Federat Med Res (MWAFMR) C1 [Liew, C.] Univ IL Chicago, Chicago, IL USA. [Liew, C.; Assmann, A.; Hu, J.; Goldfine, A.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Lipson, K. L.; Urano, F.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Sindhu, R.; Philipson, L.] Univ Chicago, Chicago, IL 60637 USA. [Lindberg, I.] Univ Maryland, Baltimore, MD 21201 USA. [Templin, A. T.; Mirmira, R. G.] Indiana Univ Sch Med, Indianapolis, IN USA. [Sonenberg, N.] McGill Univ, Montreal, PQ, Canada. [Urano, F.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2013 VL 61 IS 4 BP 787 EP 787 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 114FB UT WOS:000316725300080 ER PT J AU O-Sullivan, I Zhang, W Unterman, T Beer-Stolz, D Kahn, C AF O-Sullivan, I. Zhang, W. Unterman, T. Beer-Stolz, D. Kahn, C. TI FOXO1 IMPAIRS GLUCOSE TOLERANCE AND PROMOTES INSULIN RESISTANCE IN LIVER-SPECIFIC INSULIN RECEPTOR KNOCKOUT (LIRKO) MICE 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 25-26, 2013 CL Chicago, IL SP Cent Soc Clinl & Translat Res (CSCTR), Midwestern Sect Amer Federat Med Res (MWAFMR) C1 [O-Sullivan, I.; Zhang, W.; Unterman, T.] Univ Illinois, Chicago, IL USA. [O-Sullivan, I.; Zhang, W.; Unterman, T.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Beer-Stolz, D.] Univ Pittsburgh, Pittsburgh, PA USA. [Kahn, C.] Joslin Diabet Ctr, Boston, MA 02215 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 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2013 VL 61 IS 4 BP 789 EP 789 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 114FB UT WOS:000316725300085 ER PT J AU Keil, B Wald, LL AF Keil, Boris Wald, Lawrence L. TI Massively parallel MRI detector arrays SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Magnetic Resonance Imaging; RF coil; Phased-array; Parallel imaging; Signal-to-noise ratio ID TO-NOISE RATIO; TRANSMISSION-LINE ARRAY; RECEIVER-COIL ARRAY; NMR PHASED-ARRAY; SURFACE COILS; HUMAN BRAIN; HEAD COIL; 3 TESLA; IMAGE-RECONSTRUCTION; MULTIPLE DETECTORS AB Originally proposed as a method to increase sensitivity by extending the locally high-sensitivity of small surface coil elements to larger areas via reception, the term parallel imaging now includes the use of array coils to perform image encoding. This methodology has impacted clinical imaging to the point where many examinations are performed with an array comprising multiple smaller surface coil elements as the detector of the MR signal. This article reviews the theoretical and experimental basis for the trend towards higher channel counts relying on insights gained from modeling and experimental studies as well as the theoretical analysis of the so-called "ultimate" SNR and g-factor. We also review the methods for optimally combining array data and changes in RF methodology needed to construct massively parallel MRI detector arrays and show some examples of state-of-the-art for highly accelerated imaging with the resulting highly parallel arrays. (C) 2013 Elsevier Inc. All rights reserved. C1 [Keil, Boris] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Keil, Boris; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Keil, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM keil@nmr.mgh.harvard.edu RI Keil, Boris/P-1411-2014; Wald, Lawrence/D-4151-2009 FU NIH [P41RR014075]; NIH Blueprint Initiative; the Human Connectome Project [U01MH093765] FX We would like to thank Andreas Potthast of Siemens AG Healthcare Sector and Graham C. Wiggins, now of NYU, for their contribution to forming our understanding of massively parallel arrays and receiver configurations and Florian Wiesinger of ETH for results modeling brain arrays and the ultimate SNR. We would like to acknowledge support from NIH, Grant P41RR014075, and the NIH Blueprint Initiative; the Human Connectome Project U01MH093765. NR 105 TC 31 Z9 31 U1 2 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2013 VL 229 BP 75 EP 89 DI 10.1016/j.jmr.2013.02.001 PG 15 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 115VT UT WOS:000316840700009 PM 23453758 ER PT J AU Feinberg, DA Setsompop, K AF Feinberg, David A. Setsompop, Kawin TI Ultra-fast MRI of the human brain with simultaneous multi-slice imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Echo planar; MRI; EPI; GRASE; Simultaneous multi-slice; Multiband; MB; EVI; GRAPPA; Functional connectivity; Connectome; fMRI; Diffusion; Fiber tractography; Fast imaging; Parallel imaging; fMRI; BOLD; Multiplexed-EPI; Simultaneous Multi-Slice EPI; Blipped-CAIPI ID WHOLE-BRAIN; 7 T; ECHO; FMRI; TIME; EPI; SENSITIVITY; RESOLUTION; SENSE; RECONSTRUCTION AB The recent advancement of simultaneous multi-slice imaging using multiband excitation has dramatically. reduced the scan time of the brain. The evolution of this parallel imaging technique began over a decade ago and through recent sequence improvements has reduced the acquisition time of multi-slice EPI by over ten fold. This technique has recently become extremely useful for (i) functional MRI studies improving the statistical definition of neuronal networks, and (ii) diffusion based fiber tractography to visualize structural connections in the human brain. Several applications and evaluations are underway which show promise for this family of fast imaging sequences. (C) 2013 Elsevier Inc. All rights reserved. C1 [Feinberg, David A.] Univ Calif Berkeley, Helen Wills Inst Neurosci, Berkeley, CA 94720 USA. [Feinberg, David A.] Adv MRI Technol, Sebastopol, CA USA. [Feinberg, David A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Setsompop, Kawin] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Setsompop, Kawin] Harvard Univ, Sch Med, Boston, MA USA. RP Feinberg, DA (reprint author), Univ Calif Berkeley, Helen Wills Inst Neurosci, Berkeley, CA 94720 USA. EM david.feinberg@berkeley.edu RI Setsompop, Kawin/P-1464-2014 OI Setsompop, Kawin/0000-0003-0455-7634 FU NIH NIBIB [R00EB012107]; NINDS [R44NS073417]; NIH Blueprint for 788 Neuroscience Research [U01MH093765] FX The work was supported by grants NIH NIBIB R00EB012107, NINDS R44NS073417, the NIH Blueprint for 788 Neuroscience Research U01MH093765 the Human Connectome project. The authors thank Nikolaus Weiskopf for helpful comments on the manuscript. The authors wish to thank all their collaborators on these pulse sequences. NR 67 TC 82 Z9 82 U1 3 U2 50 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2013 VL 229 BP 90 EP 100 DI 10.1016/j.jmr.2013.02.002 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 115VT UT WOS:000316840700010 PM 23473893 ER PT J AU Jeon, HJ Park, JH Shim, EJ AF Jeon, Hong Jin Park, Jae-Hyun Shim, Eun-Jung TI Permissive Attitude Toward Suicide and Future Intent in Individuals With and Without Depression Results From a Nationwide Survey in Korea SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Suicide; permissive attitude; Korea; depression ID MENTAL-HEALTH SURVEYS; RISK-FACTORS; DSM-IV; PSYCHOLOGICAL AUTOPSY; PSYCHIATRIC-DISORDERS; 12-MONTH PREVALENCE; LIFETIME PREVALENCE; IDEATION; COMORBIDITY; POPULATION AB Many previous studies have revealed that individuals with depression have higher thought of suicide, although not always exhibiting intent. We investigated the associated factors with respect to intent for suicide in the future. A total of 1584 adults were selected through a nationwide multistage probability sampling, randomly one person per household, and through face-to-face interviews (response rate was 63.4%) using the suicidality module of the Mini-International Neuropsychiatric Interview and the Patient Health Questionnaire-9. The group with depression (n = 152) revealed a significantly higher level of future suicide intent (t = 4.65, p <0.0001) and permissive attitude (t = 4.32, p <0.0001) than did the group without depression, which regarded suicide as free from life suffering, a personal right, and a solution to a difficult situation. After adjusting for all variables in the multiple logistic regression models, permissive attitude (adjusted odds ratio, 3.69; 95% confidence interval, 1.97-6.89) was the only factor significantly associated with future suicide intent, whereas age; sex; education years; monthly income; financial, job, and family stress; physical illness; lifetime suicide attempt; and depression showed no statistical significance. The group with depression showed significantly higher levels of future suicide intent than did the group without depression in those who had a higher permissive attitude (t = 4.18, p <0.0001) but not in those who had lower permissive attitudes (t = 1.98, p = 0.067). Permissive attitude toward suicide was associated with intent for suicide in the future in individuals with depression. Permissive attitude could be evaluated and corrected to prevent suicide. C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Park, Jae-Hyun; Shim, Eun-Jung] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Dept Social & Prevent Med, Suwon 440746, Gyeonggi Do, South Korea. [Shim, Eun-Jung] Catholic Univ Daegu, Dept Psychol, Gyeongbuk, South Korea. RP Park, JH (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Dept Social & Prevent Med, 300 Cheoncheon Dong, Suwon 440746, Gyeonggi Do, South Korea. EM pjaehyun@skku.edu FU Samsung Social Mental Health Institute [SMHI 2010-04]; National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0013064] FX Funding for this study was provided by the Samsung Social Mental Health Institute (SMHI 2010-04) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0013064). NR 38 TC 6 Z9 6 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2013 VL 201 IS 4 BP 286 EP 291 DI 10.1097/NMD.0b013e318288d2c7 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 117HV UT WOS:000316945100005 PM 23538973 ER PT J AU Hahl, P Davis, T Washburn, C Rogers, JT Smith, A AF Hahl, Peter Davis, Taron Washburn, Cecilia Rogers, Jack T. Smith, Ann TI Mechanisms of neuroprotection by hemopexin: modeling the control of heme and iron homeostasis in brain neurons in inflammatory states SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE APP; heme; hemopexin; iron; neuroprotection; stroke ID AMYLOID PRECURSOR PROTEIN; HUMAN-SERUM-ALBUMIN; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; 5'-UNTRANSLATED REGION; HYPOCHLOROUS ACID; BINDING PROTEINS; OXYGENASE-1; HEMOGLOBIN AB Hemopexin provides neuroprotection in mouse models of stroke and intracerebral hemorrhage and protects neurons in vitro against heme or reactive oxygen species (ROS) toxicity via heme oxygenase-1 (HO1) activity. To model human brain neurons experiencing hemorrhages and inflammation, we used human neuroblastoma cells, hemehemopexin complexes, and physiologically relevant ROS, for example, H2O2 and HOCl, to provide novel insights into the underlying mechanism whereby hemopexin safely maintains heme and iron homeostasis. Human amyloid precursor protein (hAPP), needed for iron export from neurons, is induced similar to twofold after hemehemopexin endocytosis by iron from heme catabolism via the iron-regulatory element of hAPP mRNA. Hemehemopexin is relatively resistant to damage by ROS and retains its ability to induce the cytoprotective HO1 after exposure to tert-butylhydroperoxide, although induction is impaired, but not eliminated, by exposure to high concentrations of H2O2 in vitro. Apo-hemopexin, which predominates in non-hemolytic states, resists damage by H2O2 and HOCl, except for the highest concentrations likely in vivo. Hemealbumin and albumin are preferential targets for ROS; thus, albumin protects hemopexin in biological fluids like CSF and plasma where it is abundant. These observations provide strong evidence that hemopexin will be neuroprotective after traumatic brain injury, with heme release in the CNS, and during the ensuing inflammation. Hemopexin sequesters heme, thus preventing unregulated heme uptake that leads to toxicity; it safely delivers heme to neuronal cells; and it activates the induction of proteins including HO1 and hAPP that keep heme and iron at safe levels in neurons. C1 [Hahl, Peter; Davis, Taron; Smith, Ann] Univ Missouri, Sch Biol Sci, Kansas City, MO 64110 USA. [Washburn, Cecilia; Rogers, Jack T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Neurochem Lab,Dept Psychiat Neurosci, Charlestown, MA USA. RP Smith, A (reprint author), Univ Missouri KC, Sch Biol Sci, Div Mol Biol & Biochem, 5007 Rockhill Rd, Kansas City, MO 64110 USA. EM smithan@umkc.edu FU National Institute of Health [NIH R21DK64363]; University of Missouri Research Board; University of Missouri Kansas City RIF; Alzheimer's Association Zenith Award FX The authors state that there is no conflict of interest. We wish to thank Dr. Clare Hawkins (Heart Research Institute, Newtown, Australia) and Dr. John Dawson (Univ. of South Carolina) for helpful discussions, and Mr. Lee Likins and Dr. S. Simons (UMKC) for their advice with the statistical analyses used. Vinusha Tummala (Department of Psychiatry-Neuroscience, Massachusetts General Hospital) is thanked for her technical help in the initial stages of the APP-IRE regulation studies. The illustration for the "in this issue" is by Joe Moran (UMKC-School of Medicine) and the neuron image is courtesy of the National Institute on Aging/National Institutes of Health. This work was partially supported by the National Institute of Health Grant NIH R21DK64363, the University of Missouri Research Board, and University of Missouri Kansas City RIF (all to A.S.) and an Alzheimer's Association Zenith Award (J.T.R.). NR 73 TC 16 Z9 17 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2013 VL 125 IS 1 BP 89 EP 101 DI 10.1111/jnc.12165 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 112YR UT WOS:000316631900010 PM 23350672 ER PT J AU Ramos-Rodriguez, JJ Pacheco-Herrero, M Thyssen, D Murillo-Carretero, MI Berrocoso, E Spires-Jones, TL Bacskai, BJ Garcia-Alloza, M AF Jose Ramos-Rodriguez, Juan Pacheco-Herrero, Mar Thyssen, Diana Isabel Murillo-Carretero, Maria Berrocoso, Esther Spires-Jones, Tara L. Bacskai, Brian J. Garcia-Alloza, Monica TI Rapid beta-Amyloid Deposition and Cognitive Impairment After Cholinergic Denervation in APP/PS1 Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE beta-amyloid; Alzheimer disease; Basal forebrain; Cholinergic system; Murine p75(NTR) saporin; Senile plaques ID PRECURSOR PROTEIN-METABOLISM; ALZHEIMERS-DISEASE; TRANSGENIC MICE; A-BETA; MOUSE MODEL; IN-VIVO; MULTIPHOTON MICROSCOPY; NEUROTROPHIN RECEPTOR; NUCLEUS BASALIS; NEURONS AB Although extensive evidence supports the role of beta-amyloid (A beta) in Alzheimer disease (AD), the neurotoxic mechanisms underlying AD pathogenesis are not understood. On the other hand, neuronal loss is the pathologic feature that best correlates with cognitive impairment. We hypothesized that cholinergic neurodegeneration may lead to A beta deposition and tested this by inducing selective cholinergic lesions in APPswe/PS1dE9 mice with murine p75(NTR) saporin (mu p75-SAP). Intracerebroventricular lesions that removed approximately 50% of cholinergic innervation to the cortex and hippocampus were induced in animals with incipient (similar to 3 months) and marked (similar to 7 months of age) A beta deposition. Cranial windows were implanted, and A beta deposition was monitored in vivo using multiphoton microscopy. Deposition of A beta was increased as soon as 7 days after the lesion, and this effect was maintained up to 3 months later. Postmortem studies using immunohistochemistry with an anti-A beta antibody corroborated these findings in both cerebral cortex and hippocampus. Tau phosphorylation was also significantly increased after the lesions. Cholinergic denervation resulted in early memory impairment at 3 months of age that worsened with age (similar to 7 months); there was a synergistic effect between cholinergic denervation and the presence of APP/PS1 transgenes. Altogether, our data suggest that cholinergic denervation may trigger A beta deposition and synergistically contribute to cognitive impairment in AD patients. C1 [Jose Ramos-Rodriguez, Juan; Pacheco-Herrero, Mar; Isabel Murillo-Carretero, Maria; Garcia-Alloza, Monica] Univ Cadiz, Sch Med, Div Physiol, Cadiz 11003, Spain. [Thyssen, Diana; Spires-Jones, Tara L.; Bacskai, Brian J.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Berrocoso, Esther] Univ Cadiz, Sch Med, Dept Neurosci, Cadiz 11003, Spain. [Berrocoso, Esther] Inst Salud Carlos III, Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. RP Garcia-Alloza, M (reprint author), Univ Cadiz, Sch Med, Div Physiol, Plaza Fragela 9,4 Piso,410, Cadiz 11003, Spain. EM monica.garcia@uca.es OI Murillo-Carretero, Maria Isabel/0000-0003-4782-937X FU ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion [PS09/00969]; Junta de Andalucia, Proyectos de Excelencia [P11-CTS-7847]; Instituto de Salud Carlos III; FEDER (European Union); Fondo Europeo de Desarrollo Regional "Una manera de hacer Europa" [PI12/00675]; NIH [R01 EB000768, R00 AG033670]; [RYC-2008-02333] FX This study was supported by RYC-2008-02333, ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion (PS09/00969), Junta de Andalucia, Proyectos de Excelencia (P11-CTS-7847), Instituto de Salud Carlos III and FEDER (European Union), cofinanced by Fondo Europeo de Desarrollo Regional "Una manera de hacer Europa" PI12/00675 (Monica Garcia-Alloza), NIH R01 EB000768 (Brian J. Bacskai), and NIH R00 AG033670 (Tara L. Spires-Jones). NR 51 TC 22 Z9 23 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2013 VL 72 IS 4 BP 272 EP 285 DI 10.1097/NEN.0b013e318288a8dd PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 117HM UT WOS:000316944200001 PM 23481704 ER PT J AU Lee, SW Eddington, DK Fried, SI AF Lee, Seung Woo Eddington, Donald K. Fried, Shelley I. TI Responses to pulsatile subretinal electric stimulation: effects of amplitude and duration SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE electrical stimulation; patch-clamp cell recordings; ganglion cells; subretinal implant; retinal prosthesis ID RETINAL GANGLION-CELLS; ISOLATED CHICKEN RETINA; BIPOLAR CELLS; MAMMALIAN RETINA; AMACRINE CELLS; RABBIT RETINA; ACTIVATION; THRESHOLDS; MICROELECTRODE; DEGENERATION AB Lee SW, Eddington DK, Fried SI. Responses to pulsatile subretinal electric stimulation: effects of amplitude and duration. J Neurophysiol 109: 1954-1968, 2013. First published January 23, 2013; doi:10.1152/jn.00293.2012.-In working to improve the quality of visual percepts elicited by retinal prosthetics, considerable effort has been made to understand how retinal neurons respond to electric stimulation. Whereas responses arising from direct activation of retinal ganglion cells have been well studied, responses arising through indirect activation (e. g., secondary to activation of bipolar cells) are not as well understood. Here, we used cell-attached, patch-clamp recordings to measure the responses of rabbit ganglion cells in vitro to a wide range of stimulus-pulse parameters (amplitudes: 0-100 mu A; durations: 0.1-50 ms), applied to a 400-mu m-diameter, subretinal-stimulating electrode. The indirect responses generally consisted of multiple action potentials that were clustered into bursts, although the latency and number of spikes within a burst were highly variable. When different parameter pairs representing identical charge levels were compared, the shortest pulse durations generally elicited the most spikes. In addition, latencies were shortest, and jitter was lowest for short pulses. These findings suggest that short pulses are optimum for activation of presynaptic neurons, and therefore, short pulses are more effective for both direct as well as indirect activation. C1 [Lee, Seung Woo; Fried, Shelley I.] Vet Affairs Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA USA. [Lee, Seung Woo; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Eddington, Donald K.] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. RP Fried, SI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Simches Res Ctr, Rm 3824,185 Cambridge St, Boston, MA 02114 USA. EM Fried.Shelley@mgh.harvard.edu FU Veterans Administration [MR1I01RX000350-01A1]; National Eye Institute [R01-EY019967] FX Support for this work was provided by the Veterans Administration (MR1I01RX000350-01A1) and by the National Eye Institute (R01-EY019967). NR 46 TC 12 Z9 12 U1 1 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2013 VL 109 IS 7 BP 1954 EP 1968 DI 10.1152/jn.00293.2012 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 118AQ UT WOS:000316995200024 PM 23343891 ER PT J AU Walcott, BP Kwon, CS Sheth, SA Fehnel, CR Koffie, RM Asaad, WF Nahed, BV Coumans, JV AF Walcott, Brian P. Kwon, Churl-Su Sheth, Sameer A. Fehnel, Corey R. Koffie, Robert M. Asaad, Wael F. Nahed, Brian V. Coumans, Jean-Valery TI Predictors of cranioplasty complications in stroke and trauma patients Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE cranioplasty; trauma; infection; complication; stroke; decompressive; craniectomy; traumatic brain injury; vascular disorders ID RESISTANT STAPHYLOCOCCUS-AUREUS; CEREBRAL-ARTERY INFARCTION; INTENSIVE-CARE UNITS; DECOMPRESSIVE CRANIECTOMY; RISK-FACTORS; WOUND-INFECTION; ISCHEMIC-STROKE; BRAIN-INJURY; CONTROLLED-TRIAL; CARDIAC-SURGERY AB Object. Decompressive craniectomy mandates subsequent cranioplasty. Complications of cranioplasty may be independent of the initial craniectomy, or they may be contingent upon the craniectomy. Authors of this study aimed to identify surgery- and patient-specific risk factors related to the development of surgical site infection and other complications following cranioplasty. Methods. A consecutive cohort of patients of all ages and both sexes who had undergone cranioplasty following craniectomy for stroke or trauma at a single institution in the period from May 2004 to May 2012 was retrospectively established. Patients who had undergone craniectomy for infectious lesions or neoplasia were excluded. A logistic regression analysis was performed to model and predict determinants related to infection following cranioplasty. Results. Two hundred thirty-nine patients met the study criteria. The overall rate of complication following cranioplasty was 23.85% (57 patients). Complications included, predominantly, surgical site infection, hydrocephalus, and new-onset seizures. Logistic regression analysis identified previous reoperation (OR 3.25, 95% CI 1.30-8.11, p = 0.01) and therapeutic indication for stroke (OR 2.45, 95% CI 1.11-5.39, p = 0.03) as significantly associated with the development of cranioplasty infection. Patient age, location of cranioplasty, presence of an intracranial device, bone flap preservation method, cranioplasty material, booking method, and time interval > 90 days between initial craniectomy and cranioplasty were not predictive of the development of cranioplasty infection. Conclusions. Cranioplasty complications are common. Cranioplasty infection rates are, predicted by reoperation following craniectomy and therapeutic indication (stroke). These variables may be associated with patient-centered risk factors that increase cranioplasty infection risk. (http://thejns.org/doi/abs/10.3171/2013.1.JNS121626) C1 [Walcott, Brian P.; Kwon, Churl-Su; Sheth, Sameer A.; Koffie, Robert M.; Nahed, Brian V.; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Kwon, Churl-Su; Sheth, Sameer A.; Koffie, Robert M.; Nahed, Brian V.; Coumans, Jean-Valery] Harvard Univ, Sch Med, Boston, MA USA. [Fehnel, Corey R.] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA. [Fehnel, Corey R.] Rhode Isl Hosp, Providence, RI USA. [Asaad, Wael F.] Dept Neurosurg, Providence, RI USA. [Asaad, Wael F.] Brown Inst Brain Sci, Providence, RI USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 NR 51 TC 37 Z9 40 U1 1 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2013 VL 118 IS 4 BP 757 EP 762 DI 10.3171/2013.1.JNS121626 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 114BT UT WOS:000316715700012 PM 23394335 ER PT J AU Ngwenya, LB Chiocca, EA AF Ngwenya, Laura B. Chiocca, E. Antonio TI Postoperative ischemia SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID GLIOMA; RESECTION C1 [Ngwenya, Laura B.] Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Chiocca, E. Antonio] Brigham & Womens Faulkner Hosp, Dept Neurosurg, Boston, MA USA. [Chiocca, E. Antonio] Brigham & Womens Faulkner Hosp, Inst Neurosci, Boston, MA USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Ngwenya, LB (reprint author), Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2013 VL 118 IS 4 BP 799 EP 800 DI 10.3171/2012.8.JNS121410 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 114BT UT WOS:000316715700019 PM 23373805 ER PT J AU Boucher, J Roper, K Underhill, M Berry, D AF Boucher, Jean Roper, Kristin Underhill, Meghan Berry, Donna TI Science and Practice Aligned Within Nursing Structure and Process for Evidence-Based Practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PARIHS FRAMEWORK; IMPLEMENTATION; EXCELLENCE; HOSPITALS; OUTCOMES; INQUIRY AB Science and Practice Aligned Within Nursing (SPAWN) is an innovative method developed to guide the implementation of evidence-based practice (EBP) by oncology nurses in direct patient care settings. Science and Practice Aligned Within Nursing actualizes and addresses the important and essential practice component of EBP in oncology nursing. This article describes the development of SPAWN infrastructure, phases of the process, implementation, outcome evaluation, key insights, and lessons learned. C1 [Boucher, Jean; Roper, Kristin; Underhill, Meghan; Berry, Donna] Phyllis F Cantor Ctr Res Nursing & Patient Care S, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Boucher, J (reprint author), Phyllis F Cantor Ctr Res Nursing & Patient Care S, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jean_boucher@dfci.harvard.edu NR 30 TC 2 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD APR PY 2013 VL 43 IS 4 BP 229 EP 234 DI 10.1097/NNA.0b013e3182895a5b PG 6 WC Nursing SC Nursing GA 116WJ UT WOS:000316913700010 PM 23528689 ER PT J AU Almog, DM Padberg, FT Carmel, G Friedlander, AH AF Almog, Dov M. Padberg, Frank T., Jr. Carmel, Gwendolyhn Friedlander, Arthur H. TI Previously Unappreciated Carotid Artery Stenosis Diagnosed by Cone Beam Computerized Tomography SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PANORAMIC RADIOGRAPHS; HEART-DISEASE; ENDARTERECTOMY; ASSOCIATION; SOCIETY; TRIAL AB Stroke is the third leading cause of death in the western world. Calcification noted on cone beam computerized tomography, frequently used to evaluate the maxillofacial structures for extent of tumor, trauma, and implant placement, may indicate atherosclerotic disease in the carotid artery. Internal carotid artery stenosis is a recognized risk factor for stroke; multiple, large randomized controlled trials have demonstrated a decreased risk of stroke after repair of the stenotic artery. Recognition of calcified carotid artery plaque, on cone beam computerized tomography during the course of surgical care may offer the opportunity for stroke risk reduction. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:702-705, 2013 C1 [Almog, Dov M.] Univ Med & Dent New Jersey, New Jersey Med Sch, Vet Affairs New Jersey Healthcare Syst, Dent Serv, Newark, NJ 07103 USA. [Padberg, Frank T., Jr.] Vet Affairs New Jersey Healthcare Syst, Newark, NJ USA. [Padberg, Frank T., Jr.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Div Vasc Surg, Newark, NJ 07103 USA. [Carmel, Gwendolyhn] Vet Affairs New Jersey Healthcare Syst, Dept Surg, Vasc Lab, E Orange, NJ USA. [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Hosp Dent Serv Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, 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 NR 20 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2013 VL 71 IS 4 BP 702 EP 705 DI 10.1016/j.joms.2012.09.021 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 114MP UT WOS:000316745800018 PM 23245518 ER PT J AU Goldwaser, BR Magill, J Papadaki, ME Byl, M Kromann, R Yates, B Morency, J Kaban, LB Troulis, MJ AF Goldwaser, Batya R. Magill, John Papadaki, Maria E. Byl, Martyn Kromann, Roger Yates, Brent Morency, Joe Kaban, Leonard B. Troulis, Maria J. TI Continuous Mandibular Distraction Osteogenesis: Novel Device and Preliminary Results in Minipigs SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID GRADUAL DISTRACTION; BONE DISTRACTION AB Purpose: To develop and test a novel, hydraulic, continuous, automated distraction device capable of 3D movements for treatment of mandibular deformities. Materials and Methods: We used 2 cadaveric and 5 live female Yucatan minipigs to test the distractor. The 3 components (miniature buried distractor, external power and control box, and user interface on handheld computer) operate on a closed loop in which the hydraulic pulse strength correlates with the resistance of the bone and soft tissue. The system auto-adjusts to correct any discrepancy between the actual and desired position of mandibular fragments. The distraction protocol included 0-day latency, 1 mm (divided into 94 increments) per day, and 24 days' fixation. Clinical examination was performed and lateral and anteroposterior cephalometric radiographs were obtained preoperatively and postoperatively, at mid distraction osteogenesis (DO), end DO, and end fixation. Position information was obtained through the user interface. Results: Both cadaveric trials resulted in the desired distraction gap (11 to 12 mm), with all components functioning as designed. In 4 of the 5 live animals, distraction averaged 7.29 mm (range, 5 to 11 mm) over 12 days of activation. In 3 of the 5 live animals, the osteotomy gap filled in with bone by 24 days of fixation. Two animals were sacrificed prematurely (1 at mid DO and 1 at end DO) because vital components malfunctioned. Conclusions: The device is capable of automated, continuous, hydraulically powered DO at a rate of 1 mm/d. Future work will be directed at fortifying the device components and testing it in larger numbers of animals at varying distraction rates. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:e168-e177, 2013 C1 [Goldwaser, Batya R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Magill, John; Byl, Martyn; Morency, Joe] Phys Sci Inc, Andover, MA 01810 USA. [Papadaki, Maria E.; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Papadaki, Maria E.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Kromann, Roger; Yates, Brent] Embedded Syst Design, Atlanta, GA USA. [Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Residency Training Program, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org FU Hanson Foundation (Boston, MA); Massachusetts General Hospital OMFS Education and Research Fund; National Institutes of Health Small Business Innovation Research Grant [5R44 DE 014803-03]; Harvard Medical School Office of Enrichment Programs FX Supported in part by the Hanson Foundation (Boston, MA), the Massachusetts General Hospital OMFS Education and Research Fund, a National Institutes of Health Small Business Innovation Research Grant (5R44 DE 014803-03), and Harvard Medical School Office of Enrichment Programs. NR 28 TC 7 Z9 7 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2013 VL 71 IS 4 BP E168 EP E177 DI 10.1016/j.joms.2012.09.012 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 114MP UT WOS:000316745800003 PM 23507324 ER PT J AU Ullrich, C Morrison, RS AF Ullrich, Christina Morrison, R. Sean TI Pediatric Palliative Care Research Comes of Age: What We Stand To Learn from Children with Life-Threatening Illness SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID YOUNG-ADULTS C1 [Ullrich, Christina] Boston Childrens Hosp, Dept Med, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Ullrich, Christina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Ullrich, Christina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. RP Ullrich, C (reprint author), Boston Childrens Hosp, Dept Med, Div Pediat Hematol Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [5K23HL107452-02]; NIA NIH HHS [5K24AG022345-10] NR 8 TC 6 Z9 6 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2013 VL 16 IS 4 BP 334 EP 336 DI 10.1089/jpm.2013.9518 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 116BJ UT WOS:000316857000002 PM 23461300 ER PT J AU Leigh, AE Burgio, KL Williams, BR Kvale, E Bailey, FA AF Leigh, Alexandra E. Burgio, Kathryn L. Williams, Beverly R. Kvale, Elizabeth Bailey, F. Amos TI Hospice Emergency Kit for Veterans: A Pilot Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MEDICATION MANAGEMENT; HOME; CAREGIVERS; DIE AB Background: Although the provision of hospice emergency kits (HEKs) by home hospice agencies is thought to be widespread, little is known about their use, safety, and impact. Objective: This study evaluated HEK medication utilization, safety, diversion, and perceived impact. Design: Evaluation consisted of a retrospective patient chart abstraction and an anonymous questionnaire for home hospice nurses. Setting/subjects: Chart abstraction examined the computerized records of deceased veterans discharged to home hospice in 2009 (N = 76). The questionnaire was completed by 78 home hospice nurses from 16 agencies. Measurements: Chart abstraction examined HEK medication utilization, symptoms addressed, and safety / diversion concerns. The hospice nurse questionnaire assessed their perceptions of HEK utilization, safety, and impact, including efficacy for preventing emergency department (ED) visits and hospitalizations. Results: Of patients who received an HEK, its use was documented in 50% of cases. The most used items were morphine concentrate and antibiotics. Nurses estimated that the HEK was utilized in 66.3% of cases, with the most frequently used medications being morphine, lorazepam, promethazine, and haloperidol. Fifty-nine percent of nurses felt HEKs were helpful 100% of the time (mean = 84.2%; median = 100% of the time) and 93% felt that an emergency department (ED) visit or hospitalization was avoided by having the kit in the home. Eighteen percent believed that medications in the kit are used by someone other than the patient. Conclusions: HEKs have value as a means to alleviate many symptoms that emerge predictably in home hospice patients and may avoid unwanted hospitalizations and ED visits. C1 [Leigh, Alexandra E.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Burgio, Kathryn L.; Williams, Beverly R.; Kvale, Elizabeth; Bailey, F. Amos] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA. [Burgio, Kathryn L.; Williams, Beverly R.; Kvale, Elizabeth; Bailey, F. Amos] Univ Alabama Birmingham, Birmingham, AL USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 11G 700 South 19th St, Birmingham, AL 35233 USA. EM kburgio@uabmc.edu FU Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC) FX This researh was supported by the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC). The authors thank Donna Hix, RN, the Hospice and Palliative Care Coordinator for the BVAMC, and Shanette Granstaff, MPH, for analytic support. NR 18 TC 2 Z9 2 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2013 VL 16 IS 4 BP 356 EP 361 DI 10.1089/jpm.2012.0304 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 116BJ UT WOS:000316857000009 PM 23445251 ER PT J AU Winter, L AF Winter, Laraine TI Patient Values and Preferences for End-of-Life Treatments: Are Values Better Predictors Than a Living Will? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ADVANCE DIRECTIVES; OLDER-ADULTS; DECISION-MAKING; CARE; VALIDATION; QUALITY; HISTORY; BURDEN; HEALTH AB Background: Advance care planning is widely considered important for good treatment decision making. Patient values have been proposed as superior to standard living wills as guides to end-of-life (EOL) care decisions on behalf of decisionally incapacitated patients. Little research has examined whether values outperform living wills as predictors of treatment preferences. Objective: The study aimed to test whether patient values are associated with treatment preferences, compare values and preferences to responses from a standard living will, and determine whether some values are better predictors than others. Design: Community-dwelling elderly men and women (n = 304) were interviewed in their homes by telephone. The interview consisted of an eight-item EOL values scale, a standard living will question, preferences for four life-prolonging treatments in each of six scenarios, and sociodemographic questions. Results: Principal components analysis of the EOL values revealed two factors: (1) dignity, pain management, and reluctance to burden others; and (2) religiosity and desire for longevity and following family wishes. In regression analyses, stronger preferences for life-prolonging treatments were correlated with higher scores on factor 1 and lower scores on factor 2. But when living will responses were also entered into the regression model, only religiosity, longevity, and following family wishes predicted treatment preferences independently of the living will responses. Conclusions: Providing better guidance than a living will in determining a patient's EOL treatment preferences are (1) knowledge about a patient's religiosity, (2) patient's wishes for longevity, and (3) patient's wishes for following family preferences. Wishes for dignity and pain management and reluctance to burden others do not offer better guidance than a living will. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Winter, L (reprint author), Philadelphia VA Med Ctr, 3800 Woodland Ave, Philadelphia, PA 19104 USA. EM Laraine.winter@gmail.com NR 34 TC 3 Z9 3 U1 5 U2 29 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2013 VL 16 IS 4 BP 362 EP 368 DI 10.1089/jpm.2012.0303 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 116BJ UT WOS:000316857000010 PM 23442042 ER PT J AU Yoong, J Traeger, LN Gallagher, ER Pirl, WF Greer, JA Temel, JS AF Yoong, Jaclyn Traeger, Lara N. Gallagher, Emily R. Pirl, William F. Greer, Joseph A. Temel, Jennifer S. TI A Pilot Study To Investigate Adherence to Long-Acting Opioids among Patients with Advanced Lung Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HIV PROTEASE INHIBITORS; SELF-REPORTED ADHERENCE; QUALITY-OF-CARE; PAIN MANAGEMENT; MEDICATION ADHERENCE; DEPRESSION; BARRIERS; VALIDITY; QUESTIONNAIRES; OUTPATIENTS AB Background: Uncontrolled pain remains prevalent in patients with advanced cancer and has been associated with worse quality of life and greater health care utilization. Poor adherence to analgesics may represent a modifiable barrier to pain management. Objective: This pilot study aimed to establish feasibility/utility of evaluating self-reported adherence to long-acting (LA) opioids in patients with advanced lung cancer, and to explore rates and correlates of adherence. Methods: Consecutive patients attending an ambulatory thoracic oncology clinic with a diagnosis of advanced lung cancer and a current LA opioid regimen were approached to complete a brief questionnaire during their clinic visit. Participants reported LA opioid adherence during the past 4 weeks (0%-100%) and knowledge of their LA opioid regimen, and completed the Patient Health Questionnaire-2 (PHQ-2) depression screen. Demographic and clinical information were confirmed via electronic health record review. Results: Fifty-four eligible patients were approached to reach our target sample (n = 50; enrollment = 92.6%). Self-reported adherence to LA opioids was 85.4% (standard deviation [SD] = 21.0). Twenty-eight percent reported a frequency of medication use that did not match the prescribed daily frequency. Lower adherence was associated with inaccurate frequency (p = 0.004), positive depression screen (p = 0.005), and older age (p = 0.04). Conclusions: Our results demonstrate the feasibility of integrating self-report assessments of LA opioid adherence into a thoracic oncology clinic. Patients reported high adherence, but more than one-quarter did not accurately report the prescribed frequency of daily doses. Understanding of LA opioid regimens may be a critical indicator of adherence in patients with advanced cancer. C1 [Yoong, Jaclyn] St Vincents Hosp Melbourne, Caritas Christi Hosp, Melbourne, Vic, Australia. [Traeger, Lara N.; Gallagher, Emily R.; Pirl, William F.; Greer, Joseph A.; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Yoong, J (reprint author), Caritas Christi Hosp, St Vincents Hosp, 104 Studley Pk Rd, Kew, Vic 3101, Australia. EM jackieyoong@hotmail.com FU Massachusetts General Hospital Thoracic Oncology Quality of Life Fund FX This study was supported by the Massachusetts General Hospital Thoracic Oncology Quality of Life Fund. NR 56 TC 7 Z9 7 U1 2 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2013 VL 16 IS 4 BP 391 EP 396 DI 10.1089/jpm.2012.0400 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 116BJ UT WOS:000316857000014 PM 23445248 ER PT J AU ter Horst, EN van der Laan, AM Begieneman, MPV Hirsch, A Krijnen, PAJ Nahrendorf, M Horrevoets, AJ Niessen, HWM Piek, JJ AF ter Horst, E. N. van der Laan, A. M. Begieneman, M. P. V. Hirsch, A. Krijnen, P. A. J. Nahrendorf, M. Horrevoets, A. J. Niessen, H. W. M. Piek, J. J. TI Monocyte Subset Accumulation in the Human Heart Following Acute Myocardial Infarction and the Role of the Spleen as Monocyte Reservoir SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 203rd Winter Joint Meeting of the Pathological-Society-of-Great-Britain-and-Ireland and the Dutch-Pathological-Society (NVVP) CY JAN 08-09, 2013 CL Univ Med Ctr, Dept Pathol, Utrecht, NETHERLANDS SP Pathol Soc Great Britain & Ireland, Dutch Pathol Soc (NVVP) HO Univ Med Ctr, Dept Pathol C1 [ter Horst, E. N.; van der Laan, A. M.; Hirsch, A.; Piek, J. J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Begieneman, M. P. V.; Krijnen, P. A. J.; Horrevoets, A. J.; Niessen, H. W. M.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Nahrendorf, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD APR PY 2013 VL 229 SU 1 BP S11 EP S11 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 113VG UT WOS:000316696800035 ER PT J AU Maneta, EK Cohen, S Schulz, MS Waldinger, RJ AF Maneta, E. K. Cohen, S. Schulz, M. S. Waldinger, R. J. TI TWO TO TANGO: A DYADIC ANALYSIS OF LINKS BETWEEN BORDERLINE PERSONALITY TRAITS AND INTIMATE PARTNER VIOLENCE SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID CONFLICT-TACTICS-SCALES; DIMENSIONAL MODEL; PHYSICAL ABUSE; RISK-FACTORS; DISORDER; ORGANIZATION; EXPERIENCES; AGGRESSION; COUPLES; STRESS AB Although research has shown links between borderline personality and intimate partner violence (IPV), few studies have examined how each partner's personality traits may influence the other's behavior (Hines, 2008). This study incorporated dimensional assessments of borderline personality organization (BPO) in both partners into a dyadic model that examined associations with IPV. In a community sample of 109 couples, an Actor-Partner Interdependence Model was used to examine links between BPO traits in each partner and victimization and perpetration of IPV. Men's level of BPO traits was associated with more IPV toward and more victimization by their partners. Women's level of BPO traits was associated with their victimization only. This study is unique in examining links between BPO and IPV in couples using analyses that account for the interdependence of these variables in dyads. C1 [Maneta, E. K.] Harvard Univ, Sch Med, Childrens Hosp Boston, Cambridge, MA 02138 USA. [Cohen, S.; Waldinger, R. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Schulz, M. S.] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA. RP Maneta, EK (reprint author), 151 Merrimac St,2nd Floor, Boston, MA 02114 USA. EM manetael@gmail.com FU NIMH NIH HHS [K08 MH01555] NR 41 TC 8 Z9 8 U1 2 U2 24 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD APR PY 2013 VL 27 IS 2 BP 233 EP 243 PG 11 WC Psychiatry SC Psychiatry GA 115RL UT WOS:000316829500008 PM 23514186 ER PT J AU Maas, MB Singhal, AB AF Maas, Matthew B. Singhal, Aneesh B. TI Unwitnessed Stroke: Impact of Different Onset Times on Eligibility into Stroke Trials SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Enrollment; onset; stroke; time; trials ID ACUTE ISCHEMIC-STROKE AB Background: Patients with unwitnessed stroke represent >25% of all strokes. Clinical trials enrolling patients with unwitnessed stroke onset have conservatively used last known normal (LKN) as the time of stroke onset. We explored the impact of alternative methods of selecting onset time in unwitnessed strokes on eligibility into an acute stroke therapeutic trial using a representative sample of acute stroke subjects. Methods: We analyzed data on 641 consecutive patients with suspected stroke presenting to our hospital between January 2007 and July 2008. Time of onset was calculated by 3 methods: (1) LKN, (2) first known abnormal (FKA), and (3) midpoint between LKN and FKA. Subjects with incomplete data or a final diagnosis of non-ischemic stroke were excluded. Rates of trial eligibility based on different onset times were compared for several inclusion time windows. Results: Onset time was known in 440 subjects (69%). Of the remaining 201 patients with unwitnessed onset, 114 (57%) were "wake-up" strokes. Among unwitnessed stroke subjects, eligibility increased from 18% using LKN to 57% using FKA at 4.5 hours and 42% to 81% at 9 hours (P < .001), respectively. Overall enrollment eligibility for the full cohort increased from 36% to 48% at 4.5 hours and 61% to 73% at 9 hours (P < .001), respectively. Conclusion: Given potential advantages in safety evaluation and the historical inadequate enrollment rates in acute stroke trials, alternative onset time definitions, perhaps in combination with advanced neuroimaging methods (e. g., fluid-attenuated inversion recovery-diffusion-weighted imaging mismatch), should be considered for early-phase trials. C1 [Maas, Matthew B.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Singhal, Aneesh B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Maas, MB (reprint author), Northwestern Univ, Dept Neurol, 710 N Lake Shore Dr 11th Fl, Chicago, IL 60611 USA. EM mbmaas@northwestern.edu FU National Institutes of Health [P50NS051343, 5R01NS051412] FX Supported by National Institutes of Health grants P50NS051343 and 5R01NS051412. NR 9 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD APR PY 2013 VL 22 IS 3 BP 241 EP 243 DI 10.1016/j.jstrokecerebrovasdis.2011.08.004 PG 3 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 114GE UT WOS:000316728300009 PM 21917477 ER PT J AU Bhan, I Thadhani, R AF Bhan, Ishir Thadhani, Ravi TI Fibroblast Growth Factor-23 and Outcomes: New Answers, New Questions SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR EVENTS; PHOSPHATE-METABOLISM; MORTALITY; FGF23; HEMODIALYSIS C1 [Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM ibhan@partners.org FU NIDDK NIH HHS [K24 DK094872] NR 12 TC 0 Z9 0 U1 0 U2 30 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2013 VL 24 IS 4 BP 523 EP 525 DI 10.1681/ASN.2013020169 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 116ZK UT WOS:000316921700003 PM 23520207 ER PT J AU Dominguez, JR Shlipak, MG Whooley, MA Ix, JH AF Dominguez, Julie R. Shlipak, Michael G. Whooley, Mary A. Ix, Joachim H. TI Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GELATINASE-ASSOCIATED LIPOCALIN; INJURY MOLECULE-1 KIM-1; CORONARY-HEART-DISEASE; CARDIOVASCULAR EVENTS; CYSTATIN-C; ATHEROSCLEROSIS; COMMUNITY; KLOTHO; HEALTH AB Fibroblast growth factor-23 (FGF23) induces phosphaturia through its effects on renal tubules. Higher levels of FGF23 associate with cardiovascular disease (CVD) events and all-cause mortality, but it is unknown whether these associations differ by the degree of phosphaturia. Here, we measured serum FGF23 and 24-hour urine fractional excretion of phosphorus (FePi) in 872 outpatients with stable CVD and a mean estimated G FR of 71 ml/nnin per 1.73 m(2). During an average 7.5 years of follow-up, there were 337 deaths and 199 CVD events. Urinary Fe Pi significantly modified the association of FGF23 with each outcome (P interaction<0.001 for all-cause mortality and P P interaction<0.05 for CVD events). In models adjusted for CVD risk factors, kidney function, and PTH, those patients who had FGF23 above the median (>= 42.3 relative units [RU]/ml) but FePi below the median (<15.7%) had the highest risks of both all-cause mortality (HR=1.98, 95% CI=1.42-2.77) and CVD events (HR=1.92, 95% CI=1.25-2.94) compared with those patients who had low concentrations of FGF23 and low FePi. In summary, associations of FGF23 with mortality and CVD events are stronger in persons with lower FePi independent of PTH and kidney function. In such individuals, the renal tubular response to FGF23 may be suboptimal. J Am Soc Nephrol 24: 647-654, 2013. doi: 10.1681/ASN.2012090894 C1 [Dominguez, Julie R.; Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Dominguez, Julie R.; Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu FU National Heart, Lung, and Blood Institute Training Grant [T32 HL007261]; National Heart, Lung, and Blood Institute [R01HL096851]; Department of Veterans Epidemiology Merit Review Program; Department of Veterans Affairs Health Services Research and Development Service, National Heart, Lung, and Blood Institute [R01 HL079235]; National Heart, Lung, and Blood Institute; American Federation for Aging Research (Paul Beeson Scholars Program); Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program); Ischemia Research and Education Foundation; American Heart Association; Sandra A. Daugherty Foundation; Veterans Affairs San Diego Healthcare System FX J.R.D. was supported by National Heart, Lung, and Blood Institute Training Grant T32 HL007261. J.H.I. was supported by National Heart, Lung, and Blood Institute Grant R01HL096851. The Heart and Soul Study was supported by the Department of Veterans Epidemiology Merit Review Program, the Department of Veterans Affairs Health Services Research and Development Service, National Heart, Lung, and Blood Institute Grant R01 HL079235, the American Federation for Aging Research (Paul Beeson Scholars Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), and the Ischemia Research and Education Foundation. This ancillary study was supported by the American Heart Association and the National Heart, Lung, and Blood Institute. Fibroblast growth factor-23 and urine measurements were supported by grants from the American Heart Association and the Sandra A. Daugherty Foundation. This material is the result of work supported with resources of the Veterans Affairs San Diego Healthcare System. NR 31 TC 39 Z9 39 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2013 VL 24 IS 4 BP 647 EP 654 DI 10.1681/ASN.2012090894 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 116ZK UT WOS:000316921700016 PM 23520205 ER PT J AU Rusch, V Baldini, EH Bueno, R De Perrot, M Flores, R Hasegawa, S Klepetko, W Krug, L Lang-Lazdunski, L Pass, H Weder, W Sugarbaker, DJ AF Rusch, Valerie Baldini, Elizabeth H. Bueno, Raphael De Perrot, Marc Flores, Raja Hasegawa, Seiki Klepetko, Walter Krug, Lee Lang-Lazdunski, Loic Pass, Harvey Weder, Walter Sugarbaker, David J. CA Participants Int Mesothelioma Inte TI The role of surgical cytoreduction in the treatment of malignant pleural mesothelioma: Meeting summary of the International Mesothelioma Interest Group Congress, September 11-14, 2012, Boston, Mass SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID FEASIBILITY C1 [Rusch, Valerie] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, New York, NY 10021 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [De Perrot, Marc] Toronto Gen Hosp, Div Thorac Surg, Toronto, ON, Canada. [De Perrot, Marc] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. [Flores, Raja] Mt Sinai Med Ctr, Div Thorac Surg, New York, NY 10029 USA. [Hasegawa, Seiki] Hyogo Coll Med, Dept Surg, Nishinomiya, Hyogo 6638501, Japan. [Klepetko, Walter] Med Univ Vienna, Ctr Comprehens Canc, Dept Surg, Div Thorac Surg, Vienna, Austria. [Krug, Lee] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Krug, Lee] Weill Cornell Med Coll, New York, NY USA. [Lang-Lazdunski, Loic] Guys Hosp, Dept Thorac Surg, London SE1 9RT, England. [Pass, Harvey] NYU, Langone Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Weder, Walter] Univ Zurich Hosp, Div Thorac Surg, CH-8091 Zurich, Switzerland. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dsugarbaker@partners.org NR 11 TC 33 Z9 33 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2013 VL 145 IS 4 BP 909 EP 910 DI 10.1016/j.jtcvs.2013.01.039 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 114PA UT WOS:000316753100005 PM 23415687 ER PT J AU Sugarbaker, DJ Gill, RR Yeap, BY Wolf, AS DaSilva, MC Baldini, EH Bueno, R Richards, WG AF Sugarbaker, David J. Gill, Ritu R. Yeap, Beow Y. Wolf, Andrea S. DaSilva, Marcelo C. Baldini, Elizabeth H. Bueno, Raphael Richards, William G. TI Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT International Mesothelioma Interest Group Congress CY SEP 11-14, 2012 CL Boston, MA ID EXTRAPLEURAL PNEUMONECTOMY; PHASE-II; INTRAPLEURAL CISPLATIN; MULTIMODALITY THERAPY; TRIMODALITY THERAPY; CYTOPROTECTION AB Objective: Local recurrence limits long-term survival in patients with malignant pleural mesothelioma. We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors. Methods: Using a preoperative risk assessment algorithm we had previously developed and validated, we retrospectively identified a cohort of patients treated with cytoreductive surgery from 2001 to 2009. The patients had epithelial histologic findings on biopsy and were characterized as having a low risk of early recurrence and death (ie, tumor volume <= 500 cm(3) and were either men with a hemoglobin level of >= 13 g/dL or were women). Those patients who had received hyperthermic intraoperative cisplatin chemotherapy were compared with a comparison group of those who had not. Fisher's exact test was used to determine the balance of prognostic factors. The Kaplan-Meier method and log-rank tests were used to estimate and compare the interval to recurrence and overall survival. Cox proportional hazards regression was used for multivariate analysis. Results: The cohort criteria identified 103 patients: 72 who received hyperthermic intraoperative cisplatin chemotherapy and 31 who did not. The groups were balanced for prognostic factors, except for the use of neoadjuvant chemotherapy (more common in the comparison group). The hyperthermic intraoperative cisplatin chemotherapy group exhibited a significantly longer interval to recurrence (27.1 vs 12.8 months) and overall survival (35.3 vs 22.8 months) than the comparison group. The improved interval to recurrence and overall survival for the hyperthermic intraoperative cisplatin chemotherapy group were particularly evident among the subgroups of patients who had not received hemithoracic radiotherapy and who had pathologic stage N1 or N2 lymph node metastases. Conclusions: A favorable outcome and minimal incremental morbidity support the incorporation of hyperthermic intraoperative cisplatin chemotherapy into multimodality treatment strategies for patients with low-risk epithelial malignant pleural mesothelioma. (J Thorac Cardiovasc Surg 2013;145:955-63) C1 [Sugarbaker, David J.; Wolf, Andrea S.; DaSilva, Marcelo C.; Bueno, Raphael; Richards, William G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg, Boston, MA 02115 USA. [Gill, Ritu R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Baldini, Elizabeth H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dsugarbaker@partners.org NR 26 TC 29 Z9 30 U1 0 U2 8 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 2013 VL 145 IS 4 BP 955 EP 963 DI 10.1016/j.jtcvs.2012.12.037 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 114PA UT WOS:000316753100012 PM 23434448 ER EF